Effects of gestational age at enrollment in pregnancy exposure registries

This study aims to explore the influence of gestational age at enrollment, and enrollment before or after prenatal screening, on the estimation of drug effects in pregnancy exposure registries.

We assessed the associations between first trimester antiepileptic drug (AED) exposure and risk of spontaneous abortion and major congenital malformations in the North American AED Registry (1996-2013). We performed logistic regression analyses, conditional or unconditional on gestational age at enrollment, to estimate relative risk (RR) for first trimester AED users compared with non-users. We also compared first trimester users of valproic acid and lamotrigine. Analyses were repeated in women who enrolled before prenatal screening.

Enrollment occurred earlier among 7029 AED users than among 581 non-users; it was similar among AEDs. Comparing AED users with non-users, RR (95% confidence interval) of spontaneous abortion (n = 359) decreased from 5.1 (2.3-14.1) to 2.0 (0.9-5.6) after conditioning on gestational week at enrollment and to 1.9 (0.8-5.4) upon further restriction to before-screening enrollees. RR of congenital malformations (n = 216) changed from 3.1 (1.4-8.5) to 3.2 (1.4-9.0) after conditioning on gestational week at enrollment and to 2.0 (0.7-10.1) upon further restriction to before-screening enrollees. When comparing valproic acid users and lamotrigine users, the RR of congenital malformations was not substantially changed by conditioning or restricting.

Spontaneous abortion rates were sensitive to gestational age at enrollment. Estimates of congenital malformation risks for AED users relative to non-users were sensitive to before/after-screening enrollment. This difference was not apparent between active drugs, likely due to similar gestational age at enrollment.