School of Health Systems and Public Health and the University of Pretoria Institute for Sustainable Malaria Control (UP ISMC), University of Pretoria, Pretoria, South Africa.
Department of Paediatrics, University of Cambridge, Cambridge, UK.
Sci Total Environ. 2022 Nov 1;845:157084. doi: 10.1016/j.scitotenv.2022.157084. Epub 2022 Jul 5.
Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07-2.34; 1.61, 95 % CI 1.09-2.36; and 1.48, 95 % CI 0.78-2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.
尿道下裂是指尿道在阴茎或阴囊上的异位开口。子宫内暴露于雌激素和/或抗雄激素化学物质可能在病因学中起作用。滴滴涕和拟除虫菊酯氯菊酯和溴氰菊酯，用于控制疟疾。滴滴涕具有雌激素作用，其分解产物 DDE 具有抗雄激素作用；氯菊酯和溴氰菊酯也可以破坏雄激素途径。我们研究了母亲在怀孕期间接触这些杀虫剂与南非林波波省参与文达母婴及其环境健康检查（VHEMBE）的男孩尿道下裂之间的关系。我们测量了母体血清中和尿中拟除虫菊酯代谢物的 p,p'-DDT 和 p,p'-DDE 水平。我们对 359 名一岁男孩进行了泌尿生殖检查。共有 291 名（81.0%）有包茎，这妨碍了全面的泌尿生殖检查，最终有 68 名男孩的样本用于确定是否存在尿道下裂。诊断基于两名独立医生的一致性。我们在 68 名男孩中有 23 名（34%）诊断为尿道下裂。母亲尿液中顺式-DCCA 和反式-DCCA 代谢物的浓度与尿道下裂的风险增加有关，但其他代谢物 3-PBA 则没有（调整后的相对风险每增加 10 倍=1.58，95%CI 1.07-2.34；1.61，95%CI 1.09-2.36；1.48，95%CI 0.78-2.78）。p,p'-DDT、p,p'-DDE、3-PBA 或 cis-DBCA 与尿道下裂之间均无关联。我们观察到无包茎男孩中尿道下裂的患病率较高。产前暴露于拟除虫菊酯杀虫剂较高的男孩患尿道下裂的风险更高。鉴于拟除虫菊酯杀虫剂广泛用于疟疾控制、农业和家庭用途，我们的发现可能具有全球性意义。
