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First trimester phthalate exposure and male newborn genital anomalies
Sheela Sathyanarayana1, Richard Grady2, Emily S Barrett3
1Seattle Children's Research Institute, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
Insights
First trimester exposure to anti-androgenic phthalates, like di-ethylhexyl phthalate (DEHP), is linked to increased risks of male genital anomalies, including hydrocele, in newborns. This study highlights potential environmental impacts on male reproductive development.
Area of Science:
- Environmental Health
- Reproductive Toxicology
- Pediatric Epidemiology
Background:
- Anti-androgenic phthalates are environmental chemicals known to disrupt male genital development in rodents.
- Prenatal exposure to these chemicals may increase the incidence of genitourinary birth defects in human newborns.
Purpose of the Study:
- To investigate the association between first-trimester phthalate exposure and male genital anomalies in human infants.
- To determine if prenatal phthalate exposure contributes to birth defects in newborn males.
Main Methods:
- A multi-center cohort study (The Infant Development and the Environment Study - TIDES) recruited pregnant women in their first trimester.
- Analysis included 371 mother/male infant dyads with complete urinary phthalate and birth exam data.
- Multivariate logistic regression was used to assess the odds of genital anomalies in relation to phthalate metabolite concentrations.
Main Results:
- Hydrocele was the most common anomaly (N=30), followed by undescended testes (N=5) and hypospadias (N=3).
- A one log unit increase in di-ethylhexyl phthalate (DEHP) metabolites was associated with a 2.5-fold increased risk of any genital anomaly.
- A 3.0-fold increased risk of isolated hydrocele was observed in relation to increased DEHP metabolite levels.
Conclusions:
- First-trimester urinary DEHP metabolite concentrations are associated with higher odds of newborn male genital anomalies.
- The association was primarily driven by isolated hydrocele, an endpoint not previously linked to prenatal phthalate exposure.
- Further research is recommended to confirm these findings, including hydrocele assessment in future studies on prenatal phthalate exposure.
Background:
Anti-androgenic phthalates are environmental chemicals that affect male genital development in rodents leading to genitourinary birth defects. We examined whether first trimester phthalate exposure may exert similar effects in humans leading to an increased incidence of newborn male genital anomalies in a multi-center cohort study.
Methods:
We recruited first trimester pregnant women within The Infant Development and the Environment Study (TIDES) from 2010 to 2012 from four study centers and limited analyses to all mother/male infant dyads who had complete urinary phthalate and birth exam data (N=371). We used multivariate logistic regression to determine the odds of having a genital anomaly in relation to phthalate exposure.
Results:
Hydrocele was the primary abnormality observed in the cohort (N=30) followed by undescended testes (N=5) and hypospadias (N=3). We observed a statistically significant 2.5 fold increased risk (95% CI 1.1, 5.9) of having any anomaly and 3.0 fold increased risk (95% CI 1.2, 7.6) of isolated hydrocele in relation to a one log unit increase in the sum of di-ethylhexyl phthalate (DEHP) metabolites.
Conclusions:
First trimester urinary DEHP metabolite concentrations were associated with increased odds of any newborn genital anomaly, and this association was primarily driven by isolated hydrocele which made up the majority of anomalies in newborn males. The association with hydrocele has not been previously reported and suggests that it may be an endpoint affected by prenatal phthalate exposures in the first trimester of development. Future human studies should include hydrocele assessment in order to confirm findings.
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