Although there exists a plethora of evidence on the adverse adult health effects of negative macroeconomic change, little is known about the effects of macroeconomic change on birth outcomes. This association is inherently difficult to discern, given the lack of state-and time-specific data and the simultaneous effects of economic conditions on fetal health and economic conditions on who is born (ie, selection). Economic conditions prior and during pregnancy may affect women's choices to conceive, declines in fertility, spontaneous pregnancy loss, and elective abortion. This retrospective cohort study aimed to examine associations between state-level economic conditions during pregnancy and adverse birth outcomes from 1990 and 2013. Whereas previous studies on the topic have inadequately accounted for selection, this study used multiple methods to account for selection effects and paid special attention to changes in the association between economic trends and birth outcomes before, during, and after the Great Recession (December 2007 to June 2009). The study population included a total of 87,423,734 singleton births after selecting for women ages 15 to 44 years across the United States who met criteria based on adequate record completion. Unemployment data were gathered from the Department of Labor Statistics and individual-level birth information from the National Center for Health Statistics allcounty natality files. A binary "high unemployment" variable defined as "> 8.8%"unemployment was used, and" preconception unemployment" was defined as the average unemployment rate for 6 months prior to conception. Adverse birth outcomes analyzed included preterm birth (PTB), small for gestational age (SGA), and low birth weight. Fixed-effects logistical regressions were determined for these outcomes on the primary exposure variables (first-and second-trimester unemployment rates). Six customized models were used to control for a host of confounding variables including an interaction term between first-and second-trimester unemployment and Great Recession variables to determine whether the association between unemployment and birth outcomes differed by time period. Results show that a higher proportion of infants were born preterm during the Great Recession (10.2%) than after it (9.5%). Each increase of 1% to the unemployment rate in the first trimester was found to be associated with a 2% higher chance of PTB before the Recession. During the Recession, there was a greater impact on PTB as a 1% increase in unemployment in the first trimester of pregnancy was associated with a 16% increase in PTB. This declined to a 4% increase in the post-Recession period. No significant association was found between SGA and unemployment during pregnancy, and trends for low birth weight were similar in magnitude and direction to associations for PTB. The results did not show significant differences in the association between unemployment and PTB by maternal race/ethnicity or sociodemographics. This study enhances our understanding of how macroeconomic trends including the Great Recession influence adverse birth outcomes in the United States.