Anxiety disorders comprise a spectrum of conditions, including panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, social anxiety disorder, and phobias. Their lifetime prevalence among women has been reported to be as high as 30%, so these disorders frequently complicate pregnancy. Insomnia is also very common during pregnancy, with a prevalence of nearly 40%. Pharmacological treatment with benzodiazepines or non-benzodiazepine sedative hypnotics is frequently indicated for severe anxiety and insomnia; approximately 4% of pregnant women uses one of these classes of medication during their pregnancy. Polytherapy among women using these medications is common, with 30- 40% being co-prescribed at least two additional psychotropic medications. Benzodiazepines and non- benzodiazepine sedative hypnotics cross the human placenta and may therefore have the potential to alter normal intrauterine development of fetal growth, anatomic structures, physical functioning, and postnatal development. The American College of Obstetricians and Gynecologists recommends that decisions regarding mental health treatment during pregnancy be made jointly between a woman and her mental and obstetrical health providers prior to pregnancy. Unfortunately, rigorous and comprehensive safety data to inform the risk-benefit trade-off are sparse, evidence is conflicting, and numerous safety concerns have been raised. The objective of the proposed studies is to address this critical information gap by generating high-quality evidence on the safety of benzodiazepines and non-benzodiazepine sedative hypnotics during pregnancy considering a broad range of clinically relevant adverse pregnancy outcomes, including major congenital malformations, spontaneous abortion, preterm birth, low birth weight, small for gestational age, hypoglycemia, respiratory problems, NICU admission, and neurodevelopmental disorders. The use of large, population-based cohorts of publicly and privately insured pregnant women (N ≈ 4.5 million) will enable quantification of effects with great precision, as well as exploration of the effects for specific drugs, doses, gestational timing of exposure, and polytherapy. As is the case for all studies evaluating drug safety in pregnancy given that they are observational in nature by necessity, the most important challenges relate to the potential for confounding, as well as misclassification of exposures and outcomes as documented in existing healthcare data. The project will benefit from the multidisciplinary team’s deep experience and established track record overcoming these challenges in perinatal psychiatry research using highly innovative design and advanced computational approaches. The findings will have a direct and large public health impact by enabling treatment to be tailored for the large number of women that struggle with perinatal anxiety and sleep disorders.