(244) Neonatal and Maternal Outcomes Following Exposure to Non-Steroidal Anti-Inflammatory Drugs During Early Pregnancy: A Nationwide Cohort Study

Publication Number: 575

Background: While safety evidence of non-steroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, there is inconclusive evidence on its use during early pregnancy with limited data on neonatal and pregnancy-related complications.

Objectives: To investigate the association of congenital malformations and obstetric complications with prenatal exposure to NSAIDs.

Methods: We conducted a nationwide cohort study using Korea’s National Health Insurance Service (NHIS) claims database; the mother-offspring cohort was constructed by the NHIS. We included all live births in women aged 20-44 years between 2010-2019. We defined exposure to NSAIDs as ≥2 records of NSAIDs prescriptions during early pregnancy (first 90 days of pregnancy [first trimester] for congenital malformations; first 19 weeks for obstetric complications). Two referent groups were defined: 1) no NSAIDs prescription during the 3 months before the start of pregnancy to the delivery date (unexposed); 2) ≥2 acetaminophen prescriptions during the early pregnancy (active comparator). Outcomes of interest were major congenital malformations and obstetric complications (low birth weight, antepartum hemorrhage, and oligohydramnios). We estimated relative risks (RR) with 95% CIs using generalized linear models with propensity score stratification and weighting to adjust for various confounders.

Results: For neonatal outcome analyses, 2.38% pregnancies were exposed to NSAIDs in the first trimester among 1,819,756 pregnancies. Compared to unexposed pregnancies, the RR was 1.19 (95% CI 1.13-1.25) for congenital malformations overall, 1.25 (1.17-1.33) for cardiac malformations, and 1.29 (1.00-1.66) for oral clefts. For obstetric complication analyses, 2.72% pregnancies were exposed to NSAIDs during its first 19 weeks among 1,816,469 pregnancies. Compared to unexposed pregnancies, the RR was 1.37 (1.31-1.42) for low birth weight, 1.23 (1.13-1.33) for antepartum hemorrhage, and 1.07 (0.96-1.20) for oligohydramnios. Comparison to acetaminophen-exposed pregnancies for both neonatal and maternal outcomes also showed statistically significant results, consistent with the comparison to unexposed pregnancies.

Conclusions: Our findings showed that NSAIDs use during early pregnancy was associated with a small increased risk of overall congenital malformations and obstetric complications of low birth weight and antepartum hemorrhage. Based on the observed risks, NSAIDs should be used with more caution and accordingly, health care providers should thoroughly weigh the risks of these outcomes against the benefits of NSAIDs treatment for its major indications during early pregnancy.