Abstract

Objective: Investigate whether residential prenatal exposure to heavy metal hazardous air pollutants (HMHAPs) is associated with an increased risk of hypospadias. Methods: Data on non-syndromic hypospadias cases (n = 8981) and control patients delivered in Texas were obtained from the Texas Birth Defects Registry and matched 1:10 by birth year. Average exposure concentrations of HMHAPs were obtained from the 2005 U.S. Environmental Protection Agency National-Scale Air Toxics Assessment and categorized into quintiles. Odds ratios and 95% confidence intervals were estimated. STROBE reporting guidelines were followed. Results: We observed associations between hypospadias and prenatal HMHAP exposure. Manganese demonstrated significant increased risk of hypospadias at the medium, medium-high and high exposure quintiles; lead in the medium-high and high exposure quintiles. Cadmium, mercury and nickel demonstrated a significant inverted “U-shaped” association for exposures with significant associations in the medium and medium-high quintiles but not in the medium-low and high quintiles. Arsenic and chromium demonstrated a significant bivalent association for risk of hypospadias in a lower quintile as well as a higher quintile with non-significant intermediate quintiles. Conclusions: Using data from one of the world’s largest active surveillance birth defects registries, we identified significant associations between hypospadias and HMHAP exposures. These results should be used in counseling for maternal demographic risk factors as well as avoidance of heavy metals and their sources.

Highlights

  • The most common external male genital malformation is hypospadias, affecting 1/125 to1/300 live male births [1]

  • We investigated whether prenatal exposure to heavy metal hazardous air pollutants (HMHAPs) is associated with an increased risk of hypospadias in a subsequently delivered fetus

  • A statistically significant inverse association was seen between risk for hypospadias and number of live births, gestational age, birth weight and census tract poverty density

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Summary

Methods

The study protocol was reviewed and approved by the Texas Department of State Health Services, and Baylor College of Medicine Institutional Review Boards. The TBDR, maintained by the Birth Defects Epidemiology and Surveillance Branch of the Texas Department of State Health Services, uses an active surveillance system to identify infants and pregnancies with birth defects within 1 year after delivery. Cases are identified through routine visits by TBDR staff members to all maternity hospitals, pediatric hospitals, birthing centers and midwife facilities in Texas. During these visits, discharge lists and unit logs are checked for parameters such as preterm births, stillbirths, ICD codes for birth defects or text descriptions relevant to birth defects. All diagnosed cases are coded using the Centers for Disease

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