BACKGROUND: To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. METHODS: Cumulative prenatal exposure to xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1-2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4-5 years of age. Interactions with sex were investigated. RESULTS: /nAfter adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1-2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found. CONCLUSIONS: Our results suggest that boys' early motor development might be more vulnerable to prenatal exposure to mixtures of xenoestrogens, but associations do not persist in preschool children.

This work was supported by grants from the Spanish Ministry of Health [FIS-PI042018; FIS-PI060867; FIS-PI081151; FIS-PI09/02311; FIS-PI09/02647; FIS-PI11/00610 Council of Innovation, Science and Enterprise (Excellence Project P09-CTS-5488) and Council of Health (SAS PI-0675-2010), Instituto de Salud Carlos III [Red INMA G03/176 and CB06/02/0041]; the EU Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), the Generalitat de Catalunya-CIRIT [1999SGR 00241]; the Fundació La Marató de TV3 (Grant no. 090430); the Consejería de Salud de la Junta de Andalucía (Grant number 183/07 and 0675/10), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), the University of Oviedo, Obra Social Cajastur, and the Fundación Roger Torné. NV was supported by an FPI Grant from the Spanish Ministry of Health (BES-2009-023933) and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933). The HUSC BioBank, integrated in the Andalusia Public Health System (SSPA) and the National Biobank Network, is financed by the Institute of Health Carlos III, (Project RD09/0076/00148) and the Regional Government of Andalusia