Women's Health

The human papillomavirus vaccine does not appear to be associated with an increased risk of ovarian insufficiency, according to researchers.

Choreograph/Thinkstock

Allison L. Naleway, PhD, of the Center for Health Research at Kaiser Permanente Northwest, Portland, Ore., and her coauthors wrote that a previous case series had raised concerns about a possible link between the human papillomavirus (HPV) vaccine and primary ovarian insufficiency (POI) in six young women who developed the condition within 12 months of vaccination.

Using EHR data, researchers identified 46 women aged 11-34 years with idiopathic POI – 33 probable cases and 13 possible cases – after excluding cases with known causes. Eighteen of these cases also were excluded because they were diagnosed before the HPV vaccine was available.

They found that only 1 of the remaining 28 patients had been vaccinated against HPV before the symptom onset: a 16-year-old girl who was vaccinated about 23 months before the first clinical evaluation for delayed menarche. Their report was published in Pediatrics.

The adjusted hazard ratio for POI was therefore 0.30 after HPV vaccine, compared with 0.88 after Tdap, 1.42 after inactivated influenza vaccine, and 0.94 after meningococcal conjugate vaccine.

More than one-half of the 46 confirmed POI cases were diagnosed at age 27 years or older, and only one patient was diagnosed under 15 years of age.

“If POI is triggered by HPV or other adolescent vaccine exposure, we would have expected to see elevated incidence in the younger women who were most likely to be vaccinated, but instead we observed higher incidence in older women (greater than 26 years of age), which is consistent with 1 other population-based study of POI prevalence,” the authors wrote.

They acknowledged that studying POI as a vaccine-related adverse event was challenging because the time from symptom onset to diagnosis was variable. However, they said that 81% of their cohort was followed up for more than 2 years, and a mean of 5.14 years, so the potential for misclassification was “minimal.”

Dr. Naleway and her associates also noted that diagnoses of POI can be difficult to accurately identify, and symptoms may be masked by oral contraceptive use.

“Despite the challenges and limitations discussed above, we believe this study should lessen concern surrounding potential impact on fertility from HPV or other adolescent vaccination,” they wrote.

The Centers for Disease Control and Prevention supported the study. Three authors declared funding from pharmaceutical companies for unrelated studies. No other conflicts of interest were declared.

SOURCE: Naleway A et al. Pediatrics 2018;42(3):e20180943.

The human papillomavirus vaccine does not appear to be associated with an increased risk of ovarian insufficiency, according to researchers.

Choreograph/Thinkstock

Allison L. Naleway, PhD, of the Center for Health Research at Kaiser Permanente Northwest, Portland, Ore., and her coauthors wrote that a previous case series had raised concerns about a possible link between the human papillomavirus (HPV) vaccine and primary ovarian insufficiency (POI) in six young women who developed the condition within 12 months of vaccination.

Using EHR data, researchers identified 46 women aged 11-34 years with idiopathic POI – 33 probable cases and 13 possible cases – after excluding cases with known causes. Eighteen of these cases also were excluded because they were diagnosed before the HPV vaccine was available.

They found that only 1 of the remaining 28 patients had been vaccinated against HPV before the symptom onset: a 16-year-old girl who was vaccinated about 23 months before the first clinical evaluation for delayed menarche. Their report was published in Pediatrics.

The adjusted hazard ratio for POI was therefore 0.30 after HPV vaccine, compared with 0.88 after Tdap, 1.42 after inactivated influenza vaccine, and 0.94 after meningococcal conjugate vaccine.

More than one-half of the 46 confirmed POI cases were diagnosed at age 27 years or older, and only one patient was diagnosed under 15 years of age.

“If POI is triggered by HPV or other adolescent vaccine exposure, we would have expected to see elevated incidence in the younger women who were most likely to be vaccinated, but instead we observed higher incidence in older women (greater than 26 years of age), which is consistent with 1 other population-based study of POI prevalence,” the authors wrote.

They acknowledged that studying POI as a vaccine-related adverse event was challenging because the time from symptom onset to diagnosis was variable. However, they said that 81% of their cohort was followed up for more than 2 years, and a mean of 5.14 years, so the potential for misclassification was “minimal.”

Dr. Naleway and her associates also noted that diagnoses of POI can be difficult to accurately identify, and symptoms may be masked by oral contraceptive use.

“Despite the challenges and limitations discussed above, we believe this study should lessen concern surrounding potential impact on fertility from HPV or other adolescent vaccination,” they wrote.

The Centers for Disease Control and Prevention supported the study. Three authors declared funding from pharmaceutical companies for unrelated studies. No other conflicts of interest were declared.

SOURCE: Naleway A et al. Pediatrics 2018;42(3):e20180943.

The human papillomavirus vaccine does not appear to be associated with an increased risk of ovarian insufficiency, according to researchers.

Choreograph/Thinkstock

Allison L. Naleway, PhD, of the Center for Health Research at Kaiser Permanente Northwest, Portland, Ore., and her coauthors wrote that a previous case series had raised concerns about a possible link between the human papillomavirus (HPV) vaccine and primary ovarian insufficiency (POI) in six young women who developed the condition within 12 months of vaccination.

Using EHR data, researchers identified 46 women aged 11-34 years with idiopathic POI – 33 probable cases and 13 possible cases – after excluding cases with known causes. Eighteen of these cases also were excluded because they were diagnosed before the HPV vaccine was available.

They found that only 1 of the remaining 28 patients had been vaccinated against HPV before the symptom onset: a 16-year-old girl who was vaccinated about 23 months before the first clinical evaluation for delayed menarche. Their report was published in Pediatrics.

The adjusted hazard ratio for POI was therefore 0.30 after HPV vaccine, compared with 0.88 after Tdap, 1.42 after inactivated influenza vaccine, and 0.94 after meningococcal conjugate vaccine.

More than one-half of the 46 confirmed POI cases were diagnosed at age 27 years or older, and only one patient was diagnosed under 15 years of age.

“If POI is triggered by HPV or other adolescent vaccine exposure, we would have expected to see elevated incidence in the younger women who were most likely to be vaccinated, but instead we observed higher incidence in older women (greater than 26 years of age), which is consistent with 1 other population-based study of POI prevalence,” the authors wrote.

They acknowledged that studying POI as a vaccine-related adverse event was challenging because the time from symptom onset to diagnosis was variable. However, they said that 81% of their cohort was followed up for more than 2 years, and a mean of 5.14 years, so the potential for misclassification was “minimal.”

Dr. Naleway and her associates also noted that diagnoses of POI can be difficult to accurately identify, and symptoms may be masked by oral contraceptive use.

“Despite the challenges and limitations discussed above, we believe this study should lessen concern surrounding potential impact on fertility from HPV or other adolescent vaccination,” they wrote.

The Centers for Disease Control and Prevention supported the study. Three authors declared funding from pharmaceutical companies for unrelated studies. No other conflicts of interest were declared.

SOURCE: Naleway A et al. Pediatrics 2018;42(3):e20180943.

Low-dose aspirin for the prevention of preeclampsia has been studied for more than 25 years, often with contradictory and confusing results. Studies have enrolled patients with varying levels of risk, assessed risk differently, and used different definitions of preeclampsia as well as a variety of aspirin dosages and treatment-initiation dates. Undoubtedly, this heterogeneity has made interpretation and comparisons difficult and frustrating.

Recently, systematic reviews and meta-analyses have improved our understanding of the role of low-dose aspirin, providing solid evidence that low-dose aspirin started after the first-trimester reduces the occurrence of preeclampsia in high-risk women. Data also suggest that low-dose aspirin reduces the incidence of fetal growth restriction and preterm birth in these women.

There is reasonable evidence, moreover, that low-dose aspirin provides similar benefit in women with modest levels of risk and that it’s best to begin aspirin use at 12-14 weeks’ gestation rather than later in the second trimester. Finally, there’s also good evidence that 81 mg of aspirin is a minimum dose for effectiveness and that higher doses – as much as 150 mg – are probably more effective.

Despite this evidence and current recommendations for low-dose aspirin use by the U.S. Preventive Services Task Force and the American College of Obstetricians and Gynecologists, its use in practice is varied. Obstetricians and other obstetrics providers are not consistently making the recommendation, and pharmacists are not consistently supporting it.

Without more consistent initiation of low-dose aspirin prophylaxis and more consistent adherence, we are losing an opportunity to reduce serious maternal morbidity and mortality. We also are underutilizing an important tool for the reduction of racial and other health disparities relating to preterm birth, maternal death, and other complications of preeclampsia.


 

Dr. Lockwood: Epidemiology, etiology, and clinical value of aspirin

The use of low-dose aspirin can have a high impact, considering that preeclampsia complicates 3.4% of pregnancies nationally and accounts for at least 9% of maternal deaths (BMJ. 2013 Nov;347:f6564).

Preeclampsia also has been shown in multiple long-term epidemiologic studies to be a strong risk factor for future cardiovascular disease and metabolic disorders in women – especially when it occurs in multiple pregnancies or develops preterm. Moreover, it is associated with stillbirth, intrauterine growth restriction (IUGR), and oligohydramnios in the fetus (BMJ. 2013 Nov;347:f6564).

It is important to remember that criteria for a diagnosis of preeclampsia changed in 2013 such that the detection of proteinuria is no longer required. Preeclampsia is defined today as the new onset of hypertension and proteinuria, or hypertension and end-organ dysfunction with or without proteinuria, after 20 weeks in a previously normotensive woman, according to the ACOG Task Force on Hypertension in Pregnancy.

The leading risk factor appears to be previous preeclampsia. In a systematic review and meta-analysis of 92 cohort studies that looked at the pooled relative risk of developing preeclampsia in the presence or absence of 14 commonly reported and accepted risk factors, prior preeclampsia topped the list, putting patients at an eightfold increased risk (relative risk 8.4) (BMJ. 2016 Apr 19;353:i1753).

Nulliparity (relative risk, 2.1) and multiple gestation (RR, 2.9) presented lesser risks but still were significant, and preexisting medical conditions increased risk as well. Notably, both chronic hypertension and a body mass index (BMI) greater than 30 had a fivefold increased risk (RR, 5.1), and preexisting diabetes presented more than a threefold increased risk (RR, 3.7). The review covered more than 25 million pregnancies in 27 countries.

The etiology of preeclampsia still is not completely understood. There is evidence that underlying decidual inflammation, including increased activated macrophages and decreased uterine natural killer cells (uNK), promotes shallow placentation leading to incomplete uterine spiral artery remodeling, relative placental hypoxia, and progressive release of placental antiangiogenic substances such as soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (Am J Pathol. 2013 Sep;183[3]:841-56; Reprod Sci. 2015 Nov;22[11]:1461-7). The latter result in systemic endothelial cell damage, reduced endothelial prostacyclin (PGI2), and increased platelet thromboxane A2, triggering vasospasm and increased platelet turnover that ultimately lead to the typical signs and symptoms of preeclampsia.

The research focus traditionally has been on the placenta, but more recently the uterine decidual contribution has received more attention. A recent study published in the Proceedings of the National Academy of Sciences offers evidence that affected women have defective decidualization during and after severe preeclampsia, suggesting that the defect could be detected prior to conception.

Investigators isolated endometrial cells from women at the end of a pregnancy complicated by preeclampsia and found a transcriptional signature that persisted for years. They then linked the defect to impaired cytotrophoblast invasion (Proc Natl Acad Sci. 2017;114[40]:E8468-77). This elegant and provocative study suggests that it might be possible in the future to evaluate the endometrium and try to enhance stromal cell decidualization before pregnancy.

Currently, the rationale for using aspirin to prevent preeclampsia lies with its ability to inhibit platelet production of thromboxane and block NF-kB, a protein complex that plays a role in systemic and/or decidual inflammation. There likely are numerous mechanisms of action, however, including some that improve placentation.

Among the most recent studies on timing and dosage is a systematic review and meta-analysis of 45 randomized controlled trials with 20,909 women randomized to 50-150 mg aspirin daily or to placebo or no treatment. The investigators stratified the results by gestational age at the time of aspirin initiation and found that timing matters. Women who began aspirin at or before 16 weeks had the most significant reductions in preeclampsia (RR, 0.57) and severe preeclampsia (RR, 0.47), as well as fetal growth restriction (RR, 0.56), with a dose-response effect up to 150 mg.

When aspirin was initiated after 16 weeks, there was a much smaller reduction of preeclampsia (RR, 0.81) and no effects for severe preeclampsia or IUGR. Nor was there any dose-response effect (Am J Obstet Gynecol. 2017; 216[2]:110-20.e6).

In contrast, another recent meta-analysis of individual participant data on 32,217 women recruited in 31 randomized controlled trials found no significant difference among women who were randomized before 16 weeks versus those who were randomized at 16 weeks or later (Am J Obstet Gynecol. 2017 Feb;216[2]:121-8.e2). It’s important to note that this analysis covered other antiplatelet agents as well and that it stratified outcomes by gestational age with a slightly later cutoff point.

What do official guidelines say? The USPSTF’s recommendation, issued in 2014, calls for low-dose aspirin at 81 mg/day after 12 weeks’ gestation in women who have one or more high-risk factors, and consideration of such treatment in patients with “several” moderate-risk factors (Ann Intern Med. 2014 Dec 2;161[11]:819-26). In July 2018, ACOG reaffirmed its earlier support for low-dose aspirin in a committee opinion that recommends 81 mg/day beginning at 12-28 weeks’ gestation, optimally before 16 weeks’, for women who have one or more high-risk factors or more than one moderate-risk factor (Obstet Gynecol. 2018 Jul;132[1]:e44-e52).

My own take, based on published literature, including my own research, is that low-dose aspirin reduces the frequency of preeclampsia, particularly cases occurring preterm, as well as related IUGR, by approximately 10%-20% in moderate- and high-risk women. Regarding dose and gestational age for initiation, I have split the difference of what’s reflected in the literature and in guidelines. I advise 122 mg (a tablet-and-a-half) a day, starting at 12-14 weeks’, for patients at high and moderate levels of risk. For patients who are not seen until later, low-dose aspirin can be started up to 28 weeks’ gestation.
 

Dr. Abbott: Messaging and education to reduce disparities

Black women are not only more likely to develop preeclampsia, but they’re also more likely to have more severe complications and worse outcomes. In one analysis, black women with preeclampsia experienced an almost threefold higher risk of maternal mortality and intrauterine fetal death than did white women with the disorder (Hypertens Pregnancy. 2015 Nov;34[4]:506-15).

At Boston Medical Center, 30% of pregnant women have a diagnosis of preeclampsia or hypertension at term. In addition to 68% identifying as Hispanic/black or black, half of the families we care for have incomes less than $20,000, and 30% are non–English speaking. Low-dose prenatal aspirin is therefore an important tool for reducing racial health disparities as well as disparities created by health literacy, economic status, and language and cultural barriers. At BMC, New England’s largest safety-net hospital, we’ve found that the factors driving health disparities often overlap.

To increase the use of low-dose aspirin for women at moderate to high risk, we marry education about aspirin’s effectiveness and safety with education about the potential severity of hypertension and preeclampsia. We counsel patients who are hospitalized at delivery with gestational or chronic hypertension, or fetal growth restriction, about how preeclampsia can be very serious – contrary to what they’ve experienced or what friends or family may have shared. We also counsel them about signs and symptoms of severe preeclampsia that warrant consulting their provider. And overall, we deliberately use the term “prenatal aspirin” so that, over time and in the broader community, it will become associated with good prenatal care and risk reduction.

To counter perceived risks and dangers that we identified through focus groups and interviews, our patient education materials state that low-dose aspirin in pregnancy will not cause increased bleeding, does not reach the baby’s blood, does not increase the risk of miscarriage, and has not been shown to have negative effects on the baby’s initial development (www.prenatalaspirin.com/education-materials). We try to engage family members whenever possible, and we recognize that the black population has historical reasons to be concerned or suspicious that aspirin might not be safe for them.

Especially for underserved patients who receive prescriptions for low-dose aspirin, we must ensure that pharmacists will dispense the medication. A national survey of pharmacists (not yet published) found that over two-thirds were unaware of the USPSTF guidelines, and that only a minority would feel comfortable dispensing low-dose aspirin during pregnancy. In our community, some pharmacists have told patients to return to their physician and inquire more. Until recently, one of the major pharmacy chains placed a warning label on aspirin bottles being dispensed to women who also had an active prescription for prenatal vitamins.

We are working both with pharmacies and with pharmacy schools to impact the education of current and future pharmacists on guidelines and recommendations for low-dose aspirin prophylaxis. In addition, when I write a prescription for prenatal aspirin, starting at 12 weeks’ whenever possible, I include the message “for the purpose of trying to reduce pregnancy complications.”

Dr. Lockwood is senior vice president at University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa. He said he had no relevant financial disclosures or conflicts of interest. Dr. Abbot is a specialist in maternal-fetal medicine, the director of obstetrics and gynecology, and assistant dean for patient safety and quality improvement education at Boston Medical Center. She also is an associate professor of obstetrics and gynecology at Boston University. She disclosed a grant from the March of Dimes. Email them at [email protected].

Low-dose aspirin for the prevention of preeclampsia has been studied for more than 25 years, often with contradictory and confusing results. Studies have enrolled patients with varying levels of risk, assessed risk differently, and used different definitions of preeclampsia as well as a variety of aspirin dosages and treatment-initiation dates. Undoubtedly, this heterogeneity has made interpretation and comparisons difficult and frustrating.

Recently, systematic reviews and meta-analyses have improved our understanding of the role of low-dose aspirin, providing solid evidence that low-dose aspirin started after the first-trimester reduces the occurrence of preeclampsia in high-risk women. Data also suggest that low-dose aspirin reduces the incidence of fetal growth restriction and preterm birth in these women.

There is reasonable evidence, moreover, that low-dose aspirin provides similar benefit in women with modest levels of risk and that it’s best to begin aspirin use at 12-14 weeks’ gestation rather than later in the second trimester. Finally, there’s also good evidence that 81 mg of aspirin is a minimum dose for effectiveness and that higher doses – as much as 150 mg – are probably more effective.

Despite this evidence and current recommendations for low-dose aspirin use by the U.S. Preventive Services Task Force and the American College of Obstetricians and Gynecologists, its use in practice is varied. Obstetricians and other obstetrics providers are not consistently making the recommendation, and pharmacists are not consistently supporting it.

Without more consistent initiation of low-dose aspirin prophylaxis and more consistent adherence, we are losing an opportunity to reduce serious maternal morbidity and mortality. We also are underutilizing an important tool for the reduction of racial and other health disparities relating to preterm birth, maternal death, and other complications of preeclampsia.


 

Dr. Lockwood: Epidemiology, etiology, and clinical value of aspirin

The use of low-dose aspirin can have a high impact, considering that preeclampsia complicates 3.4% of pregnancies nationally and accounts for at least 9% of maternal deaths (BMJ. 2013 Nov;347:f6564).

Preeclampsia also has been shown in multiple long-term epidemiologic studies to be a strong risk factor for future cardiovascular disease and metabolic disorders in women – especially when it occurs in multiple pregnancies or develops preterm. Moreover, it is associated with stillbirth, intrauterine growth restriction (IUGR), and oligohydramnios in the fetus (BMJ. 2013 Nov;347:f6564).

It is important to remember that criteria for a diagnosis of preeclampsia changed in 2013 such that the detection of proteinuria is no longer required. Preeclampsia is defined today as the new onset of hypertension and proteinuria, or hypertension and end-organ dysfunction with or without proteinuria, after 20 weeks in a previously normotensive woman, according to the ACOG Task Force on Hypertension in Pregnancy.

The leading risk factor appears to be previous preeclampsia. In a systematic review and meta-analysis of 92 cohort studies that looked at the pooled relative risk of developing preeclampsia in the presence or absence of 14 commonly reported and accepted risk factors, prior preeclampsia topped the list, putting patients at an eightfold increased risk (relative risk 8.4) (BMJ. 2016 Apr 19;353:i1753).

Nulliparity (relative risk, 2.1) and multiple gestation (RR, 2.9) presented lesser risks but still were significant, and preexisting medical conditions increased risk as well. Notably, both chronic hypertension and a body mass index (BMI) greater than 30 had a fivefold increased risk (RR, 5.1), and preexisting diabetes presented more than a threefold increased risk (RR, 3.7). The review covered more than 25 million pregnancies in 27 countries.

The etiology of preeclampsia still is not completely understood. There is evidence that underlying decidual inflammation, including increased activated macrophages and decreased uterine natural killer cells (uNK), promotes shallow placentation leading to incomplete uterine spiral artery remodeling, relative placental hypoxia, and progressive release of placental antiangiogenic substances such as soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (Am J Pathol. 2013 Sep;183[3]:841-56; Reprod Sci. 2015 Nov;22[11]:1461-7). The latter result in systemic endothelial cell damage, reduced endothelial prostacyclin (PGI2), and increased platelet thromboxane A2, triggering vasospasm and increased platelet turnover that ultimately lead to the typical signs and symptoms of preeclampsia.

The research focus traditionally has been on the placenta, but more recently the uterine decidual contribution has received more attention. A recent study published in the Proceedings of the National Academy of Sciences offers evidence that affected women have defective decidualization during and after severe preeclampsia, suggesting that the defect could be detected prior to conception.

Investigators isolated endometrial cells from women at the end of a pregnancy complicated by preeclampsia and found a transcriptional signature that persisted for years. They then linked the defect to impaired cytotrophoblast invasion (Proc Natl Acad Sci. 2017;114[40]:E8468-77). This elegant and provocative study suggests that it might be possible in the future to evaluate the endometrium and try to enhance stromal cell decidualization before pregnancy.

Currently, the rationale for using aspirin to prevent preeclampsia lies with its ability to inhibit platelet production of thromboxane and block NF-kB, a protein complex that plays a role in systemic and/or decidual inflammation. There likely are numerous mechanisms of action, however, including some that improve placentation.

Among the most recent studies on timing and dosage is a systematic review and meta-analysis of 45 randomized controlled trials with 20,909 women randomized to 50-150 mg aspirin daily or to placebo or no treatment. The investigators stratified the results by gestational age at the time of aspirin initiation and found that timing matters. Women who began aspirin at or before 16 weeks had the most significant reductions in preeclampsia (RR, 0.57) and severe preeclampsia (RR, 0.47), as well as fetal growth restriction (RR, 0.56), with a dose-response effect up to 150 mg.

When aspirin was initiated after 16 weeks, there was a much smaller reduction of preeclampsia (RR, 0.81) and no effects for severe preeclampsia or IUGR. Nor was there any dose-response effect (Am J Obstet Gynecol. 2017; 216[2]:110-20.e6).

In contrast, another recent meta-analysis of individual participant data on 32,217 women recruited in 31 randomized controlled trials found no significant difference among women who were randomized before 16 weeks versus those who were randomized at 16 weeks or later (Am J Obstet Gynecol. 2017 Feb;216[2]:121-8.e2). It’s important to note that this analysis covered other antiplatelet agents as well and that it stratified outcomes by gestational age with a slightly later cutoff point.

What do official guidelines say? The USPSTF’s recommendation, issued in 2014, calls for low-dose aspirin at 81 mg/day after 12 weeks’ gestation in women who have one or more high-risk factors, and consideration of such treatment in patients with “several” moderate-risk factors (Ann Intern Med. 2014 Dec 2;161[11]:819-26). In July 2018, ACOG reaffirmed its earlier support for low-dose aspirin in a committee opinion that recommends 81 mg/day beginning at 12-28 weeks’ gestation, optimally before 16 weeks’, for women who have one or more high-risk factors or more than one moderate-risk factor (Obstet Gynecol. 2018 Jul;132[1]:e44-e52).

My own take, based on published literature, including my own research, is that low-dose aspirin reduces the frequency of preeclampsia, particularly cases occurring preterm, as well as related IUGR, by approximately 10%-20% in moderate- and high-risk women. Regarding dose and gestational age for initiation, I have split the difference of what’s reflected in the literature and in guidelines. I advise 122 mg (a tablet-and-a-half) a day, starting at 12-14 weeks’, for patients at high and moderate levels of risk. For patients who are not seen until later, low-dose aspirin can be started up to 28 weeks’ gestation.
 

Dr. Abbott: Messaging and education to reduce disparities

Black women are not only more likely to develop preeclampsia, but they’re also more likely to have more severe complications and worse outcomes. In one analysis, black women with preeclampsia experienced an almost threefold higher risk of maternal mortality and intrauterine fetal death than did white women with the disorder (Hypertens Pregnancy. 2015 Nov;34[4]:506-15).

At Boston Medical Center, 30% of pregnant women have a diagnosis of preeclampsia or hypertension at term. In addition to 68% identifying as Hispanic/black or black, half of the families we care for have incomes less than $20,000, and 30% are non–English speaking. Low-dose prenatal aspirin is therefore an important tool for reducing racial health disparities as well as disparities created by health literacy, economic status, and language and cultural barriers. At BMC, New England’s largest safety-net hospital, we’ve found that the factors driving health disparities often overlap.

To increase the use of low-dose aspirin for women at moderate to high risk, we marry education about aspirin’s effectiveness and safety with education about the potential severity of hypertension and preeclampsia. We counsel patients who are hospitalized at delivery with gestational or chronic hypertension, or fetal growth restriction, about how preeclampsia can be very serious – contrary to what they’ve experienced or what friends or family may have shared. We also counsel them about signs and symptoms of severe preeclampsia that warrant consulting their provider. And overall, we deliberately use the term “prenatal aspirin” so that, over time and in the broader community, it will become associated with good prenatal care and risk reduction.

To counter perceived risks and dangers that we identified through focus groups and interviews, our patient education materials state that low-dose aspirin in pregnancy will not cause increased bleeding, does not reach the baby’s blood, does not increase the risk of miscarriage, and has not been shown to have negative effects on the baby’s initial development (www.prenatalaspirin.com/education-materials). We try to engage family members whenever possible, and we recognize that the black population has historical reasons to be concerned or suspicious that aspirin might not be safe for them.

Especially for underserved patients who receive prescriptions for low-dose aspirin, we must ensure that pharmacists will dispense the medication. A national survey of pharmacists (not yet published) found that over two-thirds were unaware of the USPSTF guidelines, and that only a minority would feel comfortable dispensing low-dose aspirin during pregnancy. In our community, some pharmacists have told patients to return to their physician and inquire more. Until recently, one of the major pharmacy chains placed a warning label on aspirin bottles being dispensed to women who also had an active prescription for prenatal vitamins.

We are working both with pharmacies and with pharmacy schools to impact the education of current and future pharmacists on guidelines and recommendations for low-dose aspirin prophylaxis. In addition, when I write a prescription for prenatal aspirin, starting at 12 weeks’ whenever possible, I include the message “for the purpose of trying to reduce pregnancy complications.”

Dr. Lockwood is senior vice president at University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa. He said he had no relevant financial disclosures or conflicts of interest. Dr. Abbot is a specialist in maternal-fetal medicine, the director of obstetrics and gynecology, and assistant dean for patient safety and quality improvement education at Boston Medical Center. She also is an associate professor of obstetrics and gynecology at Boston University. She disclosed a grant from the March of Dimes. Email them at [email protected].

Low-dose aspirin for the prevention of preeclampsia has been studied for more than 25 years, often with contradictory and confusing results. Studies have enrolled patients with varying levels of risk, assessed risk differently, and used different definitions of preeclampsia as well as a variety of aspirin dosages and treatment-initiation dates. Undoubtedly, this heterogeneity has made interpretation and comparisons difficult and frustrating.

Recently, systematic reviews and meta-analyses have improved our understanding of the role of low-dose aspirin, providing solid evidence that low-dose aspirin started after the first-trimester reduces the occurrence of preeclampsia in high-risk women. Data also suggest that low-dose aspirin reduces the incidence of fetal growth restriction and preterm birth in these women.

There is reasonable evidence, moreover, that low-dose aspirin provides similar benefit in women with modest levels of risk and that it’s best to begin aspirin use at 12-14 weeks’ gestation rather than later in the second trimester. Finally, there’s also good evidence that 81 mg of aspirin is a minimum dose for effectiveness and that higher doses – as much as 150 mg – are probably more effective.

Despite this evidence and current recommendations for low-dose aspirin use by the U.S. Preventive Services Task Force and the American College of Obstetricians and Gynecologists, its use in practice is varied. Obstetricians and other obstetrics providers are not consistently making the recommendation, and pharmacists are not consistently supporting it.

Without more consistent initiation of low-dose aspirin prophylaxis and more consistent adherence, we are losing an opportunity to reduce serious maternal morbidity and mortality. We also are underutilizing an important tool for the reduction of racial and other health disparities relating to preterm birth, maternal death, and other complications of preeclampsia.


 

Dr. Lockwood: Epidemiology, etiology, and clinical value of aspirin

The use of low-dose aspirin can have a high impact, considering that preeclampsia complicates 3.4% of pregnancies nationally and accounts for at least 9% of maternal deaths (BMJ. 2013 Nov;347:f6564).

Preeclampsia also has been shown in multiple long-term epidemiologic studies to be a strong risk factor for future cardiovascular disease and metabolic disorders in women – especially when it occurs in multiple pregnancies or develops preterm. Moreover, it is associated with stillbirth, intrauterine growth restriction (IUGR), and oligohydramnios in the fetus (BMJ. 2013 Nov;347:f6564).

It is important to remember that criteria for a diagnosis of preeclampsia changed in 2013 such that the detection of proteinuria is no longer required. Preeclampsia is defined today as the new onset of hypertension and proteinuria, or hypertension and end-organ dysfunction with or without proteinuria, after 20 weeks in a previously normotensive woman, according to the ACOG Task Force on Hypertension in Pregnancy.

The leading risk factor appears to be previous preeclampsia. In a systematic review and meta-analysis of 92 cohort studies that looked at the pooled relative risk of developing preeclampsia in the presence or absence of 14 commonly reported and accepted risk factors, prior preeclampsia topped the list, putting patients at an eightfold increased risk (relative risk 8.4) (BMJ. 2016 Apr 19;353:i1753).

Nulliparity (relative risk, 2.1) and multiple gestation (RR, 2.9) presented lesser risks but still were significant, and preexisting medical conditions increased risk as well. Notably, both chronic hypertension and a body mass index (BMI) greater than 30 had a fivefold increased risk (RR, 5.1), and preexisting diabetes presented more than a threefold increased risk (RR, 3.7). The review covered more than 25 million pregnancies in 27 countries.

The etiology of preeclampsia still is not completely understood. There is evidence that underlying decidual inflammation, including increased activated macrophages and decreased uterine natural killer cells (uNK), promotes shallow placentation leading to incomplete uterine spiral artery remodeling, relative placental hypoxia, and progressive release of placental antiangiogenic substances such as soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (Am J Pathol. 2013 Sep;183[3]:841-56; Reprod Sci. 2015 Nov;22[11]:1461-7). The latter result in systemic endothelial cell damage, reduced endothelial prostacyclin (PGI2), and increased platelet thromboxane A2, triggering vasospasm and increased platelet turnover that ultimately lead to the typical signs and symptoms of preeclampsia.

The research focus traditionally has been on the placenta, but more recently the uterine decidual contribution has received more attention. A recent study published in the Proceedings of the National Academy of Sciences offers evidence that affected women have defective decidualization during and after severe preeclampsia, suggesting that the defect could be detected prior to conception.

Investigators isolated endometrial cells from women at the end of a pregnancy complicated by preeclampsia and found a transcriptional signature that persisted for years. They then linked the defect to impaired cytotrophoblast invasion (Proc Natl Acad Sci. 2017;114[40]:E8468-77). This elegant and provocative study suggests that it might be possible in the future to evaluate the endometrium and try to enhance stromal cell decidualization before pregnancy.

Currently, the rationale for using aspirin to prevent preeclampsia lies with its ability to inhibit platelet production of thromboxane and block NF-kB, a protein complex that plays a role in systemic and/or decidual inflammation. There likely are numerous mechanisms of action, however, including some that improve placentation.

Among the most recent studies on timing and dosage is a systematic review and meta-analysis of 45 randomized controlled trials with 20,909 women randomized to 50-150 mg aspirin daily or to placebo or no treatment. The investigators stratified the results by gestational age at the time of aspirin initiation and found that timing matters. Women who began aspirin at or before 16 weeks had the most significant reductions in preeclampsia (RR, 0.57) and severe preeclampsia (RR, 0.47), as well as fetal growth restriction (RR, 0.56), with a dose-response effect up to 150 mg.

When aspirin was initiated after 16 weeks, there was a much smaller reduction of preeclampsia (RR, 0.81) and no effects for severe preeclampsia or IUGR. Nor was there any dose-response effect (Am J Obstet Gynecol. 2017; 216[2]:110-20.e6).

In contrast, another recent meta-analysis of individual participant data on 32,217 women recruited in 31 randomized controlled trials found no significant difference among women who were randomized before 16 weeks versus those who were randomized at 16 weeks or later (Am J Obstet Gynecol. 2017 Feb;216[2]:121-8.e2). It’s important to note that this analysis covered other antiplatelet agents as well and that it stratified outcomes by gestational age with a slightly later cutoff point.

What do official guidelines say? The USPSTF’s recommendation, issued in 2014, calls for low-dose aspirin at 81 mg/day after 12 weeks’ gestation in women who have one or more high-risk factors, and consideration of such treatment in patients with “several” moderate-risk factors (Ann Intern Med. 2014 Dec 2;161[11]:819-26). In July 2018, ACOG reaffirmed its earlier support for low-dose aspirin in a committee opinion that recommends 81 mg/day beginning at 12-28 weeks’ gestation, optimally before 16 weeks’, for women who have one or more high-risk factors or more than one moderate-risk factor (Obstet Gynecol. 2018 Jul;132[1]:e44-e52).

My own take, based on published literature, including my own research, is that low-dose aspirin reduces the frequency of preeclampsia, particularly cases occurring preterm, as well as related IUGR, by approximately 10%-20% in moderate- and high-risk women. Regarding dose and gestational age for initiation, I have split the difference of what’s reflected in the literature and in guidelines. I advise 122 mg (a tablet-and-a-half) a day, starting at 12-14 weeks’, for patients at high and moderate levels of risk. For patients who are not seen until later, low-dose aspirin can be started up to 28 weeks’ gestation.
 

Dr. Abbott: Messaging and education to reduce disparities

Black women are not only more likely to develop preeclampsia, but they’re also more likely to have more severe complications and worse outcomes. In one analysis, black women with preeclampsia experienced an almost threefold higher risk of maternal mortality and intrauterine fetal death than did white women with the disorder (Hypertens Pregnancy. 2015 Nov;34[4]:506-15).

At Boston Medical Center, 30% of pregnant women have a diagnosis of preeclampsia or hypertension at term. In addition to 68% identifying as Hispanic/black or black, half of the families we care for have incomes less than $20,000, and 30% are non–English speaking. Low-dose prenatal aspirin is therefore an important tool for reducing racial health disparities as well as disparities created by health literacy, economic status, and language and cultural barriers. At BMC, New England’s largest safety-net hospital, we’ve found that the factors driving health disparities often overlap.

To increase the use of low-dose aspirin for women at moderate to high risk, we marry education about aspirin’s effectiveness and safety with education about the potential severity of hypertension and preeclampsia. We counsel patients who are hospitalized at delivery with gestational or chronic hypertension, or fetal growth restriction, about how preeclampsia can be very serious – contrary to what they’ve experienced or what friends or family may have shared. We also counsel them about signs and symptoms of severe preeclampsia that warrant consulting their provider. And overall, we deliberately use the term “prenatal aspirin” so that, over time and in the broader community, it will become associated with good prenatal care and risk reduction.

To counter perceived risks and dangers that we identified through focus groups and interviews, our patient education materials state that low-dose aspirin in pregnancy will not cause increased bleeding, does not reach the baby’s blood, does not increase the risk of miscarriage, and has not been shown to have negative effects on the baby’s initial development (www.prenatalaspirin.com/education-materials). We try to engage family members whenever possible, and we recognize that the black population has historical reasons to be concerned or suspicious that aspirin might not be safe for them.

Especially for underserved patients who receive prescriptions for low-dose aspirin, we must ensure that pharmacists will dispense the medication. A national survey of pharmacists (not yet published) found that over two-thirds were unaware of the USPSTF guidelines, and that only a minority would feel comfortable dispensing low-dose aspirin during pregnancy. In our community, some pharmacists have told patients to return to their physician and inquire more. Until recently, one of the major pharmacy chains placed a warning label on aspirin bottles being dispensed to women who also had an active prescription for prenatal vitamins.

We are working both with pharmacies and with pharmacy schools to impact the education of current and future pharmacists on guidelines and recommendations for low-dose aspirin prophylaxis. In addition, when I write a prescription for prenatal aspirin, starting at 12 weeks’ whenever possible, I include the message “for the purpose of trying to reduce pregnancy complications.”

Dr. Lockwood is senior vice president at University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa. He said he had no relevant financial disclosures or conflicts of interest. Dr. Abbot is a specialist in maternal-fetal medicine, the director of obstetrics and gynecology, and assistant dean for patient safety and quality improvement education at Boston Medical Center. She also is an associate professor of obstetrics and gynecology at Boston University. She disclosed a grant from the March of Dimes. Email them at [email protected].

Some of our readers might remember the old saying, “Take two aspirin and call me in the morning,” as advice physicians gave to patients experiencing a minor malady. Aspirin often has been called a “wonder drug” as its uses continue to expand. From its first recorded use in the Ebers papyrus as an anti-inflammatory agent, to its first use in a clinical trial showing that it induces remission of fever and joint inflammation, to the discovery that it could prevent death from heart attack, to its anticancer properties, aspirin remains one of the most researched drugs in use today. According to ClinicalTrials.gov, there are over 465 active and nearly 1,000 completed aspirin-related clinical trials around the world.

Despite its myriad benefits, aspirin has been linked to bleeding, nausea, and gastrointestinal ulcers. Additionally, more research is needed to determine the risks/benefits of daily aspirin in younger adults (under age 50 years) or older adults (over age 70 years), although the ASPREE (Aspirin in Reducing Events in the Elderly) trial, expected to be completed in 2019, is working to determine the effects of daily low-dose aspirin (100 mg) on the health of people over age 65.

It is tempting to consider aspirin one of modern medicine’s so-called silver bullets, and, for women with a history of gestational hypertension and preeclampsia, it just might be. Aspirin use, especially daily aspirin, is typically not recommended during pregnancy, and most ob.gyns. will include aspirin on the “do not take” list they give to their patients during prenatal examinations. Women at risk for developing preeclampsia are the exceptions to this general rule, and a number of clinical studies have indicated that use of low-dose aspirin can help prevent disease as well as secondary outcomes for mother (i.e., placental abruption, antepartum hemorrhage) and baby (i.e., intrauterine growth restriction, stillbirth). In addition, aspirin is an easily obtainable, low-cost preventive measure for any patient at high risk.

To discuss the value of low-dose aspirin to prevent preeclampsia and how ob.gyns. can educate their patients and other health care professionals about its benefits, we have invited Charles J. Lockwood, MD, MHCM, senior vice president of University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa, and Jodi F. Abbott, MD, MSc, MHCM, director of obstetrics and gynecology at Boston Medical Center, and associate professor of obstetrics and gynecology at Boston University, to coauthor this month’s Master Class.

Dr. Reece, who specializes in maternal-fetal medicine, is 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. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Some of our readers might remember the old saying, “Take two aspirin and call me in the morning,” as advice physicians gave to patients experiencing a minor malady. Aspirin often has been called a “wonder drug” as its uses continue to expand. From its first recorded use in the Ebers papyrus as an anti-inflammatory agent, to its first use in a clinical trial showing that it induces remission of fever and joint inflammation, to the discovery that it could prevent death from heart attack, to its anticancer properties, aspirin remains one of the most researched drugs in use today. According to ClinicalTrials.gov, there are over 465 active and nearly 1,000 completed aspirin-related clinical trials around the world.

Despite its myriad benefits, aspirin has been linked to bleeding, nausea, and gastrointestinal ulcers. Additionally, more research is needed to determine the risks/benefits of daily aspirin in younger adults (under age 50 years) or older adults (over age 70 years), although the ASPREE (Aspirin in Reducing Events in the Elderly) trial, expected to be completed in 2019, is working to determine the effects of daily low-dose aspirin (100 mg) on the health of people over age 65.

It is tempting to consider aspirin one of modern medicine’s so-called silver bullets, and, for women with a history of gestational hypertension and preeclampsia, it just might be. Aspirin use, especially daily aspirin, is typically not recommended during pregnancy, and most ob.gyns. will include aspirin on the “do not take” list they give to their patients during prenatal examinations. Women at risk for developing preeclampsia are the exceptions to this general rule, and a number of clinical studies have indicated that use of low-dose aspirin can help prevent disease as well as secondary outcomes for mother (i.e., placental abruption, antepartum hemorrhage) and baby (i.e., intrauterine growth restriction, stillbirth). In addition, aspirin is an easily obtainable, low-cost preventive measure for any patient at high risk.

To discuss the value of low-dose aspirin to prevent preeclampsia and how ob.gyns. can educate their patients and other health care professionals about its benefits, we have invited Charles J. Lockwood, MD, MHCM, senior vice president of University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa, and Jodi F. Abbott, MD, MSc, MHCM, director of obstetrics and gynecology at Boston Medical Center, and associate professor of obstetrics and gynecology at Boston University, to coauthor this month’s Master Class.

Dr. Reece, who specializes in maternal-fetal medicine, is 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. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Some of our readers might remember the old saying, “Take two aspirin and call me in the morning,” as advice physicians gave to patients experiencing a minor malady. Aspirin often has been called a “wonder drug” as its uses continue to expand. From its first recorded use in the Ebers papyrus as an anti-inflammatory agent, to its first use in a clinical trial showing that it induces remission of fever and joint inflammation, to the discovery that it could prevent death from heart attack, to its anticancer properties, aspirin remains one of the most researched drugs in use today. According to ClinicalTrials.gov, there are over 465 active and nearly 1,000 completed aspirin-related clinical trials around the world.

Despite its myriad benefits, aspirin has been linked to bleeding, nausea, and gastrointestinal ulcers. Additionally, more research is needed to determine the risks/benefits of daily aspirin in younger adults (under age 50 years) or older adults (over age 70 years), although the ASPREE (Aspirin in Reducing Events in the Elderly) trial, expected to be completed in 2019, is working to determine the effects of daily low-dose aspirin (100 mg) on the health of people over age 65.

It is tempting to consider aspirin one of modern medicine’s so-called silver bullets, and, for women with a history of gestational hypertension and preeclampsia, it just might be. Aspirin use, especially daily aspirin, is typically not recommended during pregnancy, and most ob.gyns. will include aspirin on the “do not take” list they give to their patients during prenatal examinations. Women at risk for developing preeclampsia are the exceptions to this general rule, and a number of clinical studies have indicated that use of low-dose aspirin can help prevent disease as well as secondary outcomes for mother (i.e., placental abruption, antepartum hemorrhage) and baby (i.e., intrauterine growth restriction, stillbirth). In addition, aspirin is an easily obtainable, low-cost preventive measure for any patient at high risk.

To discuss the value of low-dose aspirin to prevent preeclampsia and how ob.gyns. can educate their patients and other health care professionals about its benefits, we have invited Charles J. Lockwood, MD, MHCM, senior vice president of University of South Florida Health and dean of Morsani College of Medicine at the University of South Florida, Tampa, and Jodi F. Abbott, MD, MSc, MHCM, director of obstetrics and gynecology at Boston Medical Center, and associate professor of obstetrics and gynecology at Boston University, to coauthor this month’s Master Class.

Dr. Reece, who specializes in maternal-fetal medicine, is 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. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Pregnant women who experience severe nausea and vomiting have nearly fourfold greater odds of prenatal marijuana use compared with women not experiencing nausea and vomiting, according to data from 220,510 first-trimester screenings.

Smithore

In a research letter published in JAMA Internal Medicine, researchers reported the results of a health care system data analysis, which found a 3.80-fold greater prevalence of prenatal marijuana use among women with severe nausea and vomiting in pregnancy, compared with those who did not experience nausea and vomiting.

Among women with mild nausea and vomiting in pregnancy, there was still a significant twofold higher prevalence of marijuana use.

“Use of marijuana, an antiemetic, is increasing among pregnant women, and data from two small surveys indicate that women self-report using marijuana to alleviate nausea and vomiting in pregnancy (NVP),” wrote Kelly C. Young-Wolff, PhD, of the division of research at Kaiser Permanente Northern California, Oakland, and her coauthors.

In this study, 2% of the women experienced severe and 15% experienced mild nausea and vomiting during pregnancy.

The overall prevalence of marijuana use – assessed either by self-report or toxicological test findings – was 5.3%, with 0.7% positive on self-report only, 3.1% positive on toxicologic testing only, and 1.5% positive on both.

The authors said the findings supported the hypothesis that pregnant women were using marijuana to self-medicate for NVP. However, they also noted that clinicians may diagnose NVP more frequently among women who report using marijuana to treat it.

Dr. Young-Wolff and her coauthors said that they would not have been able to distinguish prenatal marijuana use from use before the women knew they were pregnant, “and misclassification is possible given variability in the time that marijuana is detectable in urine.

“The health effects of prenatal marijuana use are unclear, and national guidelines recommend that pregnant women discontinue use,” the authors wrote. “Patients with NVP should be screened for marijuana use and educated about effective and safe NVP treatments.”

The study was supported by the National Institute on Drug Abuse and the National Institute of Mental Health. No conflicts of interest were declared.
 

SOURCE: Young-Wolff K et al. JAMA Intern Med. 2018 Aug 20. doi: 10.1001/jamainternmed.2018.3581.

Pregnant women who experience severe nausea and vomiting have nearly fourfold greater odds of prenatal marijuana use compared with women not experiencing nausea and vomiting, according to data from 220,510 first-trimester screenings.

Smithore

In a research letter published in JAMA Internal Medicine, researchers reported the results of a health care system data analysis, which found a 3.80-fold greater prevalence of prenatal marijuana use among women with severe nausea and vomiting in pregnancy, compared with those who did not experience nausea and vomiting.

Among women with mild nausea and vomiting in pregnancy, there was still a significant twofold higher prevalence of marijuana use.

“Use of marijuana, an antiemetic, is increasing among pregnant women, and data from two small surveys indicate that women self-report using marijuana to alleviate nausea and vomiting in pregnancy (NVP),” wrote Kelly C. Young-Wolff, PhD, of the division of research at Kaiser Permanente Northern California, Oakland, and her coauthors.

In this study, 2% of the women experienced severe and 15% experienced mild nausea and vomiting during pregnancy.

The overall prevalence of marijuana use – assessed either by self-report or toxicological test findings – was 5.3%, with 0.7% positive on self-report only, 3.1% positive on toxicologic testing only, and 1.5% positive on both.

The authors said the findings supported the hypothesis that pregnant women were using marijuana to self-medicate for NVP. However, they also noted that clinicians may diagnose NVP more frequently among women who report using marijuana to treat it.

Dr. Young-Wolff and her coauthors said that they would not have been able to distinguish prenatal marijuana use from use before the women knew they were pregnant, “and misclassification is possible given variability in the time that marijuana is detectable in urine.

“The health effects of prenatal marijuana use are unclear, and national guidelines recommend that pregnant women discontinue use,” the authors wrote. “Patients with NVP should be screened for marijuana use and educated about effective and safe NVP treatments.”

The study was supported by the National Institute on Drug Abuse and the National Institute of Mental Health. No conflicts of interest were declared.
 

SOURCE: Young-Wolff K et al. JAMA Intern Med. 2018 Aug 20. doi: 10.1001/jamainternmed.2018.3581.

Pregnant women who experience severe nausea and vomiting have nearly fourfold greater odds of prenatal marijuana use compared with women not experiencing nausea and vomiting, according to data from 220,510 first-trimester screenings.

Smithore

In a research letter published in JAMA Internal Medicine, researchers reported the results of a health care system data analysis, which found a 3.80-fold greater prevalence of prenatal marijuana use among women with severe nausea and vomiting in pregnancy, compared with those who did not experience nausea and vomiting.

Among women with mild nausea and vomiting in pregnancy, there was still a significant twofold higher prevalence of marijuana use.

“Use of marijuana, an antiemetic, is increasing among pregnant women, and data from two small surveys indicate that women self-report using marijuana to alleviate nausea and vomiting in pregnancy (NVP),” wrote Kelly C. Young-Wolff, PhD, of the division of research at Kaiser Permanente Northern California, Oakland, and her coauthors.

In this study, 2% of the women experienced severe and 15% experienced mild nausea and vomiting during pregnancy.

The overall prevalence of marijuana use – assessed either by self-report or toxicological test findings – was 5.3%, with 0.7% positive on self-report only, 3.1% positive on toxicologic testing only, and 1.5% positive on both.

The authors said the findings supported the hypothesis that pregnant women were using marijuana to self-medicate for NVP. However, they also noted that clinicians may diagnose NVP more frequently among women who report using marijuana to treat it.

Dr. Young-Wolff and her coauthors said that they would not have been able to distinguish prenatal marijuana use from use before the women knew they were pregnant, “and misclassification is possible given variability in the time that marijuana is detectable in urine.

“The health effects of prenatal marijuana use are unclear, and national guidelines recommend that pregnant women discontinue use,” the authors wrote. “Patients with NVP should be screened for marijuana use and educated about effective and safe NVP treatments.”

The study was supported by the National Institute on Drug Abuse and the National Institute of Mental Health. No conflicts of interest were declared.
 

SOURCE: Young-Wolff K et al. JAMA Intern Med. 2018 Aug 20. doi: 10.1001/jamainternmed.2018.3581.

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

Breast arterial calcification and low bone mass (LBM) were strongly linked to risk of coronary artery disease in asymptomatic women, according to a cross-sectional registry study.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

The results suggest that breast arterial calcification – easily visible on every mammogram – “provides an independent and incremental predictive value over conventional risk factors,” wrote Yeonyee E. Yoon, MD, and colleagues from Seoul National University Bundang Hospital in Seongnam, South Korea.

In addition, they show that “atherosclerosis imaging allows a more direct visualization of the cumulative effects of all risk determinants in an individual patient,” they noted. The report is in JACC: Cardiovascular Imaging.

The researchers evaluated 2,100 asymptomatic women aged at least 40 years in the Women Health Registry Study for Bone, Breast, and Coronary Artery Disease (BBC study). All underwent a self-referred health evaluation that included simultaneous dual-energy x-ray absorptiometry (DXA), coronary computed tomography angiography (CCTA), and digital mammography. They predicted the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) with the Korean Risk Prediction Model (KRPM) and Pooled Cohort Equation (PCE).

Overall, Dr. Yoon and colleagues found that 199 patients (9.5%) had BAC and 716 patients (34.1%) had LBM, with 235 patients (11.2%) having coronary artery calcification (CAC) and 328 with coronary artery plaque (CAP, 15.6%). BAC presence was associated with CAC (unadjusted odds ratio, 3.54), with mild (OR, 2.84) and severe BAC scores (OR, 5.50) having a greater association with CAC. All associations were statistically significant at P less than .001.

LBM also had a positive link with CAC that grew with its severity. Specifically, the odds ratio of CAC with osteopenia, defined as a T-score between –1.0 and –2.5, was 2.06, and that for osteoporosis, defined as a T-score at or below –2.5, was 3.21. All links were significant at P less than .001.

Similarly, BAC and LBM were also significantly tied to coronary artery plaque, with mild (OR, 2.61) and moderate (OR, 4.15) BAC severity as well as osteopenia (OR, 1.76) and osteoporosis (OR 2.82) being significantly associated with CAP (all P less than .001).

In a multivariable analysis, BAC presence and BAC score were significantly associated with CAC and CAP after adjustment for 10-year ASCVD risk. Predictions for CAC and CAP under the KRPM and PCE curve analyses showed a significant increase of areas under the curve (0.71 vs. 0.64), while adding BAC presence significantly increased the AUCs for the KRPM curve analysis (0.61 vs 0.64).

“Being able to predict CAC or CAP presence in an individual patient based on the presence and severity of BAC in addition to the use of conventional risk stratification algorithms may help clinicians decide when to recommend further cardiac tests and how aggressive interventions to prescribe in order to prevent the onset of clinical CAD,” the researchers noted.

They added that patients were all self-referred women, and results may not be generalizable to a larger population. The study’s retrospective nature also is a limitation, the researchers wrote. However, they said they are planning a future trial that will attempt to determine whether there is a long-term clinical benefit to identifying BAC and LBM in women without symptoms of CAD.

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea; the Ministry of Science, ICT, and Future Planning; and the Seoul National University Bundang Hospital Research Fund. The authors report no relevant financial disclosures.

SOURCE: Yoon YE et al. JACC: Cardiovasc Imaging. 2018 Aug 15. doi: 10.1016/j.jcmg.2018.07.004.

Breast arterial calcification and low bone mass (LBM) were strongly linked to risk of coronary artery disease in asymptomatic women, according to a cross-sectional registry study.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

The results suggest that breast arterial calcification – easily visible on every mammogram – “provides an independent and incremental predictive value over conventional risk factors,” wrote Yeonyee E. Yoon, MD, and colleagues from Seoul National University Bundang Hospital in Seongnam, South Korea.

In addition, they show that “atherosclerosis imaging allows a more direct visualization of the cumulative effects of all risk determinants in an individual patient,” they noted. The report is in JACC: Cardiovascular Imaging.

The researchers evaluated 2,100 asymptomatic women aged at least 40 years in the Women Health Registry Study for Bone, Breast, and Coronary Artery Disease (BBC study). All underwent a self-referred health evaluation that included simultaneous dual-energy x-ray absorptiometry (DXA), coronary computed tomography angiography (CCTA), and digital mammography. They predicted the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) with the Korean Risk Prediction Model (KRPM) and Pooled Cohort Equation (PCE).

Overall, Dr. Yoon and colleagues found that 199 patients (9.5%) had BAC and 716 patients (34.1%) had LBM, with 235 patients (11.2%) having coronary artery calcification (CAC) and 328 with coronary artery plaque (CAP, 15.6%). BAC presence was associated with CAC (unadjusted odds ratio, 3.54), with mild (OR, 2.84) and severe BAC scores (OR, 5.50) having a greater association with CAC. All associations were statistically significant at P less than .001.

LBM also had a positive link with CAC that grew with its severity. Specifically, the odds ratio of CAC with osteopenia, defined as a T-score between –1.0 and –2.5, was 2.06, and that for osteoporosis, defined as a T-score at or below –2.5, was 3.21. All links were significant at P less than .001.

Similarly, BAC and LBM were also significantly tied to coronary artery plaque, with mild (OR, 2.61) and moderate (OR, 4.15) BAC severity as well as osteopenia (OR, 1.76) and osteoporosis (OR 2.82) being significantly associated with CAP (all P less than .001).

In a multivariable analysis, BAC presence and BAC score were significantly associated with CAC and CAP after adjustment for 10-year ASCVD risk. Predictions for CAC and CAP under the KRPM and PCE curve analyses showed a significant increase of areas under the curve (0.71 vs. 0.64), while adding BAC presence significantly increased the AUCs for the KRPM curve analysis (0.61 vs 0.64).

“Being able to predict CAC or CAP presence in an individual patient based on the presence and severity of BAC in addition to the use of conventional risk stratification algorithms may help clinicians decide when to recommend further cardiac tests and how aggressive interventions to prescribe in order to prevent the onset of clinical CAD,” the researchers noted.

They added that patients were all self-referred women, and results may not be generalizable to a larger population. The study’s retrospective nature also is a limitation, the researchers wrote. However, they said they are planning a future trial that will attempt to determine whether there is a long-term clinical benefit to identifying BAC and LBM in women without symptoms of CAD.

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea; the Ministry of Science, ICT, and Future Planning; and the Seoul National University Bundang Hospital Research Fund. The authors report no relevant financial disclosures.

SOURCE: Yoon YE et al. JACC: Cardiovasc Imaging. 2018 Aug 15. doi: 10.1016/j.jcmg.2018.07.004.

Breast arterial calcification and low bone mass (LBM) were strongly linked to risk of coronary artery disease in asymptomatic women, according to a cross-sectional registry study.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

The results suggest that breast arterial calcification – easily visible on every mammogram – “provides an independent and incremental predictive value over conventional risk factors,” wrote Yeonyee E. Yoon, MD, and colleagues from Seoul National University Bundang Hospital in Seongnam, South Korea.

In addition, they show that “atherosclerosis imaging allows a more direct visualization of the cumulative effects of all risk determinants in an individual patient,” they noted. The report is in JACC: Cardiovascular Imaging.

The researchers evaluated 2,100 asymptomatic women aged at least 40 years in the Women Health Registry Study for Bone, Breast, and Coronary Artery Disease (BBC study). All underwent a self-referred health evaluation that included simultaneous dual-energy x-ray absorptiometry (DXA), coronary computed tomography angiography (CCTA), and digital mammography. They predicted the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) with the Korean Risk Prediction Model (KRPM) and Pooled Cohort Equation (PCE).

Overall, Dr. Yoon and colleagues found that 199 patients (9.5%) had BAC and 716 patients (34.1%) had LBM, with 235 patients (11.2%) having coronary artery calcification (CAC) and 328 with coronary artery plaque (CAP, 15.6%). BAC presence was associated with CAC (unadjusted odds ratio, 3.54), with mild (OR, 2.84) and severe BAC scores (OR, 5.50) having a greater association with CAC. All associations were statistically significant at P less than .001.

LBM also had a positive link with CAC that grew with its severity. Specifically, the odds ratio of CAC with osteopenia, defined as a T-score between –1.0 and –2.5, was 2.06, and that for osteoporosis, defined as a T-score at or below –2.5, was 3.21. All links were significant at P less than .001.

Similarly, BAC and LBM were also significantly tied to coronary artery plaque, with mild (OR, 2.61) and moderate (OR, 4.15) BAC severity as well as osteopenia (OR, 1.76) and osteoporosis (OR 2.82) being significantly associated with CAP (all P less than .001).

In a multivariable analysis, BAC presence and BAC score were significantly associated with CAC and CAP after adjustment for 10-year ASCVD risk. Predictions for CAC and CAP under the KRPM and PCE curve analyses showed a significant increase of areas under the curve (0.71 vs. 0.64), while adding BAC presence significantly increased the AUCs for the KRPM curve analysis (0.61 vs 0.64).

“Being able to predict CAC or CAP presence in an individual patient based on the presence and severity of BAC in addition to the use of conventional risk stratification algorithms may help clinicians decide when to recommend further cardiac tests and how aggressive interventions to prescribe in order to prevent the onset of clinical CAD,” the researchers noted.

They added that patients were all self-referred women, and results may not be generalizable to a larger population. The study’s retrospective nature also is a limitation, the researchers wrote. However, they said they are planning a future trial that will attempt to determine whether there is a long-term clinical benefit to identifying BAC and LBM in women without symptoms of CAD.

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea; the Ministry of Science, ICT, and Future Planning; and the Seoul National University Bundang Hospital Research Fund. The authors report no relevant financial disclosures.

SOURCE: Yoon YE et al. JACC: Cardiovasc Imaging. 2018 Aug 15. doi: 10.1016/j.jcmg.2018.07.004.

Pregnant lesbian and bisexual women who seek abortions are more likely than are their heterosexual counterparts to be the victims of violence by the men who impregnated them, a new study finds.

Rachel K. Jones, PhD, of the Guttmacher Institute, New York, and her associates also found that these sexual minority women, plus a group of individuals who described their sexual orientation as “something else,” were much more likely to report exposure to sexual and physical violence.

“No patient should be presumed to be heterosexual for any reason, including a pregnancy history. All pregnancies – like all patients – should be treated as unique and operating within the dynamic and interconnected circumstances of peoples’ lives, which may encompass differences in sexual orientation and exposure to violence,” the researchers wrote. Their report is in Obstetrics & Gynecology.

Previous research has suggested that nonheterosexual women are more likely than are straight women to become pregnant unintentionally. There also are signs suggesting that they have more abortions, too, although the findings are iffy, the study authors wrote.

For this study, Dr. Jones and her associates examined questionnaire answers of 8,380 women who responded to the Guttmacher Institute’s 2014 Abortion Patient Survey. All were undergoing abortions at 87 U.S. nonhospital facilities that performed 30 or more abortions each per year.

Of the sample, about 9% declined to describe their sexual orientation. Of the rest, 94% described themselves as heterosexual; of those, 41% were white, 28% were black, and 22% were Hispanic. Most were in their 20s, 47% were never married, and 48% had incomes below the federal poverty level.

Women also described themselves as bisexual (4%), “something else” (1%), and lesbian (0.4%). All these groups were more likely than were heterosexuals to be below the federal poverty level; more than half of the lesbian and bisexual respondents said they had previously given birth.

Fifteen percent of lesbians said their current pregnancy was caused by forced sex, compared with 1% of heterosexuals and 3% of bisexuals. (P less than .001).

Bisexuals (9%) and lesbians (33%) were more likely than were heterosexuals (4%) to say the men who impregnated them had physically abused them. The same was true for sexual abuse, which was reported by 7% of bisexuals, 35% of lesbians, and 2% of heterosexuals. After the researchers controlled for various factors including age and race, lesbians remained much more likely to report physical abuse, sexual abuse, and forced sex at the hands of the men who impregnated them (odds ratios = 15, 25, and 10, respectively, P less than .001).

“Exposure to physical and sexual violence was substantially higher among each of the sexual minority groups compared with their heterosexual counterparts, sometimes by a factor of 15 or more,” the study authors wrote. “We found that lesbian respondents had the highest levels of exposure to violence, perhaps because this population was more likely to have had sex with a man only in the context of forced sex.”

The researchers noted that their study has various limitations, such as low numbers of sexual minority women and the 4-year gap since the data were collected.

SOURCE: Jones R et al. Obstet Gynecol. 2018 Sep;132(3):605-11.

Pregnant lesbian and bisexual women who seek abortions are more likely than are their heterosexual counterparts to be the victims of violence by the men who impregnated them, a new study finds.

Rachel K. Jones, PhD, of the Guttmacher Institute, New York, and her associates also found that these sexual minority women, plus a group of individuals who described their sexual orientation as “something else,” were much more likely to report exposure to sexual and physical violence.

“No patient should be presumed to be heterosexual for any reason, including a pregnancy history. All pregnancies – like all patients – should be treated as unique and operating within the dynamic and interconnected circumstances of peoples’ lives, which may encompass differences in sexual orientation and exposure to violence,” the researchers wrote. Their report is in Obstetrics & Gynecology.

Previous research has suggested that nonheterosexual women are more likely than are straight women to become pregnant unintentionally. There also are signs suggesting that they have more abortions, too, although the findings are iffy, the study authors wrote.

For this study, Dr. Jones and her associates examined questionnaire answers of 8,380 women who responded to the Guttmacher Institute’s 2014 Abortion Patient Survey. All were undergoing abortions at 87 U.S. nonhospital facilities that performed 30 or more abortions each per year.

Of the sample, about 9% declined to describe their sexual orientation. Of the rest, 94% described themselves as heterosexual; of those, 41% were white, 28% were black, and 22% were Hispanic. Most were in their 20s, 47% were never married, and 48% had incomes below the federal poverty level.

Women also described themselves as bisexual (4%), “something else” (1%), and lesbian (0.4%). All these groups were more likely than were heterosexuals to be below the federal poverty level; more than half of the lesbian and bisexual respondents said they had previously given birth.

Fifteen percent of lesbians said their current pregnancy was caused by forced sex, compared with 1% of heterosexuals and 3% of bisexuals. (P less than .001).

Bisexuals (9%) and lesbians (33%) were more likely than were heterosexuals (4%) to say the men who impregnated them had physically abused them. The same was true for sexual abuse, which was reported by 7% of bisexuals, 35% of lesbians, and 2% of heterosexuals. After the researchers controlled for various factors including age and race, lesbians remained much more likely to report physical abuse, sexual abuse, and forced sex at the hands of the men who impregnated them (odds ratios = 15, 25, and 10, respectively, P less than .001).

“Exposure to physical and sexual violence was substantially higher among each of the sexual minority groups compared with their heterosexual counterparts, sometimes by a factor of 15 or more,” the study authors wrote. “We found that lesbian respondents had the highest levels of exposure to violence, perhaps because this population was more likely to have had sex with a man only in the context of forced sex.”

The researchers noted that their study has various limitations, such as low numbers of sexual minority women and the 4-year gap since the data were collected.

SOURCE: Jones R et al. Obstet Gynecol. 2018 Sep;132(3):605-11.

Pregnant lesbian and bisexual women who seek abortions are more likely than are their heterosexual counterparts to be the victims of violence by the men who impregnated them, a new study finds.

Rachel K. Jones, PhD, of the Guttmacher Institute, New York, and her associates also found that these sexual minority women, plus a group of individuals who described their sexual orientation as “something else,” were much more likely to report exposure to sexual and physical violence.

“No patient should be presumed to be heterosexual for any reason, including a pregnancy history. All pregnancies – like all patients – should be treated as unique and operating within the dynamic and interconnected circumstances of peoples’ lives, which may encompass differences in sexual orientation and exposure to violence,” the researchers wrote. Their report is in Obstetrics & Gynecology.

Previous research has suggested that nonheterosexual women are more likely than are straight women to become pregnant unintentionally. There also are signs suggesting that they have more abortions, too, although the findings are iffy, the study authors wrote.

For this study, Dr. Jones and her associates examined questionnaire answers of 8,380 women who responded to the Guttmacher Institute’s 2014 Abortion Patient Survey. All were undergoing abortions at 87 U.S. nonhospital facilities that performed 30 or more abortions each per year.

Of the sample, about 9% declined to describe their sexual orientation. Of the rest, 94% described themselves as heterosexual; of those, 41% were white, 28% were black, and 22% were Hispanic. Most were in their 20s, 47% were never married, and 48% had incomes below the federal poverty level.

Women also described themselves as bisexual (4%), “something else” (1%), and lesbian (0.4%). All these groups were more likely than were heterosexuals to be below the federal poverty level; more than half of the lesbian and bisexual respondents said they had previously given birth.

Fifteen percent of lesbians said their current pregnancy was caused by forced sex, compared with 1% of heterosexuals and 3% of bisexuals. (P less than .001).

Bisexuals (9%) and lesbians (33%) were more likely than were heterosexuals (4%) to say the men who impregnated them had physically abused them. The same was true for sexual abuse, which was reported by 7% of bisexuals, 35% of lesbians, and 2% of heterosexuals. After the researchers controlled for various factors including age and race, lesbians remained much more likely to report physical abuse, sexual abuse, and forced sex at the hands of the men who impregnated them (odds ratios = 15, 25, and 10, respectively, P less than .001).

“Exposure to physical and sexual violence was substantially higher among each of the sexual minority groups compared with their heterosexual counterparts, sometimes by a factor of 15 or more,” the study authors wrote. “We found that lesbian respondents had the highest levels of exposure to violence, perhaps because this population was more likely to have had sex with a man only in the context of forced sex.”

The researchers noted that their study has various limitations, such as low numbers of sexual minority women and the 4-year gap since the data were collected.

SOURCE: Jones R et al. Obstet Gynecol. 2018 Sep;132(3):605-11.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

The first vaginal ring contraceptive that can be used for 1 year has been approved by the Food and Drug Administration.

The FDA granted approval of Annovera (segesterone acetate and ethinyl estradiol vaginal system), a reusable donut-shaped ring, to the Population Council. The nonbiodegradable, flexible vaginal system is placed in the vagina for 3 weeks followed by 1 week out of the vagina, at which time women may experience a menstrual period. This schedule is repeated every 4 weeks for 13 28-day menstrual cycles.

The contraceptive ring is washed and stored in a compact case for the 7 days when it is not in use. Annovera does not require refrigeration prior to dispensing and can withstand storage temperatures up to 30° C (86° F).

“Today’s approval builds on available birth control options,” said Victor Crentsil, MD, acting deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research.

The efficacy and safety of Annovera were studied in three, open-label clinical trials with healthy women ranging from 18 to 40 years of age. Based on the results, about 2%-4% of women may get pregnant during the first year they use Annovera.

Annovera carries a boxed warning regarding cigarette smoking and serious cardiovascular events. Women over age 35 who smoke should not use Annovera. Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use.

Annovera is contraindicated for women with a high risk of arterial or venous thrombotic diseases; a history of breast cancer or another estrogen- or progestin-sensitive cancer; liver tumors, acute hepatitis, or severe (decompensated) cirrhosis; undiagnosed abnormal uterine bleeding; hypersensitivity to any of the components of Annovera; and use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, according to an FDA press release.

The most common side effects of Annovera are similar to those of other combined hormonal contraceptive products and include headache, nausea and vomiting, yeast infections, abdominal pain, dysmenorrhea, breast tenderness, irregular bleeding, diarrhea, and genital itching.

The FDA is requiring postmarketing studies to further evaluate the risks of venous thromboembolism and the effects of CYP3A-modulating drugs and tampon use on the pharmacokinetics of Annovera.

[email protected]

The first vaginal ring contraceptive that can be used for 1 year has been approved by the Food and Drug Administration.

The FDA granted approval of Annovera (segesterone acetate and ethinyl estradiol vaginal system), a reusable donut-shaped ring, to the Population Council. The nonbiodegradable, flexible vaginal system is placed in the vagina for 3 weeks followed by 1 week out of the vagina, at which time women may experience a menstrual period. This schedule is repeated every 4 weeks for 13 28-day menstrual cycles.

The contraceptive ring is washed and stored in a compact case for the 7 days when it is not in use. Annovera does not require refrigeration prior to dispensing and can withstand storage temperatures up to 30° C (86° F).

“Today’s approval builds on available birth control options,” said Victor Crentsil, MD, acting deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research.

The efficacy and safety of Annovera were studied in three, open-label clinical trials with healthy women ranging from 18 to 40 years of age. Based on the results, about 2%-4% of women may get pregnant during the first year they use Annovera.

Annovera carries a boxed warning regarding cigarette smoking and serious cardiovascular events. Women over age 35 who smoke should not use Annovera. Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use.

Annovera is contraindicated for women with a high risk of arterial or venous thrombotic diseases; a history of breast cancer or another estrogen- or progestin-sensitive cancer; liver tumors, acute hepatitis, or severe (decompensated) cirrhosis; undiagnosed abnormal uterine bleeding; hypersensitivity to any of the components of Annovera; and use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, according to an FDA press release.

The most common side effects of Annovera are similar to those of other combined hormonal contraceptive products and include headache, nausea and vomiting, yeast infections, abdominal pain, dysmenorrhea, breast tenderness, irregular bleeding, diarrhea, and genital itching.

The FDA is requiring postmarketing studies to further evaluate the risks of venous thromboembolism and the effects of CYP3A-modulating drugs and tampon use on the pharmacokinetics of Annovera.

[email protected]

The first vaginal ring contraceptive that can be used for 1 year has been approved by the Food and Drug Administration.

The FDA granted approval of Annovera (segesterone acetate and ethinyl estradiol vaginal system), a reusable donut-shaped ring, to the Population Council. The nonbiodegradable, flexible vaginal system is placed in the vagina for 3 weeks followed by 1 week out of the vagina, at which time women may experience a menstrual period. This schedule is repeated every 4 weeks for 13 28-day menstrual cycles.

The contraceptive ring is washed and stored in a compact case for the 7 days when it is not in use. Annovera does not require refrigeration prior to dispensing and can withstand storage temperatures up to 30° C (86° F).

“Today’s approval builds on available birth control options,” said Victor Crentsil, MD, acting deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research.

The efficacy and safety of Annovera were studied in three, open-label clinical trials with healthy women ranging from 18 to 40 years of age. Based on the results, about 2%-4% of women may get pregnant during the first year they use Annovera.

Annovera carries a boxed warning regarding cigarette smoking and serious cardiovascular events. Women over age 35 who smoke should not use Annovera. Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use.

Annovera is contraindicated for women with a high risk of arterial or venous thrombotic diseases; a history of breast cancer or another estrogen- or progestin-sensitive cancer; liver tumors, acute hepatitis, or severe (decompensated) cirrhosis; undiagnosed abnormal uterine bleeding; hypersensitivity to any of the components of Annovera; and use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, according to an FDA press release.

The most common side effects of Annovera are similar to those of other combined hormonal contraceptive products and include headache, nausea and vomiting, yeast infections, abdominal pain, dysmenorrhea, breast tenderness, irregular bleeding, diarrhea, and genital itching.

The FDA is requiring postmarketing studies to further evaluate the risks of venous thromboembolism and the effects of CYP3A-modulating drugs and tampon use on the pharmacokinetics of Annovera.

[email protected]