Illicit substance exposure in pregnancy and infant mortality risk: a nationwide Taiwan study

To investigate the association between prenatal illicit substance exposure and infant mortality, addressing the unclear links between specific and multiple substances and increased mortality.

This 16-year retrospective cohort study used Taiwan's National Health Insurance Research Database, the Taiwan Maternal and Child Health dataset, and the Integrated Illegal Drug Database, including 1 937 301 pregnant women who delivered from 2004 to 2019. Among them, 11 477 used illicit drugs during pregnancy, with a matched control group of 45 908 non-users based on maternal age, income, and childbirth year. Of the drug users, 26.9% used multiple substances, primarily methamphetamine and opioids. The primary outcome was all-cause mortality within the first year of life, with analyses stratified by substance type and timing of exposure. Cox regression models were employed to assess mortality, with results presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A P-value below .05 was considered statistically significant.

Infant from illicit drug-exposed mothers had a higher all-cause mortality rate (0.7%) compared to the control group (0.4%). Polysubstance use, which in most cases involved methamphetamine or opioids, was significantly associated with increased mortality risk (aHR 1.53, 95% CI 1.00-2.34), whereas no single substance alone-including methamphetamine (aHR 1.38, 95% CI 0.87-2.19) or opioids (aHR 1.63, 95% CI 0.98-2.72)-showed a statistically significant association. 3,4-Methylenedioxymethamphetamine, ketamine, and cannabis were likewise not linked to increased mortality. Mortality risk increased with drug exposure during pregnancy, with borderline significant associations in the first (aHR 1.82, 95% CI 0.98-3.37) and second trimesters (aHR 1.96, 95% CI 0.99-3.86), suggesting heightened vulnerability during early to mid-gestation.

One-year infant mortality is elevated among women with illicit substance use, with a higher proportion of deaths attributed to preterm birth and hypoxic events. The highest mortality risk was observed among those with polysubstance use. The findings underscore a dire public health issue, associating prenatal illicit substance exposure, notably multiple substances use, opioids, and methamphetamine, with heightened infant mortality rates, calling for targeted interventions and further research.