EUROmediCAT signal detection: an evaluation of selected congenital anomaly-medication associations.
- Given JE Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, United Kingdom.
- Loane M Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, United Kingdom.
- Luteijn JM Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom.
- Morris JK Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom.
- de Jong van den Berg LT Department of Pharmacy, University of Groningen, the Netherlands.
- Garne E Paediatric Department, Hospital Lillebaelt, Kolding, Denmark.
- Addor MC Division of Medical Genetics, CHUV, Lausanne, Switzerland.
- Barisic I Department of Medical Genetics and Reproductive Health, Children's University Hospital Zagreb, Croatia.
- de Walle H Eurocat Northern Netherlands, University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
- Gatt M Department of Health Information and Research, Guardamangia, Malta.
- Klungsoyr K Medical Birth Registry of Norway, the Norwegian Institute of Public Health and Department of Global Public Health and Primary Care, University of Bergen, Norway.
- Khoshnood B Paris Registry of Congenital Anomalies, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Biostatistics and Epidemiology, INSERM U1153, Maternité de Port-Royal, PARIS, France.
- Latos-Bielenska A Polish Registry of Congenital Malformations, Department of Medical Genetics, Poznan, Poland.
- Nelen V Provinciaal Instituut voor Hygiene (PIH), Antwerp, Belgium.
- Neville AJ IMER Registry (Emilia Romagna Registry of Birth Defects), Centre for Clinical and Epidemiological Research, University of Ferrara and Azienda Ospedaliero Univerisitarion di Ferrara, Italy.
- O'Mahony M Health Service Executive, Cork, Ireland.
- Pierini A Epidemiology and Health Promotion Macro-Area Working Group, Unit of Environmental Epidemiology and Disease Registries, CNR Institute of Clinical Physiology, Pisa, Italy.
- Tucker D CARIS - Congenital Anomaly Register and Information Service for Wales, Public Health Wales, Swansea, United Kingdom.
- Wiesel A Mainz Model Birth Registry, University Children's Hospital Mainz, Germany.
- Dolk H Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, United Kingdom. h.dolk@ulster.ac.uk.
- 2016-03-31
Published in:
- British journal of clinical pharmacology. - 2016
congenital anomalies
drug-induced anomalies
pharmacoepidemiology
pharmacovigilance
pregnancy
signal evaluation
Abnormalities, Drug-Induced
Adverse Drug Reaction Reporting Systems
Congenital Abnormalities
Europe
Female
Humans
Infant, Newborn
Pregnancy
Registries
English
AIMS
To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation.
METHODS
Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level of Anatomic Therapeutic Chemical classification) and chemical subgroup (4th level) were analysed using a 50% false detection rate. After excluding antiepileptics, antidiabetics, antiasthmatics and SSRIs/psycholeptics already under investigation, 27 associations were evaluated. If evidence for a signal persisted after data validation, a literature review was conducted for prior evidence of human teratogenicity.
RESULTS
Thirteen out of 27 CA-medication exposure signals, based on 389 exposed cases, passed data validation. There was some prior evidence in the literature to support six signals (gastroschisis and levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1.70-22.93); hypospadias and pregnadien derivatives (OR 1.40, 95% CI 1.10-1.76); hypospadias and synthetic ovulation stimulants (OR 1.89, 95% CI 1.28-2.70). Antipropulsives produced a signal for syndactyly while the literature revealed a signal for hypospadias. There was no prior evidence to support the remaining six signals involving the ordinary salt combinations, propulsives, bulk-forming laxatives, hydrazinophthalazine derivatives, gonadotropin releasing hormone analogues and selective serotonin agonists.
CONCLUSION
Signals which strengthened prior evidence should be prioritized for further investigation, and independent evidence sought to confirm the remaining signals. Some chance associations are expected and confounding by indication is possible.
To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation.
METHODS
Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level of Anatomic Therapeutic Chemical classification) and chemical subgroup (4th level) were analysed using a 50% false detection rate. After excluding antiepileptics, antidiabetics, antiasthmatics and SSRIs/psycholeptics already under investigation, 27 associations were evaluated. If evidence for a signal persisted after data validation, a literature review was conducted for prior evidence of human teratogenicity.
RESULTS
Thirteen out of 27 CA-medication exposure signals, based on 389 exposed cases, passed data validation. There was some prior evidence in the literature to support six signals (gastroschisis and levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1.70-22.93); hypospadias and pregnadien derivatives (OR 1.40, 95% CI 1.10-1.76); hypospadias and synthetic ovulation stimulants (OR 1.89, 95% CI 1.28-2.70). Antipropulsives produced a signal for syndactyly while the literature revealed a signal for hypospadias. There was no prior evidence to support the remaining six signals involving the ordinary salt combinations, propulsives, bulk-forming laxatives, hydrazinophthalazine derivatives, gonadotropin releasing hormone analogues and selective serotonin agonists.
CONCLUSION
Signals which strengthened prior evidence should be prioritized for further investigation, and independent evidence sought to confirm the remaining signals. Some chance associations are expected and confounding by indication is possible.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1111/bcp.12947
- PMID 27028286
- Persistent URL
- https://sonar.ch/global/documents/141015
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