Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure
By S. Swan, Katharina M. Main, Fan Liu, Sara Stewart, Robin Kruse, A.M. Calafat, C. S. Mao, Joseph Redmon, C. Ternand, Shannon Sullivan and 1 more. Environmental Health Perspectives, 2005
1,596 citations recorded by the source corpus.
Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2–36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.
Subfields: Health, Toxicology and Mutagenesis, Pediatrics, Perinatology and Child Health
View Paper: https://www.semanticscholar.org/paper/2998a0fac573bc64f188cfb0b6dbdb7612a5e730
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Health, Toxicology and Mutagenesis
In Pediatrics, Perinatology and Child Health
Citations in the corpus
- Prenatal environmental exposures, epigenetics, and disease (2011, neutral): “While not all studies have been consistent, prenatal exposure to phthalates has been associated with shortened gestational age [92,93] and with a number of adverse reproductive and developmental effects including decreased anogenital distance among newborn boys [90], undescended testis (exposure to ”
- Endocrine disruptors: from endocrine to metabolic disruption. (2011, background): “Maternal urine levels of metabolites of DEHP (benzylbutyl phthalate, diethyl phthalate, and dibutyl phthalate) are associated with a higher risk of incomplete testicular descent for male human infants and are inversely correlated with the anogenital distance (68, 69).”
- Bisphenol A and human health: a review of the literature. (2013, background): “Similarly, shorter adjusted AGD may indicate antiandrogenic exposures during embryonic development in humans [99], and the current study indicates that the relative AGD may persist through childhood and the post-pubertal period [94], although more studies need to be done to verify this endpoint in h”
- Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age (2005, result): “However, our observations on the associations between mBP and mEP and markers of Leydig cell function, in particular, are consistent with the American study (Swan et al. 2005) in terms of an antiandrogenic effect of phthalate exposure in infants boys, assessed by two different biomarkers.”