Children’s Health | Cryptorchidism and hypospadias study both abnormalities. We selected controls from the 8,541 boys without cryptorchidism or hypospadias if their age was compatible with the observed age range of cases. For statistical power, three times more controls than cases were approached for participation. Parents of cases and controls were invited to participate in the study, and after written informed consent a research nurse inter- viewed the mother with a structured ques- tionnaire during a home visit approximately 11 weeks (median) after giving birth (5th and 95th percentiles, 6 and 27 weeks). If present, the father was also interviewed. This study was approved by the institutional review board. The participation rate among mothers was 86% (78 of 91) for cryptorchidism cases, 84% (56 of 67) for hypospadias cases, and 68% (313 of 462) for controls. This partici- pation produced 443 mother–child pairs, including the four boys with both abnormali- ties. Paternal information was available for 326 of the 443 subjects (74%), in which the paternal information was provided by the biologic father in 91 subjects (28% overall, and 24 and 38% for controls and cases, respectively) and was ﬁlled out by the mother because of the father’s absence in 235 subjects (72%). The paternal questionnaire was con- sidered a nonresponse when mothers could not provide core information on the biologic father regarding the country of origin of his parents, date of birth, or occupational history. Data collection. A research nurse completed structured questionnaires during interviews with parents. Rotterdam is a multicultural city in which the main groups of immigrants origi- nate from Turkey, Morocco, Surinam, and the Netherlands Antilles, the latter two being Dutch-speaking countries. When necessary because of language problems, a qualified interpreter read the questions aloud from translated written questionnaires in the Turkish or Moroccan-Arabic language. The maternal questionnaire gathered information on per- sonal characteristics, health, pregnancy aspects, diet, and occupational history. The paternal questionnaire collected data on personal char- acteristics, health, and occupation. Personal characteristics were age, height, weight, educa- tion, country of origin, and lifestyle factors such as smoking habits and alcohol use during the past 12 months. Education level was deﬁned as low (≤ 9 years), intermediate (10–14 years), or high (≥ 15 years). The country of origin of the mother and father was based on the country of birth of their parents (i.e., the newborn’s grand- parents) as defined by Statistics Netherlands (Keij 2000). The country of origin assigned to foreigners (defined as someone with at least one parent born abroad) is that of the mother if both parents are born abroad; otherwise, it is the country of birth of the parent that was born abroad (Keij 2000). Self-perceived general health was measured with a four-point ordinal scale and dichoto- mized into good health versus less than good health (Ware et al. 1996). Information was also collected on time to pregnancy (in months), parity, weeks of gestation, birth weight (grams), folic acid supplements, contraceptive pill use before the last pregnancy, and whether the preg- nancy was induced by assisted reproduction technologies (ART). Infants were defined as small for gestational age (SGA) when their birth weight was more than two standard deviations below the reference value for their gestational age (Usher and McLean 1969). Preterm deliv- ery was deﬁned as a birth before 35 weeks of gestation (10th percentile). We ascertained dietary patterns during the ﬁrst 6 months of pregnancy. One general question distinguished vegetarian diets and diets rich in vegetables, fruits, meat, or fish. A phytoestrogen-specific food questionnaire was developed to differentiate categories of exposure based on a semiquantitative estima- tion of the intake of food products containing isoﬂavonoids and lignans, which are considered the most important naturally occurring phyto- estrogens. The questionaire was developed for this study by TNO Food and Nutrition Research (Zeist, the Netherlands; Brants 1999). For the questionnaire, food products were selected that may contribute to isoﬂavonoid or lignan intake based on previous research (Brants 1999). For soy consumption, all known soy products were selected except soy oil and soy sauce, because they contain little or no bio- logically active isoﬂavonoids. Lignan-containing products were selected for their contribution to the total lignan intake, which was estimated on the basis of their lignan contents (according to food-constituent tables) and the use of the product in the general population (including nonusers) or in the group of users (Brants 1999). We also considered the feeding patterns in Surinam, Turkish, or Moroccan culture (the main groups of immigrants in Rotterdam). We quantified the average daily intake of phyto- estrogens (based on consumption per week) by multiplying frequency of use by portion size by the concentration of phytoestrogens according to food-constituent tables (Brants 1999). The intakes per product were added up to the total intake of lignans and isoﬂavonoids to allow dif- ferentiation of subjects with high, intermediate, and low intake, based on tertiles. We derived occupational exposure from generic questions on paid employment (yes/no) and jobs held in the year before delivery. The focus was on chemicals that may have endocrine activity (Van Tongeren et al. 2002) or that have previously been described as male reproductive toxicants (Tielemans et al. 1999a). For the few parents with multiple jobs, the job with most working hours was selected at the time of the ﬁrst trimester (for Environmental Health Perspectives • VOLUME 112 | NUMBER 15 | November 2004 mothers) or around fertilization (for fathers). Parents without a job were considered as having no occupational exposures. Additional ques- tions were asked about job title, type of busi- ness, name of employer, and activities in the job. A checklist was used for self-reported expo- sure (yes/no) to ionizing radiation, physical exposures, and classes of chemical substances that have been linked to human reproductive impairment, such as solvents, pesticides, and heavy metals (Tielemans et al. 1999a). Subjects were classified as being exposed to solvents when reporting contact in their job to industrial cleaning products (degreasers), paints, printing inks, glues, or industrial cleaning products (Tielemans et al. 1999b). We also assessed occupational exposure by applying a job-exposure matrix (JEM) for potential EDs (Van Tongeren et al. 2002). The JEM was based on the judgment of occu- pational hygienists who estimated for particu- lar jobs the exposure to seven categories of potential EDs (e.g., pesticides and polychlori- nated organic compounds) (Van Tongeren et al. 2002). A person in a particular job was assigned “probable exposure = yes” if the experts judged that it was probable that a reasonable proportion of workers had some exposure. An overall classiﬁcation of “proba- ble exposure to potential EDs = yes” was given to a job if at least one of the seven expo- sure categories was scored as “yes.” Statistics. The agreement between self- reported exposure and exposure classiﬁcation derived from the JEM was determined by the weighted Cohen’s κ. A κ value < 0.4 was con- sidered poor agreement, 0.4–0.6 moderate agreement, and > 0.6 good agreement (Landis and Koch 1977). We computed frequency counts, crude odds ratios (ORs), and 95% conﬁdence inter- vals (95% CIs) for all potential risk factors. Continuous risk factors were categorized into three or four categories for ease of interpreta- tion. Trends were assessed by a chi-square test for trends in 2 × 3 or 2 × 4 tables. Logistic regression analysis with stepwise forward selection on univariate risk factors was used to arrive at a multivariable model for either outcome, with a significance level of 0.05 for retained variables. In addition, exposure variables of interest were also included in a multivariable model when this factor was sta- tistically significantly associated with either cryptorchidism or hypospadias in the univari- ate analysis and the factor caused a change by ≥ 15% in the coefﬁcient of other risk factors in the model. Interactions of all variables were also tested for significance. The 95% CIs around the ORs were derived from the indi- vidual Wald’s statistics, except for variables with cell frequencies of ﬁve or fewer, in which case likelihood-based conﬁdence intervals are given. Because information on fathers was not 1571