Decrease in anogenital distance among male infants with prenatal phthalate exposure.
Level 3 - non-randomized controlled study
Prospective observational cohort study evaluating prenatal exposure and infant physical outcomes.
PubMed 16079079 · doi:10.1289/ehp.8100
What was done
In an observational study, researchers measured anogenital distance (AGD), penile volume, and testicular descent in 134 boys aged 2 to 36 months. Anogenital index (AGI) was calculated as AGD divided by weight (mm/kg) and adjusted for age. Nine phthalate monoester metabolites were measured in maternal prenatal urine samples for 85 boys to evaluate associations between prenatal phthalate exposure and infant genital development using regression models and quartile comparisons.
What was found
AGD correlated significantly with penile volume (R = 0.27, p = 0.001) and incomplete testicular descent (R = 0.20, p = 0.02). Four prenatal urinary metabolites—monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)—were inversely related to age-adjusted AGI (p-values 0.007 to 0.097). Comparing the highest to lowest exposure quartiles, the odds ratio for shorter-than-expected AGI was 10.2 (95% CI, 2.5 to 42.2) for MBP, 4.7 for MEP (p < 0.05), 3.8 for MBzP (p < 0.05), and 9.1 for MiBP (p < 0.05). Age-adjusted AGI decreased significantly with an increasing summary phthalate score (p = 0.009).
Why it matters
This was the first human study to link environmental levels of prenatal phthalate exposure to reduced anogenital distance and markers of incomplete virilization, aligning with effects previously demonstrated in animal models.
Limits
The sample with biomarker data was small (n = 85), producing wide confidence intervals. The abstract does not specify gestational age at maternal urine sampling or control for potential unmeasured maternal and environmental confounders.
Cited by
- supports Research by Dr. Shanna Swan demonstrated the occurrence of the phthalate syndrome in human male infants.