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

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.

Medication Use and Pain Management in Pregnancy: A Critical Review

“…Substantial increases in prescription opioid use among pregnant women have been observed, and the prevalence of opioid dependence and illicit opioid use among pregnant women has increased over the past decade . Among parturients in a tertiary facility in the United States, the prevalence of opioid dependence increased by 127% between 1998 to 2011, and the proportion of pregnant women filling opioid prescriptions for opioid dependence increased by 250% between 1995 and 2009 in a cohort study . Calls to an Australian obstetric drug information service related to oxycodone increased significantly between 2007 and 2016, rising from 3.8% of psychotropic/addictive‐related calls in 2007 ( n = 395) to 6.0% of calls in 2016 ( n = 897) (D. Kennedy, personal communication).…”

“…The literature evaluating the teratogenicity of opioid use in early pregnancy is limited (Table ), and studies frequently have weaknesses with outcome and exposure measurement . In a large Norwegian population‐based cohort study, Nezvalová‐Henriksen and colleagues found no statistically significant associations between neonatal codeine exposure and congenital malformations.…”

“…The literature evaluating the teratogenicity of opioid use in early pregnancy is limited (Table 3), and studies frequently have weaknesses with outcome and exposure measurement. 40 In a large Norwegian population-based cohort study, Nezvalov a-Henriksen and colleagues 71 found no statistically significant associations between neonatal codeine exposure and congenital malformations. A large case-control study found that first trimester maternal opioid use (where codeine and hydrocodone represented 69% of reported exposures) was significantly associated with some congenital heart defects as well as spina bifida and gastroschisis, 82 but the study had a high risk for recall bias because women were asked to recall their medication use in pregnancy up to 2 years postnatally.…”

Use of opioids during pregnancy and effects of pregnancy outcomes

“…Several studies have shown that the use of opioids during pregnancy increases the risk for birth abnormalities such as neural tube defects, gastroschisis, congenital heart defects, clubfoot, and neonatal abstinence syndrome . However, data on use of opioids during pregnancy and delivery outcomes is scarce.…”

“…4,[8][9][10][11] Several studies have shown that the use of opioids during pregnancy increases the risk for birth abnormalities such as neural tube defects, gastroschisis, congenital heart defects, clubfoot, and neonatal abstinence syndrome. 8,[12][13][14] However, data on use of opioids during pregnancy and delivery outcomes is scarce. A Norwegian study observed that self-reported codeine used anytime during pregnancy was associated with an increased risk for planned caesarean sections, and codeine used in the third trimester of pregnancy was associated with acute caesarean sections and postpartum haemorrhage.…”