RT Journal Article SR Electronic T1 Methadone, Pierre Robin sequence and other congenital anomalies: case–control study JF Archives of Disease in Childhood - Fetal and Neonatal Edition JO Arch Dis Child Fetal Neonatal Ed FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health SP 151 OP 157 DO 10.1136/archdischild-2019-316804 VO 105 IS 2 A1 Brian Cleary A1 Maria Loane A1 Marie-Claude Addor A1 Ingeborg Barisic A1 Hermien E K de Walle A1 Carlos Matias Dias A1 Miriam Gatt A1 Kari Klungsoyr A1 Bob McDonnell A1 Amanda Neville A1 Anna Pierini A1 Anke Rissmann A1 David F Tucker A1 Oscar Zurriaga A1 Helen Dolk YR 2020 UL http://fn.bmj.com/content/105/2/151.abstract AB Objective 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.Design/setting 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, 1995–2011.Patients Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 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’ 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.Results 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% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1–12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2).Conclusions 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–benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.