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Brazil sees first live birth from deceased-donor uterus transplant
The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation. 
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation.
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation.
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
FROM THE LANCET
Parental leave for residents
Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
Amazon Alexa
Apple Podcasts
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Spotify
Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Neurologic Disease Eventually Affects Half of Women and One-Third of Men
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Don’t push women into preterm delivery after myomectomy
LAS VEGAS –
The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.
Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.
Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.
The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*
He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.
Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.
The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.
Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).
There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.
Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.
There was no external funding for the work, and Dr. King didn’t have any disclosures.
SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.
*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
LAS VEGAS –
The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.
Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.
Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.
The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*
He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.
Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.
The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.
Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).
There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.
Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.
There was no external funding for the work, and Dr. King didn’t have any disclosures.
SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.
*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
LAS VEGAS –
The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.
Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.
Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.
The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*
He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.
Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.
The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.
Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).
There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.
Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.
There was no external funding for the work, and Dr. King didn’t have any disclosures.
SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.
*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
REPORTING FROM AAGL GLOBAL CONGRESS
Key clinical point: Vaginal trial of labor is safe after myomectomy, at least if the uterine cavity wasn’t entered.
Major finding: Sixty-five percent of women who didn’t have their uterine cavities entered had vaginal deliveries, a success rate similar to labor after C-section.
Study details: Review of 102 pregnancies with live births after myomectomy at Northwestern University, Chicago
Disclosures: There was no external funding, and the lead investigator didn’t have any disclosures.
Source: King N et al. 2018 AAGL Global Congress, Abstract 162.
Self-report of prenatal marijuana use not very reliable
Even in the setting of legalized marijuana use, estimated prevalence of marijuana use during pregnancy was lower by self-report than it was by umbilical cord testing.
Torri D. Metz, MD, of the University of Utah Health, Salt Lake City, and her colleagues surveyed women at two urban hospitals in Colorado, which has legalized both medical and recreational use of marijuana. They found that, while 6% of the 116 women in the study reported using marijuana in the past 30 days, umbilical cord testing showed as many as 22% had detectable levels of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic, and 10% had levels above quantification.
The majority of studies of maternal marijuana use during pregnancy rely on self-report, so this could affect attempts to assess the effects of such prenatal use, they said.
Adverse outcomes associated with marijuana use during pregnancy include fetal growth restriction, small for gestational age, preterm birth, and adverse neurodevelopmental outcomes, studies have shown.
Read more in Obstetrics & Gynecology.
Even in the setting of legalized marijuana use, estimated prevalence of marijuana use during pregnancy was lower by self-report than it was by umbilical cord testing.
Torri D. Metz, MD, of the University of Utah Health, Salt Lake City, and her colleagues surveyed women at two urban hospitals in Colorado, which has legalized both medical and recreational use of marijuana. They found that, while 6% of the 116 women in the study reported using marijuana in the past 30 days, umbilical cord testing showed as many as 22% had detectable levels of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic, and 10% had levels above quantification.
The majority of studies of maternal marijuana use during pregnancy rely on self-report, so this could affect attempts to assess the effects of such prenatal use, they said.
Adverse outcomes associated with marijuana use during pregnancy include fetal growth restriction, small for gestational age, preterm birth, and adverse neurodevelopmental outcomes, studies have shown.
Read more in Obstetrics & Gynecology.
Even in the setting of legalized marijuana use, estimated prevalence of marijuana use during pregnancy was lower by self-report than it was by umbilical cord testing.
Torri D. Metz, MD, of the University of Utah Health, Salt Lake City, and her colleagues surveyed women at two urban hospitals in Colorado, which has legalized both medical and recreational use of marijuana. They found that, while 6% of the 116 women in the study reported using marijuana in the past 30 days, umbilical cord testing showed as many as 22% had detectable levels of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic, and 10% had levels above quantification.
The majority of studies of maternal marijuana use during pregnancy rely on self-report, so this could affect attempts to assess the effects of such prenatal use, they said.
Adverse outcomes associated with marijuana use during pregnancy include fetal growth restriction, small for gestational age, preterm birth, and adverse neurodevelopmental outcomes, studies have shown.
Read more in Obstetrics & Gynecology.
FROM OBSTETRICS & GYNECOLOGY
Common AEDs confer modestly increased risk of major congenital malformations
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
REPORTING FROM AES 2018
Key clinical point:
Major finding: The malformation rate was 5% in exposed pregnancies.
Study details: The MONEAD study comprised 351 pregnant women with epilepsy, 109 nonpregnant women with epilepsy, and 105 healthy pregnant women.
Disclosures: The National Institutes of Health funded the study; Dr. Meador reported no financial disclosures.
Source: Meador KJ et al. AES 2018, Abstract 3.231.
Empowering women through self-managed abortion
Consider Ashley, a 22-year-old G3P2, 8 weeks pregnant, on Medicaid and living in rural Arkansas. The victim of intimate partner violence, she just broke up with her boyfriend and feels she does not have the financial or emotional resources to raise another child; she has no family in town to turn to and wants to be the best parent she can be to her 10-month-old and 3-year old.
In Arkansas, as in many other states and the District of Columbia, Medicaid covers abortion only for rape, incest, or danger to the woman’s life. Arkansas, as well as many other states, requires women to wait 48 hours following counseling before they can proceed with abortion. Waiting periods exacerbate Ashley’s tenuous situation. Will her boss give her time off from work? How will she get to the clinic? Who will watch her children? And lost wages and greater expenses are not the only problems she faces. Arkansas requires a legal contract between the abortion provider and a physician with hospital admitting privileges to provide medical abortion. The result: Only one clinic in Arkansas can legally provide medical abortion for its entire female population. For our impoverished young mother of two, the best choice is the most difficult. And she is far from alone.
Since 2010, many states have passed numerous laws restricting access to safe abortion. As geography plays a growing role in determining access, women and health care providers actively seek ways to circumvent barriers. Telemedicine, initially designed to expedite primary care for patients whose access was hampered by Boston traffic, now brings quality health care to areas lacking providers.1 Telemedicine works for a variety of medical services, from prescribing antibiotics to performing neurosurgery; reproductive health care is part of this digital revolution.2 In 2008, Iowa’s Planned Parenthood of the Heartland began using telemedicine to offer medical abortion.3
As approved by the Food and Drug Administration, medical abortion is the termination of a pregnancy of up to 10 weeks’ gestation using a combination of mifepristone and misoprostol, the former taken to block progesterone receptors, the latter to cause expulsion of the pregnancy. Today, about a third of all abortions in the United States are medical abortions. Because current FDA regulations require that mifepristone be dispensed by a physician, patients usually receive the medications after an in-person evaluation by a health care provider in a clinic.
Two models of telemedicine could improve access for Ashley.
In the first, like the Iowa Planned Parenthood model, remote clinic staff evaluate patients with history and physical examination, ultrasonography, and hemoglobin measurement; the information is forwarded to an off-site physician who has a video discussion with the patient and remotely dispenses the medication for eligible candidates. Between 2008 and 2015, Iowa Planned Parenthood provided 8,765 medical abortions using this model.3 Clinically adverse events, such as hospital admission, surgery, blood transfusion, and death occurred in 16 (0.18%) with no ectopic pregnancies or death.3 For comparison, the rate of severe maternal morbidity in the United States is 1.4%, approximately 10 times the rate with this model of medical abortion.4
In the second model of fully self-managed telemedicine abortion, patients complete a checklist that is reviewed by a provider who sends the medications through the mail. For safety, women must be able to determine their eligibility through the checklist, manage the medications, and self-assess for abortion completion. The World Health Organization endorses self-managed abortion as an option when there is “a source of accurate information and access to a health care provider should they need or want it at any stage of the process.”5 Women on Web, an organization that has provided telemedicine abortion to women globally, has recently begun providing services to the United States after sweeping restrictions vastly increased the number of requests from U.S. women. The U.S. service, Aid Access, operates similarly and for $95 provides online consultation, shipping of the medications, and Skype or phone calls for questions.6
Self-managed abortion has a bad reputation, in part from anti-abortion activists who seek to punish women who attempt to end their pregnancies themselves, but also because of its association with pre–Roe v. Wade “back alley” unsafe abortions. Neither perspective recognizes the benefits of safe self-managed abortion. Some states have criminalized self-induced abortion; both the American College of Obstetricians and Gynecologists and the American Medical Association have voiced opposition to such laws to ensure that women do not fear prosecution for seeking medical care for complications.
Given the landscape of abortion access in the United States, where legal constraints, lack of insurance, and a dearth of providers may create insurmountable barriers, we support self-managed abortion for the following reasons:
- Access barriers: The complexity and number of legal restrictions to abortion care have made it unavailable/unaffordable through traditional clinic visits in many parts of the United States. With the addition of Justice Brett M. Kavanaugh to the Supreme Court, restrictions are likely to increase.
- Safety: The evidence-based assessment of the World Health Organization is that in-person clinical evaluation is unnecessary if the appropriate checklists, educational information, and access to a provider are available.
- Autonomy and equity: Even without the barriers mentioned above, self-managed telemedicine abortion remains a patient-centered option. Often more accessible and less expensive, inherently more private, it is bound to appeal to many women.
This decade has seen unprecedented challenges to comprehensive safe reproductive health care, with no relief in sight. In the decades prior to Roe v. Wade, illegal abortions were responsible for 20% of all maternal mortality in the United States. As government, national medical organizations, and the public become more aware of our intolerably high maternal mortality rate, these actors are increasingly driven to bring our maternal health to parity with our industrialized peers. Restricting access to safe abortion runs counter to that goal. Two hundred forty years of American history teach us that legal restrictions do not prevent abortions, because they do not eliminate the reasons for which women seek abortion. Legal restrictions do, however, prevent women from ending pregnancies in the safest manner possible. The inability to obtain safe abortions invariably leads to dead women – our mothers, daughters, sisters, and wives. In this country’s harsh political climate, we must protect a woman’s right to choose. By advocating for innovative approaches to protect women’s reproductive choices, we empower women and save lives.
Dr. Anwar is an obstetrician/gynecologist at Michigan State University in Flint and Dr. Espey is professor and chair of obstetrics and gynecology at the University of New Mexico, Albuquerque. Neither of them have conflicts of interest. Email them at [email protected].
References
1. “How a ‘Stupid Idea’ Gave Birth to Telemedicine,” MedPageToday. Dec 15, .
2. J Neurosurg Pediatr. 2016 Dec;25(6):753-7.
3. Obstet Gynecol. 2017 Oct;130(4):778-82.
4. Centers for Disease Control and Prevention. Severe Maternal Morbidity in the United States.
5. Guttmacher Rep Public Policy. 2018;21:41-7.
6. “International ‘safe abortions by mail’ service can now ship to women in US,” The Hill, Nov 7, 2018.
Consider Ashley, a 22-year-old G3P2, 8 weeks pregnant, on Medicaid and living in rural Arkansas. The victim of intimate partner violence, she just broke up with her boyfriend and feels she does not have the financial or emotional resources to raise another child; she has no family in town to turn to and wants to be the best parent she can be to her 10-month-old and 3-year old.
In Arkansas, as in many other states and the District of Columbia, Medicaid covers abortion only for rape, incest, or danger to the woman’s life. Arkansas, as well as many other states, requires women to wait 48 hours following counseling before they can proceed with abortion. Waiting periods exacerbate Ashley’s tenuous situation. Will her boss give her time off from work? How will she get to the clinic? Who will watch her children? And lost wages and greater expenses are not the only problems she faces. Arkansas requires a legal contract between the abortion provider and a physician with hospital admitting privileges to provide medical abortion. The result: Only one clinic in Arkansas can legally provide medical abortion for its entire female population. For our impoverished young mother of two, the best choice is the most difficult. And she is far from alone.
Since 2010, many states have passed numerous laws restricting access to safe abortion. As geography plays a growing role in determining access, women and health care providers actively seek ways to circumvent barriers. Telemedicine, initially designed to expedite primary care for patients whose access was hampered by Boston traffic, now brings quality health care to areas lacking providers.1 Telemedicine works for a variety of medical services, from prescribing antibiotics to performing neurosurgery; reproductive health care is part of this digital revolution.2 In 2008, Iowa’s Planned Parenthood of the Heartland began using telemedicine to offer medical abortion.3
As approved by the Food and Drug Administration, medical abortion is the termination of a pregnancy of up to 10 weeks’ gestation using a combination of mifepristone and misoprostol, the former taken to block progesterone receptors, the latter to cause expulsion of the pregnancy. Today, about a third of all abortions in the United States are medical abortions. Because current FDA regulations require that mifepristone be dispensed by a physician, patients usually receive the medications after an in-person evaluation by a health care provider in a clinic.
Two models of telemedicine could improve access for Ashley.
In the first, like the Iowa Planned Parenthood model, remote clinic staff evaluate patients with history and physical examination, ultrasonography, and hemoglobin measurement; the information is forwarded to an off-site physician who has a video discussion with the patient and remotely dispenses the medication for eligible candidates. Between 2008 and 2015, Iowa Planned Parenthood provided 8,765 medical abortions using this model.3 Clinically adverse events, such as hospital admission, surgery, blood transfusion, and death occurred in 16 (0.18%) with no ectopic pregnancies or death.3 For comparison, the rate of severe maternal morbidity in the United States is 1.4%, approximately 10 times the rate with this model of medical abortion.4
In the second model of fully self-managed telemedicine abortion, patients complete a checklist that is reviewed by a provider who sends the medications through the mail. For safety, women must be able to determine their eligibility through the checklist, manage the medications, and self-assess for abortion completion. The World Health Organization endorses self-managed abortion as an option when there is “a source of accurate information and access to a health care provider should they need or want it at any stage of the process.”5 Women on Web, an organization that has provided telemedicine abortion to women globally, has recently begun providing services to the United States after sweeping restrictions vastly increased the number of requests from U.S. women. The U.S. service, Aid Access, operates similarly and for $95 provides online consultation, shipping of the medications, and Skype or phone calls for questions.6
Self-managed abortion has a bad reputation, in part from anti-abortion activists who seek to punish women who attempt to end their pregnancies themselves, but also because of its association with pre–Roe v. Wade “back alley” unsafe abortions. Neither perspective recognizes the benefits of safe self-managed abortion. Some states have criminalized self-induced abortion; both the American College of Obstetricians and Gynecologists and the American Medical Association have voiced opposition to such laws to ensure that women do not fear prosecution for seeking medical care for complications.
Given the landscape of abortion access in the United States, where legal constraints, lack of insurance, and a dearth of providers may create insurmountable barriers, we support self-managed abortion for the following reasons:
- Access barriers: The complexity and number of legal restrictions to abortion care have made it unavailable/unaffordable through traditional clinic visits in many parts of the United States. With the addition of Justice Brett M. Kavanaugh to the Supreme Court, restrictions are likely to increase.
- Safety: The evidence-based assessment of the World Health Organization is that in-person clinical evaluation is unnecessary if the appropriate checklists, educational information, and access to a provider are available.
- Autonomy and equity: Even without the barriers mentioned above, self-managed telemedicine abortion remains a patient-centered option. Often more accessible and less expensive, inherently more private, it is bound to appeal to many women.
This decade has seen unprecedented challenges to comprehensive safe reproductive health care, with no relief in sight. In the decades prior to Roe v. Wade, illegal abortions were responsible for 20% of all maternal mortality in the United States. As government, national medical organizations, and the public become more aware of our intolerably high maternal mortality rate, these actors are increasingly driven to bring our maternal health to parity with our industrialized peers. Restricting access to safe abortion runs counter to that goal. Two hundred forty years of American history teach us that legal restrictions do not prevent abortions, because they do not eliminate the reasons for which women seek abortion. Legal restrictions do, however, prevent women from ending pregnancies in the safest manner possible. The inability to obtain safe abortions invariably leads to dead women – our mothers, daughters, sisters, and wives. In this country’s harsh political climate, we must protect a woman’s right to choose. By advocating for innovative approaches to protect women’s reproductive choices, we empower women and save lives.
Dr. Anwar is an obstetrician/gynecologist at Michigan State University in Flint and Dr. Espey is professor and chair of obstetrics and gynecology at the University of New Mexico, Albuquerque. Neither of them have conflicts of interest. Email them at [email protected].
References
1. “How a ‘Stupid Idea’ Gave Birth to Telemedicine,” MedPageToday. Dec 15, .
2. J Neurosurg Pediatr. 2016 Dec;25(6):753-7.
3. Obstet Gynecol. 2017 Oct;130(4):778-82.
4. Centers for Disease Control and Prevention. Severe Maternal Morbidity in the United States.
5. Guttmacher Rep Public Policy. 2018;21:41-7.
6. “International ‘safe abortions by mail’ service can now ship to women in US,” The Hill, Nov 7, 2018.
Consider Ashley, a 22-year-old G3P2, 8 weeks pregnant, on Medicaid and living in rural Arkansas. The victim of intimate partner violence, she just broke up with her boyfriend and feels she does not have the financial or emotional resources to raise another child; she has no family in town to turn to and wants to be the best parent she can be to her 10-month-old and 3-year old.
In Arkansas, as in many other states and the District of Columbia, Medicaid covers abortion only for rape, incest, or danger to the woman’s life. Arkansas, as well as many other states, requires women to wait 48 hours following counseling before they can proceed with abortion. Waiting periods exacerbate Ashley’s tenuous situation. Will her boss give her time off from work? How will she get to the clinic? Who will watch her children? And lost wages and greater expenses are not the only problems she faces. Arkansas requires a legal contract between the abortion provider and a physician with hospital admitting privileges to provide medical abortion. The result: Only one clinic in Arkansas can legally provide medical abortion for its entire female population. For our impoverished young mother of two, the best choice is the most difficult. And she is far from alone.
Since 2010, many states have passed numerous laws restricting access to safe abortion. As geography plays a growing role in determining access, women and health care providers actively seek ways to circumvent barriers. Telemedicine, initially designed to expedite primary care for patients whose access was hampered by Boston traffic, now brings quality health care to areas lacking providers.1 Telemedicine works for a variety of medical services, from prescribing antibiotics to performing neurosurgery; reproductive health care is part of this digital revolution.2 In 2008, Iowa’s Planned Parenthood of the Heartland began using telemedicine to offer medical abortion.3
As approved by the Food and Drug Administration, medical abortion is the termination of a pregnancy of up to 10 weeks’ gestation using a combination of mifepristone and misoprostol, the former taken to block progesterone receptors, the latter to cause expulsion of the pregnancy. Today, about a third of all abortions in the United States are medical abortions. Because current FDA regulations require that mifepristone be dispensed by a physician, patients usually receive the medications after an in-person evaluation by a health care provider in a clinic.
Two models of telemedicine could improve access for Ashley.
In the first, like the Iowa Planned Parenthood model, remote clinic staff evaluate patients with history and physical examination, ultrasonography, and hemoglobin measurement; the information is forwarded to an off-site physician who has a video discussion with the patient and remotely dispenses the medication for eligible candidates. Between 2008 and 2015, Iowa Planned Parenthood provided 8,765 medical abortions using this model.3 Clinically adverse events, such as hospital admission, surgery, blood transfusion, and death occurred in 16 (0.18%) with no ectopic pregnancies or death.3 For comparison, the rate of severe maternal morbidity in the United States is 1.4%, approximately 10 times the rate with this model of medical abortion.4
In the second model of fully self-managed telemedicine abortion, patients complete a checklist that is reviewed by a provider who sends the medications through the mail. For safety, women must be able to determine their eligibility through the checklist, manage the medications, and self-assess for abortion completion. The World Health Organization endorses self-managed abortion as an option when there is “a source of accurate information and access to a health care provider should they need or want it at any stage of the process.”5 Women on Web, an organization that has provided telemedicine abortion to women globally, has recently begun providing services to the United States after sweeping restrictions vastly increased the number of requests from U.S. women. The U.S. service, Aid Access, operates similarly and for $95 provides online consultation, shipping of the medications, and Skype or phone calls for questions.6
Self-managed abortion has a bad reputation, in part from anti-abortion activists who seek to punish women who attempt to end their pregnancies themselves, but also because of its association with pre–Roe v. Wade “back alley” unsafe abortions. Neither perspective recognizes the benefits of safe self-managed abortion. Some states have criminalized self-induced abortion; both the American College of Obstetricians and Gynecologists and the American Medical Association have voiced opposition to such laws to ensure that women do not fear prosecution for seeking medical care for complications.
Given the landscape of abortion access in the United States, where legal constraints, lack of insurance, and a dearth of providers may create insurmountable barriers, we support self-managed abortion for the following reasons:
- Access barriers: The complexity and number of legal restrictions to abortion care have made it unavailable/unaffordable through traditional clinic visits in many parts of the United States. With the addition of Justice Brett M. Kavanaugh to the Supreme Court, restrictions are likely to increase.
- Safety: The evidence-based assessment of the World Health Organization is that in-person clinical evaluation is unnecessary if the appropriate checklists, educational information, and access to a provider are available.
- Autonomy and equity: Even without the barriers mentioned above, self-managed telemedicine abortion remains a patient-centered option. Often more accessible and less expensive, inherently more private, it is bound to appeal to many women.
This decade has seen unprecedented challenges to comprehensive safe reproductive health care, with no relief in sight. In the decades prior to Roe v. Wade, illegal abortions were responsible for 20% of all maternal mortality in the United States. As government, national medical organizations, and the public become more aware of our intolerably high maternal mortality rate, these actors are increasingly driven to bring our maternal health to parity with our industrialized peers. Restricting access to safe abortion runs counter to that goal. Two hundred forty years of American history teach us that legal restrictions do not prevent abortions, because they do not eliminate the reasons for which women seek abortion. Legal restrictions do, however, prevent women from ending pregnancies in the safest manner possible. The inability to obtain safe abortions invariably leads to dead women – our mothers, daughters, sisters, and wives. In this country’s harsh political climate, we must protect a woman’s right to choose. By advocating for innovative approaches to protect women’s reproductive choices, we empower women and save lives.
Dr. Anwar is an obstetrician/gynecologist at Michigan State University in Flint and Dr. Espey is professor and chair of obstetrics and gynecology at the University of New Mexico, Albuquerque. Neither of them have conflicts of interest. Email them at [email protected].
References
1. “How a ‘Stupid Idea’ Gave Birth to Telemedicine,” MedPageToday. Dec 15, .
2. J Neurosurg Pediatr. 2016 Dec;25(6):753-7.
3. Obstet Gynecol. 2017 Oct;130(4):778-82.
4. Centers for Disease Control and Prevention. Severe Maternal Morbidity in the United States.
5. Guttmacher Rep Public Policy. 2018;21:41-7.
6. “International ‘safe abortions by mail’ service can now ship to women in US,” The Hill, Nov 7, 2018.
Prenatal, postnatal neuroimaging IDs most Zika-related brain injuries
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: In 82 pregnant women, prenatal neuroimaging identified fetal abnormalities in 3 cases, while postnatal neuroimaging in 53 of the remaining 79 cases yielded an additional 7 cases with mild abnormalities.
Study details: A prospective longitudinal cohort study of 82 pregnant women with clinical evidence of probable Zika infection in Colombia and the United States.
Disclosures: This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
Source: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26; doi: 10.1001/jamapediatrics.2018.4138.
Infertility appears to be increased among women with epilepsy
NEW ORLEANS – based on a retrospective study presented at the annual meeting of the American Epilepsy Society.
Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.
However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.
It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.
The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.
The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.
Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.
In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.
Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).
The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.
The investigation was funded by the Epilepsy Foundation and Lundbeck.
SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.
NEW ORLEANS – based on a retrospective study presented at the annual meeting of the American Epilepsy Society.
Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.
However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.
It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.
The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.
The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.
Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.
In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.
Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).
The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.
The investigation was funded by the Epilepsy Foundation and Lundbeck.
SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.
NEW ORLEANS – based on a retrospective study presented at the annual meeting of the American Epilepsy Society.
Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.
However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.
It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.
The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.
The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.
Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.
In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.
Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).
The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.
The investigation was funded by the Epilepsy Foundation and Lundbeck.
SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.
REPORTING FROM AES 2018
Key clinical point: Women with epilepsy may have more difficulty conceiving or carrying a pregnancy to term than women without epilepsy.
Major finding: The rate of infertility is 9.2% and the rate of impaired fecundity is 22.5% among women with epilepsy.
Study details: A retrospective analysis of 373 participants in the Epilepsy Birth Control Registry.
Disclosures: The investigation was funded by the Epilepsy Foundation and Lundbeck.
Source: MacEachern DB et al. AES 2018, Abstract 1.426.
Frontal lobe epilepsy elevates seizure risk during pregnancy
based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.
The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.
“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”
For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.
The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.
Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.
The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.
Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.
Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.
SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.
based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.
The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.
“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”
For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.
The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.
Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.
The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.
Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.
Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.
SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.
based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.
The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.
“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”
For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.
The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.
Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.
The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.
Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.
Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.
SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.
REPORTING FROM AES 2018
Key clinical point: Women with focal epilepsy, especially frontal lobe epilepsy, may need closer monitoring during pregnancy.
Major finding: Compared with baseline, seizures were more frequent during pregnancy in 53% of women with frontal lobe epilepsy.
Study details: An analysis of prospectively collected data from 114 pregnancies.
Disclosures: Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.
Source: Voinescu PE et al. AES 2018, Abstract 3.236.