In utero opioid exposure and birth outcomes: a systematic review and meta-analysis

Abstract

Abstract Background The nonmedical use of opioids during pregnancy, either those prescribed or obtained illegally, is a worldwide public health issue. Opioids pass through the placental barrier, which can expose the fetus to maternal opioid use; opioid-exposed babies may experience Neonatal Abstinence Syndrome (or Neonatal Opioid Withdrawal). We conducted a systematic review and meta-analysis to investigate how maternal opioid use during pregnancy may impact infants' birth outcomes. Methods We searched PubMed, Embase, PsycInfo, and the Web of Science, and identified 90 articles that met our inclusion criteria. Cohort, case-control and cross-sectional studies comparing birth outcomes of any opioid-exposed group (prescribed or obtained illegally) and a non-exposed comparison group were eligible for our systematic review. An adapted version of the Newcastle-Ottawa-Scale was used for quality assessment of the studies. Due to high heterogeneity between studies, we used random effects models to estimate pooled effects. Results In meta-analyses, opioid-exposed infants had lower birthweight (mean difference (MD):-405.9 grams, 95%CI: -472.26,-339.54, N = 37 studies), smaller head circumference (MD:-1.19 cm, 95%CI:-1.41, -0.96,N=22 studies), shorter gestational age (MD:-0.93 weeks, 95%CI: -1.20, -0.66,N= 34 studies), and shorter birth length (MD:-0.97 cm, 95%CI: -1.20, -0.74, N = 15 studies). The pooled relative risk of fatal outcomes was higher among the exposed infants: (RR:2.64, 95%CI: 1.06,6.59). Almost half of the studies were rated as poor, based on the Newcastle Ottawa Scale. Conclusions Our meta-analysis provides evidence of a link between opioid use during pregnancy and multiple adverse infant birth outcomes. Efforts should focus on increasing awareness about risks associated with opioid use and provide access to harm reduction measures for people who use opioids preconceptionally and in pregnancy. Key messages This meta-analysis provides insight into the magnitude of effects of in-utero opioid exposure on birth outcomes among the included studies. The findings highlight the importance of access to harm reduction measures in the periconceptional period and during pregnancy for people who use opioids.