Sex-specific association of co-exposures to melamine and phthalates in children with their early renal injury

Studies concerning the effect of co-exposure to melamine and phthalates on kidney function in children are rare. Thus, this study examines the above-mentioned relationship and their sex-different effect. Whether the exposure of the two chemicals from their mothers, when children were in the womb during the third trimester, affected renal injury markers in children afterwards is also examined. This study was from Taiwan Maternal and Infant Cohort Study cohort established in October 2012 to enroll third-trimester pregnant mothers up to May 2015. Their offspring were subsequently recruited between 2016 and 2020 as our study children. One-spot urine specimens were collected from both pregnant mothers (2012–2015) and study children (2016–2020) for the simultaneous measurement of melamine and 11 phthalate metabolites. Daily intakes of melamine and five phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), and DEP (Diethyl phthalate), were estimated using a creatinine excretion-based model in both study children and their mothers. Two early markers of renal injury, microalbumin and N-acetyl-beta-D-glucosaminidas (NAG), were measured in urine samples of study children (2016–2020). A total of 552 eligible children were studied, with a mean age of 4 years. We found that boys in the highest quartile of estimated melamine intake (≥0.68 μg/kg/day) had significantly higher urine ACR levels and in the highest quartile of estimated phthalate intake of DEHP (≥5.36 μg/kg/day), DEP (≥0.89 μg/kg/day), and DiBP (≥1.19 μg/kg/day) had significantly higher urine NAG levels when compared to the combined three lowest quartile ones as comparison groups. No significant associations were found between their mothers’ phthalates and melamine intake during the third trimester and urine ACR and NAG in children. We conclude that children (particularly boys) with high co-exposure of melamine and certain phthalate chemicals among children have increased early markers of kidney injury.