First trimester phthalate exposure and anogenital distance in newborns.
Level 3 - non-randomized controlled study
Prospective multi-center observational cohort study with newborn follow-up.
PubMed 25697839 · doi:10.1093/humrep/deu363
What was done
The Infant Development and the Environment Study (TIDES) prospectively recruited pregnant women (<13 weeks gestation) across four US centers from 2010 to 2012. First-trimester maternal urine was measured for specific gravity-adjusted phthalate metabolites. At or shortly after birth, genital measurements were taken for 753 infants (366 boys, 373 girls). Measured outcomes included anoscrotal distance (AGDAS), anopenile distance (AGDAP), and penile width (PW) in boys, and anofourchette distance (AGDAF) and anoclitoral distance (AGDAC) in girls. Multivariable regression models adjusted for infant age at examination, gestational age, weight-for-length Z-score, time of urine collection, maternal age, and study center.
What was found
Three diethylhexyl phthalate (DEHP) metabolites were inversely associated with AGDAS in male newborns (β, 95% CI per log10 increase): mono-2-ethylhexyl phthalate (MEHP) -1.12 (-2.16, -0.07), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) -1.43 (-2.49, -0.38), and mono-2-ethyl-5-hydroxyhexyl (MEHHP) -1.28 (-2.29, -0.27). Associations of similar magnitude were observed for AGDAP in boys. Associations with penile width were weaker and non-significant. No other phthalates were associated with male genital measures, and no phthalates were associated with AGD measures in female newborns.
Why it matters
This study provides prospective human evidence that ambient maternal first-trimester DEHP exposure is associated with shortened anogenital distance in male infants, supporting animal models of prenatal anti-androgenic endocrine disruption.
Limits
Exposure assessment relied on a single first-trimester spot urine sample, which may have led to exposure misclassification. Significant differences across study centers indicate challenges in standardizing neonatal genital measurements. Long-term functional reproductive consequences were not assessed.
Cited by
- supports Research by Dr. Shanna Swan demonstrated the occurrence of the phthalate syndrome in human male infants.