Anogenital distances are strongly related to gestational age and birthweight and later, to growth. They track through early life and are highly reliable measures in both sexes.

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.

We investigated the potential endocrine disruptive effect of prenatal exposure to persistent organic pollutants (POPs) through maternal diet, by measuring anogenital distance in newborns and young children. We included 231 mothers and their newborns measured at birth from the Rhea study in Crete, Greece and the Hmar study in Barcelona, Spain and 476 mothers and their children measured between 1 and 2 years from the Rhea study. We used food frequency questionnaires to assess maternal diet and estimated plasma dioxin-like activity by the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR-CALUX®) and other POPs in maternal samples. We defined a "high-fat diet" score, as a prenatal exposure estimate, that incorporated intakes of red meat, processed meat, fatty fish, seafood, eggs and high-fat dairy products during pregnancy. Increasing maternal "high-fat diet" score was related to increasing dioxin-like activity and serum concentrations of lipophilic persistent organic pollutants in maternal blood. An inverse dose-response association was found between "high-fat diet" score and anoscrotal distance in newborn males. The highest tertile of the maternal score was associated with -4.2 mm (95% CI -6.6 to -1.8) reduction in anoscrotal distance of newborn males, compared to the lowest tertile. A weak positive association was found between the "high-fat diet" score and anofourchetal distance in newborn females. In young children we found no association between maternal "high-fat diet" score and anogenital distances. In conclusion, maternal high-fat diet may be linked to high prenatal exposure to persistent organic pollutants and endocrine disruptive effects, resulting to phenotypic alterations of the reproductive system.

Graphical abstract

12 months later, the patient was readmitted with fever (38.5uC), dyspnoea and cough for 2 days. He appeared ill. His body temperature was 36.7uC, respiratory rate was 26 breaths?min -1 , pulse was 108 beats?min -1 and O 2 saturation was 93%. On chest auscultation, he had decreased breath sounds over the right hemi-thorax. S 1 and S 2 cardiac sounds were normal with no murmur and the rest of examination was normal.His chest radiography (CXR) on admission is shown in figure 1.