First trimester phthalate exposure and male newborn genital anomalies

Environ Res. 2016 Nov;151:777-782. doi: 10.1016/j.envres.2016.07.043. Epub 2016 Aug 23.


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.

Keywords: Hydrocele; Hypospadias; Phthalate; Undescended testis.

MeSH terms

  • Air Pollutants / toxicity*
  • Air Pollutants / urine
  • Cohort Studies
  • Female
  • Genitalia, Male / abnormalities*
  • Humans
  • Infant, Newborn
  • Logistic Models
  • Male
  • Maternal Exposure / adverse effects*
  • Multivariate Analysis
  • Phthalic Acids / toxicity*
  • Phthalic Acids / urine
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology*
  • United States / epidemiology
  • Urogenital Abnormalities / chemically induced
  • Urogenital Abnormalities / epidemiology*


  • Air Pollutants
  • Phthalic Acids
  • phthalic acid