Thesis (Ph.D.) - Indiana University, Department of Psychological and Brain Sciences, 2021Understanding consequences of prenatal exposure to psychiatric and analgesic medications is important because use of these medications among pregnant women is relatively common and increasing. Rodent experiments have shown effects of perinatal exposure to specific medications; however, these findings might not apply to humans. Human observational studies have been used to study prenatal exposure to psychiatric and analgesic medications rather than randomized control trials due to ethical concerns about exposing offspring to potentially harmful substances. However, it is unclear the extent to which the statistical associations documented in observational studies are due to causal mechanisms or background factors that differ among exposed and unexposed pregnancies (i.e., confounding factors). Therefore, the aim of my dissertation research was to evaluate consequences of prenatal exposure to psychiatric and analgesic medications on risk for adverse birth outcomes and neurodevelopmental problems by seeking converging evidence from multiple observational designs that target both measured and unmeasured confounding. The first study showed that after accounting for confounding, prenatal antidepressant exposure was associated with a small increased risk of preterm birth (PTB) but no increased risk of small for gestational age (SGA), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The second study suggested that observed associations between prenatal exposure to prescribed opioid analgesics (POAs) and risk for PTB and SGA were largely due to unmeasured confounding factors, although I could not rule out small independent associations. The third study evaluated the consequences of combined exposure to POAs and selective-serotine reuptake inhibitor antidepressants on risk for PTB and SGA and suggested that the medications do not interact to increase the risk of either outcome. These findings may provide reassurance to women considering antidepressant and POA use during pregnancy. They also highlight the importance of screening pregnant women and women of childbearing age and providing evidence-based treatments to at-risk women.