Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.
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ABSTRACT: Objective
To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors.Methods
We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.Results
Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53).Conclusions
We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.
SUBMITTER: Wiggs KK
PROVIDER: S-EPMC7836668 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeWe described the medication use during pregnancy in the French population using the French Pregnancy Cohort (FPC).MethodsThe FPC was built with the sampling of all pregnant women included in the French Echantillon généraliste des bénéficiaires (EGB), which is a 1/97th representative sample of the population covered by the French health insurance. The EGB includes anonymized information on the socio-demographic and medical characteristics of beneficiaries, and the health care services they have received such as diagnoses and procedure codes as well as data on filled reimbursed medication; EGB also includes data on hospital stays in all public and private French health facilities. Each filled prescription record contains information on drug brand and generic names, date of prescription and date of dispensing, quantity dispensed, mode of administration, duration of prescription, dosage, and prescribing physician specialty. FPC includes data on all pregnancies of women in the EGB (2010-2013). Date of entry in the FPC is the first day of pregnancy regardless of pregnancy outcome (spontaneous abortions or planned abortions (with or without medical reasons), deliveries), and data on women are collected retrospectively for a period of one year before pregnancy, and prospectively during pregnancy, and up to one year after delivery. The prevalence of prescribed medications before, during and after pregnancy was compared; comparison was also done between trimesters. Pregnancy outcomes are described and include spontaneous and planned abortions, livebirths, and stillbirths.ResultsFPC includes data on 36,065 pregnancies. Among them, 27,253 (75.6%) resulted in a delivery including 201 stillbirths (0.7%). The total number of spontaneous abortions was 6,718 (18.6%), and planned abortions 2,094 (5.8%). The prevalence of filled medication use was 91.1%, 89.9%, and 95.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (first trimester exposure, 76.4% vs. exposure in the year prior to pregnancy, 91.1% (p < .01)), post-pregnancy medication use was above the pre-pregnancy level (95.6%). Maternal depression was the most prevalent comorbidity during pregnancy (20%), and post-partum depression was higher in those who delivered a stillborn infant (38.8%) as well as in those with a spontaneous (19.5%) or planned abortion (22.4%) compared to those with a liveborn (12.0%).ConclusionFPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. FPC has the advantage of including a representative sample of French pregnant women, and study medications only available in France in addition to others available worldwide.
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| S-EPMC7736493 | biostudies-literature
Project description:PurposeThis study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use.MethodsWe studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester.ResultsADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden).ConclusionADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.
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Project description:ImportanceWomen with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital malformations (MCMs) in their offspring.ObjectiveTo investigate the prevalence of MCMs after prenatal exposure to 8 commonly used ASM monotherapies and changes in MCM prevalence over time.Design, setting, and participantsThis was a prospective, observational, longitudinal cohort study conducted from June 1999 to October 2022. Since 1999, physicians from more than 40 countries enrolled ASM-treated WWE before pregnancy outcome was known and followed up their offspring until 1 year after birth. Participants aged 14 to 55 years who were exposed to 8 of the most frequently used ASMs during pregnancy were included in this study. Data were analyzed from April to September 2023.ExposureMaternal use of ASMs at conception.Main outcomes and measuresMCMs were assessed 1 year after birth by a committee blinded to type of exposure. Teratogenic outcomes across exposures were compared by random-effects logistic regression adjusting for potential confounders and prognostic factors.ResultsA total of 10 121 prospective pregnancies exposed to ASM monotherapy met eligibility criteria. Of those, 9840 were exposed to the 8 most frequently used ASMs. The 9840 pregnancies occurred in 8483 women (mean [range] age, 30.1 [14.1-55.2] years). MCMs occurred in 153 of 1549 pregnancies for valproate (9.9%; 95% CI, 8.5%-11.5%), 9 of 142 for phenytoin (6.3%; 95% CI, 3.4%-11.6%), 21 of 338 for phenobarbital (6.2%; 95% CI, 4.1%-9.3%), 121 of 2255 for carbamazepine (5.4%; 95% CI, 4.5%-6.4%), 10 of 204 for topiramate (4.9%; 95% CI, 2.7%-8.8%), 110 of 3584 for lamotrigine (3.1%; 95% CI, 2.5%-3.7%), 13 of 443 for oxcarbazepine (2.9%; 95% CI, 1.7%-5.0%), and 33 of 1325 for levetiracetam (2.5%; 95% CI, 1.8%-3.5%). For valproate, phenobarbital, and carbamazepine, there was a significant increase in the prevalence of MCMs associated with increasing dose of the ASM. Overall prevalence of MCMs decreased from 6.1% (153 of 2505) during the period 1998 to 2004 to 3.7% (76 of 2054) during the period 2015 to 2022. This decrease over time was significant in univariable logistic analysis but not after adjustment for changes in ASM exposure pattern.Conclusions and relevanceOf all ASMs with meaningful data, the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine. Prevalence of MCMs was higher with phenytoin, valproate, carbamazepine, and phenobarbital, and dose dependent for the latter 3 ASMs. The shift in exposure pattern over time with a declining exposure to valproate and carbamazepine and greater use of lamotrigine and levetiracetam was associated with a 39% decline in prevalence of MCMs, a finding that has major public health implications.
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