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Continuation of pregnancy after first-trimester exposure to mifepristone: Is there a risk?
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Free communications and posters / Reproductive Toxicology 31 (2011) 255–268
not seem to be of great concern, but more data are necessary to confirm these results. doi:10.1016/j.reprotox.2010.12.024
Strategies for pursuing community involvement in OTIS research studies M.S. Elizabeth Conover, Kathleen Caldwell Nebraska Teratogen Information Service, United States
Continuation of pregnancy after first-trimester exposure to mifepristone: Is there a risk? Nathalie Bernard a , Marie-Pierre Cournot b , Patrick Carlier c , Martine Alt d , Claude E. Barjhoux e , Marie-Andrée Bos-Thompson f , Elisabeth Elefant b , Thierry Vial a a
Centre de Pharmacovigilance de Lyon, France Centre de Référence sur les Agents Tératogènes, Paris, France c Paris Fernand Widal, France d Strasbourg, France e Grenoble, Paris, France f Montpellier, France b
Introduction: Mifepristone is commonly used for the early termination of intra-uterine pregnancy in combination with a prostaglandin analog (misoprostol or gemeprost), or alone for softening and dilating the cervix prior to mechanical cervical dilatation. In case of failure or protocol interruption, some women may decide to continue their pregnancy. Few data is available on the outcome of pregnancies exposed to mifepristone in early pregnancy. The aim of this study is to report the prospective follow-up of pregnancies after exposure to mifepristone during the first trimester. The main outcome was the rate of major congenital malformations. Methods: Prospective data collected by the 16 participating centers was analyzed. Exclusion criteria were requests received after week 22 after the last menstrual period (LMP) to ensure a purely prospective design and subsequent termination of pregnancies without pathological examination of the fetus. Data on the maternal history and drug exposures were collected during the first contact, and pregnancy outcomes were documented at follow-up. Results: Data were obtained on 121 pregnancies. The mean age of patients was 28.7 years and the mean gestational age at the time of request was 13.9 weeks of pregnancy. Sixty-two patients were exposed to mifepristone only, and 59 to both mifepristone and misoprostol. There were 108 live births (89.2%), 12 spontaneous abortions (9.9%) including 2 with pathological examination, and 1 termination of pregnancy after subsequent diagnosis of Down syndrome. After exclusion of this latter case, 6 birth defects (4 major and 2 minor) were observed among the 110 examinable newborns or fetuses. The resulting rate of major congenital malformations was 3.6% (95% CI = 0.1–7.1%) with 2 cases among 53 assessable fetuses or neonates in the mifepristone-only exposed patients (Claude Bernard Horner syndrome with stridor and possible periconceptional cytomegalovirus infection; major hydrocephaly) and 2 cases among 57 live births in the combined mifepristone–misoprostol exposed patients (Moebius syndrome; one infant with retrognathism, slight cleft palate, trismus, major swallowing disorder, club foot with four toes, incomplete genital development and mild hypoplasia of the cerebellar vermis). Conclusion: This prospective study suggests that first-trimester exposure to mifepristone is not associated with an increased risk of major malformations. Interestingly, the two cases of major malformation in the mifepristone–misoprostol exposed patients were consistent with the typical malformation pattern described after exposure to misoprostol alone. Despite limitations due to the sample size, such findings provide reassuring data for risk evaluation in case of pregnancy continuation after mifepristone exposure.
Recruitment of participants in teratogen research studies is one of the biggest barriers to gathering data on exposures. More effective strategies for enrollment of study participants allow for larger numbers and improve the statistical significance of OTIS studies. It also provides the leverage necessary to enhance funding and study opportunities through OTIS. Nebraska has a relatively small TIS (Teratogen Information Service). As such, our volume of callers is less than other TIS’. In addition, most of our callers are health care providers, a group which historically has been low yield for use in patient recruitment. In an effort to compensate for this, the NE-TIS has utilized multiple approaches to enhancing our referrals to OTIS research projects: (1) Mailings to a list of medical providers who practice in the specialty area most likely to utilize medications of interest. For example, we sent letters to all of the rheumatologists in Nebraska with OTIS study information and referral details. (2) Including information on current OTIS research projects in all lectures and grand rounds presentations, and continuing education offerings to physicians/nurses/pharmacists. (3) Designing a simple enrollment form and attaching it to the relevant OTIS fact sheet; encouraging all genetics personnel to give this to their prenatal patients. (4) Developing a fax form that promotes OTIS research projects, and including it with fact sheets that are sent to health providers who make inquiries to NE-TIS on relevant agents. (5) Requesting grant funds from the Heartland Genetics Consortium to distribute OTIS fact sheet binders to 750 Midwestern obstetricians, midwives, genetic counselors and other healthcare providers. Extensive information on OTIS research projects was prominently included in the binder. (6) Networking with local providers, including public health clinics and large obstetrical practices, to enlist their assistance in enrolling patients for research studies. Our multi-faceted approach has resulted in the NE-TIS becoming a significant resource for OTIS studies. However, some of our efforts have been much more effective than others. Perhaps the most expensive and lowest yield were the mailings to medical specialists and the OTIS fact sheet binders. It is difficult to track all referrals that may eventually come from these strategies, but the numbers appear to be low. Including information in lectures and talks is inexpensive and low effort, but has not been an obvious source of research subjects. Attaching research enrollment fax forms to the fact sheets we send our in response to TIS inquiries has resulted in occasional referrals. Our greatest successes have come from networking. Numerous referrals have come from the other genetic counselors in our division. They offer an OTIS fact sheet to their patients on a relevant subject, and then remind them that it contains information gathered from prior patients who were willing to participate in studies. This “law of reciprocity” (someone who is given something of value often wants to reciprocate) is a gentle way of encouraging participation in future research studies. Finally, many of our referrals have come through one nurse practitioner in a large obstetrical clinic who has utilized our service for many years and who has benefited first hand from teratogen information and research. Our conclusion is that strong long-term relationships, and offering something of value (teratogen information and fact sheets) in exchange for participation, is the inexpensive and effective cornerstone of recruitment. doi:10.1016/j.reprotox.2010.12.026
doi:10.1016/j.reprotox.2010.12.025
Free communications and posters / Reproductive Toxicology 31 (2011) 255–268
not seem to be of great concern, but more data are necessary to confirm these results. doi:10.1016/j.reprotox.2010.12.024
Strategies for pursuing community involvement in OTIS research studies M.S. Elizabeth Conover, Kathleen Caldwell Nebraska Teratogen Information Service, United States
Continuation of pregnancy after first-trimester exposure to mifepristone: Is there a risk? Nathalie Bernard a , Marie-Pierre Cournot b , Patrick Carlier c , Martine Alt d , Claude E. Barjhoux e , Marie-Andrée Bos-Thompson f , Elisabeth Elefant b , Thierry Vial a a
Centre de Pharmacovigilance de Lyon, France Centre de Référence sur les Agents Tératogènes, Paris, France c Paris Fernand Widal, France d Strasbourg, France e Grenoble, Paris, France f Montpellier, France b
Introduction: Mifepristone is commonly used for the early termination of intra-uterine pregnancy in combination with a prostaglandin analog (misoprostol or gemeprost), or alone for softening and dilating the cervix prior to mechanical cervical dilatation. In case of failure or protocol interruption, some women may decide to continue their pregnancy. Few data is available on the outcome of pregnancies exposed to mifepristone in early pregnancy. The aim of this study is to report the prospective follow-up of pregnancies after exposure to mifepristone during the first trimester. The main outcome was the rate of major congenital malformations. Methods: Prospective data collected by the 16 participating centers was analyzed. Exclusion criteria were requests received after week 22 after the last menstrual period (LMP) to ensure a purely prospective design and subsequent termination of pregnancies without pathological examination of the fetus. Data on the maternal history and drug exposures were collected during the first contact, and pregnancy outcomes were documented at follow-up. Results: Data were obtained on 121 pregnancies. The mean age of patients was 28.7 years and the mean gestational age at the time of request was 13.9 weeks of pregnancy. Sixty-two patients were exposed to mifepristone only, and 59 to both mifepristone and misoprostol. There were 108 live births (89.2%), 12 spontaneous abortions (9.9%) including 2 with pathological examination, and 1 termination of pregnancy after subsequent diagnosis of Down syndrome. After exclusion of this latter case, 6 birth defects (4 major and 2 minor) were observed among the 110 examinable newborns or fetuses. The resulting rate of major congenital malformations was 3.6% (95% CI = 0.1–7.1%) with 2 cases among 53 assessable fetuses or neonates in the mifepristone-only exposed patients (Claude Bernard Horner syndrome with stridor and possible periconceptional cytomegalovirus infection; major hydrocephaly) and 2 cases among 57 live births in the combined mifepristone–misoprostol exposed patients (Moebius syndrome; one infant with retrognathism, slight cleft palate, trismus, major swallowing disorder, club foot with four toes, incomplete genital development and mild hypoplasia of the cerebellar vermis). Conclusion: This prospective study suggests that first-trimester exposure to mifepristone is not associated with an increased risk of major malformations. Interestingly, the two cases of major malformation in the mifepristone–misoprostol exposed patients were consistent with the typical malformation pattern described after exposure to misoprostol alone. Despite limitations due to the sample size, such findings provide reassuring data for risk evaluation in case of pregnancy continuation after mifepristone exposure.
Recruitment of participants in teratogen research studies is one of the biggest barriers to gathering data on exposures. More effective strategies for enrollment of study participants allow for larger numbers and improve the statistical significance of OTIS studies. It also provides the leverage necessary to enhance funding and study opportunities through OTIS. Nebraska has a relatively small TIS (Teratogen Information Service). As such, our volume of callers is less than other TIS’. In addition, most of our callers are health care providers, a group which historically has been low yield for use in patient recruitment. In an effort to compensate for this, the NE-TIS has utilized multiple approaches to enhancing our referrals to OTIS research projects: (1) Mailings to a list of medical providers who practice in the specialty area most likely to utilize medications of interest. For example, we sent letters to all of the rheumatologists in Nebraska with OTIS study information and referral details. (2) Including information on current OTIS research projects in all lectures and grand rounds presentations, and continuing education offerings to physicians/nurses/pharmacists. (3) Designing a simple enrollment form and attaching it to the relevant OTIS fact sheet; encouraging all genetics personnel to give this to their prenatal patients. (4) Developing a fax form that promotes OTIS research projects, and including it with fact sheets that are sent to health providers who make inquiries to NE-TIS on relevant agents. (5) Requesting grant funds from the Heartland Genetics Consortium to distribute OTIS fact sheet binders to 750 Midwestern obstetricians, midwives, genetic counselors and other healthcare providers. Extensive information on OTIS research projects was prominently included in the binder. (6) Networking with local providers, including public health clinics and large obstetrical practices, to enlist their assistance in enrolling patients for research studies. Our multi-faceted approach has resulted in the NE-TIS becoming a significant resource for OTIS studies. However, some of our efforts have been much more effective than others. Perhaps the most expensive and lowest yield were the mailings to medical specialists and the OTIS fact sheet binders. It is difficult to track all referrals that may eventually come from these strategies, but the numbers appear to be low. Including information in lectures and talks is inexpensive and low effort, but has not been an obvious source of research subjects. Attaching research enrollment fax forms to the fact sheets we send our in response to TIS inquiries has resulted in occasional referrals. Our greatest successes have come from networking. Numerous referrals have come from the other genetic counselors in our division. They offer an OTIS fact sheet to their patients on a relevant subject, and then remind them that it contains information gathered from prior patients who were willing to participate in studies. This “law of reciprocity” (someone who is given something of value often wants to reciprocate) is a gentle way of encouraging participation in future research studies. Finally, many of our referrals have come through one nurse practitioner in a large obstetrical clinic who has utilized our service for many years and who has benefited first hand from teratogen information and research. Our conclusion is that strong long-term relationships, and offering something of value (teratogen information and fact sheets) in exchange for participation, is the inexpensive and effective cornerstone of recruitment. doi:10.1016/j.reprotox.2010.12.026
doi:10.1016/j.reprotox.2010.12.025