title: First trimester phthalate exposure and male newborn genital anomalies.
abstract: 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.
authors: Seattle 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. Electronic address: sheela.sathyanarayana@seattlechildrens.org.
authors: Sheela
authors: S
authors: Sathyanarayana
authors: Seattle Children's Research Institute, Seattle, WA, USA.
authors: Richard
authors: R
authors: Grady
authors: Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors: Emily S
authors: ES
authors: Barrett
authors: Department of Endocrinology, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: Bruce
authors: B
authors: Redmon
authors: Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA.
authors: Ruby H N
authors: RHN
authors: Nguyen
authors: Division of Urology, Department of Surgery, Nemours/Alfred I DuPont Hospital for Children, DE, USA.
authors: Julia S
authors: JS
authors: Barthold
authors: Departments of Psychiatry and Pediatrics, University of California, San Francisco, USA.
authors: Nicole R
authors: NR
authors: Bush
authors: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai , New York City, NY, USA.
authors: Shanna H
authors: SH
authors: Swan
mesh_terms: D000393:Air Pollutants / Q000633:toxicity* / Q000652:urine; D015331:Cohort Studies; D005260:Female; D005837:Genitalia, Male / Q000002:abnormalities*; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D015999:Multivariate Analysis; D010795:Phthalic Acids / Q000633:toxicity* / Q000652:urine; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology; D014564:Urogenital Abnormalities / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D000393:Air Pollutants; D010795:Phthalic Acids; C032279:phthalic acid
keywords: Hydrocele; Hypospadias; Phthalate; Undescended testis