Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review

Opioid use and abuse have increased dramatically in recent years, particularly among women.

We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations.

We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies.

We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process.

Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies.

Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation.

Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement.

Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.