The association between gestational age at delivery and neonatal abstinence syndrome: A systematic review and meta-analysis

Objectives: Some evidence suggests that infants born at later gestational age (GA) are at higher risk of developing neonatal abstinence syndrome (NAS). This systematic review estimated the association between GA at delivery and development of NAS in infants born to women on opioid agonist therapy (OAT). Methods: MEDLINE/PubMed, Scopus, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials were searched from January 2000 to April 2023. Studies reporting data on the association between GA and NAS among pregnant women being treated with OAT were eligible for inclusion. Random effects meta-analysis was used to estimate the mean difference in GA between infants affected by NAS and unaffected infants; odds ratio (OR) for the association between preterm birth and NAS; and OR for the association between gestational week and NAS. Results: Of 966 records identified, 38 studies were eligible for this review. The pooled mean difference in GA between infants affected by NAS and unaffected infants was 0.62 weeks (95% CI: 0.08–1.16, I2=90.7%). The odds of developing NAS were estimated to increase by 3% per gestational week (OR 1.03, 95% CI: 0.997-1.06, I2=84.2%). The OR for the association between preterm birth and developing NAS was estimated to be 0.87 (95% CI: 0.63-1.21, I2=85.7%). Conclusions: The data included in this review demonstrate that higher GA is unlikely to be associated with an increased risk of NAS, although poor study quality and significant study heterogeneity were observed.