In Utero Exposure to Dioxins and Dioxin-like Compounds and Anogenital Distance in Newborns and Infants

Abstract

Background: Anogenital distance in animals is used as a measure of fetal androgen action. Prenatal exposure to dioxins and dioxin-like compounds in rodents causes reproductive changes in male offspring and decreases anogenital distance.Objective: We assessed whether in utero exposure to dioxins and dioxin-like compounds adversely influences anogenital distance in newborns and young children (median age, 16 months; range, 1–31 months).Methods: We measured anogenital distance among participants of the “Rhea” mother–child cohort study in Crete and the Hospital del Mar (HMAR) cohort in Barcelona. Anogenital distance (AGD; anus to upper penis), anoscrotal distance (ASD; anus to scrotum), and penis width (PW) were measured in 119 newborn and 239 young boys; anoclitoral (ACD; anus to clitoris) and anofourchetal distance (AFD; anus to fourchette) were measured in 118 newborn and 223 young girls. We estimated plasma dioxin-like activity in maternal blood samples collected at delivery with the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX®) bioassay.Results: Anogenital distances were sexually dimorphic, being longer in males than females. Plasma dioxin-like activity was negatively associated with AGD in male newborns. The estimated change in AGD per 10 pg CALUX®–toxic equivalent/g lipid increase was –0.44 mm (95% CI: –0.80, –0.08) after adjusting for confounders. Negative but smaller and nonsignificant associations were observed for AGD in young boys. No associations were found in girls.Conclusions: Male infants may be susceptible to endocrine-disrupting effects of dioxins. Our findings are consistent with the experimental animal evidence used by the Food and Agriculture Organization/World Health Organization to set recommendations for human dioxin intake.

WHO/UNEP global surveys of PCDDs, PCDFs, PCBs and DDTs in human milk and benefit–risk evaluation of breastfeeding

“…However, these effects were often transient and their clinical relevance discussed (Koopman-Esseboom et al 1994, 1996; Pluim et al 1993; Weisglas-Kuperus et al 1995, 2000, 2004). Very recently, a study from Spain and Greece reported a negative relationship between maternal levels of DL compounds and anogenital distance in newborns (Vafeiadi et al 2013). Many of these studies could not differentiate between possible effects of DL compounds (in TEQ) or PCBs due to their simultaneous occurrence in human milk.…”

In Utero Exposure to Compounds with Dioxin-like Activity and Birth Outcomes

“…Sex-specific results in our study and others suggest greater susceptibility of male infants to the effects of environmental contaminants with dioxin-like activity. 37,53 Some experimental animal studies support this hypothesis, including sex-specific transgenerational effects on the reproductive system. 54 the mechanisms through which growth restriction induced by in utero dioxin exposure might be more pronounced in boys remain unclear.…”

“…35 Pregnant women were enrolled from 2006 to 2010 in 11 maternity units located in copenhagen, Denmark; Heraklion, greece; Oslo and akershus, norway; Barcelona and Sabadell, Spain; and Bradford, england. [36][37][38][39][40][41] all research procedures were approved by the local ethical committees, and written informed consent was obtained from all women participating in the studies. rules for ethical conduct are stated in the technical annex to the contract with the eU commission (contract no.…”

Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta

“…Exposure in utero has been related to a number of adverse health endpoints in children, including a higher risk for overweight, alterations in psychomotor and cognitive development or urogenital abnormalities in male newborns (Forns et al 2012; Palmer et al 2009; Puertas et al 2010; Valvi et al 2013), and several studies have reported sex specific effects occurring by mechanisms that remain poorly understood (Fernandez et al 2007; Papadopoulou et al 2013; Vafeiadi et al 2013; Valvi et al 2012 ).…”