Hypospadias in boys born to mothers exposed to dichlorodiphenyltrichloroethane and pyrethroid insecticides

Abstract

PDS 72: Environmental health issues in LMIC, Exhibition Hall (PDS), Ground floor, August 28, 2019, 10:30 AM - 12:00 PM Background: Hypospadias is the ectopic opening of the male urethra and related in vivo to maternal estrogenic and/or anti-androgenic exposures. We examined the relationship between maternal exposure to DDT and pyrethroids and hypospadias in a malaria endemic area. Dichlorodiphenyltrichloroethane (DDT) and the pyrethroids cypermethrin and deltamethrin are used to control malaria. In vitro, DDT is estrogenic and its breakdown product, dichlorodiphenyldichloroethylene (DDE) is anti-androgenic. Cypermethrin, and permethrin are metabolized to cis-3-and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis- and trans-DCCA) and the most common pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Deltamethrin breaks down to the metabolites 3-PBA and cis-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DBCA). DCCA and 3-PBA are anti-androgenic. Methods: We measured peripartum levels of DDT and DDE in maternal blood and the pyrethroid metabolites cis- and trans-DCCA, 3-PBA and cis-DBCA in maternal urine in a birth cohort and examined boys at age one year for hypospadias (n=359). Due to the high prevalence of phimosis (n=291, 81.1%), which prevented examination for hypospadias, we restricted analyses to boys without phimosis (n= 68). Results: Hypospadias was observed in 32 boys. Maternal cis-DCCA, trans-DCCA and 3-PBA urinary concentrations were significantly associated with increased relative risks (RR) of having a boy with hypospadias (RR 1.90 (95% CI: 1.31, 2.75), 1.82 (95% CI: 1.27, 2.63) and 1.85 (95% CI: 1.06, 3.22), respectively). There were no significant associations between DDT, DDE and DBCA and hypospadias. Conclusions: Boys examined had very high prevalence of phimosis and hypospadias. Mothers with high urinary concentrations of 3-PBA and DCCA had significantly greater risks of having a son with hypospadias. This is the first study to report associations between maternal pyrethroid exposure and hypospadias. Hormonal mechanisms might be involved in the etiology. Given the extensive global use of pyrethroids, our findings raise health concerns for other populations with high usage for malaria control, home use or agricultural purposes.