Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun;139(6):e20164131.
doi: 10.1542/peds.2016-4131.

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

Jennifer N Lind  1   2 , Julia D Interrante  3   4 , Elizabeth C Ailes  3 , Suzanne M Gilboa  3 , Sara Khan  3   5   6 , Meghan T Frey  3 , April L Dawson  3 , Margaret A Honein  3 , Nicole F Dowling  3 , Hilda Razzaghi  3   2 , Andreea A Creanga  7   8 , Cheryl S Broussard  3
Affiliations

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

Jennifer N Lind et al. Pediatrics. 2017 Jun.

Abstract

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

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

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

Study selection: 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 extraction: 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.

Results: 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.

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

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Flowchart for inclusion of studies in a systematic review of prenatal opioid exposure and congenital malformations.
FIGURE 2
FIGURE 2
Risk of bias across studies included in a systematic review of prenatal opioid exposure and congenital malformations. (A) Studies with an unexposed comparison group (n = 46). (B) Studies with an exposed comparison group (n = 15). (C) Descriptive studies (n = 7).
See this image and copyright information in PMC

References

    1. National Institute on Drug Abuse; US Department of Health and Human Services. Research Report Series: Prescription Drug Abuse. Bethesda, MD: National Institute on Drug Abuse, US Department of Health and Human Services; 2014. (NIH Publication Number 15-4881).
    1. Mack KA, Jones CM, Paulozzi LJ, Centers for Disease Control and Prevention (CDC) Vital signs: overdoses of prescription opioid pain relievers and other drugs among women–United States, 1999–2010. MMWR Morb Mortal Wkly Rep. 2013;62(26):537–542. - PMC - PubMed
    1. Paulozzi LJ, Mack KA, Hockenberry JM, Division of Unintentional Injury Prevention, National Center for Injury Prevention and Control, CDC Vital signs: variation among states in prescribing of opioid pain relievers and benzodiazepines - United States, 2012. MMWR Morb Mortal Wkly Rep. 2014;63(26):563–568. - PMC - PubMed
    1. Ailes EC, Dawson AL, Lind JN, et al. Centers for Disease Control and Prevention (CDC) Opioid prescription claims among women of reproductive age United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2015;64(2):37–41. - PMC - PubMed
    1. Jones CM, Logan J, Gladden RM, Bohm MK. Vital signs: demographic and substance use trends among heroin users - United States, 2002–2013. MMWR Morb Mortal Wkly Rep. 2015;64(26):719–725. - PMC - PubMed

Publication types