Infants' prenatal exposure to opioids and the association with birth outcomes: A systematic review and meta-analysis

Richard Graeve; Arin A Balalian; Matthias Richter; Heike Kielstein; Astrid Fink; Silvia S Martins; Morgan M Philbin; Pam Factor-Litvak

doi:10.1111/ppe.12805

Infants' prenatal exposure to opioids and the association with birth outcomes: A systematic review and meta-analysis

Paediatr Perinat Epidemiol. 2022 Jan;36(1):125-143. doi: 10.1111/ppe.12805. Epub 2021 Nov 10.

Authors

Richard Graeve¹, Arin A Balalian², Matthias Richter³, Heike Kielstein⁴, Astrid Fink³, Silvia S Martins², Morgan M Philbin⁵, Pam Factor-Litvak²

Affiliations

¹ Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
³ Institute of Medical Sociology (IMS), Interdisciplinary Centre for Health Sciences, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
⁴ Institut fuer Anatomie und Zellbiologie, MLU Halle-Wittenberg, Halle (Saale), Germany.
⁵ Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.

PMID: 34755358
DOI: 10.1111/ppe.12805

Abstract

Background: Prenatal exposure to opioids (PEO) is a worldwide public health issue. Opioids cross the placental barrier and may affect the developing foetus and the birth outcomes.

Objectives: This review aimed to explore newborns' weight, length and head circumference, preterm birth, and perinatal death as primary outcomes in relation to PEO. The secondary outcomes were gestational age at birth, Apgar scores and length of hospitalisation after delivery.

Data sources: PubMed, Embase, PsycInfo and the Web of Science.

Study selection and data extraction: Inclusion criteria were (i) cohort, case-control or cross-sectional peer-reviewed studies published in English through 1 March 2021; (ii) comparing outcomes between prenatal exposed and unexposed groups to opioids (prescribed or obtained illegally). Exclusion criteria were foetal alcohol syndrome and non-opioid primary exposure.

Synthesis: Data were extracted by two authors. The Newcastle-Ottawa Quality Assessment Scale was used for study quality assessment. Due to heterogeneity across studies, we used random effects models to obtain pooled standardised mean difference (SMD), pooled risk ratio (RR) and 95% confidence interval (CI).

Results: Data from 80 studies were extracted. In meta-analyses, opioid-exposed neonates had lower birthweight (SMD -0.77, 95% CI -0.90, -0.64, I² = 82%), smaller head circumference (SMD -0.67, 95% CI -0.86, -0.48, I² = 84%), shorter birth length (SMD -0.97, 95% CI -1.24, -0.70, I² = 91%) and gestational age (SMD -0.45, 95% CI -0.60, -0.30, I² = 80%) than unexposed neonates. Pooled risks of neonatal death and preterm birth were higher among opioid-exposed compared to unexposed neonates (RR 4.05, 95% CI 2.12, 7.72, I² = 73%; and RR 1.92, 95% CI 1.57, 2.35, I² = 99%).

Conclusions: We found increased risks of adverse birth outcomes in relation to PEO. Caution should be used in interpreting the findings, as many studies were rated as poor quality, and with substantial inter-study heterogeneity. Future studies should ensure comparability of opioid-exposed and -unexposed group to strengthen internal validity.

Keywords: birth outcomes; birthweight; foetal growth; perinatal death; prenatal opioid exposure; preterm birth.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Analgesics, Opioid / adverse effects
Cross-Sectional Studies
Female
Humans
Infant, Newborn
Placenta
Pregnancy
Premature Birth*
Prenatal Exposure Delayed Effects* / chemically induced
Prenatal Exposure Delayed Effects* / epidemiology

Substances

Analgesics, Opioid