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Opioids cross the placental barrier and may affect the developing foetus and the birth outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This review aimed to explore newborns\u2019 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data sources<\/jats:title><jats:p>PubMed, Embase, PsycInfo and the Web of Science.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study selection and data extraction<\/jats:title><jats:p>Inclusion criteria were (i) cohort, case\u2010control or cross\u2010sectional peer\u2010reviewed studies published in English through 1\u00a0March 2021; (ii) comparing outcomes between prenatal exposed and unexposed groups to opioids (prescribed or obtained illegally). Exclusion criteria were foetal alcohol syndrome and non\u2010opioid primary exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Synthesis<\/jats:title><jats:p>Data were extracted by two authors. The Newcastle\u2010Ottawa 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data from 80\u00a0studies were extracted. In meta\u2010analyses, opioid\u2010exposed neonates had lower birthweight (SMD \u22120.77, 95% CI \u22120.90, \u22120.64, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a082%), smaller head circumference (SMD \u22120.67, 95% CI \u22120.86, \u22120.48, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a084%), shorter birth length (SMD \u22120.97, 95% CI \u22121.24, \u22120.70, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a091%) and gestational age (SMD \u22120.45, 95% CI \u22120.60, \u22120.30, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a080%) than unexposed neonates. Pooled risks of neonatal death and preterm birth were higher among opioid\u2010exposed compared to unexposed neonates (RR 4.05, 95% CI 2.12, 7.72, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a073%; and RR 1.92, 95% CI 1.57, 2.35, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a099%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010study heterogeneity. Future studies should ensure comparability of opioid\u2010exposed and \u2010unexposed group to strengthen internal validity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ppe.12805","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T12:04:09Z","timestamp":1636545849000},"page":"125-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Infants\u2019 prenatal exposure to opioids and the association with birth outcomes: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"36","author":[{"given":"Richard","family":"Graeve","sequence":"first","affiliation":[{"name":"Medical Faculty Martin Luther University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-7833","authenticated-orcid":false,"given":"Arin A.","family":"Balalian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-3332","authenticated-orcid":false,"given":"Matthias","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Medical Sociology (IMS) Interdisciplinary Centre for Health Sciences Medical Faculty Martin Luther University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Kielstein","sequence":"additional","affiliation":[{"name":"Institut fuer Anatomie und Zellbiologie MLU Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Fink","sequence":"additional","affiliation":[{"name":"Institute of Medical Sociology (IMS) Interdisciplinary Centre for Health Sciences Medical Faculty Martin Luther University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-9993","authenticated-orcid":false,"given":"Silvia S.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7608-7921","authenticated-orcid":false,"given":"Morgan M.","family":"Philbin","sequence":"additional","affiliation":[{"name":"Department of Sociomedical Sciences Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1884","authenticated-orcid":false,"given":"Pam","family":"Factor\u2010Litvak","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"United Nations Office on Drugs and Crime.World Drug Report. 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