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

This meta-analyses of 4,238,685 children from high-income countries found that while prenatal exposure to any drugs of dependency increased SIDS risk this was greatest for infants prenatally exposed to opioids and methadone. Further research to examine associations in low- and middle-income countries is needed. 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.

Automated summary

This meta-analysis found that infants prenatally exposed to opioids and methadone have the highest risk of sudden infant death syndrome (SIDS). Prenatal exposure to any drugs of dependency increases the risk of SIDS. Further research is needed to examine associations in low- and middle-income countries.