Malformation surveillance and maternal drug exposure: the MADRE project

Article type: Research Article

Authors: Robert, E.^; | Vollset, S.E. | Botto, L. | Lancaster, P.A.L. | Merlob, P. | Mastroiacovo, P. | Cocchi, G. | Ashizawa, M. | Sakamoto, S. | Orioli, I.

Affiliations: Central-East France Registry of congenital malformations, Institut Européen des Génomutations, 86, rue E. Locard, F-69005 Lyon, France | Section for Medical Informatics and Statistics, University of Bergen, Bergen, Norway | International Center for Birth Defects, ICARO-ASM, Rome, Italy | AIHW National Perinatal Statistics Unit, University of Sydney, Sydney, N.S.W., Australia | Department of Neonatology, Beilinson Medical Center, Petah-Tikva, Israel | IPIMC, Servizio Epidemiologia e Clinica Difetti Congeniti, Policlinico Universitario A. Gemelli, Rome, Italy | Emilia Romagna Registry of Congenital Malformations (IMER), Bologna, Italy | Japanese Red Cross Nursing College, Shibuya-ku, Tokyo, Japan | Japan Maternal Health and Welfare, Sadohara-Cho, Ichigaya, Tokyo, Japan | Departamento de Genetica, Universidade Federal do Rio de Janeiro, Brazil

Note: [] Corresponding author. Tel. (+ 33-78) 25 82 10; Fax (+ 33-78) 36 61 82.

Abstract: A project implemented within the framework of the International Clearinghouse for Birth Defect Monitoring Systems is named MADRE: MAlformation DRug Exposure surveillance. The idea is to survey the simultaneous occurrence of malformations and first-trimester drug exposures. In a 2-year period 1990–91, this has yielded 1448 infants known to have been exposed to drugs and that are known to have malformations. Cases have been reported by eight programs: Australia, Central-East France, Israel, Italy IPIMC, Italy IMER, Japan Red Cross Hospitals, Japan Maternal Health and Welfare, and South America. By searching this databank for associations between drugs and malformations, specific relationships can be detected. The 9th revision of the WHO International Classification of Diseases, adapted by the British Paediatric Association, known as ICD9/BPA is used for coding malformations. This is a hierarchical system with 5 digits as the maximum level of specification of each malformation. The ATC (Anatomical Therapeutic Chemical) classifications system is used for coding drugs. This is a multiple level, hierarchical classification with up to 7 digits for specifying each drug. Up to five drugs and malformations are coded for each case using ATC and ICD9/BPA classifications, and all observed drug-malformation pairs form the basis for the analysis. For each drug-malformation combination where three or more cases are observed, a set of 2×2 tables is formed and analyzed as in case-control studies. The odds ratio for the pair, stratified for program, gives the relative risk for the malformation in question, comparing use of the specific drug with all other drugs. Well known or controversial associations were tested in the collected material, and at this stage only one new association is suggested, that is between cardiac defects and maternal treatment with thyroid hormones. This finding has to be further explored with new data.

Keywords: Surveillance, Malformation, Birth defect registry, Drug exposure, Teratogen, Case-control study

DOI: 10.3233/JRS-1994-6201

Journal: International Journal of Risk and Safety in Medicine, vol. 6, no. 2, pp. 75-118, 1994