EUROmediCAT signal detection: an evaluation of selected congenital anomaly-medication associations

Joanne E. Given, Maria Loane, Johannes M. Luteijn, Joan K. Morris, Lolkje T. W. de Jong-van den Berg, Ester Garne, Marie-Claude Addor, Ingeborg Barisic, Hermien de Walle, Miriam Gatt, Kari Klungsoyr, Babak Khoshnood, Anna Latos-Bielenska, Vera Nelen, Amanda J. Neville, Mary O'Mahony, Anna Pierini, David Tucker, Awi Wiesel, Helen Dolk*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

13 Citaten (Scopus)
247 Downloads (Pure)


AimsTo evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation.

MethodsData 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.

ResultsThirteen 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.

ConclusionSignals 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.

Originele taal-2English
Pagina's (van-tot)1094-1109
Aantal pagina's16
TijdschriftBritish Journal of Clinical Pharmacology
Nummer van het tijdschrift4
StatusPublished - okt-2016

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