Maternal Pregnancy Levels of Polychlorinated Biphenyls and Risk of Hypospadias and Cryptorchidism in Male Offspring

Background

The etiologies of the male urogenital anomalies cryptorchidism and hypospadias are poorly understood. It has been suggested, however, that in utero hormone levels may be related to risk. Endocrine-disrupting chemicals, including polychlorinated biphenyl (PCB) compounds, may alter hormone levels and thereby affect the fetus.

Objectives

To examine whether in utero PCB exposure is related to cryptorchidism and hypospadias, we examined PCB levels among pregnant women enrolled in the Collaborative Perinatal Project (CPP).

Methods

The CPP enrolled pregnant women at 12 U.S. medical centers between 1959 and 1965. For the present research, we analyzed third-trimester serum samples from the mothers of 230 sons with cryptorchidism, 201 sons with hypospadias, and 593 sons with neither condition. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression and examined the associations of each anomaly with individual PCB congener levels, sum of PCBs, and several functional groupings of PCBs.

Results

In general, the ORs for cryptorchidism or hypospadias showed no notable associations with individual PCB congener levels or functional groupings of PCBs. However, the ORs and 95% CIs for the sum of PCBs associated with hypospadias were as follows: 0–1.9 μg/L, reference group; 2–2.9 μg/L, OR = 1.57, 95% CI, 1.05–2.34; 3–3.9 μg/L, OR = 1.45, 95% CI, 0.90–2.34; and ≥ 4.0 μg/L, OR = 1.69, 95% CI, 1.06–2.68; p-value for trend = 0.08.

Conclusions

Given the large number of associations examined, these findings do not strongly support the hypothesis that PCBs are associated with cryptorchidism or hypospadias. Because population serum PCB levels at the time of sample collection were considerably higher than levels at present, it is unlikely that current PCB exposure is related to the development of either anomaly.     

Exposure to brominated flame retardants,perfluorinated compounds,phthalates and phenols in European birth cohorts: ENRIECO evaluation,first human biomonitoring results,and recommendations

There are emerging concerns about potential effects on child health and development of early-life exposure to substances such as brominated flame retardants (BFRs), perfluorinated compounds (PFCs), phthalates and phenols (including bisphenol A (BPA)); pregnancy and birth cohort studies are ideally designed to study such concerns prospectively. As part of the ENRIECO project, we evaluated existing human biomonitoring data for these substances in European birth cohorts and develop recommendations for more harmonized methods that will enable combination and comparison of cohort data in the future. The ENRIECO inventory shows that 20 European birth cohorts have measured or are measuring BFRs (N = 10), PFCs (N = 11), phthalates (N = 16) or phenols (N = 8). Generally, samples were collected prenatally or at birth and measurements involved few subjects in each cohort (a few hundred maximum). Biological matrices, timing, and analytical methods of the measurements varied between cohorts. Few cohorts have measured at multiple time points or in children. In European cohorts, levels of BFRs were very low and at least 10-fold lower than in US; levels of PFCs and phthalates have decreased over the last decade since the phasing out of certain of these compounds; concentrations of phenols are comparable to those in the US. Although there is little published data in the cohorts now, many measurements are ongoing and we recommend that cohorts start working towards combined and comparison studies. Specific recommendations for use of existing data include the development of conversion models for the different media used for measurement of persistent chemicals, and inter-laboratory comparisons and calibrations. Recommendations for further data collection include more evaluation of exposure to these chemicals in children; repeated measurements of non-persistent chemicals; validation and harmonisation of questionnaires; and the development of mechanisms for fast European birth cohort response for the detection and prioritisation of new chemicals of concern.