SIDS is associated with prenatal drug use: a meta-analysis and systematic review of 4 238 685 infants

Objective: To conduct a meta-analysis to determine the association between prenatal drug exposure and risk of sudden infant death syndrome (SIDS).

Design: Studies were searched using PubMed, Medline and Embase and restricted to English, with no publication date limit. Selected studies included published cohort, population or case studies comparing the incidence of SIDS among drug-exposed with drug-free controls. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Data were pooled using a random-effects model to evaluate risk ratios (RR).

Setting: High-income countries.

Patients: Children with a history of prenatal drug exposure.

Interventions: None.

Main outcome measures: RR of SIDS between drug-exposed and control infants.

Results: Sixteen studies (36 730 infants with any prenatal drug exposure, 21 661 exposed to opioids, 21 571 exposed to cocaine, 5031 exposed to methadone compared with 4 201 955 with no exposure). Any prenatal drug exposure was associated with an increased crude risk of SIDS (RR 7.84, 95% CI 5.21 to 11.81). Prenatal opioid exposure had the highest associative crude risk of SIDS (RR 9.76, 95% CI 5.28 to 18.05), followed by methadone (RR 9.52, 95% CI 4.60 to 19.70) and cocaine (RR 4.40, 95% CI 2.52 to 7.67). Increased crude risk persisted after adjusting for socioeconomic factors (RR 4.24, 95% CI 1.39 to 12.88). The incidence of SIDS for this cohort decreased between 1972 and 2020 but remained significantly higher than controls.

Conclusion: Exposure to any drug of dependency during pregnancy is associated with an increased risk of SIDS after controlling for socioeconomic factors. Further study to evaluate mechanisms and contribution of other confounders (eg, smoking) is warranted.