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Dairy exposure during pregnancy and the risk of isolated hypospadias and cryptorchidism in offspring
Sigurd Elias Stette, MSc., MD.1, Andreas Ernst, MD., Ph.D.2, Cecilia Ramlau-Hansen, MSc., Ph.D.3, Yazan F. H. Rawashdeh, MD., Ph.D.1.
1Aarhus University, Aarhus N, Denmark, 2Aarhus University - Department of Public Health, Aarhus C, Denmark, 3Aarhus University - Department of Public Health, Aarhus, Denmark.

BACKGROUND: The aetiology for hypospadias and cryptorchidism remains largely unknown. Environmental endocrine disruptors have been suspected to play a role. Dairy is a source of phytoestrogens and exogenous oestrogens, which could potentially affect male sexual development. Dairy has been linked to reduced semen quality and early puberty in male, but itís role in hypospadias and cryptorchidism is unknown. We set out to investigate whether food consumption during pregnancy is associated with increased risk of cryptorchidism and hypospadias in male offspring. METHODS: The cohort study included 33,922 pregnancies with singleton male offspring from the Danish National Birth Cohort recruited between 1996 and 2002. The mean (standard deviation) follow-up time was 17.4 (2.9) years. Second trimester consumption in g/day of 40 food groups, was assessed via food frequency questionnaire on 360 food items, standard recipes and standard portion sizes. The exposure was defined by grouping dairy foods based on fat content more or less than 3.5% into a low fat dairy and a high fat dairy food group, and by defining the sum of all dairy consumption as the total dairy exposure. The study population was divided into four quartiles of consumption for each of the three exposures. We acquired hypospadias and cryptorchidism diagnoses from the Danish National Patient Registry. Hazard Ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression adjusting for maternal age based on official records, as well as self-reported alcohol consumption, smoking and pre-pregnancy BMI, from a telephone interview in week 30 of gestation. RESULTS: In total, 942 (2.8%) male offspring were diagnosed with cryptorchidism and 237 (0.7%) with hypospadias. In comparison to the first quartile of low fat dairy intake, the HR for cryptorchidism among women in quartile 2 were HR: 0.77, 95% CI 0.63, 0.93. In a sub-analysis, quartile 1 and 4 were seen to have a significantly increased HR in reference to quartile 2. High-fat dairy exposure was not associated with cryptorchidism. Hypospadias had no significant association to dairy exposures. The results were not sensitive to total caloric intake, overall dietary patterns or organic food preferences. CONCLUSION: We found that the second quartile of low fat dairy consumption during pregnancy, was associated with lower risk of cryptorchidism in comparison to the first quartile. The associations were insensitive to total caloric intake, organic food preferences and overall dietary patterns. Maternal high fat dairy intake was not associated with cryptorchidism, and hypospadias was not related to maternal dairy consumption. Risk of exposure misclassification due to the use of food frequency questionnaire, standard portions sizes and standard recipes is the main caveat of the study. If the association between low-fat dairy consumption during pregnancy and the risk of cryptorchidism in offspring is verified, it could inform advice on diet in pregnancy. These findings were made based on historic data and might be hard to apply today, as dietary trends and patterns might have changed significantly since.


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