Introduction: Increased rates of maternal opioid use during pregnancy have resulted in increased rates of post-natal opioid withdrawal, termed neonatal abstinence syndrome (NAS). Some evidence suggests that infants born at later gestational ages are at higher risk of developing NAS. The objective of this review was to estimate the association between gestational age at birth and development of NAS.
Methods: A comprehensive search strategy, developed with the aid of a medical librarian, included PubMed, Embase, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials. Studies that were published after January 2000 and presented results on the association between gestational age and development of NAS were included. Study eligibility was confirmed by two reviewers. Pooled unadjusted odds ratios (OR) for the association between preterm birth and NAS, and mean differences (MD) in gestational age between affected and unaffected babies were combined using a random effects model, and heterogeneity was assessed using the I2 statistic.
Results: Of the 2,064 citations identified, 135 were eligible for full-text review, and 29 were included in the review. Almost all (n=28) of the studies used a cohort design. The pooled OR for the association between preterm birth and NAS revealed no association (13 studies; OR 0.94; 95% confidence interval [CI]: 0.62, 1.41), but high heterogeneity between the studies (I2=85.4%). The pooled estimate of the MD in gestational age between babies affected by NAS and those not affected was 0.96 weeks (95% CI: 0.25, 1.67), with heterogeneity among the nine studies (I2=77.5%).
Conclusion: The current evidence is unclear regarding the association between gestational age at birth and development of NAS. This association was not the primary objective in most of the studies, and heterogeneity among studies was marked. Further research is required to clarify this relationship.