Most prenatal exposure to teratogenic medication happens before prenatal care is initiated, which is often after strict abortion ban cutoffs, a cross-sectional study found.
Among a sample of privately-insured people, 5.8% of pregnancies with live deliveries were exposed to teratogenic medications versus 3.1% of those with nonlive outcomes -- and that exposure happened by 6 weeks' gestation in a quarter of those pregnancies (1.3% of all pregnancies), reported Almut Winterstein, PhD, of the University of Florida's College of Pharmacy and Center for Drug Evaluation and Safety in Gainesville, and colleagues.
By that time, 84% of patients had not initiated prenatal care; on average, patients initiated prenatal care at 56 days, authors wrote in .
Winterstein told that authors were "aware of the pattern of teratogen exposure during pregnancy, but we had not seen it in the context of prenatal care initiation," and that this research illuminates the magnitude of the problem.
"We wanted to quantify what proportion of pregnancies with teratogenic exposure has the opportunity to discuss the risk with their prenatal care provider and consider pregnancy termination," Winterstein said.
Of the 639,994 total pregnancies, nearly three-quarters were live deliveries, while a quarter had a nonlive outcome, such as abortion or stillbirth. Live deliveries had a mean maternal age of 30.9 versus 31.6 for those with nonlive outcomes. Out of the total, 32,500 pregnancies were exposed to teratogenic medicine at any time during gestation.
By 15 weeks' gestation, teratogenic medicine exposure had occurred in nearly half of all exposed pregnancies (2.5% of all pregnancies). Yet, among live deliveries, 16.8% still had yet to initiate care, which was even higher at 58.3% among nonlive outcomes.
One in 16 pregnancies are exposed to potentially teratogenic medications, which can cause fetal abnormalities, and the highest exposure happens in the first trimester.
"While some of these exposures result in pregnancy loss, others are not known before delivery and result in infant death or serious lifelong outcomes," Winterstein said, also urging lawmakers to consider further abortion exceptions for risk for serious birth defects. Winterstein said future research should look at what leads to pregnancies exposed to teratogenic medications in order to improve risk mitigation strategies.
"If prenatal exposure to teratogenic medications occurs, it is critical that prenatal care be initiated expeditiously to allow physician-patient discussions about pregnancy termination within legal abortion windows," authors concluded.
David Hackney, MD, a maternal-fetal medicine doctor at Case Western Reserve University in Cleveland, who was not involved in the study, told that "most pregnancies after teratogenic exposure will continue normally even though statistical odds of structural birth defects increase." While it might not make a huge difference on a population level, the risk still exists, and thus work to limit prenatal exposure to teratogens is still worthwhile, he said.
He also emphasized that "obstetric providers are deeply dependent upon primary care and other medical specialities ... as we cannot intervene prior to conception for the patients who are never in the first place referred to us."
"This is even more important now after Dobbs in the face of stringent bans, many of which cruelly make no exceptions for fetal conditions or teratogenic exposures, though was also quite suboptimal before Dobbs," Hackney said.
Authors used the MarketScan Commercial Database, which keeps billing data for people with employer-sponsored health insurance in the U.S., to look at pregnancies that ended between January 2017 and December 2019 among individuals who had continuous health plan enrollment from 90 days prior to conception and 30 days after pregnancy end.
They tracked 137 teratogenic medicines, the most common being those that acted on the renin angiotensin system, anticonvulsants, systemic antimycotics, antineoplastics, isotretinoin, and warfarin. They excluded sex hormones, infertility treatments, opioids, misoprostol, methotrexate, and ergotamine derivatives. The 2 weeks between the last menstrual period and conception was excluded from the analysis.
They measured medication utilization with National Drug Codes on pharmacy claims and medical encounter claims with Healthcare Common Procedure Coding System codes. Prenatal care initiation was based on encounters with obstetricians or other doctors that were coded indicating prenatal care or pregnancy. A previously developed algorithm identified pregnancy episodes. Analysis was based on three common gestational age cutoffs for abortion laws: 6, 15, and 22 weeks.
Authors note that teratogenic medication exposure was higher among nonlive pregnancies and it was possible the algorithm missed pregnancies that didn't result in reimbursed clinical care, such as some elective abortions. Another limitation is the possibility of overestimating gestational age, which could result in overestimating prenatal exposure. Additionally, it's possible pregnant people talked with their doctor via phone or message prior to a visit, though it's unlikely teratogenic risk would be discussed at that time.
Disclosures
Winterstein reported receiving grants from Merck Sharp & Dohme as well as personal fees from Merck Sharp & Dohme, Bayer KG, Ipsen, Arbor Pharmaceuticals, and Genentech.
Co-authors reported receiving personal fees from Harmony Biosciences, Axsome Therapeutics, Biohaven, and Myovant Sciences to serve on pregnancy registry scientific advisory committees.
Primary Source
JAMA Network Open
Winterstein AG, et al "Prenatal care initiation and exposure to teratogenic medications" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2023.54298.