Infant neurodevelopment and behavior in Guadeloupe after lead exposure and Zika maternal infection during pregnancy.

BACKGROUND: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy. METHODS: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions. RESULTS: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses. DISCUSSION/CONCLUSION: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor function.

Simultaneous exposure to both Zika virus and household insecticides during pregnancy, and fetal growth and infant developmental behavior outcomes at 18 months, in Guadeloupe.

BACKGROUND: Perinatal infection with Zika virus (ZIKV) could result in adverse growth, developmental and behavioral outcomes, while insecticides used to control mosquitoes are neurotoxic. OBJECTIVES: We aim to study the role played by exposure during pregnancy to both ZIKV and household insecticides in newborn health, development and behavior at age of 18 months. METHODS: Maternal and cord blood samples from a cohort of pregnant women (created during Guadeloupe's Zika epidemic of 2016) were used to identify ZIKV infection during pregnancy. A self-administered questionnaire at birth documented prenatal household use of insecticides. Birth weight and head circumference were collected from maternity records (n = 708). Infant development and behaviors were documented at 18 months of age through the Ages and Stages Questionnaire and the Quebec Longitudinal Study of Child Development (n = 409). Logistic and linear regression models were performed, taking into account confounding factors. RESULTS: Use of household insecticides was associated with smaller head circumference and lower birth weight among newborns from mothers not exposed to ZIKV: 0.3 cm (95% CI: 0.6, 0) and -82 g (95% CI: 165, 0), respectively. Similar decreases were observed with ZIKV exposure among mothers not reporting household insecticides use, and with presence of both exposures. The combined presence of ZIKV exposure and insecticide use was associated with lower ASQ fine motor scores (-3.9; 95% CI: 7.3, -0.4), and higher hyperactivity scores (0.8; 95% CI: 0.0, 1.5), compared to no exposure to either. A higher opposition score was observed in association with ZIKV exposure among non-users of insecticide (0.6; 95% CI: 0.0, 1.2). CONCLUSION: Adverse neurodevelopmental outcomes at 18 months of age were observed with prenatal ZIKV exposure, and with higher magnitude when mothers reported use of household insecticides. At birth, rates of adverse fetal growth were however similar for the combined presence of exposure and either of the exposures.

To which mixtures are French pregnant women mainly exposed? A combination of the second French total diet study with the EDEN and ELFE cohort studies.

Pregnant women and their unborn child are exposed to a large number of substances during pregnancy. Some of these substances may cross the placenta, resulting in exposure of the foetus. There is growing evidence that certain substances could interact to produce a mixture effect. It is therefore essential to identify the main mixtures mothers are exposed to. This study aimed to identify the major mixtures French pregnant women included in EDEN and ELFE cohorts were exposed to, on the basis of the 441 substances analysed in the second French total diet study. Exposure systems and the composition of substances were identified from co-exposures using sparse non-negative matrix under-approximation to generate the main mixtures. Individuals were clustered to define clusters with similar co-exposure profiles. Six clusters associated with eight mixtures were identified. For example in ELFE, cluster 2 comprising 10% of the population was characterised by mixtures "Pest-1" mainly contains pesticides and "TE-F-PAH″ contains trace elements, furans and polycyclic aromatic hydrocarbons. Five other clusters were also described with their associated mixtures. Similar results were observed for EDEN. This study helps to prioritise mixtures for which it is crucial to investigate possible toxicological effects and to recommend epidemiological studies concerning health effects.

Environmental contaminants and child's growth.

Experimental data have suggested that some contaminants in the environment may increase the risk of obesity. Infants can be exposed to chemicals either prenatally, by trans-placental passage of chemicals, or postnatally by their own diet and by other external pathways (air inhalation, dust, hand-to-mouth exposure) after birth. To provide a review of epidemiological evidence on the association between prenatal exposure to chemicals and prenatal and postnatal growth, we present the literature from systematic review articles and international meta-analyses, when available, or recent research articles when summarizing articles were not available. The most studied contaminants in this field were persistent organic pollutants (e.g. organochlorinated pesticides, polychlorinated biphenyls), non-persistent pollutants (e.g. phthalates, bisphenol A), toxic heavy metals (i.e. cadmium, lead and mercury), arsenic, mycotoxins and acrylamide. Mounting evidence suggests that child's growth may be associated with prenatal or postnatal exposures to environmental contaminants. Improving exposure assessment and studying the contaminants as mixtures should allow to gain knowledge about the environmental determinants of growth and obesity.

Dietary acrylamide intake during pregnancy and anthropometry at birth in the French EDEN mother-child cohort study.

BACKGROUND AND AIM: Acrylamide is a contaminant formed in a wide variety of carbohydrate-containing foods during frying or baking at high temperatures. Recent studies have suggested reduced foetal growth after exposure to high levels of acrylamide during pregnancy. OBJECTIVE: To study the relationship between maternal dietary acrylamide intake during pregnancy and their offspring's anthropometry at birth. DESIGN: In our population of 1471 mother-child pairs from two French cities, Nancy and Poitiers, dietary acrylamide intake during pregnancy was assessed by combining maternal food frequency questionnaires with data on food contamination at the national level, provided by the second "French Total Diet Study". Newborns weighing less than the 10th percentile, according to a customised definition, were defined as small for gestational age (SGA). Linear and logistic regression models were used to study continuous and binary outcomes respectively, adjusting for the study centre, maternal age at delivery, height, education, parity, smoking during pregnancy, the newborn's gestational age at birth and sex. RESULTS: The median and interquartile range of dietary acrylamide intake were 19.2µg/day (IQR, 11.8;30.3). Each 10µg/day increase in acrylamide intake was associated with an odds-ratio for SGA of 1.11 (95% Confidence Interval: 1.03,1.21), birth length change of -0.05cm (95% CI: -0.11,0.00) and birth weight change of -9.8g (95% CI: -21.3,1.7). CONCLUSIONS: Our results, consistent with both experimental and epidemiological studies, add to the evidence of an effect of acrylamide exposure on the risk of SGA and suggest an effect on foetal growth, for both weight and length.