title: Risk factors for hypospadias.
abstract: Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential risk factors for hypospadias. Cases were identified from the hospital information system, and referents were recruited through the parents of the cases. Both parents of cases and referents completed written questionnaires that they received through the mail. Logistic regression analyses were used to assess the independent contribution of different factors to the risk of hypospadias. The final database included 583 cases and 251 referents. Hypospadias more often occurred in children whose father had hypospadias (OR=9.7; 95%CI: 1.3-74.0) and in children with a low birth weight (OR=2.3; 95%CI: 1.2-4.2). Indications for elevated risks were found when mothers were DES-daughters (OR=3.5; 95%CI: 0.8-15.6), fathers were subfertile (OR=1.8; 95%CI: 0.7-4.5), the parents had undergone fertility treatment (OR=2.3; 95%CI: 0.9-5.8), and in twin or triplet pregnancies (OR=2.0; 95%CI: 0.8-5.1). Maternal use of iron supplements (OR=2.2; 95%CI: 0.8-6.0), maternal smoking (OR=1.5; 95%CI: 1.0-2.4), paternal prescriptive drug use (OR=2.6; 95%CI: 1.1-6.6), and paternal exposure to pesticides (OR=2.1; 95%CI: 0.6-7.1) during the 3 months immediately prior to conception or in the first trimester of pregnancy also appeared to increase the risk of hypospadias. The associations found in this study support the hypothesis that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones play a role in the etiology of hypospadias.
authors.affiliation: Department of Epidemiology and Biostatistics (133), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. m.brouwers@epib.umcn.nl
authors.forename: Marijn M
authors.initials: MM
authors.lastname: Brouwers
authors.forename: Wouter F J
authors.initials: WF
authors.lastname: Feitz
authors.forename: Luc A J
authors.initials: LA
authors.lastname: Roelofs
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Robert P E
authors.initials: RP
authors.lastname: de Gier
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
mesh_terms: D002648:Child; D019992:Databases as Topic; D019587:Dietary Supplements / Q000009:adverse effects; D004054:Diethylstilbestrol / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007021:Hypospadias / Q000209:etiology*; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007248:Infertility, Male / Q000150:complications; D007501:Iron / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D009035:Mothers; D009426:Netherlands / Q000453:epidemiology; D018812:Paternal Exposure; D010575:Pesticides / Q000009:adverse effects; D047489:Preconception Injuries; D011247:Pregnancy; D011272:Pregnancy, Multiple; D011297:Prenatal Exposure Delayed Effects; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D014131:Trace Elements / Q000009:adverse effects
chemical_list: D004968:Estrogens, Non-Steroidal; D010575:Pesticides; D014131:Trace Elements; D004054:Diethylstilbestrol; D007501:Iron