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Under new ACC-AHA criteria, more pregnant women at risk of hypertension, adverse outcomes
A total of 164 new diagnoses (5.6%) of lower range stage 1 hypertension were made when the revised American Heart Association and the American College of Cardiology (ACC-AHA) Task Force on Clinical Practice Guidelines for chronic hypertension in adults were applied to a population of 2,947 pregnant women.
These patients had a significantly increased risk of preeclampsia as well as an increased risk of gestational diabetes mellitus and preterm birth, compared with normotensive patients, according to a study published in Obstetrics & Gynecology.
Elizabeth F. Sutton, PhD, and her associates at Magee-Womens Research Institute in Pittsburgh, used data from a Eunice Kennedy Shriver National Institute of Child Health and Human Development study. It included 2,947 pregnant women with singleton pregnancies where 94% of women were normotensive prior to 25 weeks of gestation. The researchers identified 164 new cases (6%) of lower range stage 1 hypertension under the ACC-AHA guidelines. Patients were then randomized to receive 60 mg of aspirin (1,399 normotensive patients, 66 stage 1 hypertension patients) or placebo (1,384 normotensive patients, 98 stage 1 hypertension patients).
The women had their blood pressure (BP) measured at 25 weeks of gestation or prior, and those patients with a systolic BP between 130 mm Hg and 139 mm Hg or diastolic BP between 80 mm and 89 mm were reclassified as having stage 1 hypertension under the new ACC-AHA guidelines; outcomes were compared with normotensive women with a systolic BP of 130 mm Hg and diastolic BP of 80 mm Hg. The researchers also performed a sensitivity analysis that restricted enrollment to 1,661 women who were at 20 weeks of gestation or prior, they said.
“Of important note, as a result of eligibility criterion excluding women with chronic hypertension (greater than 135/85 mm Hg) at enrollment, the enrollment BP range within the stage 1 hypertension group was limited to lower range stage 1 hypertension, that is, 130-135, 80-85 mm Hg, or both,” Dr. Sutton and her colleagues wrote.
The researchers found a significantly increased risk of preeclampsia among hypertensive pregnant women in the placebo group (15%) compared with normotensive (5%) women (relative risk, 2.66; 95% confidence interval, 1.56-4.54; P less than .01). These patients also had an increased risk of gestational diabetes mellitus (6%) compared with normotensive (2.5%; P = .03) pregnant women as well as an increased risk of preterm birth (4% vs. 1%; P = .01). Among women with stage 1 hypertension who received low-dose aspirin, there were no significant differences regarding the rate of preeclampsia, gestational diabetes mellitus, or preterm birth risk.
“Although prepregnancy BPs would be ideal for diagnosis, prior studies have shown that women do not consistently seek primary care outside of pregnancy,” Dr. Sutton and her colleagues wrote. “In the United States, preconception care engagement rates are between 18% and 45% in reproductive-aged women; thus, early pregnancy BPs may be all that is available for the obstetrician.”
Limitations to the secondary analysis included the original study’s exclusion of BPs higher than 135/85 mm Hg and the small sample size of patients who met the new criteria for stage 1 hypertension. The researchers also noted an increased risk of preeclampsia among patients with intake systolic BP between 120 mm Hg and 129 mm Hg, “with a smaller magnitude of risk compared with stage 1 hypertension.
“These findings suggest preliminarily that when considering preeclampsia risk based on early pregnancy BP, perhaps BP could be considered as a continuous variable rather than categorical,” Dr. Sutton and her colleagues noted.
This study was supported in part by the American Heart Association and the Eunice Kennedy Shriver NICHD. The authors reported no relevant financial conflicts of interest.
SOURCE: Sutton EF et al. Obstet Gynecol. 2018 Oct doi: 10.1097/AOG.0000000000002870.
I have significant concerns that, were ob.gyns. to adopt the ACC-AHA guidelines for chronic hypertension in adults and apply them to pregnant women, it would have great implications, as about 25% of all pregnant women have these findings.
Under the new criteria, there would be an additional 1 million pregnant women diagnosed with prehypertension or stage 1 hypertension. The new criteria will not only overdiagnose prehypertension in these women, it will cause more women to receive antihypertension medications.
The ACC-AHA criteria apply only to patients who have their blood pressure (BP) recorded prior to pregnancy or prior to 20 weeks of gestation. This study included women at up to 25 weeks of gestation, which means some already had been developing the condition. The Sutton et al. data also do not follow the new ACC-AHA criteria because the criteria require two BP readings, and the current study shows only one elevation which is, in my opinion, more dangerous.
Any time new criteria and screening are introduced, there always should be preparations for what happens next. There is no doubt that the ACC-AHA criteria, performed using two BP readings, is associated with hypertension, but what should clinicians do with that information? Prospective studies aimed at evaluating whether a woman with hypertension prior to or early in pregnancy may benefit from more intensive screening and other interventions to prevent hypertensive disorders and gestational diabetes in pregnancy are needed.
Baha Sibai, MD, is a visiting professor in the department of obstetrics, gynecology, and reproductive sciences at The University of Texas Health Sciences Center at Houston. He was asked to comment on the study by Sutton et al. He reported no relevant financial conflicts of interest.
I have significant concerns that, were ob.gyns. to adopt the ACC-AHA guidelines for chronic hypertension in adults and apply them to pregnant women, it would have great implications, as about 25% of all pregnant women have these findings.
Under the new criteria, there would be an additional 1 million pregnant women diagnosed with prehypertension or stage 1 hypertension. The new criteria will not only overdiagnose prehypertension in these women, it will cause more women to receive antihypertension medications.
The ACC-AHA criteria apply only to patients who have their blood pressure (BP) recorded prior to pregnancy or prior to 20 weeks of gestation. This study included women at up to 25 weeks of gestation, which means some already had been developing the condition. The Sutton et al. data also do not follow the new ACC-AHA criteria because the criteria require two BP readings, and the current study shows only one elevation which is, in my opinion, more dangerous.
Any time new criteria and screening are introduced, there always should be preparations for what happens next. There is no doubt that the ACC-AHA criteria, performed using two BP readings, is associated with hypertension, but what should clinicians do with that information? Prospective studies aimed at evaluating whether a woman with hypertension prior to or early in pregnancy may benefit from more intensive screening and other interventions to prevent hypertensive disorders and gestational diabetes in pregnancy are needed.
Baha Sibai, MD, is a visiting professor in the department of obstetrics, gynecology, and reproductive sciences at The University of Texas Health Sciences Center at Houston. He was asked to comment on the study by Sutton et al. He reported no relevant financial conflicts of interest.
I have significant concerns that, were ob.gyns. to adopt the ACC-AHA guidelines for chronic hypertension in adults and apply them to pregnant women, it would have great implications, as about 25% of all pregnant women have these findings.
Under the new criteria, there would be an additional 1 million pregnant women diagnosed with prehypertension or stage 1 hypertension. The new criteria will not only overdiagnose prehypertension in these women, it will cause more women to receive antihypertension medications.
The ACC-AHA criteria apply only to patients who have their blood pressure (BP) recorded prior to pregnancy or prior to 20 weeks of gestation. This study included women at up to 25 weeks of gestation, which means some already had been developing the condition. The Sutton et al. data also do not follow the new ACC-AHA criteria because the criteria require two BP readings, and the current study shows only one elevation which is, in my opinion, more dangerous.
Any time new criteria and screening are introduced, there always should be preparations for what happens next. There is no doubt that the ACC-AHA criteria, performed using two BP readings, is associated with hypertension, but what should clinicians do with that information? Prospective studies aimed at evaluating whether a woman with hypertension prior to or early in pregnancy may benefit from more intensive screening and other interventions to prevent hypertensive disorders and gestational diabetes in pregnancy are needed.
Baha Sibai, MD, is a visiting professor in the department of obstetrics, gynecology, and reproductive sciences at The University of Texas Health Sciences Center at Houston. He was asked to comment on the study by Sutton et al. He reported no relevant financial conflicts of interest.
A total of 164 new diagnoses (5.6%) of lower range stage 1 hypertension were made when the revised American Heart Association and the American College of Cardiology (ACC-AHA) Task Force on Clinical Practice Guidelines for chronic hypertension in adults were applied to a population of 2,947 pregnant women.
These patients had a significantly increased risk of preeclampsia as well as an increased risk of gestational diabetes mellitus and preterm birth, compared with normotensive patients, according to a study published in Obstetrics & Gynecology.
Elizabeth F. Sutton, PhD, and her associates at Magee-Womens Research Institute in Pittsburgh, used data from a Eunice Kennedy Shriver National Institute of Child Health and Human Development study. It included 2,947 pregnant women with singleton pregnancies where 94% of women were normotensive prior to 25 weeks of gestation. The researchers identified 164 new cases (6%) of lower range stage 1 hypertension under the ACC-AHA guidelines. Patients were then randomized to receive 60 mg of aspirin (1,399 normotensive patients, 66 stage 1 hypertension patients) or placebo (1,384 normotensive patients, 98 stage 1 hypertension patients).
The women had their blood pressure (BP) measured at 25 weeks of gestation or prior, and those patients with a systolic BP between 130 mm Hg and 139 mm Hg or diastolic BP between 80 mm and 89 mm were reclassified as having stage 1 hypertension under the new ACC-AHA guidelines; outcomes were compared with normotensive women with a systolic BP of 130 mm Hg and diastolic BP of 80 mm Hg. The researchers also performed a sensitivity analysis that restricted enrollment to 1,661 women who were at 20 weeks of gestation or prior, they said.
“Of important note, as a result of eligibility criterion excluding women with chronic hypertension (greater than 135/85 mm Hg) at enrollment, the enrollment BP range within the stage 1 hypertension group was limited to lower range stage 1 hypertension, that is, 130-135, 80-85 mm Hg, or both,” Dr. Sutton and her colleagues wrote.
The researchers found a significantly increased risk of preeclampsia among hypertensive pregnant women in the placebo group (15%) compared with normotensive (5%) women (relative risk, 2.66; 95% confidence interval, 1.56-4.54; P less than .01). These patients also had an increased risk of gestational diabetes mellitus (6%) compared with normotensive (2.5%; P = .03) pregnant women as well as an increased risk of preterm birth (4% vs. 1%; P = .01). Among women with stage 1 hypertension who received low-dose aspirin, there were no significant differences regarding the rate of preeclampsia, gestational diabetes mellitus, or preterm birth risk.
“Although prepregnancy BPs would be ideal for diagnosis, prior studies have shown that women do not consistently seek primary care outside of pregnancy,” Dr. Sutton and her colleagues wrote. “In the United States, preconception care engagement rates are between 18% and 45% in reproductive-aged women; thus, early pregnancy BPs may be all that is available for the obstetrician.”
Limitations to the secondary analysis included the original study’s exclusion of BPs higher than 135/85 mm Hg and the small sample size of patients who met the new criteria for stage 1 hypertension. The researchers also noted an increased risk of preeclampsia among patients with intake systolic BP between 120 mm Hg and 129 mm Hg, “with a smaller magnitude of risk compared with stage 1 hypertension.
“These findings suggest preliminarily that when considering preeclampsia risk based on early pregnancy BP, perhaps BP could be considered as a continuous variable rather than categorical,” Dr. Sutton and her colleagues noted.
This study was supported in part by the American Heart Association and the Eunice Kennedy Shriver NICHD. The authors reported no relevant financial conflicts of interest.
SOURCE: Sutton EF et al. Obstet Gynecol. 2018 Oct doi: 10.1097/AOG.0000000000002870.
A total of 164 new diagnoses (5.6%) of lower range stage 1 hypertension were made when the revised American Heart Association and the American College of Cardiology (ACC-AHA) Task Force on Clinical Practice Guidelines for chronic hypertension in adults were applied to a population of 2,947 pregnant women.
These patients had a significantly increased risk of preeclampsia as well as an increased risk of gestational diabetes mellitus and preterm birth, compared with normotensive patients, according to a study published in Obstetrics & Gynecology.
Elizabeth F. Sutton, PhD, and her associates at Magee-Womens Research Institute in Pittsburgh, used data from a Eunice Kennedy Shriver National Institute of Child Health and Human Development study. It included 2,947 pregnant women with singleton pregnancies where 94% of women were normotensive prior to 25 weeks of gestation. The researchers identified 164 new cases (6%) of lower range stage 1 hypertension under the ACC-AHA guidelines. Patients were then randomized to receive 60 mg of aspirin (1,399 normotensive patients, 66 stage 1 hypertension patients) or placebo (1,384 normotensive patients, 98 stage 1 hypertension patients).
The women had their blood pressure (BP) measured at 25 weeks of gestation or prior, and those patients with a systolic BP between 130 mm Hg and 139 mm Hg or diastolic BP between 80 mm and 89 mm were reclassified as having stage 1 hypertension under the new ACC-AHA guidelines; outcomes were compared with normotensive women with a systolic BP of 130 mm Hg and diastolic BP of 80 mm Hg. The researchers also performed a sensitivity analysis that restricted enrollment to 1,661 women who were at 20 weeks of gestation or prior, they said.
“Of important note, as a result of eligibility criterion excluding women with chronic hypertension (greater than 135/85 mm Hg) at enrollment, the enrollment BP range within the stage 1 hypertension group was limited to lower range stage 1 hypertension, that is, 130-135, 80-85 mm Hg, or both,” Dr. Sutton and her colleagues wrote.
The researchers found a significantly increased risk of preeclampsia among hypertensive pregnant women in the placebo group (15%) compared with normotensive (5%) women (relative risk, 2.66; 95% confidence interval, 1.56-4.54; P less than .01). These patients also had an increased risk of gestational diabetes mellitus (6%) compared with normotensive (2.5%; P = .03) pregnant women as well as an increased risk of preterm birth (4% vs. 1%; P = .01). Among women with stage 1 hypertension who received low-dose aspirin, there were no significant differences regarding the rate of preeclampsia, gestational diabetes mellitus, or preterm birth risk.
“Although prepregnancy BPs would be ideal for diagnosis, prior studies have shown that women do not consistently seek primary care outside of pregnancy,” Dr. Sutton and her colleagues wrote. “In the United States, preconception care engagement rates are between 18% and 45% in reproductive-aged women; thus, early pregnancy BPs may be all that is available for the obstetrician.”
Limitations to the secondary analysis included the original study’s exclusion of BPs higher than 135/85 mm Hg and the small sample size of patients who met the new criteria for stage 1 hypertension. The researchers also noted an increased risk of preeclampsia among patients with intake systolic BP between 120 mm Hg and 129 mm Hg, “with a smaller magnitude of risk compared with stage 1 hypertension.
“These findings suggest preliminarily that when considering preeclampsia risk based on early pregnancy BP, perhaps BP could be considered as a continuous variable rather than categorical,” Dr. Sutton and her colleagues noted.
This study was supported in part by the American Heart Association and the Eunice Kennedy Shriver NICHD. The authors reported no relevant financial conflicts of interest.
SOURCE: Sutton EF et al. Obstet Gynecol. 2018 Oct doi: 10.1097/AOG.0000000000002870.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: gestational diabetes, and preterm birth.
Major finding: Pregnant women with newly diagnosed stage 1 hypertension not randomized to receive aspirin had a significantly higher risk of preeclampsia (15%) and a higher risk of gestational diabetes (6%) and preterm birth (4%), compared with normotensive pregnant women.
Study details: A secondary analysis of 2,947 women who were originally enrolled in a study by the Eunice Kennedy Shriver NICHD between 1989 and 1992.
Disclosures: This study was supported in part by the American Heart Association and the Eunice Kennedy Shriver NICHD. The authors reported no relevant financial conflicts of interest.
Source: Sutton EF et al. Obstet Gynecol. 2018 Oct doi:10.1097/AOG.0000000000002870.
Gestational weight outside guidelines adversely affects mothers, babies
Gestational weight gain above or below the level recommended by the Institute of Medicine (IOM) guidelines resulted in significantly worse outcomes for mothers and babies, according to data from nearly 30,000 women.
Previous studies of the relationship between gestational weight gain and maternal and neonatal outcomes have been limited by “small sample sizes, single sites, restricted reporting of outcomes, and a lack of racial-ethnic diversity,” Michelle A. Kominiarek, MD, of Northwestern University in Chicago and her colleagues wrote . To determine the effects of gestational weight gain on a large and more diverse population, the researchers conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network’s Assessment of Perinatal Excellence study. The findings were published in Obstetrics & Gynecology.
Gestational weight gain above the amount recommended by IOM guidelines was significantly associated with adverse outcomes in neonates, including macrosomia (adjusted odds ratio, 2.66), shoulder dystocia (aOR, 1.74), and neonatal hypoglycemia (aOR, 1.60).
In further multivariate analysis, adverse maternal outcomes associated with gestational weight gain above that recommended by the guidelines included hypertensive diseases of pregnancy for any parity (aOR, 1.84) and increased risk of cesarean delivery in nulliparous and multiparous women (aORs, 1.44 and 1.26, respectively).
Gestational weight gain below the recommended amount was associated with both spontaneous (aOR, 1.50) and indicated (aOR, 1.34) preterm birth. Weight gain above the guidelines was associated with a greater risk of indicated preterm birth only (aOR, 1.24).
The study population included 29,861 women at 25 hospitals over a 3-year period. Of these, 51% had gestational weight gains above the amount recommended by the IOM guidelines and 21% had gestational weight gains below it. The researchers calculated gestational weight gain by subtracting prepregnancy weight from delivery weight or, if prepregnancy weight was not available, by subtracting weight at the first prenatal visit at 13 weeks of gestation or earlier from delivery weight.
The study findings were limited by the use of self-reported prepregnancy weight and the possible effects of changes to the guidelines with respect to obese patients, the researchers said. However, the results support those from previous studies, and the “noted strengths include analysis of 29,861 women representative of the United States with rigorous ascertainment of outcomes and calculation of gestational weight gain to account for the wide range of gestational ages at delivery,” Dr. Kominiarek and her associates wrote.
Overall, the data support efforts to educate women on health behaviors and how gestational weight gain affects them and their infants, and additional research is needed to help women meet their goals for appropriate gestational weight, the researchers concluded.
SOURCE: Kominiarek MA et al. Obstet Gynecol. 2018 Oct;132(4):875-81.
“We are struggling with an obesity epidemic in this country, and pregnancy accounts for a risk time for women to gain excessive weight,” Martina L. Badell, MD, said in an interview. “This is a very well-designed large study which attempted to systematically evaluate the adverse perinatal outcomes associated with inappropriate weight gain in pregnancy across a diverse group of women.”
She emphasized that “the take home message is the importance of counseling regarding weight gain in pregnancy and monitoring it closely in real time as the associated risks are significant and potentially avoidable. The first step to solving a problem is adequately quantifying it, and this study does just that. The next step is giving this information to pregnant women along with making weight gain a part of the discussion prior to pregnancy and at every prenatal visit.”
Dr. Badell added, “Ideally, the weight gain for an individual pregnant women would be tracked and discussed with her during each prenatal visit. If she is below or above the recommendations, the risks associated with this could be discussed along with strategies to get/stay on track. In an ideal world, women struggling with weight gain goals in pregnancy would have access to a dietitian. However, in reality, ob.gyn. offices will likely need to come up with patient education handouts or staff education.”
Another useful avenue for research would be assessing the effects of patient education, Dr. Badell said. “The next best step would be implementing a study to assess if education of women during pregnancy about their individual weight gain at each visit and discussion regarding perinatal risks affects ultimate weight gain and reduces risks. Additionally, education could begin in the preconception phase as this knowledge is likely important even prior to pregnancy. Finally, studies are needed on interventions such as working with dietitians or patient education classes once a woman has been identified as not being within weight gain goals to evaluate if these can alter weight gain and improve outcomes.”
Dr. Badell is a maternal-fetal medicine specialist in the department of gynecology and obstetrics at Emory University, Atlanta. She was asked to comment on the findings of Kominiarek MA et al. Dr. Badell had no relevant financial conflicts to disclose.
“We are struggling with an obesity epidemic in this country, and pregnancy accounts for a risk time for women to gain excessive weight,” Martina L. Badell, MD, said in an interview. “This is a very well-designed large study which attempted to systematically evaluate the adverse perinatal outcomes associated with inappropriate weight gain in pregnancy across a diverse group of women.”
She emphasized that “the take home message is the importance of counseling regarding weight gain in pregnancy and monitoring it closely in real time as the associated risks are significant and potentially avoidable. The first step to solving a problem is adequately quantifying it, and this study does just that. The next step is giving this information to pregnant women along with making weight gain a part of the discussion prior to pregnancy and at every prenatal visit.”
Dr. Badell added, “Ideally, the weight gain for an individual pregnant women would be tracked and discussed with her during each prenatal visit. If she is below or above the recommendations, the risks associated with this could be discussed along with strategies to get/stay on track. In an ideal world, women struggling with weight gain goals in pregnancy would have access to a dietitian. However, in reality, ob.gyn. offices will likely need to come up with patient education handouts or staff education.”
Another useful avenue for research would be assessing the effects of patient education, Dr. Badell said. “The next best step would be implementing a study to assess if education of women during pregnancy about their individual weight gain at each visit and discussion regarding perinatal risks affects ultimate weight gain and reduces risks. Additionally, education could begin in the preconception phase as this knowledge is likely important even prior to pregnancy. Finally, studies are needed on interventions such as working with dietitians or patient education classes once a woman has been identified as not being within weight gain goals to evaluate if these can alter weight gain and improve outcomes.”
Dr. Badell is a maternal-fetal medicine specialist in the department of gynecology and obstetrics at Emory University, Atlanta. She was asked to comment on the findings of Kominiarek MA et al. Dr. Badell had no relevant financial conflicts to disclose.
“We are struggling with an obesity epidemic in this country, and pregnancy accounts for a risk time for women to gain excessive weight,” Martina L. Badell, MD, said in an interview. “This is a very well-designed large study which attempted to systematically evaluate the adverse perinatal outcomes associated with inappropriate weight gain in pregnancy across a diverse group of women.”
She emphasized that “the take home message is the importance of counseling regarding weight gain in pregnancy and monitoring it closely in real time as the associated risks are significant and potentially avoidable. The first step to solving a problem is adequately quantifying it, and this study does just that. The next step is giving this information to pregnant women along with making weight gain a part of the discussion prior to pregnancy and at every prenatal visit.”
Dr. Badell added, “Ideally, the weight gain for an individual pregnant women would be tracked and discussed with her during each prenatal visit. If she is below or above the recommendations, the risks associated with this could be discussed along with strategies to get/stay on track. In an ideal world, women struggling with weight gain goals in pregnancy would have access to a dietitian. However, in reality, ob.gyn. offices will likely need to come up with patient education handouts or staff education.”
Another useful avenue for research would be assessing the effects of patient education, Dr. Badell said. “The next best step would be implementing a study to assess if education of women during pregnancy about their individual weight gain at each visit and discussion regarding perinatal risks affects ultimate weight gain and reduces risks. Additionally, education could begin in the preconception phase as this knowledge is likely important even prior to pregnancy. Finally, studies are needed on interventions such as working with dietitians or patient education classes once a woman has been identified as not being within weight gain goals to evaluate if these can alter weight gain and improve outcomes.”
Dr. Badell is a maternal-fetal medicine specialist in the department of gynecology and obstetrics at Emory University, Atlanta. She was asked to comment on the findings of Kominiarek MA et al. Dr. Badell had no relevant financial conflicts to disclose.
Gestational weight gain above or below the level recommended by the Institute of Medicine (IOM) guidelines resulted in significantly worse outcomes for mothers and babies, according to data from nearly 30,000 women.
Previous studies of the relationship between gestational weight gain and maternal and neonatal outcomes have been limited by “small sample sizes, single sites, restricted reporting of outcomes, and a lack of racial-ethnic diversity,” Michelle A. Kominiarek, MD, of Northwestern University in Chicago and her colleagues wrote . To determine the effects of gestational weight gain on a large and more diverse population, the researchers conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network’s Assessment of Perinatal Excellence study. The findings were published in Obstetrics & Gynecology.
Gestational weight gain above the amount recommended by IOM guidelines was significantly associated with adverse outcomes in neonates, including macrosomia (adjusted odds ratio, 2.66), shoulder dystocia (aOR, 1.74), and neonatal hypoglycemia (aOR, 1.60).
In further multivariate analysis, adverse maternal outcomes associated with gestational weight gain above that recommended by the guidelines included hypertensive diseases of pregnancy for any parity (aOR, 1.84) and increased risk of cesarean delivery in nulliparous and multiparous women (aORs, 1.44 and 1.26, respectively).
Gestational weight gain below the recommended amount was associated with both spontaneous (aOR, 1.50) and indicated (aOR, 1.34) preterm birth. Weight gain above the guidelines was associated with a greater risk of indicated preterm birth only (aOR, 1.24).
The study population included 29,861 women at 25 hospitals over a 3-year period. Of these, 51% had gestational weight gains above the amount recommended by the IOM guidelines and 21% had gestational weight gains below it. The researchers calculated gestational weight gain by subtracting prepregnancy weight from delivery weight or, if prepregnancy weight was not available, by subtracting weight at the first prenatal visit at 13 weeks of gestation or earlier from delivery weight.
The study findings were limited by the use of self-reported prepregnancy weight and the possible effects of changes to the guidelines with respect to obese patients, the researchers said. However, the results support those from previous studies, and the “noted strengths include analysis of 29,861 women representative of the United States with rigorous ascertainment of outcomes and calculation of gestational weight gain to account for the wide range of gestational ages at delivery,” Dr. Kominiarek and her associates wrote.
Overall, the data support efforts to educate women on health behaviors and how gestational weight gain affects them and their infants, and additional research is needed to help women meet their goals for appropriate gestational weight, the researchers concluded.
SOURCE: Kominiarek MA et al. Obstet Gynecol. 2018 Oct;132(4):875-81.
Gestational weight gain above or below the level recommended by the Institute of Medicine (IOM) guidelines resulted in significantly worse outcomes for mothers and babies, according to data from nearly 30,000 women.
Previous studies of the relationship between gestational weight gain and maternal and neonatal outcomes have been limited by “small sample sizes, single sites, restricted reporting of outcomes, and a lack of racial-ethnic diversity,” Michelle A. Kominiarek, MD, of Northwestern University in Chicago and her colleagues wrote . To determine the effects of gestational weight gain on a large and more diverse population, the researchers conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network’s Assessment of Perinatal Excellence study. The findings were published in Obstetrics & Gynecology.
Gestational weight gain above the amount recommended by IOM guidelines was significantly associated with adverse outcomes in neonates, including macrosomia (adjusted odds ratio, 2.66), shoulder dystocia (aOR, 1.74), and neonatal hypoglycemia (aOR, 1.60).
In further multivariate analysis, adverse maternal outcomes associated with gestational weight gain above that recommended by the guidelines included hypertensive diseases of pregnancy for any parity (aOR, 1.84) and increased risk of cesarean delivery in nulliparous and multiparous women (aORs, 1.44 and 1.26, respectively).
Gestational weight gain below the recommended amount was associated with both spontaneous (aOR, 1.50) and indicated (aOR, 1.34) preterm birth. Weight gain above the guidelines was associated with a greater risk of indicated preterm birth only (aOR, 1.24).
The study population included 29,861 women at 25 hospitals over a 3-year period. Of these, 51% had gestational weight gains above the amount recommended by the IOM guidelines and 21% had gestational weight gains below it. The researchers calculated gestational weight gain by subtracting prepregnancy weight from delivery weight or, if prepregnancy weight was not available, by subtracting weight at the first prenatal visit at 13 weeks of gestation or earlier from delivery weight.
The study findings were limited by the use of self-reported prepregnancy weight and the possible effects of changes to the guidelines with respect to obese patients, the researchers said. However, the results support those from previous studies, and the “noted strengths include analysis of 29,861 women representative of the United States with rigorous ascertainment of outcomes and calculation of gestational weight gain to account for the wide range of gestational ages at delivery,” Dr. Kominiarek and her associates wrote.
Overall, the data support efforts to educate women on health behaviors and how gestational weight gain affects them and their infants, and additional research is needed to help women meet their goals for appropriate gestational weight, the researchers concluded.
SOURCE: Kominiarek MA et al. Obstet Gynecol. 2018 Oct;132(4):875-81.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: Gestational weight gain or loss is a significant risk factor for adverse maternal and neonatal outcomes.
Major finding: Gestational weight gain above the recommended amount was significantly associated with adverse outcomes in neonates, including macrosomia (adjusted odds ratio, 2.66), shoulder dystocia (aOR, 1.74), and neonatal hypoglycemia (aOR, 1.60).
Study details: The data came from 29,861 women who delivered at 25 hospitals across the United States on randomly selected days during a 3-year period.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported in part by various grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Research Resources.
Source: Kominiarek MA et al. Obstet Gynecol. 2018 Oct;132(4):875-81.
Congenital syphilis rates continue skyrocketing alongside other STDs
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Key clinical point: Newborn syphilis cases have more than doubled in 5 years along with substantial increases in chlamydia, gonorrhea, and syphilis.
Major finding: 918 cases of newborn syphilis were reported in 37 states in 2017.
Study details: The findings are based on data from public health notifiable disease reports and multiple federal and private surveillance projects.
Disclosures: The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
Source: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017.
Obesity plays role in sleep-disordered breathing in pregnancy
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
FROM JOURNAL OF SLEEP RESEARCH
Key clinical point:
Major finding: The relationship between hypertension in pregnancy and sleep-disordered breathing is only significant for more severe sleep-disordered breathing.
Study details: Prospective case-control study in 80 pregnant women.
Disclosures: The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
Source: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
Ulipristal reduces bleeding with contraceptive implant
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point:
Major finding: Treatment with ulipristal was associated with 5 fewer bleeding days per month, compared with placebo (P = .002).
Study details: The double-blind, placebo-controlled trial involved 65 women with etonogestrel implants who reported more than one bleeding episode in a 24-day time frame.
Disclosures: The study was funded by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences (NCATS). The authors reported financial disclosures related to Bayer and Merck.
Source: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
Pregnancy registries are a valuable resource
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
Clearance rates for some antiepileptic drugs rise during pregnancy
Certain antiepileptic drugs show significant increases in clearance rates during pregnancy, which may be associated with increased seizure rates, research suggests.
Paula E. Voinescu, MD, PhD, of Brigham and Women’s Hospital, Boston, and her coauthors conducted a prospective, observational study of 44 pregnancies in 40 women with epilepsy who were treated with antiepileptic drugs. The women were enrolled preconception or in early pregnancy, then kept daily diaries of medication doses, adherence, and seizures, while antiepileptic drug concentrations were measured every 1-3 months.
The investigators found that levetiracetam reached a mean maximal clearance during the first trimester that was 71% higher than baseline clearance (P = .0001), and its clearance level remained high throughout pregnancy.
“This is important information for clinicians who manage women on levetiracetam as they may opt to begin TDM [therapeutic drug monitoring] as early as possible in pregnancy,” the investigators wrote. The report was published online Sept. 5 in Neurology.
The authors noted that there was significant variability between participants in clearance rates of levetiracetam, ranging from 1.42-fold to 2.02-fold baseline clearance, and they suggested that pharmacogenetic differences may play a role.
“Levetiracetam is mainly excreted unchanged by the kidneys, and the changes in clearance are consistent with the time course of increased glomerular filtration rate during pregnancy,” they wrote. “The pathophysiology of the interparticipant variability in clearance fluctuation during pregnancy and of the race influence observed for levetiracetam are difficult to explain with the known pharmacokinetic data.”
Both oxcarbazepine and topiramate also reached significantly higher mean maximal clearances during the second trimester than at baseline (63% and 39% higher, respectively), and their elevated clearance persisted into the third trimester.
However, there were no significant changes in clearance rates of total or free phenytoin or valproic acid during pregnancy.
Among the 15 women for whom researchers had complete seizure history and antiepileptic drug concentrations, 40% experienced a worsening of seizure frequency during at least one trimester.
Overall, lower individualized ratio-to-target concentrations of drug were associated with increased seizure frequency in the first and second trimester, but not in the third trimester.
While the study did not compare seizure outcomes between patients who were managed with TDM and those who were not, the authors suggested that their data supported the use of TDM during pregnancy.
“The finding of lower AED RTC [antiepileptic drug ratio to concentration] at different trimesters suggests that in outpatient clinical practice, possible changes in AED dosing varied by trimester may be clinically important for patient care.”
The study was supported by the National Institutes of Health, the American Brain Foundation, the American Epilepsy Society, the Epilepsy Foundation, and the Karger Fund. Four authors declared support, honoraria, and/or other funding from the pharmaceutical industry, and five also declared support from the study funding bodies.
SOURCE: Voinescu P et al. Neurology. 2018 Sep 5. doi: 10.1212/WNL.0000000000006240.
Certain antiepileptic drugs show significant increases in clearance rates during pregnancy, which may be associated with increased seizure rates, research suggests.
Paula E. Voinescu, MD, PhD, of Brigham and Women’s Hospital, Boston, and her coauthors conducted a prospective, observational study of 44 pregnancies in 40 women with epilepsy who were treated with antiepileptic drugs. The women were enrolled preconception or in early pregnancy, then kept daily diaries of medication doses, adherence, and seizures, while antiepileptic drug concentrations were measured every 1-3 months.
The investigators found that levetiracetam reached a mean maximal clearance during the first trimester that was 71% higher than baseline clearance (P = .0001), and its clearance level remained high throughout pregnancy.
“This is important information for clinicians who manage women on levetiracetam as they may opt to begin TDM [therapeutic drug monitoring] as early as possible in pregnancy,” the investigators wrote. The report was published online Sept. 5 in Neurology.
The authors noted that there was significant variability between participants in clearance rates of levetiracetam, ranging from 1.42-fold to 2.02-fold baseline clearance, and they suggested that pharmacogenetic differences may play a role.
“Levetiracetam is mainly excreted unchanged by the kidneys, and the changes in clearance are consistent with the time course of increased glomerular filtration rate during pregnancy,” they wrote. “The pathophysiology of the interparticipant variability in clearance fluctuation during pregnancy and of the race influence observed for levetiracetam are difficult to explain with the known pharmacokinetic data.”
Both oxcarbazepine and topiramate also reached significantly higher mean maximal clearances during the second trimester than at baseline (63% and 39% higher, respectively), and their elevated clearance persisted into the third trimester.
However, there were no significant changes in clearance rates of total or free phenytoin or valproic acid during pregnancy.
Among the 15 women for whom researchers had complete seizure history and antiepileptic drug concentrations, 40% experienced a worsening of seizure frequency during at least one trimester.
Overall, lower individualized ratio-to-target concentrations of drug were associated with increased seizure frequency in the first and second trimester, but not in the third trimester.
While the study did not compare seizure outcomes between patients who were managed with TDM and those who were not, the authors suggested that their data supported the use of TDM during pregnancy.
“The finding of lower AED RTC [antiepileptic drug ratio to concentration] at different trimesters suggests that in outpatient clinical practice, possible changes in AED dosing varied by trimester may be clinically important for patient care.”
The study was supported by the National Institutes of Health, the American Brain Foundation, the American Epilepsy Society, the Epilepsy Foundation, and the Karger Fund. Four authors declared support, honoraria, and/or other funding from the pharmaceutical industry, and five also declared support from the study funding bodies.
SOURCE: Voinescu P et al. Neurology. 2018 Sep 5. doi: 10.1212/WNL.0000000000006240.
Certain antiepileptic drugs show significant increases in clearance rates during pregnancy, which may be associated with increased seizure rates, research suggests.
Paula E. Voinescu, MD, PhD, of Brigham and Women’s Hospital, Boston, and her coauthors conducted a prospective, observational study of 44 pregnancies in 40 women with epilepsy who were treated with antiepileptic drugs. The women were enrolled preconception or in early pregnancy, then kept daily diaries of medication doses, adherence, and seizures, while antiepileptic drug concentrations were measured every 1-3 months.
The investigators found that levetiracetam reached a mean maximal clearance during the first trimester that was 71% higher than baseline clearance (P = .0001), and its clearance level remained high throughout pregnancy.
“This is important information for clinicians who manage women on levetiracetam as they may opt to begin TDM [therapeutic drug monitoring] as early as possible in pregnancy,” the investigators wrote. The report was published online Sept. 5 in Neurology.
The authors noted that there was significant variability between participants in clearance rates of levetiracetam, ranging from 1.42-fold to 2.02-fold baseline clearance, and they suggested that pharmacogenetic differences may play a role.
“Levetiracetam is mainly excreted unchanged by the kidneys, and the changes in clearance are consistent with the time course of increased glomerular filtration rate during pregnancy,” they wrote. “The pathophysiology of the interparticipant variability in clearance fluctuation during pregnancy and of the race influence observed for levetiracetam are difficult to explain with the known pharmacokinetic data.”
Both oxcarbazepine and topiramate also reached significantly higher mean maximal clearances during the second trimester than at baseline (63% and 39% higher, respectively), and their elevated clearance persisted into the third trimester.
However, there were no significant changes in clearance rates of total or free phenytoin or valproic acid during pregnancy.
Among the 15 women for whom researchers had complete seizure history and antiepileptic drug concentrations, 40% experienced a worsening of seizure frequency during at least one trimester.
Overall, lower individualized ratio-to-target concentrations of drug were associated with increased seizure frequency in the first and second trimester, but not in the third trimester.
While the study did not compare seizure outcomes between patients who were managed with TDM and those who were not, the authors suggested that their data supported the use of TDM during pregnancy.
“The finding of lower AED RTC [antiepileptic drug ratio to concentration] at different trimesters suggests that in outpatient clinical practice, possible changes in AED dosing varied by trimester may be clinically important for patient care.”
The study was supported by the National Institutes of Health, the American Brain Foundation, the American Epilepsy Society, the Epilepsy Foundation, and the Karger Fund. Four authors declared support, honoraria, and/or other funding from the pharmaceutical industry, and five also declared support from the study funding bodies.
SOURCE: Voinescu P et al. Neurology. 2018 Sep 5. doi: 10.1212/WNL.0000000000006240.
FROM NEUROLOGY
Key clinical point: Some antiepileptic drugs show higher clearance rates during pregnancy, which could increase seizure risk.
Major finding: The mean maximal clearance rate of levetiracetam in the first trimester is 71% higher than baseline.
Study details: Prospective observational study in 40 women with 44 pregnancies.
Disclosures: The study was supported by the National Institutes of Health, the American Brain Foundation, the American Epilepsy Society, the Epilepsy Foundation, and the Karger Fund. Four authors declared support, honoraria, and/or other funding from the pharmaceutical industry, and five also declared support from the study funding bodies.
Source: Voinescu P et al. Neurology. 2018 Sep 5. doi: 10.1212/WNL.0000000000006240
Age, risk factors should guide chlamydia, gonorrhea screening of HIV-infected women
WASHINGTON – Among HIV-infected women, those aged 18-29 years had the highest rates of gonorrhea and chlamydia. These results suggest that screening for these sexually transmitted infections (STIs) should be based on age and risk in HIV-infected women, said Jodie Dionne-Odom, MD, of the University of Alabama at Birmingham.
Annual screening for gonorrhea and chlamydia is recommended for all sexually active adults with HIV, but prevalence varies by gender, age, and risk behavior, Dr. Dionne-Odom said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.
Dr. Odom and her colleagues calculated annual testing and positivity rates during 2007-2016 for chlamydia and gonorrhea among women engaged in HIV care in eight U.S. cities as part of the Centers for AIDS Research (CFAR) Clinical Networks and Integrated Clinical Services (CNICS) longitudinal cohort.
They assessed demographic data based on the most recent year the patient was in care and used validated surveys (AUDIT-C and ASSIST) to assess risk behaviors in the past 3-6 months. They collected information from 5,084 women and 158,745 HIV primary care and women’s health visits.
The median patient age was 47 years; 62.1% of the patients were black; 70% had CD4 counts greater than 350; and 73.6% had HIV viral loads of less than 500 copies/mL. In terms of reported risk, 60.6% of the women were sexually active, (85.5% of whom reported monogamy); 13.1% had problem alcohol use, and 11.6% had active drug use.
Sampling for gonorrhea and chlamydia were mostly from urogenital sites (86.6%), 6.6% were extragenital, and 6.8% were “other.” Nearly all (98.5%) of 23,492 chlamydia tests and 95.7% of 23,324 gonorrhea tests used nucleic acid amplification, Dr. Dionne-Odom said.
During the most recent year in care, 42.7% of women were tested for gonorrhea and chlamydia, and 3.4% were positive, with the annual positivity rates over the study ranging from 1.5% to 3.2% for chlamydia and 0.9% to 1.5% for gonorrhea. However, Dr. Dionne-Odom and her colleagues found that the prevalence of STIs was inversely related to patient age, with gonorrhea and chlamydia positivity in 2016 being 16% for chlamydia and 3.9% for gonorrhea among women aged 18-24 years, compared with 1.1% and 0.7%, respectively, for women older than 50 years.
“As with national data on women, HIV-infected women aged 18-29 years had the highest rates of gonorrhea and chlamydia. Our results show that targeted screening for chlamydia and gonorrhea in women with HIV based on age and risk is warranted,” Dr. Dionne-Odom concluded.
Dr. Dionne-Odom reported that she had no relevant disclosures.
WASHINGTON – Among HIV-infected women, those aged 18-29 years had the highest rates of gonorrhea and chlamydia. These results suggest that screening for these sexually transmitted infections (STIs) should be based on age and risk in HIV-infected women, said Jodie Dionne-Odom, MD, of the University of Alabama at Birmingham.
Annual screening for gonorrhea and chlamydia is recommended for all sexually active adults with HIV, but prevalence varies by gender, age, and risk behavior, Dr. Dionne-Odom said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.
Dr. Odom and her colleagues calculated annual testing and positivity rates during 2007-2016 for chlamydia and gonorrhea among women engaged in HIV care in eight U.S. cities as part of the Centers for AIDS Research (CFAR) Clinical Networks and Integrated Clinical Services (CNICS) longitudinal cohort.
They assessed demographic data based on the most recent year the patient was in care and used validated surveys (AUDIT-C and ASSIST) to assess risk behaviors in the past 3-6 months. They collected information from 5,084 women and 158,745 HIV primary care and women’s health visits.
The median patient age was 47 years; 62.1% of the patients were black; 70% had CD4 counts greater than 350; and 73.6% had HIV viral loads of less than 500 copies/mL. In terms of reported risk, 60.6% of the women were sexually active, (85.5% of whom reported monogamy); 13.1% had problem alcohol use, and 11.6% had active drug use.
Sampling for gonorrhea and chlamydia were mostly from urogenital sites (86.6%), 6.6% were extragenital, and 6.8% were “other.” Nearly all (98.5%) of 23,492 chlamydia tests and 95.7% of 23,324 gonorrhea tests used nucleic acid amplification, Dr. Dionne-Odom said.
During the most recent year in care, 42.7% of women were tested for gonorrhea and chlamydia, and 3.4% were positive, with the annual positivity rates over the study ranging from 1.5% to 3.2% for chlamydia and 0.9% to 1.5% for gonorrhea. However, Dr. Dionne-Odom and her colleagues found that the prevalence of STIs was inversely related to patient age, with gonorrhea and chlamydia positivity in 2016 being 16% for chlamydia and 3.9% for gonorrhea among women aged 18-24 years, compared with 1.1% and 0.7%, respectively, for women older than 50 years.
“As with national data on women, HIV-infected women aged 18-29 years had the highest rates of gonorrhea and chlamydia. Our results show that targeted screening for chlamydia and gonorrhea in women with HIV based on age and risk is warranted,” Dr. Dionne-Odom concluded.
Dr. Dionne-Odom reported that she had no relevant disclosures.
WASHINGTON – Among HIV-infected women, those aged 18-29 years had the highest rates of gonorrhea and chlamydia. These results suggest that screening for these sexually transmitted infections (STIs) should be based on age and risk in HIV-infected women, said Jodie Dionne-Odom, MD, of the University of Alabama at Birmingham.
Annual screening for gonorrhea and chlamydia is recommended for all sexually active adults with HIV, but prevalence varies by gender, age, and risk behavior, Dr. Dionne-Odom said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.
Dr. Odom and her colleagues calculated annual testing and positivity rates during 2007-2016 for chlamydia and gonorrhea among women engaged in HIV care in eight U.S. cities as part of the Centers for AIDS Research (CFAR) Clinical Networks and Integrated Clinical Services (CNICS) longitudinal cohort.
They assessed demographic data based on the most recent year the patient was in care and used validated surveys (AUDIT-C and ASSIST) to assess risk behaviors in the past 3-6 months. They collected information from 5,084 women and 158,745 HIV primary care and women’s health visits.
The median patient age was 47 years; 62.1% of the patients were black; 70% had CD4 counts greater than 350; and 73.6% had HIV viral loads of less than 500 copies/mL. In terms of reported risk, 60.6% of the women were sexually active, (85.5% of whom reported monogamy); 13.1% had problem alcohol use, and 11.6% had active drug use.
Sampling for gonorrhea and chlamydia were mostly from urogenital sites (86.6%), 6.6% were extragenital, and 6.8% were “other.” Nearly all (98.5%) of 23,492 chlamydia tests and 95.7% of 23,324 gonorrhea tests used nucleic acid amplification, Dr. Dionne-Odom said.
During the most recent year in care, 42.7% of women were tested for gonorrhea and chlamydia, and 3.4% were positive, with the annual positivity rates over the study ranging from 1.5% to 3.2% for chlamydia and 0.9% to 1.5% for gonorrhea. However, Dr. Dionne-Odom and her colleagues found that the prevalence of STIs was inversely related to patient age, with gonorrhea and chlamydia positivity in 2016 being 16% for chlamydia and 3.9% for gonorrhea among women aged 18-24 years, compared with 1.1% and 0.7%, respectively, for women older than 50 years.
“As with national data on women, HIV-infected women aged 18-29 years had the highest rates of gonorrhea and chlamydia. Our results show that targeted screening for chlamydia and gonorrhea in women with HIV based on age and risk is warranted,” Dr. Dionne-Odom concluded.
Dr. Dionne-Odom reported that she had no relevant disclosures.
REPORTING FROM THE 2018 STD PREVENTION CONFERENCE
Key clinical point: Targeted screening for chlamydia and gonorrhea in women with HIV based on age, risk is warranted.
Major finding: Chlamydia infections were seen in 16% and gonorrhea in 3.9% of HIV-infected women aged 18-24 years and in 1.1% and 0.7%, respectively, in women over age 50.
Study details: Data analysis of 5,084 women in 8 U.S. cities during 2007-2016.
Disclosures: Dr. Dionne-Odom reported that she had no relevant disclosures.
Two red flags spell trouble ahead in spontaneous coronary artery dissection
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
MUNICH –
Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.
CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.
SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.
CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.
In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.
Of note, one-third of patients had no cardiovascular risk factors.
The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.
Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.
The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.
Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.
“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.
Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”
“Are you doing that in your practice?” asked Dr. Serruys.
“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”
Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.
“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point: SCAD occurring during the peripartum period or in patients with connective tissue disease identifies subgroups at high risk for major adverse cardiovascular events within 30 days.
Major finding: Patients with spontaneous coronary artery dissection and comorbid connective tissue disease were at 8.7-fold increased risk of major adverse cardiovascular events within 30 days.
Study details: CanSCAD is an ongoing, prospective, multicenter, observational study in 750 patients with confirmed spontaneous coronary artery dissection.
Disclosures: CanSCAD is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier.
Vaginal intraepithelial neoplasia: What to do when dysplasia persists after hysterectomy
Vaginal intraepithelial neoplasia (VAIN) is a condition that frequently poses therapeutic dilemmas for gynecologists. VAIN represents dysplastic changes to the epithelium of the vaginal mucosa, and like cervical neoplasia, the extent of disease is characterized as levels I, II, or III dependent upon the depth of involvement in the epithelial layer by dysplastic cells. While VAIN itself typically is asymptomatic and not a harmful condition, it carries a 12% risk of progression to invasive vaginal carcinoma, so accurate identification, thorough treatment, and ongoing surveillance are essential.1
VAIN is associated with high-risk human papillomavirus (HPV) infection, tobacco use, and prior cervical dysplasia. Of women with VAIN, 65% have undergone a prior hysterectomy for cervical dysplasia, which emphasizes the nondefinitive nature of such an intervention.2 These women should be very closely followed for at least 20 years with vaginal cytologic and/or HPV surveillance. High-risk HPV infection is present in 85% of women with VAIN, and the presence of high-risk HPV is a predictor for recurrent VAIN. Recurrent and persistent VAIN also is more common in postmenopausal women and those with multifocal disease.
The most common location for VAIN is at the upper third of the vagina (including the vaginal cuff). It commonly arises within the vaginal fornices, which may be difficult to fully visualize because of their puckered appearance, redundant vaginal tissues, and extensive vaginal rogation.
A diagnosis of VAIN is typically obtained from vaginal cytology which reveals atypical or dysplastic cells. Such a result should prompt the physician to perform vaginal colposcopy and directed biopsies. Comprehensive visualization of the vaginal cuff can be limited in cases where the vaginal fornices are tethered, deeply puckered, or when there is significant mucosal rogation.
The application of 4% acetic acid or Lugol’s iodine are techniques that can enhance the detection of dysplastic vaginal mucosa. Lugol’s iodine selectively stains normal, glycogenated cells, and spares dysplastic glycogen-free cells. The sharp contrast between the brown iodine-stained tissues and the white dysplastic tissues aids in detection of dysplastic areas.
If colposcopic biopsy reveals low grade dysplasia (VAIN I) it does not require intervention, and has a very low rate of conversion to invasive vaginal carcinoma. However moderate- and high-grade vaginal dysplastic lesions should be treated because of the potential for malignant transformation.
Options for treatment of VAIN include topical, ablative, and excisional procedures. Observation also is an option but should be reserved for patients who are closely monitored with repeated colposcopic examinations, and probably should best be reserved for patients with VAIN I or II lesions.
Excisional procedures
The most common excisional procedure employed for VAIN is upper vaginectomy. In this procedure, the surgeon grasps and tents up the vaginal mucosa, incises the mucosa without penetrating the subepithelial tissue layers such as bladder and rectum. The vaginal mucosa then is carefully separated from the underlying endopelvic fascial plane. The specimen should be oriented, ideally on a cork board, with pins or sutures to ascribe margins and borders. Excision is best utilized for women with unifocal disease, or those who fail or do not tolerate ablative or topical interventions.
The most significant risks of excision include the potential for damage to underlying pelvic visceral structures, which is particularly concerning in postmenopausal women with thin vaginal epithelium. Vaginectomy is commonly associated with vaginal shortening or narrowing, which can be deleterious for quality of life. Retrospective series have described a 30% incidence of recurrence after vaginectomy, likely secondary to incomplete excision of all affected tissue.3
Ablation
Ablation of dysplastic foci with a carbon dioxide (CO2) laser is a common method for treatment of VAIN. CO2 laser should ablate tissue to a 1.5 mm minimum depth.3 The benefit of using CO2 laser is its ability to treat multifocal disease in situ without an extensive excisional procedure.
It is technically more straightforward than upper vaginectomy with less blood loss and shorter surgical times, and it can be easily accomplished in an outpatient surgical or office setting. However, one of its greatest limitations is the difficulty in visualizing all lesions and therefore adequately treating all sites. The vaginal rogations also make adequate laser ablation challenging because laser only is able to effectively ablate tissue that is oriented perpendicular to the laser beam.
In addition, there is no pathologic confirmation of adequacy of excision or margin status. These features may contribute to the modestly higher rates of recurrence of dysplasia following laser ablation, compared with vaginectomy.3 It also has been associated with more vaginal scarring than vaginectomy, which can have a negative effect on sexual health.
Topical agents
The most commonly utilized topical therapy for VAIN is the antimetabolite chemotherapeutic agent 5-fluorouracil (5FU). A typical schedule for 5FU treatment is to apply vaginally, at night, once a week for 8 weeks.4 Because it can cause extensive irritation to the vulvar and urethral epithelium, patients are recommended to apply barrier creams or ointments before and following the use of 5FU for several days, wash hands thoroughly after application, and to rinse and shower in the morning after rising. Severe irritation occurs in up to 16% of patients, but in general it is very well tolerated.
Its virtue is that it is able to conform and travel to all parts of the vaginal mucosa, including those that are poorly visualized within the fornices or vaginal folds. 5FU does not require a hospitalization or surgical procedure, can be applied by the patient at home, and preserves vaginal length and function. In recent reports, 5FU is associated with the lowest rates of recurrence (10%-30%), compared with excision or ablation, and therefore is a very attractive option for primary therapy.3 However, it requires patients to have a degree of comfort with vaginal application of drug and adherence with perineal care strategies to minimize the likelihood of toxicity.
The immune response modifier, imiquimod, that is commonly used in the treatment of vulvar dysplasia also has been described in the treatment of VAIN. It appears to have high rates of clearance (greater than 75%) and be most effective in the treatment of VAIN I.5 It requires application under colposcopic guidance three times a week for 8 weeks, which is a laborious undertaking for both patient and physician. Like 5FU, imiquimod is associated with vulvar and perineal irritation.
Vaginal estrogens are an alternative topical therapy for moderate- and high-grade VAIN and particularly useful for postmenopausal patients. They have been associated with a high rate (up to 90%) of resolution on follow-up vaginal cytology testing and are not associated with toxicities of the above stated therapies.6 Vaginal estrogen can be used alone or in addition to other therapeutic strategies. For example, it can be added to the nontreatment days of 5FU or postoperatively prescribed following laser or excisional procedures.
Radiation
Intracavitary brachytherapy is a technique in which a radiation source is placed within a cylinder or ovoids and placed within the vagina.7 Typically 45 Gy is delivered to a depth 0.5mm below the vaginal mucosal surface (“point z”). Recurrence occurs is approximately 10%-15% of patients, and toxicities can be severe, including vaginal stenosis and ulceration. This aggressive therapy typically is best reserved for cases that are refractory to other therapies. Following radiation, subsequent treatments are more difficult because of radiation-induced changes to the vaginal mucosa that can affect healing.
Vaginal dysplasia is a relatively common sequelae of high-risk HPV, particularly among women who have had a prior hysterectomy for cervical dysplasia. Because of anatomic changes following hysterectomy, adequate visualization and comprehensive vaginal treatment is difficult. Therefore, surgeons should avoid utilization of hysterectomy as a routine strategy to “cure” dysplasia as it may fail to achieve this cure and make subsequent evaluations and treatments of persistent dysplasia more difficult. Women who have had a hysterectomy for dysplasia should be closely followed for several decades, and they should be counseled that they have a persistent risk for vaginal disease. When VAIN develops, clinicians should consider topical therapies as primary treatment options because they may minimize toxicity and have high rates of enduring response.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant conflicts of interest.
References
1. Gynecol Oncol. 2016 Jun;141(3):507-10.
2. Arch Gynecol Obstet. 2016 Feb;293(2):415-9.
3. Anticancer Res. 2013 Jan;33(1):29-38.
4. Obstet Gynecol. 2017 Dec;130(6):1237-43.
5. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:129-36.
6. J Low Genit Tract Dis. 2014 Apr;18(2):115-21.
7. Gynecol Oncol. 2007 Jul;106(1):105-11.
Vaginal intraepithelial neoplasia (VAIN) is a condition that frequently poses therapeutic dilemmas for gynecologists. VAIN represents dysplastic changes to the epithelium of the vaginal mucosa, and like cervical neoplasia, the extent of disease is characterized as levels I, II, or III dependent upon the depth of involvement in the epithelial layer by dysplastic cells. While VAIN itself typically is asymptomatic and not a harmful condition, it carries a 12% risk of progression to invasive vaginal carcinoma, so accurate identification, thorough treatment, and ongoing surveillance are essential.1
VAIN is associated with high-risk human papillomavirus (HPV) infection, tobacco use, and prior cervical dysplasia. Of women with VAIN, 65% have undergone a prior hysterectomy for cervical dysplasia, which emphasizes the nondefinitive nature of such an intervention.2 These women should be very closely followed for at least 20 years with vaginal cytologic and/or HPV surveillance. High-risk HPV infection is present in 85% of women with VAIN, and the presence of high-risk HPV is a predictor for recurrent VAIN. Recurrent and persistent VAIN also is more common in postmenopausal women and those with multifocal disease.
The most common location for VAIN is at the upper third of the vagina (including the vaginal cuff). It commonly arises within the vaginal fornices, which may be difficult to fully visualize because of their puckered appearance, redundant vaginal tissues, and extensive vaginal rogation.
A diagnosis of VAIN is typically obtained from vaginal cytology which reveals atypical or dysplastic cells. Such a result should prompt the physician to perform vaginal colposcopy and directed biopsies. Comprehensive visualization of the vaginal cuff can be limited in cases where the vaginal fornices are tethered, deeply puckered, or when there is significant mucosal rogation.
The application of 4% acetic acid or Lugol’s iodine are techniques that can enhance the detection of dysplastic vaginal mucosa. Lugol’s iodine selectively stains normal, glycogenated cells, and spares dysplastic glycogen-free cells. The sharp contrast between the brown iodine-stained tissues and the white dysplastic tissues aids in detection of dysplastic areas.
If colposcopic biopsy reveals low grade dysplasia (VAIN I) it does not require intervention, and has a very low rate of conversion to invasive vaginal carcinoma. However moderate- and high-grade vaginal dysplastic lesions should be treated because of the potential for malignant transformation.
Options for treatment of VAIN include topical, ablative, and excisional procedures. Observation also is an option but should be reserved for patients who are closely monitored with repeated colposcopic examinations, and probably should best be reserved for patients with VAIN I or II lesions.
Excisional procedures
The most common excisional procedure employed for VAIN is upper vaginectomy. In this procedure, the surgeon grasps and tents up the vaginal mucosa, incises the mucosa without penetrating the subepithelial tissue layers such as bladder and rectum. The vaginal mucosa then is carefully separated from the underlying endopelvic fascial plane. The specimen should be oriented, ideally on a cork board, with pins or sutures to ascribe margins and borders. Excision is best utilized for women with unifocal disease, or those who fail or do not tolerate ablative or topical interventions.
The most significant risks of excision include the potential for damage to underlying pelvic visceral structures, which is particularly concerning in postmenopausal women with thin vaginal epithelium. Vaginectomy is commonly associated with vaginal shortening or narrowing, which can be deleterious for quality of life. Retrospective series have described a 30% incidence of recurrence after vaginectomy, likely secondary to incomplete excision of all affected tissue.3
Ablation
Ablation of dysplastic foci with a carbon dioxide (CO2) laser is a common method for treatment of VAIN. CO2 laser should ablate tissue to a 1.5 mm minimum depth.3 The benefit of using CO2 laser is its ability to treat multifocal disease in situ without an extensive excisional procedure.
It is technically more straightforward than upper vaginectomy with less blood loss and shorter surgical times, and it can be easily accomplished in an outpatient surgical or office setting. However, one of its greatest limitations is the difficulty in visualizing all lesions and therefore adequately treating all sites. The vaginal rogations also make adequate laser ablation challenging because laser only is able to effectively ablate tissue that is oriented perpendicular to the laser beam.
In addition, there is no pathologic confirmation of adequacy of excision or margin status. These features may contribute to the modestly higher rates of recurrence of dysplasia following laser ablation, compared with vaginectomy.3 It also has been associated with more vaginal scarring than vaginectomy, which can have a negative effect on sexual health.
Topical agents
The most commonly utilized topical therapy for VAIN is the antimetabolite chemotherapeutic agent 5-fluorouracil (5FU). A typical schedule for 5FU treatment is to apply vaginally, at night, once a week for 8 weeks.4 Because it can cause extensive irritation to the vulvar and urethral epithelium, patients are recommended to apply barrier creams or ointments before and following the use of 5FU for several days, wash hands thoroughly after application, and to rinse and shower in the morning after rising. Severe irritation occurs in up to 16% of patients, but in general it is very well tolerated.
Its virtue is that it is able to conform and travel to all parts of the vaginal mucosa, including those that are poorly visualized within the fornices or vaginal folds. 5FU does not require a hospitalization or surgical procedure, can be applied by the patient at home, and preserves vaginal length and function. In recent reports, 5FU is associated with the lowest rates of recurrence (10%-30%), compared with excision or ablation, and therefore is a very attractive option for primary therapy.3 However, it requires patients to have a degree of comfort with vaginal application of drug and adherence with perineal care strategies to minimize the likelihood of toxicity.
The immune response modifier, imiquimod, that is commonly used in the treatment of vulvar dysplasia also has been described in the treatment of VAIN. It appears to have high rates of clearance (greater than 75%) and be most effective in the treatment of VAIN I.5 It requires application under colposcopic guidance three times a week for 8 weeks, which is a laborious undertaking for both patient and physician. Like 5FU, imiquimod is associated with vulvar and perineal irritation.
Vaginal estrogens are an alternative topical therapy for moderate- and high-grade VAIN and particularly useful for postmenopausal patients. They have been associated with a high rate (up to 90%) of resolution on follow-up vaginal cytology testing and are not associated with toxicities of the above stated therapies.6 Vaginal estrogen can be used alone or in addition to other therapeutic strategies. For example, it can be added to the nontreatment days of 5FU or postoperatively prescribed following laser or excisional procedures.
Radiation
Intracavitary brachytherapy is a technique in which a radiation source is placed within a cylinder or ovoids and placed within the vagina.7 Typically 45 Gy is delivered to a depth 0.5mm below the vaginal mucosal surface (“point z”). Recurrence occurs is approximately 10%-15% of patients, and toxicities can be severe, including vaginal stenosis and ulceration. This aggressive therapy typically is best reserved for cases that are refractory to other therapies. Following radiation, subsequent treatments are more difficult because of radiation-induced changes to the vaginal mucosa that can affect healing.
Vaginal dysplasia is a relatively common sequelae of high-risk HPV, particularly among women who have had a prior hysterectomy for cervical dysplasia. Because of anatomic changes following hysterectomy, adequate visualization and comprehensive vaginal treatment is difficult. Therefore, surgeons should avoid utilization of hysterectomy as a routine strategy to “cure” dysplasia as it may fail to achieve this cure and make subsequent evaluations and treatments of persistent dysplasia more difficult. Women who have had a hysterectomy for dysplasia should be closely followed for several decades, and they should be counseled that they have a persistent risk for vaginal disease. When VAIN develops, clinicians should consider topical therapies as primary treatment options because they may minimize toxicity and have high rates of enduring response.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant conflicts of interest.
References
1. Gynecol Oncol. 2016 Jun;141(3):507-10.
2. Arch Gynecol Obstet. 2016 Feb;293(2):415-9.
3. Anticancer Res. 2013 Jan;33(1):29-38.
4. Obstet Gynecol. 2017 Dec;130(6):1237-43.
5. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:129-36.
6. J Low Genit Tract Dis. 2014 Apr;18(2):115-21.
7. Gynecol Oncol. 2007 Jul;106(1):105-11.
Vaginal intraepithelial neoplasia (VAIN) is a condition that frequently poses therapeutic dilemmas for gynecologists. VAIN represents dysplastic changes to the epithelium of the vaginal mucosa, and like cervical neoplasia, the extent of disease is characterized as levels I, II, or III dependent upon the depth of involvement in the epithelial layer by dysplastic cells. While VAIN itself typically is asymptomatic and not a harmful condition, it carries a 12% risk of progression to invasive vaginal carcinoma, so accurate identification, thorough treatment, and ongoing surveillance are essential.1
VAIN is associated with high-risk human papillomavirus (HPV) infection, tobacco use, and prior cervical dysplasia. Of women with VAIN, 65% have undergone a prior hysterectomy for cervical dysplasia, which emphasizes the nondefinitive nature of such an intervention.2 These women should be very closely followed for at least 20 years with vaginal cytologic and/or HPV surveillance. High-risk HPV infection is present in 85% of women with VAIN, and the presence of high-risk HPV is a predictor for recurrent VAIN. Recurrent and persistent VAIN also is more common in postmenopausal women and those with multifocal disease.
The most common location for VAIN is at the upper third of the vagina (including the vaginal cuff). It commonly arises within the vaginal fornices, which may be difficult to fully visualize because of their puckered appearance, redundant vaginal tissues, and extensive vaginal rogation.
A diagnosis of VAIN is typically obtained from vaginal cytology which reveals atypical or dysplastic cells. Such a result should prompt the physician to perform vaginal colposcopy and directed biopsies. Comprehensive visualization of the vaginal cuff can be limited in cases where the vaginal fornices are tethered, deeply puckered, or when there is significant mucosal rogation.
The application of 4% acetic acid or Lugol’s iodine are techniques that can enhance the detection of dysplastic vaginal mucosa. Lugol’s iodine selectively stains normal, glycogenated cells, and spares dysplastic glycogen-free cells. The sharp contrast between the brown iodine-stained tissues and the white dysplastic tissues aids in detection of dysplastic areas.
If colposcopic biopsy reveals low grade dysplasia (VAIN I) it does not require intervention, and has a very low rate of conversion to invasive vaginal carcinoma. However moderate- and high-grade vaginal dysplastic lesions should be treated because of the potential for malignant transformation.
Options for treatment of VAIN include topical, ablative, and excisional procedures. Observation also is an option but should be reserved for patients who are closely monitored with repeated colposcopic examinations, and probably should best be reserved for patients with VAIN I or II lesions.
Excisional procedures
The most common excisional procedure employed for VAIN is upper vaginectomy. In this procedure, the surgeon grasps and tents up the vaginal mucosa, incises the mucosa without penetrating the subepithelial tissue layers such as bladder and rectum. The vaginal mucosa then is carefully separated from the underlying endopelvic fascial plane. The specimen should be oriented, ideally on a cork board, with pins or sutures to ascribe margins and borders. Excision is best utilized for women with unifocal disease, or those who fail or do not tolerate ablative or topical interventions.
The most significant risks of excision include the potential for damage to underlying pelvic visceral structures, which is particularly concerning in postmenopausal women with thin vaginal epithelium. Vaginectomy is commonly associated with vaginal shortening or narrowing, which can be deleterious for quality of life. Retrospective series have described a 30% incidence of recurrence after vaginectomy, likely secondary to incomplete excision of all affected tissue.3
Ablation
Ablation of dysplastic foci with a carbon dioxide (CO2) laser is a common method for treatment of VAIN. CO2 laser should ablate tissue to a 1.5 mm minimum depth.3 The benefit of using CO2 laser is its ability to treat multifocal disease in situ without an extensive excisional procedure.
It is technically more straightforward than upper vaginectomy with less blood loss and shorter surgical times, and it can be easily accomplished in an outpatient surgical or office setting. However, one of its greatest limitations is the difficulty in visualizing all lesions and therefore adequately treating all sites. The vaginal rogations also make adequate laser ablation challenging because laser only is able to effectively ablate tissue that is oriented perpendicular to the laser beam.
In addition, there is no pathologic confirmation of adequacy of excision or margin status. These features may contribute to the modestly higher rates of recurrence of dysplasia following laser ablation, compared with vaginectomy.3 It also has been associated with more vaginal scarring than vaginectomy, which can have a negative effect on sexual health.
Topical agents
The most commonly utilized topical therapy for VAIN is the antimetabolite chemotherapeutic agent 5-fluorouracil (5FU). A typical schedule for 5FU treatment is to apply vaginally, at night, once a week for 8 weeks.4 Because it can cause extensive irritation to the vulvar and urethral epithelium, patients are recommended to apply barrier creams or ointments before and following the use of 5FU for several days, wash hands thoroughly after application, and to rinse and shower in the morning after rising. Severe irritation occurs in up to 16% of patients, but in general it is very well tolerated.
Its virtue is that it is able to conform and travel to all parts of the vaginal mucosa, including those that are poorly visualized within the fornices or vaginal folds. 5FU does not require a hospitalization or surgical procedure, can be applied by the patient at home, and preserves vaginal length and function. In recent reports, 5FU is associated with the lowest rates of recurrence (10%-30%), compared with excision or ablation, and therefore is a very attractive option for primary therapy.3 However, it requires patients to have a degree of comfort with vaginal application of drug and adherence with perineal care strategies to minimize the likelihood of toxicity.
The immune response modifier, imiquimod, that is commonly used in the treatment of vulvar dysplasia also has been described in the treatment of VAIN. It appears to have high rates of clearance (greater than 75%) and be most effective in the treatment of VAIN I.5 It requires application under colposcopic guidance three times a week for 8 weeks, which is a laborious undertaking for both patient and physician. Like 5FU, imiquimod is associated with vulvar and perineal irritation.
Vaginal estrogens are an alternative topical therapy for moderate- and high-grade VAIN and particularly useful for postmenopausal patients. They have been associated with a high rate (up to 90%) of resolution on follow-up vaginal cytology testing and are not associated with toxicities of the above stated therapies.6 Vaginal estrogen can be used alone or in addition to other therapeutic strategies. For example, it can be added to the nontreatment days of 5FU or postoperatively prescribed following laser or excisional procedures.
Radiation
Intracavitary brachytherapy is a technique in which a radiation source is placed within a cylinder or ovoids and placed within the vagina.7 Typically 45 Gy is delivered to a depth 0.5mm below the vaginal mucosal surface (“point z”). Recurrence occurs is approximately 10%-15% of patients, and toxicities can be severe, including vaginal stenosis and ulceration. This aggressive therapy typically is best reserved for cases that are refractory to other therapies. Following radiation, subsequent treatments are more difficult because of radiation-induced changes to the vaginal mucosa that can affect healing.
Vaginal dysplasia is a relatively common sequelae of high-risk HPV, particularly among women who have had a prior hysterectomy for cervical dysplasia. Because of anatomic changes following hysterectomy, adequate visualization and comprehensive vaginal treatment is difficult. Therefore, surgeons should avoid utilization of hysterectomy as a routine strategy to “cure” dysplasia as it may fail to achieve this cure and make subsequent evaluations and treatments of persistent dysplasia more difficult. Women who have had a hysterectomy for dysplasia should be closely followed for several decades, and they should be counseled that they have a persistent risk for vaginal disease. When VAIN develops, clinicians should consider topical therapies as primary treatment options because they may minimize toxicity and have high rates of enduring response.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant conflicts of interest.
References
1. Gynecol Oncol. 2016 Jun;141(3):507-10.
2. Arch Gynecol Obstet. 2016 Feb;293(2):415-9.
3. Anticancer Res. 2013 Jan;33(1):29-38.
4. Obstet Gynecol. 2017 Dec;130(6):1237-43.
5. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:129-36.
6. J Low Genit Tract Dis. 2014 Apr;18(2):115-21.
7. Gynecol Oncol. 2007 Jul;106(1):105-11.