Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies

Sarayani, Amir; Albogami, Yasser; Thai, Thuy Nhu; Smolinski, Nicole E; Patel, Preya; Wang, Yanning; Nduaguba, Sabina O; Rasmussen, Sonja A.; Winterstein, Almut G.

doi:10.1016/j.ajog.2022.01.004

Cited by 21 publications

(13 citation statements)

References 43 publications

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“…We used a previously developed algorithm to identify pregnancy episodes, which Sarayani et al have successfully used in other evaluations of prenatal exposure. This algorithm is based on validated measures of pregnancy outcomes (also providing the date of pregnancy end) and gestational age to determine conception date, resulting in timed pregnancy episodes .…”

Section: Methodsmentioning

confidence: 99%

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Smolinski,

Sarayani,

Thai

et al. 2024

JAMA Netw Open

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ImportanceTeratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy.ObjectivesTo determine pregnancy rates during valproic acid use and concomitant contraception use across indications.Design, Setting, and ParticipantsThis retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days’ supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023.Main Outcomes and MeasuresTreatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined.ResultsThe cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]).Conclusions and RelevanceIn this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.

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Section: Methodsmentioning

confidence: 99%

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Smolinski,

Sarayani,

Thai

et al. 2024

JAMA Netw Open

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“…We estimated the LMP using two distinct methods, depending on the presence of procedures for abortion, sonography, and diagnosis for preterm delivery within each episode, as described in Figure 1B [ 3 - 5 ].…”

Section: Methodsmentioning

confidence: 99%

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus

Jung,

Song,

Keum

et al. 2023

Epidemiol Health

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OBJECTIVES This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

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“…One study suggests 1 in 16 pregnancies in the United States is exposed to teratogenic medications. 15 These patients, like all patients, should receive comprehensive pregnancy options counseling and have their decision to carry to term or have an abortion affirmed by their provider and in legal statute.…”

Section: All Chronic Health Conditions Make Pregnancy Intention and D...mentioning

confidence: 99%

“…Given that half of all pregnancies in the United States are unplanned, 14 it is not inconceivable for someone who is prescribed a teratogenic medicine to learn they are pregnant after the fact, resulting in higher risk of fetal anomalies. One study suggests 1 in 16 pregnancies in the United States is exposed to teratogenic medications 15 . These patients, like all patients, should receive comprehensive pregnancy options counseling and have their decision to carry to term or have an abortion affirmed by their provider and in legal statute.…”

Section: All Chronic Health Conditions Make Pregnancy Intention and D...mentioning

confidence: 99%

Dobbs and disability: Implications of abortion restrictions for people with chronic health conditions

Hassan

Yates

Hing

et al. 2022

Health Services Research

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Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies

Cited by 21 publications

References 43 publications

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus

Dobbs and disability: Implications of abortion restrictions for people with chronic health conditions

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