68. Do stressful life events during pregnancy modify associations between phthalates and anogenital distance in newborns? (lay summary)

Arbuckle TE, MacPherson SH, Barrett E, Muckle G, Séguin JR, Foster WG, Sathyanarayana S, Dodds L, Fisher M, Agarwal A, Monnier P, Walker M, Fraser WD. Environmental Research. 2019 Oct;177:108593. doi: 10.1016/j.envres.2019.108593

Phthalates are a group of chemicals that are suspected of being endocrine disruptors. Endocrine disrupting chemicals can interfere with hormone systems and produce adverse effects on child development and reproduction. Phthalates are used in plastics to soften and increase flexibility. They’re also used in many consumer products (e.g., hair spray, nail polish, shampoo).

Anogenital distance (AGD) is the distance between the anus and penis in boys and between the anus and clitoris in girls and has been used as a marker of prenatal reproductive development.  AGD in boys is thought to be a marker of early fetal androgen (male sex hormone) exposure and masculinization.  AGD in boys is usually longer than in girls.  Some phthalates have been identified by other researchers as androgen disruptors, thought to be associated with shorter AGD in boys.

One US study reported that higher levels of some phthalates in mother’s urine during pregnancy was associated with a shorter anogenital distance in infant boys, but only if the woman reported no stressful life events during pregnancy. The objective of this study was to test whether similar results would be observed in the MIREC Study.

Phthalate levels were measured in first trimester urine of MIREC participants.  As part of the MIREC-ID Study, women were asked about stressful events during their pregnancy.  Women reporting one or more stressful life events during pregnancy were considered the “high stressor” group, whereas women reporting no events were considered a “lower stressor” group.  Shortly after birth, the infant’s weight, length, and anogenital distances were measured.  The total amount of the androgen disrupting phthalates in mother’s urine was calculated.  Statistical models were fit to examine associations between mother’s phthalate levels and AGD for each stressor group.

Data were available for 153 female and 147 male infants.  The sum of androgen disrupting phthalates was associated with significantly longer AGDs in females from the higher stressor group. In males, all phthalates were associated with longer AGD, regardless of stressor group.  In contrast to the US study, the MIREC study did not observe shorter AGDs in male infants prenatally exposed to phthalates, regardless of maternal stressor level.

In conclusion, this study was not able to replicate the findings of the US study.  Whether the association observed between longer anogenital distance in female infants and maternal urine levels of androgen disrupting phthalates is real, or would have any long-lasting effect on the reproductive health of females is unknown and needs to be investigated further.  Further research with other populations and measures of maternal stress may shed light on whether prenatal stress is an important factor in modifying associations between phthalates (or other chemicals) and anogenital distance.