The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies

This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot metaanalysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, 8 = -0.169, 95% CI = - 0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal n-ary sumation DEHP exposure with z-SBP (8 = -0.109, 95% CI = -0.163 to -0.055) and zdiastolic BP (DBP, 8 = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (8 = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal n-ary sumation DEHP exposure and triglycerides (8 = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to n-ary sumation DEHP throughout gestation was associated with a decrease in insulin (8 = -0.074, 95% CI = -0.144 to -0.004) and glucose (8 = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (8 = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal n-ary sumation DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.