Methadone, Pierre Robin sequence and other congenital anomalies: case-control study

Brian Cleary, Maria Loane, Marie-Claude Addor, Ingeborg Barisic, HEK de Walle, Carlos Matias Dias, Miriam Gatt, Kari Klungsoyr, Bob McDonnell, Amanda Neville, Anna Pierini, Anke Rissmann, David Tucker, Oscar Zurriaga, Helen Dolk

Research output: Contribution to journalArticle

Abstract

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.
LanguageEnglish
PagesF1-F7
Number of pages7
JournalArchives of Disease in Childhood - Fetal and Neonatal Edition
Volume0
Issue number10.1136/archdischild-2019-316804
DOIs
Publication statusPublished - 22 Jun 2019

Fingerprint

Pierre Robin Syndrome
Methadone
Case-Control Studies
Pregnancy
Cleft Palate
International Classification of Diseases
Registries
Malta
Pediatrics
Croatia
Fetal Death
Portugal
Wales
Live Birth
Norway
Switzerland
Ireland
Netherlands
Spain
Opioid Analgesics

Keywords

  • Methadone
  • Congenital Anomalies
  • Pierre Robin
  • Birth Defects
  • Craniofacial anomaly
  • EUROCAT
  • opioid use disorder
  • cleft palate
  • methadone
  • Pierre Robin sequence

Cite this

Cleary, Brian ; Loane, Maria ; Addor, Marie-Claude ; Barisic, Ingeborg ; de Walle, HEK ; Dias, Carlos Matias ; Gatt, Miriam ; Klungsoyr, Kari ; McDonnell, Bob ; Neville, Amanda ; Pierini, Anna ; Rissmann, Anke ; Tucker, David ; Zurriaga, Oscar ; Dolk, Helen. / Methadone, Pierre Robin sequence and other congenital anomalies: case-control study. In: Archives of Disease in Childhood - Fetal and Neonatal Edition. 2019 ; Vol. 0, No. 10.1136/archdischild-2019-316804. pp. F1-F7.
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abstract = "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/settingThis 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.PatientsCases 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.ResultsAmong 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).ConclusionsThese 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.",
keywords = "Methadone, Congenital Anomalies, Pierre Robin, Birth Defects, Craniofacial anomaly, EUROCAT, opioid use disorder, cleft palate, methadone, Pierre Robin sequence",
author = "Brian Cleary and Maria Loane and Marie-Claude Addor and Ingeborg Barisic and {de Walle}, HEK and Dias, {Carlos Matias} and Miriam Gatt and Kari Klungsoyr and Bob McDonnell and Amanda Neville and Anna Pierini and Anke Rissmann and David Tucker and Oscar Zurriaga and Helen Dolk",
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Cleary, B, Loane, M, Addor, M-C, Barisic, I, de Walle, HEK, Dias, CM, Gatt, M, Klungsoyr, K, McDonnell, B, Neville, A, Pierini, A, Rissmann, A, Tucker, D, Zurriaga, O & Dolk, H 2019, 'Methadone, Pierre Robin sequence and other congenital anomalies: case-control study', Archives of Disease in Childhood - Fetal and Neonatal Edition, vol. 0, no. 10.1136/archdischild-2019-316804, pp. F1-F7. https://doi.org/10.1136/archdischild-2019-316804

Methadone, Pierre Robin sequence and other congenital anomalies: case-control study. / Cleary, Brian; Loane, Maria; Addor, Marie-Claude; Barisic, Ingeborg ; de Walle, HEK; Dias, Carlos Matias; Gatt, Miriam; Klungsoyr, Kari; McDonnell, Bob; Neville, Amanda; Pierini, Anna; Rissmann, Anke; Tucker, David; Zurriaga, Oscar; Dolk, Helen.

In: Archives of Disease in Childhood - Fetal and Neonatal Edition, Vol. 0, No. 10.1136/archdischild-2019-316804, 22.06.2019, p. F1-F7.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methadone, Pierre Robin sequence and other congenital anomalies: case-control study

AU - Cleary, Brian

AU - Loane, Maria

AU - Addor, Marie-Claude

AU - Barisic, Ingeborg

AU - de Walle, HEK

AU - Dias, Carlos Matias

AU - Gatt, Miriam

AU - Klungsoyr, Kari

AU - McDonnell, Bob

AU - Neville, Amanda

AU - Pierini, Anna

AU - Rissmann, Anke

AU - Tucker, David

AU - Zurriaga, Oscar

AU - Dolk, Helen

N1 - AAM was uploaded as Word File. Downloaded and converted to PDF and reuploaded. Marie

PY - 2019/6/22

Y1 - 2019/6/22

N2 - 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/settingThis 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.PatientsCases 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.ResultsAmong 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).ConclusionsThese 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.

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/settingThis 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.PatientsCases 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.ResultsAmong 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).ConclusionsThese 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.

KW - Methadone

KW - Congenital Anomalies

KW - Pierre Robin

KW - Birth Defects

KW - Craniofacial anomaly

KW - EUROCAT

KW - opioid use disorder

KW - cleft palate

KW - methadone

KW - Pierre Robin sequence

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M3 - Article

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