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Meta-Analysis
. 2022 May 11;22(1):401.
doi: 10.1186/s12884-022-04733-9.

Opioid exposure during pregnancy and the risk of congenital malformation: a meta-analysis of cohort studies

Xinrui Wang #  1   2 , Yushu Wang #  1   2 , Borui Tang  2 , Xin Feng  3
Affiliations
Meta-Analysis

Opioid exposure during pregnancy and the risk of congenital malformation: a meta-analysis of cohort studies

Xinrui Wang et al. BMC Pregnancy Childbirth. .

Abstract

Background: Opioid exposure during pregnancy has increased alarmingly in recent decades. However, the association between prenatal opioid exposure and congenital malformation risk has still been controversial. We aim to assess the association between opioid exposure during pregnancy and the risk of congenital malformations.

Method: PubMed, Embase, and Cochrane library of clinical trials were systematically searched to September 13th, 2021. Cohort studies reporting risk of congenital malformation after opioid exposure compared with non-exposure during pregnancy were included. Risk of studies was appraised with the ROBINS-I tool. Meta-analysis was conducted using the random-effects model. Subgroup analyses were conducted for the primary outcome based on indication, exposed period, whether adjusted data was used, and risk of bias assessment. Meta-regression was performed to evaluate the relation of publication year.

Main results: Eighteen cohort studies with 7,077,709 patients were included. The results showed a significant increase in the risk of overall congenital malformation (RR = 1.30, 95%CI: 1.11-1.53), major malformation (RR = 1.57, 95%CI:1.11-2.22), central nervous system malformation (RR = 1.36, 95% CI:1.19-1.55), and limb malformation (RR = 2.27, 95%CI:1.29-4.02) with opioid exposure during pregnancy. However, the predictive interval conveyed a different result on overall congenital malformation (95%PI: 0.82-2.09) and major malformation (95%PI: 0.82-2.09). No association between opioid exposure and overall congenital malformation in the first trimester (RR = 1.12, 95%CI:0.97-1.31) and prescribed for analgesic or antitussive treatment (RR = 1.03, 95%CI:0.94-1.13) were observed. In subgroups that study provided data adjusted for confounders (RR = 1.06, 95%CI:0.93-1.20) or identified moderate or serious risk of bias (RR = 1.00, 95%Cl: 0.85-1.16; RR = 1.21, 95%Cl: 1.60-2.68), no association was found.

Conclusion: Opioid exposed in the first trimester or prescribed for analgesic or antitussive treatment did not increase the risk of overall congenital malformation. The findings should be discussed in caution considering the situation of individual patients and weigh out its potential risk of congenital malformation.

Trial registration: Registration number: CRD42021279445 .

Keywords: Congenital malformation; Opioid; Pregnancy; meta-analysis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow-chart of studies selection
Fig. 2
Fig. 2
Forest plot of opioid exposure during pregnancy and the risk of congenital malformation; TE, treatment effect; SE, standard error; IV, inverse variance test; CI, confidence interval; df, degrees of freedom
Fig. 3
Fig. 3
Forest plot of opioid exposure during pregnancy and the risk of specific congenital malformation; RR, risk ratio; CI, confidence interval
Fig. 4
Fig. 4
Summary of sensitivity analysis by leave-one-out method
See this image and copyright information in PMC

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