Investigating NSAID Exposure Effects

As the etiologically relevant exposure window, the outcome assessment window, and the covariate assessment window differ by study outcome, we created two separate study cohorts. First, cohort 1 was constructed for the analysis of congenital malformations by setting the window of interest between the last menstrual period (LMP) to LMP+90 (hereafter, first trimester), and we excluded the following: (1) pregnancies with exposure to known teratogenic drugs (e.g., antineoplastic agent, warfarin, lithium, systemic retinoids, misoprostol, thalidomide, androgens, antiepileptic medications [valproate, topiramate, carbamazepine, oxcarbazepine, phenobarbital, phenytoin]); (2) infants with chromosomal abnormalities, genetic syndromes, and malformation syndromes with known causes; (3) pregnancies with no NSAID prescription during the first trimester, but with ≥1 NSAID prescription within 3 months before the LMP (LMP-90 to LMP-1); and (4) pregnancies with only 1 NSAID prescription during the first trimester to minimize potential for misclassification of exposure. Second, cohort 2 was constructed for the analysis of nonmalformation outcomes of low birth weight, antepartum hemorrhage, and oligohydramnios, by setting a broader window to evaluate the effects of exposure prior to the outcome assessment period (LMP to 19 week of gestation [hereafter, early pregnancy]), where we excluded (1) pregnancies with no NSAID prescription during early pregnancy, but with ≥1 NSAID prescription within 3 months before the LMP, and (2) pregnancies with only 1 NSAID prescription during early pregnancy.