AbstractWith nearly 10% of women consuming alcohol during pregnancy, fetal alcohol spectrum disorders (FASDs) are becoming an increasing concern for clinicians and policymakers interested in the field of healthcare. Known as the range of mental and/or physical disabilities that occur among individuals with prenatal alcohol exposure, FASDs can result in dysmorphic features, problems with physical growth, neurobehavioral and cognitive problems that not only increase risk of various diseases, but also premature mortality. We investigated whether the diagnosis of FASDs result in increased risk of hospitalizations and mortality, with respect to FASD domains and relative diseases, when age effects are controlled for. The data for this study was taken from the National Health Insurance Service – National Sample Cohort (NHIS-NSC) between 2003 and 2013. The population attributable risk (PAR) statistic was used to estimate the percentage of hospitalizations and mortality attributable to FASDs and other factors. A time-dependent Cox proportional hazards model with age of diagnosis as the time-scale was employed to calculate adjusted hazard ratios and 95% CIs for hospitalizations and mortality among FASD populations compared to their general population peers. Among the 3,103 FASD cases, 27.5% experienced hospitalizations and 12.5% died. Overall, FASDs accounted for 853 FASD-attributable hospitalizations (51.0% of all hospitalizations in the study population) and 387 mortality events (34.5% of all deaths in the study population). 20.52% of hospitalizations and 21.35% of mortalities were attributable to FASDs in this population. Compared to the control group, FASD patients had a 1.25-fold (HR: 1.25, 95% CI: 1.05–1.49, p = 0.0114) increased risk of hospitalizations and a 1.33-fold (HR: 1.33, 95% CI: 1.07–1.67, p = 0.0118) increased risk of all-cause mortality. The most common cause for hospitalization was diseases of the nervous system, which accounted for 450 FASD-attributable hospitalizations (96.2% of all nervous system hospitalizations in the study population). In fact, FASD patients were 52 times more likely to be hospitalized for nervous system diseases than their peers (HR: 51.78, 95% CI: 29.09–92.17, p < .0001). The most common cause for mortality was neoplasms, which accounted for 94 FASD-attributable deaths (28.7% of all neoplasm deaths in the study population). However, FASD patients did not have increased risk of neoplasm mortality than the general population (HR: 0.88, 95% CI: 0.59–1.32, p < .0001). Overall, this study found that individuals diagnosed with FASDs have increased risk of both hospitalizations and mortality, compared to their general population peers. This is particularly so for diseases of the nervous system, which showed a 52-fold increase in hospitalizations and four-fold increase in mortality for FASD patients in our study. Likewise, while the association between FASDs and neoplasm mortality was not significant in our investigation, more attention by neurologists and related healthcare providers regarding the link between these two factors is necessary.Trial Registration: Institutional Review Board of Yonsei University’s Health System: Y-2019-0174.