Lifestyle and Environment · Environmental Exposures

Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012)

Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM

Environmental health perspectives, 2016
DOI 10.1289/ehp.1509870 PMID 26672060 PMC PMC4937858

RRM Academy Synopsis

Low prenatal phthalates had no consistent link to anogenital distance

A Danish cohort study of 245 mother-son pairs found that phthalate levels in pregnancy showed no consistent link to anogenital distance in boys. Anogenital distance is the span from anus to genitals, measured at 3 months of age. Median phthalate levels were about two to four times lower than in a Swedish study.

Key Findings

  • The authors found no consistent association between any prenatal phthalate and anogenital distance or penile width in the boys, and no dose-dependent pattern.
  • Most estimates were negative for exposures above the lowest quartile. The pattern was inconsistent across exposure levels, and the associations were not statistically significant (p > 0.05).
  • For the shorter distance (anus to scrotum), boys in the third quartile of monoethyl phthalate exposure averaged −1.68 mm (95% CI: −3.56, 0.20 mm) against boys in the lowest quartile.
  • Median phthalate metabolite levels were about two to four times lower than in a recent Swedish study that sampled urine in the first trimester.

Interpretation

The Odense Child Cohort is a prospective cohort that enrolled 42.9% of eligible pregnant women in Odense. Urine was collected around week 28 of pregnancy, and sons were examined 3 months after the expected date of birth. Women of non-Caucasian origin were left out. The result is null at low exposure levels: boys with higher prenatal phthalate levels showed no significant trend toward a shorter distance. The authors note that one urine sample may miss exposure during the sensitive window of development.

RRM Context

Restorative reproductive medicine looks for root causes in both partners. Male development is part of that picture. Earlier studies in the United States and Sweden linked higher phthalate exposure before birth to a shorter distance in boys. Studies of adult men associate the distance with semen quality and testosterone.

Abstract

Background

Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported.

Objective

We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273).

Methods

In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score.

Results

Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05).

Conclusion

We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population. CITATION: Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010-2012). Environ Health Perspect 124:1107-1113; http://dx.doi.org/10.1289/ehp.1509870.

Topics

By this author

Related research

Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals
Tina Kold Jensen, Hanne Frederiksen, Henriette Boye Kyhl, Tina Harmer Lassen, Shanna H Swan, Carl-Gustaf Bornehag, Niels E Skakkebaek, Katharina M Main, Dorte Vesterholm Lind, Steffen Husby, Anna-Maria Andersson
T Jensen, H Frederiksen, H Kyhl, T Lassen, S Swan, C Bornehag, N Skakkebaek, K Main, D Lind, S Husby, A Andersson
PMID 26672060 26672060 DOI 10.1289/ehp.1509870 10.1289/ehp.1509870 Jensen et al. 2016, Jensen 2016