Obstetrics

NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”

The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.

As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.

Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.

In regard to women of child-bearing age, Dr. Shah recommends that family planning and contraception should be discussed at the initial visit and every subsequent visit. Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.

Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.

If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.

What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.

Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.

NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”

The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.

As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.

Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.

In regard to women of child-bearing age, Dr. Shah recommends that family planning and contraception should be discussed at the initial visit and every subsequent visit. Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.

Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.

If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.

What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.

Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.

NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”

The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.

As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.

Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.

In regard to women of child-bearing age, Dr. Shah recommends that family planning and contraception should be discussed at the initial visit and every subsequent visit. Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.

Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.

If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.

What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.

Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.

Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

CASE Placenta accreta spectrum following uncomplicated vaginal delivery

Imagine you are an obstetric hospitalist taking call at a level II maternal level of care hospital. Your patient is a 35-year-old woman, gravida 2, para 1, with a past history of retained placenta requiring dilation and curettage and intravenous antibiotics for endomyometritis. This is an in vitro fertilization pregnancy that has progressed normally, and the patient labored spontaneously at 38 weeks’ gestation. Following an uncomplicated vaginal delivery, the placenta has not delivered, and you attempt a manual placental extraction after a 40-minute third stage. While there is epidural analgesia and you can reach the uterine fundus, you are unable to create a separation plane between the placenta and uterus.

What do you do next?

Placenta accreta spectrum (PAS) includes a broad range of clinical scenarios with abnormal placental attachment as their common denominator. The condition has classically been defined pathologically, with chorionic villi attaching directly to the myometrium (“accreta”) or extending more deeply into the myometrium (“increta”) or attaching to surrounding tissues and structures (“percreta”).¹ It is most commonly encountered in patients with low placental implantation on a prior cesarean section scar; indeed, placenta previa, particularly with a history of cesarean delivery, is the strongest risk factor for the development of PAS.² In addition to abnormal placental attachment, these placental attachments are often hypervascular and can lead to catastrophic hemorrhage if not managed appropriately. For this reason, patients with sonographic or radiologic signs of PAS should be referred to specialized centers for further workup, counseling, and delivery planning.³

Although delivery at a specialized PAS center has been associated with improved patient outcomes,⁴ not all patients with PAS will be identified in the antepartum period. Ultrasonography may miss up to 40% to 50% of PAS cases, particularly when the sonologist has not been advised to look for the condition,⁵ and not all patients with PAS will have a previa implanted in a prior cesarean scar. A recent study found that these patients with nonprevia PAS were identified by imaging less than 40% of the time and were significantly less likely to be managed by a specialized team of clinicians.⁶ Thus, it falls upon every obstetric care provider to be aware of this diagnosis, promptly recognize its unanticipated presentations, and have a plan to optimize patient safety.

Step 1: Recognition

While PAS is classically defined as a pathologic condition, no clinician has the luxury of histology in the delivery room. Researchers have variously defined PAS clinically, with the common trait of abnormal placental adherence.^7-9 The TABLE compares published definitions that have been used in the literature. While some definitions include hemorrhage, no clinician wants to induce significant hemorrhage to confirm their patient’s diagnosis. Thus, practically, the clinical PAS diagnosis comes down to abnormal placental attachment: If it is apparent that some or all of the placenta will not separate from the uterine wall with digital manipulation or careful curettage, then PAS should be suspected, and appropriate steps should be taken before further removal attempts.

At cesarean delivery, the PAS diagnosis may be aided by visual cues. With placenta previa, the lower uterine segment may bulge and take on a bluish hue, distinctly different from the upper healthy myometrium. PAS may also manifest with neovascularization, particularly behind the bladder. As with vaginal births, the placenta will fail to separate after the delivery, and controlled traction on the umbilical cord can produce a “dimple sign,” or visible myometrial retraction at the site of implantation (FIGURE 1). Finally, if the diagnosis is still in doubt, attempts to gently form a cleavage plane between the placenta and myometrium will be unsuccessful if PAS is present.⁸

Step 2: Initial management—pause, plan

Most importantly, do not attempt to forcibly remove the placenta. It can be left attached to the uterus until appropriate resources are secured. Efforts to forcibly remove an adherent placenta may well lead to major hemorrhage, and thus it falls on the patient’s care team to pause and plan for PAS care at this point. FIGURE 2 displays an algorithm for patient management. Further steps depend primarily on whether or not the patient is already hemorrhaging. In a stable situation, the patient should be counseled regarding the abnormal findings and the suspected PAS diagnosis. This includes the possibility of further procedures, blood transfusion, and hysterectomy. Local resources, including nursing, anesthesia, and the blood bank, should be notified about the situation and for the potential to call in specialized services. If on-site experienced specialists are not available, then patient transfer to a PAS specialty center should be strongly considered. While awaiting additional help or transport, the patient requires close monitoring for gross and physiologic signs of hemorrhage. If pursued, transport to a PAS specialty center should be expedited.

If the patient is already hemorrhaging or unstable, then appropriate local resources must be activated. At a minimum, this requires an obstetrician and anesthesiologist at the bedside and activation of hemorrhage protocols (eg, a massive transfusion protocol). If blood products are unavailable, consider whether they can be transported from other nearby blood banks, and start that process promptly. Next, contact backup services. Based on local resources and clinical severity, this may include maternal-fetal medicine specialists, pelvic surgeons, general and trauma surgeons, intensivists, interventional radiologists, and transfusion specialists. Even if the patient cannot be safely transferred to another hospital, the obstetrician can call an outside PAS specialist to discuss next steps in care and begin transfer plans, assuming the patient can be stabilized. Based on the Maternal Levels of Care definitions published by the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine,¹⁰ patients with PAS should be managed at level III or level IV centers. However, delivery units at every level of maternal care should have a protocol for securing local help and reaching an appropriate consultant if a PAS case is encountered. Know which center in your area specializes in PAS so that when an unanticipated case arises, you know who to call.

Continue to: Step 3: Ultimate management—mobilize and prepare for bleeding...

Step 3: Ultimate management—mobilize and prepare for bleeding

If diagnosis occurs intraoperatively at a PAS specialty center, or if safe transport is not possible, then the team should mobilize for the possibility of hysterectomy and prepare for massive bleeding, which can occur regardless of the treatment chosen. Many patients require or will opt for hysterectomy. For example, a patient who has finished childbearing may consent to a hysterectomy upon hearing she likely has PAS. In patients with suspected PAS who are actively hemorrhaging or are unstable, hysterectomy is required.

Uterine conservation may be considered in stable patients who strongly desire future childbearing or uterine retention. This often requires leaving densely adherent placental tissue in situ and thus requires thorough counseling regarding the risks of delayed hemorrhage, infection, and emergent hysterectomy.¹¹ This may not be desirable or safe for some patients, so informed consent is crucial. In such cases, we strongly recommend consultation with a PAS specialist, even if that requires immediate control of the placental blood supply (such as with arterial embolization), and transfer to a PAS specialty center.

Clinical scenarios

Vaginal delivery

The patient in the opening case was never expected to have PAS given her normal placental location and absence of a uterine scar. Even though she had some possible PAS risk factors (past retained placenta with instrumentation and in vitro fertilization), her absolute risk for the condition was low. Nevertheless, inability to create a separation plane should be considered PAS until proven otherwise. Although at this point many obstetricians would move to an operating room for uterine curettage, we recommend that the care team pause and put measures in place for possible PAS and hemorrhage. This involves notification of the blood bank, crossmatching of blood products, alerting the anesthesia team, and having a clear plan in place should a major hemorrhage ensue. This may involve use of balloon tamponade, activation of an interventional radiology team, or possible laparotomy with arterial ligations or hysterectomy. Avoidance of a prolonged third stage should be balanced against the need for preparation with these cases.

It is important for clinicians to bear in mind, and communicate to the patient, that hysterectomy is the standard of care for PAS. Significant delays in performing an indicated hysterectomy can lead to coagulopathy and patient instability. Timeliness is key; we find that delays in the decision to perform an indicated hysterectomy are often at the root of the cause for worsened morbidity in patients with unanticipated PAS. With an unscarred uterus and no placenta previa, a postpartum hysterectomy can be performed by many obstetrician-gynecologists experienced in this abdominal procedure.

Cesarean delivery

Undiagnosed PAS may present at cesarean delivery with or without placenta previa and a prior uterine scar. With this combination, PAS is often visually apparent upon opening the abdominal cavity (TABLE and FIGURE 1). Such surgical findings call for a clinical pause, as further actions at this point can lead to catastrophic hemorrhage. The obstetrician should consider a series of questions:

1. Are appropriate surgical and transfusion resources immediately available? If yes, they should be notified in case they are needed urgently. If not, then the obstetrician should ask whether the delivery must occur now.

2. Is this a scheduled delivery with a stable patient and fetus? If so, then closing the abdominal incision, monitoring the patient and fetus, and either transferring the patient to a PAS center or awaiting appropriate local specialists may be a lifesaving step.

3. Is immediate delivery required? If the fetus must be delivered, then it is imperative to create a hysterotomy out of the way of the placenta. Disrupting the adherent placenta with either an incision or manual manipulation may trigger a massive hemorrhage and should be avoided. This may require rectus muscle transection or creating a “T” incision on the skin to reach the uterine fundus and creating a hysterotomy over the top or even the back of the uterus. Once the fetus is delivered and lack of uterine hemorrhage confirmed (both abdominally and vaginally), the hysterotomy and abdomen can be closed with anticipation of urgent patient transfer to a PAS team or center.

4. Is the patient hemorrhaging? If the patient is hemorrhaging and closure is not an option, then recruitment of local emergent surgical teams is warranted, even if that requires packing the abdomen until an appropriate surgeon can arrive.

Diagnosis at cesarean delivery requires expedited and complex patient counseling. A patient who is unstable or hemorrhaging needs to be told that hysterectomy is lifesaving in this situation. For patients who are stable, it may be appropriate to close the abdomen and leave the placenta in situ, perform comprehensive counseling, and assess the possibility of transfer to a specialty center.

Summary

All obstetric care providers should be familiar with the clinical presentation of undiagnosed accreta spectrum. While hemorrhage is often part of the diagnosis, recognition of abnormal placental adherence and PAS-focused management should ideally be undertaken before this occurs. Once PAS is suspected, avoidance of further placental disruption may save significant morbidity, even if that means leaving the placenta attached until appropriate resources can be obtained. A local protocol for consultation, emergency transfer, and deployment of local resources should be part of every delivery unit’s emergency preparedness plan.

CASE Outcome

This patient is stabilized, with an adherent, retained placenta and no signs of hemorrhage. You administer uterotonics and notify your anesthesiologist and backup obstetrician that you have a likely case of accreta spectrum. A second intravenous line is placed, and blood products are crossmatched. The closest level III hospital is called, and they accept your patient for transfer. There, she is counseled about PAS, and she expresses no desire for future childbearing. After again confirming no placental separation in the operating room, the patient is moved immediately to perform laparotomy and total abdominal hysterectomy through a Pfannenstiel incision. She does not require a blood transfusion, and the pathology returns with grade I placenta accreta spectrum. ●

CASE Placenta accreta spectrum following uncomplicated vaginal delivery

Imagine you are an obstetric hospitalist taking call at a level II maternal level of care hospital. Your patient is a 35-year-old woman, gravida 2, para 1, with a past history of retained placenta requiring dilation and curettage and intravenous antibiotics for endomyometritis. This is an in vitro fertilization pregnancy that has progressed normally, and the patient labored spontaneously at 38 weeks’ gestation. Following an uncomplicated vaginal delivery, the placenta has not delivered, and you attempt a manual placental extraction after a 40-minute third stage. While there is epidural analgesia and you can reach the uterine fundus, you are unable to create a separation plane between the placenta and uterus.

What do you do next?

Placenta accreta spectrum (PAS) includes a broad range of clinical scenarios with abnormal placental attachment as their common denominator. The condition has classically been defined pathologically, with chorionic villi attaching directly to the myometrium (“accreta”) or extending more deeply into the myometrium (“increta”) or attaching to surrounding tissues and structures (“percreta”).¹ It is most commonly encountered in patients with low placental implantation on a prior cesarean section scar; indeed, placenta previa, particularly with a history of cesarean delivery, is the strongest risk factor for the development of PAS.² In addition to abnormal placental attachment, these placental attachments are often hypervascular and can lead to catastrophic hemorrhage if not managed appropriately. For this reason, patients with sonographic or radiologic signs of PAS should be referred to specialized centers for further workup, counseling, and delivery planning.³

Although delivery at a specialized PAS center has been associated with improved patient outcomes,⁴ not all patients with PAS will be identified in the antepartum period. Ultrasonography may miss up to 40% to 50% of PAS cases, particularly when the sonologist has not been advised to look for the condition,⁵ and not all patients with PAS will have a previa implanted in a prior cesarean scar. A recent study found that these patients with nonprevia PAS were identified by imaging less than 40% of the time and were significantly less likely to be managed by a specialized team of clinicians.⁶ Thus, it falls upon every obstetric care provider to be aware of this diagnosis, promptly recognize its unanticipated presentations, and have a plan to optimize patient safety.

Step 1: Recognition

While PAS is classically defined as a pathologic condition, no clinician has the luxury of histology in the delivery room. Researchers have variously defined PAS clinically, with the common trait of abnormal placental adherence.^7-9 The TABLE compares published definitions that have been used in the literature. While some definitions include hemorrhage, no clinician wants to induce significant hemorrhage to confirm their patient’s diagnosis. Thus, practically, the clinical PAS diagnosis comes down to abnormal placental attachment: If it is apparent that some or all of the placenta will not separate from the uterine wall with digital manipulation or careful curettage, then PAS should be suspected, and appropriate steps should be taken before further removal attempts.

At cesarean delivery, the PAS diagnosis may be aided by visual cues. With placenta previa, the lower uterine segment may bulge and take on a bluish hue, distinctly different from the upper healthy myometrium. PAS may also manifest with neovascularization, particularly behind the bladder. As with vaginal births, the placenta will fail to separate after the delivery, and controlled traction on the umbilical cord can produce a “dimple sign,” or visible myometrial retraction at the site of implantation (FIGURE 1). Finally, if the diagnosis is still in doubt, attempts to gently form a cleavage plane between the placenta and myometrium will be unsuccessful if PAS is present.⁸

Step 2: Initial management—pause, plan

Most importantly, do not attempt to forcibly remove the placenta. It can be left attached to the uterus until appropriate resources are secured. Efforts to forcibly remove an adherent placenta may well lead to major hemorrhage, and thus it falls on the patient’s care team to pause and plan for PAS care at this point. FIGURE 2 displays an algorithm for patient management. Further steps depend primarily on whether or not the patient is already hemorrhaging. In a stable situation, the patient should be counseled regarding the abnormal findings and the suspected PAS diagnosis. This includes the possibility of further procedures, blood transfusion, and hysterectomy. Local resources, including nursing, anesthesia, and the blood bank, should be notified about the situation and for the potential to call in specialized services. If on-site experienced specialists are not available, then patient transfer to a PAS specialty center should be strongly considered. While awaiting additional help or transport, the patient requires close monitoring for gross and physiologic signs of hemorrhage. If pursued, transport to a PAS specialty center should be expedited.

If the patient is already hemorrhaging or unstable, then appropriate local resources must be activated. At a minimum, this requires an obstetrician and anesthesiologist at the bedside and activation of hemorrhage protocols (eg, a massive transfusion protocol). If blood products are unavailable, consider whether they can be transported from other nearby blood banks, and start that process promptly. Next, contact backup services. Based on local resources and clinical severity, this may include maternal-fetal medicine specialists, pelvic surgeons, general and trauma surgeons, intensivists, interventional radiologists, and transfusion specialists. Even if the patient cannot be safely transferred to another hospital, the obstetrician can call an outside PAS specialist to discuss next steps in care and begin transfer plans, assuming the patient can be stabilized. Based on the Maternal Levels of Care definitions published by the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine,¹⁰ patients with PAS should be managed at level III or level IV centers. However, delivery units at every level of maternal care should have a protocol for securing local help and reaching an appropriate consultant if a PAS case is encountered. Know which center in your area specializes in PAS so that when an unanticipated case arises, you know who to call.

Continue to: Step 3: Ultimate management—mobilize and prepare for bleeding...

Step 3: Ultimate management—mobilize and prepare for bleeding

If diagnosis occurs intraoperatively at a PAS specialty center, or if safe transport is not possible, then the team should mobilize for the possibility of hysterectomy and prepare for massive bleeding, which can occur regardless of the treatment chosen. Many patients require or will opt for hysterectomy. For example, a patient who has finished childbearing may consent to a hysterectomy upon hearing she likely has PAS. In patients with suspected PAS who are actively hemorrhaging or are unstable, hysterectomy is required.

Uterine conservation may be considered in stable patients who strongly desire future childbearing or uterine retention. This often requires leaving densely adherent placental tissue in situ and thus requires thorough counseling regarding the risks of delayed hemorrhage, infection, and emergent hysterectomy.¹¹ This may not be desirable or safe for some patients, so informed consent is crucial. In such cases, we strongly recommend consultation with a PAS specialist, even if that requires immediate control of the placental blood supply (such as with arterial embolization), and transfer to a PAS specialty center.

Clinical scenarios

Vaginal delivery

The patient in the opening case was never expected to have PAS given her normal placental location and absence of a uterine scar. Even though she had some possible PAS risk factors (past retained placenta with instrumentation and in vitro fertilization), her absolute risk for the condition was low. Nevertheless, inability to create a separation plane should be considered PAS until proven otherwise. Although at this point many obstetricians would move to an operating room for uterine curettage, we recommend that the care team pause and put measures in place for possible PAS and hemorrhage. This involves notification of the blood bank, crossmatching of blood products, alerting the anesthesia team, and having a clear plan in place should a major hemorrhage ensue. This may involve use of balloon tamponade, activation of an interventional radiology team, or possible laparotomy with arterial ligations or hysterectomy. Avoidance of a prolonged third stage should be balanced against the need for preparation with these cases.

It is important for clinicians to bear in mind, and communicate to the patient, that hysterectomy is the standard of care for PAS. Significant delays in performing an indicated hysterectomy can lead to coagulopathy and patient instability. Timeliness is key; we find that delays in the decision to perform an indicated hysterectomy are often at the root of the cause for worsened morbidity in patients with unanticipated PAS. With an unscarred uterus and no placenta previa, a postpartum hysterectomy can be performed by many obstetrician-gynecologists experienced in this abdominal procedure.

Cesarean delivery

Undiagnosed PAS may present at cesarean delivery with or without placenta previa and a prior uterine scar. With this combination, PAS is often visually apparent upon opening the abdominal cavity (TABLE and FIGURE 1). Such surgical findings call for a clinical pause, as further actions at this point can lead to catastrophic hemorrhage. The obstetrician should consider a series of questions:

1. Are appropriate surgical and transfusion resources immediately available? If yes, they should be notified in case they are needed urgently. If not, then the obstetrician should ask whether the delivery must occur now.

2. Is this a scheduled delivery with a stable patient and fetus? If so, then closing the abdominal incision, monitoring the patient and fetus, and either transferring the patient to a PAS center or awaiting appropriate local specialists may be a lifesaving step.

3. Is immediate delivery required? If the fetus must be delivered, then it is imperative to create a hysterotomy out of the way of the placenta. Disrupting the adherent placenta with either an incision or manual manipulation may trigger a massive hemorrhage and should be avoided. This may require rectus muscle transection or creating a “T” incision on the skin to reach the uterine fundus and creating a hysterotomy over the top or even the back of the uterus. Once the fetus is delivered and lack of uterine hemorrhage confirmed (both abdominally and vaginally), the hysterotomy and abdomen can be closed with anticipation of urgent patient transfer to a PAS team or center.

4. Is the patient hemorrhaging? If the patient is hemorrhaging and closure is not an option, then recruitment of local emergent surgical teams is warranted, even if that requires packing the abdomen until an appropriate surgeon can arrive.

Diagnosis at cesarean delivery requires expedited and complex patient counseling. A patient who is unstable or hemorrhaging needs to be told that hysterectomy is lifesaving in this situation. For patients who are stable, it may be appropriate to close the abdomen and leave the placenta in situ, perform comprehensive counseling, and assess the possibility of transfer to a specialty center.

Summary

All obstetric care providers should be familiar with the clinical presentation of undiagnosed accreta spectrum. While hemorrhage is often part of the diagnosis, recognition of abnormal placental adherence and PAS-focused management should ideally be undertaken before this occurs. Once PAS is suspected, avoidance of further placental disruption may save significant morbidity, even if that means leaving the placenta attached until appropriate resources can be obtained. A local protocol for consultation, emergency transfer, and deployment of local resources should be part of every delivery unit’s emergency preparedness plan.

CASE Outcome

This patient is stabilized, with an adherent, retained placenta and no signs of hemorrhage. You administer uterotonics and notify your anesthesiologist and backup obstetrician that you have a likely case of accreta spectrum. A second intravenous line is placed, and blood products are crossmatched. The closest level III hospital is called, and they accept your patient for transfer. There, she is counseled about PAS, and she expresses no desire for future childbearing. After again confirming no placental separation in the operating room, the patient is moved immediately to perform laparotomy and total abdominal hysterectomy through a Pfannenstiel incision. She does not require a blood transfusion, and the pathology returns with grade I placenta accreta spectrum. ●

CASE Placenta accreta spectrum following uncomplicated vaginal delivery

Imagine you are an obstetric hospitalist taking call at a level II maternal level of care hospital. Your patient is a 35-year-old woman, gravida 2, para 1, with a past history of retained placenta requiring dilation and curettage and intravenous antibiotics for endomyometritis. This is an in vitro fertilization pregnancy that has progressed normally, and the patient labored spontaneously at 38 weeks’ gestation. Following an uncomplicated vaginal delivery, the placenta has not delivered, and you attempt a manual placental extraction after a 40-minute third stage. While there is epidural analgesia and you can reach the uterine fundus, you are unable to create a separation plane between the placenta and uterus.

What do you do next?

Placenta accreta spectrum (PAS) includes a broad range of clinical scenarios with abnormal placental attachment as their common denominator. The condition has classically been defined pathologically, with chorionic villi attaching directly to the myometrium (“accreta”) or extending more deeply into the myometrium (“increta”) or attaching to surrounding tissues and structures (“percreta”).¹ It is most commonly encountered in patients with low placental implantation on a prior cesarean section scar; indeed, placenta previa, particularly with a history of cesarean delivery, is the strongest risk factor for the development of PAS.² In addition to abnormal placental attachment, these placental attachments are often hypervascular and can lead to catastrophic hemorrhage if not managed appropriately. For this reason, patients with sonographic or radiologic signs of PAS should be referred to specialized centers for further workup, counseling, and delivery planning.³

Although delivery at a specialized PAS center has been associated with improved patient outcomes,⁴ not all patients with PAS will be identified in the antepartum period. Ultrasonography may miss up to 40% to 50% of PAS cases, particularly when the sonologist has not been advised to look for the condition,⁵ and not all patients with PAS will have a previa implanted in a prior cesarean scar. A recent study found that these patients with nonprevia PAS were identified by imaging less than 40% of the time and were significantly less likely to be managed by a specialized team of clinicians.⁶ Thus, it falls upon every obstetric care provider to be aware of this diagnosis, promptly recognize its unanticipated presentations, and have a plan to optimize patient safety.

Step 1: Recognition

While PAS is classically defined as a pathologic condition, no clinician has the luxury of histology in the delivery room. Researchers have variously defined PAS clinically, with the common trait of abnormal placental adherence.^7-9 The TABLE compares published definitions that have been used in the literature. While some definitions include hemorrhage, no clinician wants to induce significant hemorrhage to confirm their patient’s diagnosis. Thus, practically, the clinical PAS diagnosis comes down to abnormal placental attachment: If it is apparent that some or all of the placenta will not separate from the uterine wall with digital manipulation or careful curettage, then PAS should be suspected, and appropriate steps should be taken before further removal attempts.

At cesarean delivery, the PAS diagnosis may be aided by visual cues. With placenta previa, the lower uterine segment may bulge and take on a bluish hue, distinctly different from the upper healthy myometrium. PAS may also manifest with neovascularization, particularly behind the bladder. As with vaginal births, the placenta will fail to separate after the delivery, and controlled traction on the umbilical cord can produce a “dimple sign,” or visible myometrial retraction at the site of implantation (FIGURE 1). Finally, if the diagnosis is still in doubt, attempts to gently form a cleavage plane between the placenta and myometrium will be unsuccessful if PAS is present.⁸

Step 2: Initial management—pause, plan

Most importantly, do not attempt to forcibly remove the placenta. It can be left attached to the uterus until appropriate resources are secured. Efforts to forcibly remove an adherent placenta may well lead to major hemorrhage, and thus it falls on the patient’s care team to pause and plan for PAS care at this point. FIGURE 2 displays an algorithm for patient management. Further steps depend primarily on whether or not the patient is already hemorrhaging. In a stable situation, the patient should be counseled regarding the abnormal findings and the suspected PAS diagnosis. This includes the possibility of further procedures, blood transfusion, and hysterectomy. Local resources, including nursing, anesthesia, and the blood bank, should be notified about the situation and for the potential to call in specialized services. If on-site experienced specialists are not available, then patient transfer to a PAS specialty center should be strongly considered. While awaiting additional help or transport, the patient requires close monitoring for gross and physiologic signs of hemorrhage. If pursued, transport to a PAS specialty center should be expedited.

If the patient is already hemorrhaging or unstable, then appropriate local resources must be activated. At a minimum, this requires an obstetrician and anesthesiologist at the bedside and activation of hemorrhage protocols (eg, a massive transfusion protocol). If blood products are unavailable, consider whether they can be transported from other nearby blood banks, and start that process promptly. Next, contact backup services. Based on local resources and clinical severity, this may include maternal-fetal medicine specialists, pelvic surgeons, general and trauma surgeons, intensivists, interventional radiologists, and transfusion specialists. Even if the patient cannot be safely transferred to another hospital, the obstetrician can call an outside PAS specialist to discuss next steps in care and begin transfer plans, assuming the patient can be stabilized. Based on the Maternal Levels of Care definitions published by the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine,¹⁰ patients with PAS should be managed at level III or level IV centers. However, delivery units at every level of maternal care should have a protocol for securing local help and reaching an appropriate consultant if a PAS case is encountered. Know which center in your area specializes in PAS so that when an unanticipated case arises, you know who to call.

Continue to: Step 3: Ultimate management—mobilize and prepare for bleeding...

Step 3: Ultimate management—mobilize and prepare for bleeding

If diagnosis occurs intraoperatively at a PAS specialty center, or if safe transport is not possible, then the team should mobilize for the possibility of hysterectomy and prepare for massive bleeding, which can occur regardless of the treatment chosen. Many patients require or will opt for hysterectomy. For example, a patient who has finished childbearing may consent to a hysterectomy upon hearing she likely has PAS. In patients with suspected PAS who are actively hemorrhaging or are unstable, hysterectomy is required.

Uterine conservation may be considered in stable patients who strongly desire future childbearing or uterine retention. This often requires leaving densely adherent placental tissue in situ and thus requires thorough counseling regarding the risks of delayed hemorrhage, infection, and emergent hysterectomy.¹¹ This may not be desirable or safe for some patients, so informed consent is crucial. In such cases, we strongly recommend consultation with a PAS specialist, even if that requires immediate control of the placental blood supply (such as with arterial embolization), and transfer to a PAS specialty center.

Clinical scenarios

Vaginal delivery

The patient in the opening case was never expected to have PAS given her normal placental location and absence of a uterine scar. Even though she had some possible PAS risk factors (past retained placenta with instrumentation and in vitro fertilization), her absolute risk for the condition was low. Nevertheless, inability to create a separation plane should be considered PAS until proven otherwise. Although at this point many obstetricians would move to an operating room for uterine curettage, we recommend that the care team pause and put measures in place for possible PAS and hemorrhage. This involves notification of the blood bank, crossmatching of blood products, alerting the anesthesia team, and having a clear plan in place should a major hemorrhage ensue. This may involve use of balloon tamponade, activation of an interventional radiology team, or possible laparotomy with arterial ligations or hysterectomy. Avoidance of a prolonged third stage should be balanced against the need for preparation with these cases.

It is important for clinicians to bear in mind, and communicate to the patient, that hysterectomy is the standard of care for PAS. Significant delays in performing an indicated hysterectomy can lead to coagulopathy and patient instability. Timeliness is key; we find that delays in the decision to perform an indicated hysterectomy are often at the root of the cause for worsened morbidity in patients with unanticipated PAS. With an unscarred uterus and no placenta previa, a postpartum hysterectomy can be performed by many obstetrician-gynecologists experienced in this abdominal procedure.

Cesarean delivery

Undiagnosed PAS may present at cesarean delivery with or without placenta previa and a prior uterine scar. With this combination, PAS is often visually apparent upon opening the abdominal cavity (TABLE and FIGURE 1). Such surgical findings call for a clinical pause, as further actions at this point can lead to catastrophic hemorrhage. The obstetrician should consider a series of questions:

1. Are appropriate surgical and transfusion resources immediately available? If yes, they should be notified in case they are needed urgently. If not, then the obstetrician should ask whether the delivery must occur now.

2. Is this a scheduled delivery with a stable patient and fetus? If so, then closing the abdominal incision, monitoring the patient and fetus, and either transferring the patient to a PAS center or awaiting appropriate local specialists may be a lifesaving step.

3. Is immediate delivery required? If the fetus must be delivered, then it is imperative to create a hysterotomy out of the way of the placenta. Disrupting the adherent placenta with either an incision or manual manipulation may trigger a massive hemorrhage and should be avoided. This may require rectus muscle transection or creating a “T” incision on the skin to reach the uterine fundus and creating a hysterotomy over the top or even the back of the uterus. Once the fetus is delivered and lack of uterine hemorrhage confirmed (both abdominally and vaginally), the hysterotomy and abdomen can be closed with anticipation of urgent patient transfer to a PAS team or center.

4. Is the patient hemorrhaging? If the patient is hemorrhaging and closure is not an option, then recruitment of local emergent surgical teams is warranted, even if that requires packing the abdomen until an appropriate surgeon can arrive.

Diagnosis at cesarean delivery requires expedited and complex patient counseling. A patient who is unstable or hemorrhaging needs to be told that hysterectomy is lifesaving in this situation. For patients who are stable, it may be appropriate to close the abdomen and leave the placenta in situ, perform comprehensive counseling, and assess the possibility of transfer to a specialty center.

Summary

All obstetric care providers should be familiar with the clinical presentation of undiagnosed accreta spectrum. While hemorrhage is often part of the diagnosis, recognition of abnormal placental adherence and PAS-focused management should ideally be undertaken before this occurs. Once PAS is suspected, avoidance of further placental disruption may save significant morbidity, even if that means leaving the placenta attached until appropriate resources can be obtained. A local protocol for consultation, emergency transfer, and deployment of local resources should be part of every delivery unit’s emergency preparedness plan.

CASE Outcome

This patient is stabilized, with an adherent, retained placenta and no signs of hemorrhage. You administer uterotonics and notify your anesthesiologist and backup obstetrician that you have a likely case of accreta spectrum. A second intravenous line is placed, and blood products are crossmatched. The closest level III hospital is called, and they accept your patient for transfer. There, she is counseled about PAS, and she expresses no desire for future childbearing. After again confirming no placental separation in the operating room, the patient is moved immediately to perform laparotomy and total abdominal hysterectomy through a Pfannenstiel incision. She does not require a blood transfusion, and the pathology returns with grade I placenta accreta spectrum. ●

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

A version of this article first appeared on WebMD.com.

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

A version of this article first appeared on WebMD.com.

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

A version of this article first appeared on WebMD.com.

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.