Associations of prenatal exposure to non-steroidal anti-inflammatory drugs with preterm birth and small-for-gestational age among women with autoimmune disorders

Background: Prenatal non-steroidal anti-inflammatory drug (NSAID) use is common, especially in early gestation prior to pregnancy recognition and among people with autoimmune conditions. However, the effects of NSAID exposure on birthweight and gestational age are not known.

Objectives: We estimated associations between prenatal NSAID exposure and preterm birth and small for gestational age among women with autoimmune conditions.

Methods: Participants were enrolled in the MotherToBaby cohort and had an autoimmune disorder and singleton live birth >20 weeks gestation (n=2003). We characterized self-reported NSAID exposure over gestation for timing, duration, and average daily dose. Outcomes were preterm birth (i.e. <37 weeks gestation) and small for gestational age (SGA; <10th percentile birthweight). We used Poisson regression to estimate associations between NSAID exposure and study outcomes adjusting for demographics, co-use of other medications (Model 1), and disease severity at baseline (Model 2). Secondarily, we considered the role of acetaminophen use by individually matching NSAID users to controls on cumulative dose of acetaminophen exposure.

Results: Overall, 15% of women reported NSAID use in pregnancy, with most use in the first trimester. No NSAID use exposure variables were associated with risk of preterm birth. Any NSAID use was associated with 1.7 (95%CI 1.2, 2.5) times greater risk of SGA and this estimate was attenuated to 1.5 (95%CI 1.0, 2.3) after adjustment for baseline disease severity. All other NSAID exposure variables were associated with SGA with similar magnitude. After matching on acetaminophen exposure, associations between any NSAID use and preterm birth and SGA were 0.8 (95%CI 0.6, 1.4) and 1.8 (95%CI 1.1, 2.9).

Conclusions: NSAID use in pregnancy is associated with SGA but not preterm birth. Future research should explore mechanisms that may explain these findings. Future research must also consider alternative explanations for these associations.