{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T14:55:02Z","timestamp":1758120902802,"version":"3.44.0"},"reference-count":41,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Arch Dis Child Fetal Neonatal Ed"],"accepted":{"date-parts":[[2019,5,14]]},"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design\/setting<\/jats:title>\n                  <jats:p>This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995\u20132011.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75\u2009603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks\u2019 gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95%\u2009CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1\u201312 cases per 10\u2009000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95%\u2009CI 2.7 to 9.2).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk\u2013benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/archdischild-2019-316804","type":"journal-article","created":{"date-parts":[[2019,6,22]],"date-time":"2019-06-22T17:19:15Z","timestamp":1561223955000},"page":"151-157","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Methadone, Pierre Robin sequence and other congenital anomalies: case\u2013control study"],"prefix":"10.1136","volume":"105","author":[{"given":"Brian","family":"Cleary","sequence":"first","affiliation":[{"name":"Pharmacy Department, Rotunda Hospital, Dublin, Ireland"},{"name":"School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland"}]},{"given":"Maria","family":"Loane","sequence":"additional","affiliation":[{"name":"Centre for Maternal, Fetal and Infant Research, INHR, Ulster University, Newtowanbbey, UK"}]},{"given":"Marie-Claude","family":"Addor","sequence":"additional","affiliation":[{"name":"Division Autonome de Genetique Medicale, Registre Vaudois des Malformations, Vaud, Switzerland"}]},{"given":"Ingeborg","family":"Barisic","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia"}]},{"given":"Hermien E K","family":"de Walle","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}]},{"given":"Carlos","family":"Matias Dias","sequence":"additional","affiliation":[{"name":"Centro de Estudos e registo de A C, Lisbon, Portugal"}]},{"given":"Miriam","family":"Gatt","sequence":"additional","affiliation":[{"name":"Department of Health Information, Malta Congenital Anomalies Registry, G\u2019mangia, Malta"}]},{"given":"Kari","family":"Klungsoyr","sequence":"additional","affiliation":[{"name":"Medical Birth Register of Norway, Nasjonalt folkehelseinstitutt, Oslo, Norway"}]},{"given":"Bob","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Health Service Executive, Dublin, Ireland"}]},{"given":"Amanda","family":"Neville","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero - Universitaria di Ferrara, Registro IMER, Ferrara, Italy"}]},{"given":"Anna","family":"Pierini","sequence":"additional","affiliation":[{"name":"Istituto di Fisiologia Clinica CNR, Pisa, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9437-2790","authenticated-orcid":false,"given":"Anke","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University, Magdeburg, Germany"}]},{"given":"David F","family":"Tucker","sequence":"additional","affiliation":[{"name":"Congenital Anomaly Register and Information Service for Wales, Public Health Wales, Swansea, UK"}]},{"given":"Oscar","family":"Zurriaga","sequence":"additional","affiliation":[{"name":"Centro Superior de Investigaci\u00f3n en Salud P\u00fablica, Valencia, Spain"},{"name":"Direccion General de Investigaci\u00f3n y Salud P\u00fablica, Valencia, Spain"}]},{"given":"Helen","family":"Dolk","sequence":"additional","affiliation":[{"name":"University of Ulster, Jordanstown, UK"}]}],"member":"239","published-online":{"date-parts":[[2019,6,22]]},"reference":[{"key":"2025090511230909000_105.2.151.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8545(05)70362-4"},{"key":"2025090511230909000_105.2.151.2","doi-asserted-by":"crossref","DOI":"10.1542\/peds.58.5.681","article-title":"Differential effects of maternal heroin and methadone use on birthweight","volume":"58","author":"Kandall","year":"1976","journal-title":"Pediatrics"},{"key":"2025090511230909000_105.2.151.3","doi-asserted-by":"publisher","DOI":"10.1080\/10550490802266276"},{"key":"2025090511230909000_105.2.151.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1402780"},{"key":"2025090511230909000_105.2.151.5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.4526"},{"key":"2025090511230909000_105.2.151.6","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-2615"},{"key":"2025090511230909000_105.2.151.7","doi-asserted-by":"publisher","DOI":"10.1597\/08-061.1"},{"key":"2025090511230909000_105.2.151.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.329"},{"key":"2025090511230909000_105.2.151.9","doi-asserted-by":"publisher","DOI":"10.1597\/05-008.1"},{"key":"2025090511230909000_105.2.151.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.10.004"},{"key":"2025090511230909000_105.2.151.11","unstructured":"Saal H , Bender P , Hopkin R . 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