{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:39:39Z","timestamp":1793399979889,"version":"4.5.0"},"reference-count":96,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"\n CONTEXT:<\/jats:title>\n Opioid use and abuse have increased dramatically in recent years, particularly among women.<\/jats:p>\n <\/jats:sec>\n \n OBJECTIVES:<\/jats:title>\n We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations.<\/jats:p>\n <\/jats:sec>\n \n DATA SOURCES:<\/jats:title>\n We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies.<\/jats:p>\n <\/jats:sec>\n \n STUDY SELECTION:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n DATA EXTRACTION:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS:<\/jats:title>\n Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1542\/peds.2016-4131","type":"journal-article","created":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T09:10:12Z","timestamp":1495185012000},"source":"Crossref","is-referenced-by-count":145,"title":["Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review"],"prefix":"10.1542","volume":"139","author":[{"given":"Jennifer N.","family":"Lind","sequence":"first","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"},{"name":"US Public Health Service, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia D.","family":"Interrante","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Ailes","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Gilboa","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"},{"name":"Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia;"},{"name":"Carter Consulting, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan T.","family":"Frey","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Honein","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Dowling","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Razzaghi","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia;"},{"name":"US Public Health Service, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea A.","family":"Creanga","sequence":"additional","affiliation":[{"name":"Department of International Health and"},{"name":"International Center for Maternal and Newborn Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl S.","family":"Broussard","sequence":"additional","affiliation":[{"name":"Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for 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