Spina bi®da and parental occupation: Results from three malformation monitoring programs in Europe B.M. Blatter 1 , N. Roeleveld 1 , E. Bermejo 2 , M.L. MartõÂnez-FrõÂas 2 , C. Siel 3 & A.E. Czeizel 3 1 Department of Epidemiology, University of Nijmegen, The Netherlands; 2 Spanish Collaborative Study on Congenital Malformations, Department of Pharmacology, Facultad de Medicina, University Complutense of Madrid, Spain; 3 Department of Human Genetics and Teratology, `B. Johan' National Center for Epidemiology, Hungary Accepted in revised form 31 March 2000 Abstract. As the evidence for an association between spina bi®da and parental agricultural occupations is inconclusive, we evaluated this association and the potential associations between spina bi®da and other parental occupations. Three register-based case±ref- erent studies were conducted in Sweden, Spain, and Hungary. From the registries of congenital malfor- mations in each country, 482, 478, and 1119 cases with spina bi®da were identi®ed, respectively. Identi®ed as referents were 964, 434, and 1489 children without abnormalities. Information on parental occupation was available in the registries from questionnaires or interviews conducted among the parents. Occupations with a potential for physical or chemical exposure were compared to non-exposed occupations. In- creased odds ratios (ORs) were observed for women in agricultural occupations in Sweden (OR: 1.8, 95% CI: 0.8±4.2) and in Spain (OR: 2.2, 95% CI: 0.8±5.9), but not in Hungary (OR: 1.1, 95% CI: 0.7±1.7). Several other parental occupations were analysed, but the associations with spina bi®da were inconsistent. Concluding, the results are not totally consistent but point to an increased risk of spina bi®da among women in agricultural occupations. Key words: Agriculture, Neural tube defects, Occupation, Pregnancy, Spina bi®da Introduction As the occurrence of spina bi®da varies strongly with socio-economic status in several countries [1], a search for occupational and environmental causes, next to dietary factors, seems indicated. Maternal occupa- tional exposure before conception and up to the 28th day of postconceptional development may have a direct eect on the morphogenesis of the neural tube. Paternal occupational exposure could result in genetic damage to germ cells and in the presence of terato- genic substances in the seminal ¯uid, which might lead to neural tube defects also [2±5]. Studies on neural tube defects have revealed an increased risk of spina bi®da for women working as nurses [6] and hairdressers [7], and for agricultural workers [7, 8]. Among men a threefold increased risk was found for painters, both for spina bi®da and anencephaly [9±11]. Other studies showed an in- creased risk of spina bi®da for printers, transport and communication workers [9], agricultural workers, bricklayers [7], welders, electronic equipment opera- tors, policemen, and vehicle manufacturers [12]. It should be stressed that except for male painters and male and female agricultural workers, very few ®nd- ings have been repeated in two or more studies. We conducted a case±referent study on spina bi®da and parental occupation in the Netherlands [13]. Increased risks were observed for fathers working as a welder (OR: 2.1) or transport worker (OR: 1.4), for cleaning women (OR: 1.9), and particularly for women working in the agricultural sector (OR: 5.6, 95% CI: 1.8±17.8). However, no associations were found between spina bi®da and maternal pesticide use or any other agriculture-related exposure, but the numbers exposed were small [14]. A Finnish study did not ®nd an association between pesticide use and central nervous system defects either [15]. The main focus of this study was to get more support for the hypothesis of a relation between ag- ricultural occupations and spina bi®da. In addition to agricultural occupations, our secondary interest was to evaluate associations with other parental oc- cupations that were previously associated with spina bi®da. Data were used from registries that were members or former members of the International Clearinghouse for Birth Defects Monitoring Systems [16]. Three studies were conducted in Sweden, Spain, and Hungary, with some dierences in methodology, study population and data collection. Population and methods European registries for congenital malformations were selected from the International Clearinghouse European Journal of Epidemiology 16: 343±351, 2000. Ó 2000 Kluwer Academic Publishers. Printed in the Netherlands.