Ob.Gyn. News

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.