Margulis AV, D'Onofrio B, Almqvist C, McElrath T, Oberg AS, Plana E, Rothman KJ, Hernandez-Diaz S. Antiepileptic drugs in pregnancy and duration of pregnancy, birth weight, length, and head circumference. Poster presented at the 34th ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 25, 2018. Prague, Czech Republic. [abstract] Pharmacoepidemiol Drug Saf. 2018 Aug; 27(S2):234. doi: 10.1002/pds.4629

BACKGROUND: Antiepileptic drugs (AEDs) have been linked to reduced pregnancy duration, birth weight (BW), length (BL), and head circumference (HC). Dose‐response effects have not been well characterized for these outcomes; such effects are known for valproic acid and birth defects.

OBJECTIVES: Explore the effect of maternal AED use in pregnancy on pregnancy duration, BW, BL, and HC and dose‐response effects on these outcomes. Methods: We identified all infants born in Sweden to women who used AEDs in pregnancy in 1996‐2013 and used linear regression to assess associations of interest, adjusting for age, year, smoking habits, body mass index, epilepsy, etc. The reference was lamotrigine use. In AED‐specific dose analyses (2006‐), we compared tertiles of mean daily dose during pregnancy; the bottom tertile was the reference.

The study cohort had 6720 AED‐exposed infants. AED use in pregnancy increased over the study period. The most common AEDs were lamotrigine (34% of infants), carbamazepine (31%), and valproic acid (17%); 68% of AED‐exposed infants had a mother with epilepsy. For lamotrigine‐exposed infants, mean pregnancy duration was 39.5 weeks (w); BW, 3471 g; BL, 50.0 cm; and HC, 34.8 cm. Compared with infants in the low‐dose tertile (mean, 41 mg/d), those in the highdose tertile (mean, 454 mg/d) were born 0.3 w earlier (95% confidence interval, −0.6, 0), 11 g lighter (−95, 73), and 0.1 cm shorter (−0.3, 0.4); HC was similar. Relative to lamotrigine‐exposed infants, infants exposed to carbamazepine were born 0.2 w earlier (−0.3, 0), 69 g lighter (−112, −26), and 0.3 cm shorter (−0.5, −0.1); HC was 0.3 cm smaller (−0.5, −0.2). Compared with infants in the bottom tertile of carbamazepine dose (mean, 186 mg/d), infants exposed to high dose (mean, 905 mg/d) were born 0.8 w earlier (−1.2, −0.3), 170 g lighter (−288, −52), and 0.7 cm shorter (−1.2, −0.1); HC was 0.5 cm smaller (−0.8, −0.1). Infants exposed to valproic acid were 27 g lighter (−79, 24), 0.1 cm longer (−0.1, 0.4), and HC was 0.2 cm smaller (−0.4 to 0.0) than lamotrigine‐exposed infants but pregnancy duration was similar. Dose analyses did not show a clear pattern; confidence intervals were wide. HC was 0.6 cm smaller (−1.1, −0.1) in infants in the top dose tertile of valproic acid (mean, 1349 mg/d) relative to the bottom tertile (mean, 211 mg/d).

CONCLUSIONS: Relative to lamotrigine, infants exposed to carbamazepine were born slightly earlier and were slightly smaller. Effects were stronger at higher doses. A dose‐response effect on HC was seen for valproic acid.

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