Nerea Lertxundi

Polybrominated diphenyl ethers (PBDEs) in breast milk and neuropsychological development in infants

Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children’s neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209.

Thyroxine levels during pregnancy in healthy women and early child neurodevelopment.

Background: The fetus depends on maternal thyroid hormones during pregnancy for normal brain development. Little is known about the effects of subclinical hypothyroidism and mild hypothyroxinemia during pregnancy on neurodevelopment of the child. Methods: We evaluated a population-based birth cohort in Spain. A total of 1761 children and their mothers were included in the main analyses. Serum levels of free thyroxine and thyrotropin were measured in pregnant women. Mental and psychomotor development of their children was assessed using the Bayley Scales of Infant Development during the second year of life. Results: Low free thyroxine levels (<5th percentile) and self-reported prepregnancy thyroid disorder without medical treatment were associated with a decrease of mental scores (Beta = −3.4 [95% confidence interval= −6.7 to −0.2]) and −5.5 [−8.9 to −2.0], respectively). No association between thyrotropin levels and mental scores or psychomotor scores was observed. Conclusions: Low free thyroxine levels in healthy pregnant women are related to a moderate delay in child neurodevelopment. The impairment is similar in magnitude to that observed in mothers with untreated prepregnancy thyroid disorder. The value of screening pregnant women for thyroid function requires further assessment, particularly in mildly iodine-deficient areas.

Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors.

Background: Air pollution effects on children’s neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway. Objective: We aimed to assess whether prenatal exposure to residential air pollution is associated with impaired infant mental development, and whether antioxidant/detoxification factors modulate this association. Methods: In the Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project, 2,644 pregnant women were recruited during their first trimester. Nitrogen dioxide (NO2) and benzene were measured with passive samplers covering the study areas. Land use regression models were developed for each pollutant to predict average outdoor air pollution levels for the entire pregnancy at each residential address. Maternal diet was obtained at first trimester through a validated food frequency questionnaire. Around 14 months, infant mental development was assessed using Bayley Scales of Infant Development. Results: Among the 1,889 children included in the analysis, mean exposure during pregnancy was 29.0 μg/m3 for NO2 and 1.5 μg/m3 for benzene. Exposure to NO2 and benzene showed an inverse association with mental development, although not statistically significant, after adjusting for potential confounders [β (95% confidence interval) = –0.95 (–3.90, 1.89) and –1.57 (–3.69, 0.56), respectively, for a doubling of each compound]. Stronger inverse associations were estimated for both pollutants among infants whose mothers reported low intakes of fruits/vegetables during pregnancy [–4.13 (–7.06, –1.21) and –4.37 (–6.89, –1.86) for NO2 and benzene, respectively], with little evidence of associations in the high-intake group (interaction p-values of 0.073 and 0.047). Inverse associations were also stronger in non-breast-fed infants and infants with low maternal vitamin D, but effect estimates and interactions were not significant. Conclusions: Our findings suggest that prenatal exposure to residential air pollutants may adversely affect infant mental development, but potential effects may be limited to infants whose mothers report low antioxidant intakes.

Circulating 25-Hydroxyvitamin D3 in Pregnancy and Infant Neuropsychological Development

OBJECTIVE: To investigate whether circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy is associated with neuropsychological development in infants. METHODS: The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5±2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11–23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D3 were calculated by using linear regression analysis. RESULTS: The median plasma value of 25(OH)D3 in pregnancy was 29.6 ng/mL (interquartile range, 21.8–37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D3 concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D3 concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63–4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36–4.28) in comparison with those of mothers with 25(OH)D3 concentrations <20 ng/mL. CONCLUSIONS: Higher circulating concentration of maternal 25(OH)D3 in pregnancy was associated with improved mental and psychomotor development in infants.

Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two Southern European birth cohort studies

BACKGROUND Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine mechanisms. METHODS We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 ± 15) of children aged 11-22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure. RESULTS The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: -2.72; 95% CI: -5.35, -0.10) and RHEA (score reduction: -3.71; 95% CI: -8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA. CONCLUSIONS This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors.

Iodine Supplementation During Pregnancy and Infant Neuropsychological Development INMA Mother and Child Cohort Study

Iodine supplementation during pregnancy is a common practice in developed countries. However, scant evidence is available regarding the safety and effectiveness of maternal iodine supplementation with regard to child neuropsychological development. We previously reported an inverse association between iodine supplementation and the psychomotor development of infants in a birth cohort from Valencia, Spain. In the present study, we assessed this association in a wider sample of mother and child pairs from 3 other regions in Spain. Neuropsychological development was assessed using the Bayley Scales of Infant Development in 1,519 infants (median age, 16 months) between 2006 and 2009. In multivariate analyses, maternal consumption of 150 μg/day or more of iodine from supplements was related to a 1.5-fold increase in the odds of a psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7-fold increase in the odds of a mental score less than 85 (95% confidence interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were only partially verified. The results of the present study suggest that, at least in these regions, iodine supplementation does not improve infant neuropsychological development at 1 year of age. Further research is needed on the risks and benefits of supplementary iodine for both maternal thyroid function and child neurodevelopment.

Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N=1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure. Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores. Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (β [95%CI]=-1.36 [-2.61, -0.11]). Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life. Results of the present study suggest that, although breastfeeding increases childrens blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure.

Indoor air pollution from gas cooking and infant neurodevelopment.

Background: Gas cooking is a main source of indoor air pollutants, including nitrogen dioxide and particles. Because concerns are emerging for neurodevelopmental effects of air pollutants, we examined the relationship between indoor gas cooking during pregnancy and infant neurodevelopment. Methods: Pregnant mothers were recruited between 2004 and 2008 to a prospective birth cohort study (INfancia y Medio Ambiente) in Spain during the first trimester of pregnancy. Third-trimester questionnaires collected information about the use of gas appliances at home. At age 11 to 22 months, children were assessed for mental development using the Bayley Scales of Infant Development. Linear regression models examined the association of gas cooking and standardized mental development scores (n=1887 mother–child pairs). Results: Gas cookers were present in 44% of homes. Gas cooking was related to a small decrease in the mental development score compared with use of other cookers (−2.5 points [95% confidence interval=−4.0 to −0.9]) independent of social class, maternal education, and other measured potential confounders. This decrease was strongest in children tested after the age of 14 months (−3.1 points [−5.1 to −1.1]) and when gas cooking was combined with less frequent use of an extractor fan. The negative association with gas cooking was relatively consistent across strata defined by social class, education, and other covariates. Conclusions: This study suggests a small adverse effect of indoor air pollution from gas cookers on the mental development of young children.

Folic Acid Supplements During Pregnancy and Child Psychomotor Development After the First Year of Life

IMPORTANCE Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear. OBJECTIVE To examine the association between the use of high dosages of FA supplements during pregnancy and child neuropsychological development after the first year of life. DESIGN, SETTING, AND PATIENTS The multicenter prospective mother-child cohort Infancia y Medio Ambiente (INMA) Project recruited pregnant women from 4 areas of Spain (Asturias, Sabadell, Gipuzkoa, and Valencia) between November 2003 and January 2008. Pregnant women completed an interviewer-administered questionnaire on the usual dietary folate intake and FA supplements at 10 to 13 weeks and 28 to 32 weeks of gestation. The main analyses were based on a sample of 2213 children with complete information on neuropsychological development and FA supplement intake during pregnancy. Multiple linear and logistic regression analyses were used to explore the effects of FA supplements on child neuropsychological development. MAIN OUTCOMES AND MEASURES Neuropsychological development was assessed using the Bayley Scales of Infant Development. We calculated mental scale and psychomotor scale scores. One SD below the mean established a delay in neurodevelopment (score <85). RESULTS A high proportion of women (57.3%) did not reach the recommended dosages of FA supplements (400 μg/d), but 25.2% women took more than 1000 μg/d of FA supplements (3.5% consuming >5000 μg/d). In multivariate analysis, we observed that children whose mothers used FA supplement dosages higher than 5000 μg/d during pregnancy had a statistically significantly lower mean psychomotor scale score (difference, -4.35 points; 95% CI, -8.34 to -0.36) than children whose mothers used a recommended dosage of FA supplements (400-1000 μg/d). An increased risk of delayed psychomotor development (psychomotor scale score <85) was also evident among children whose mothers took FA supplement dosages higher than 5000 μg/d, although the association was not statistically significant (odds ratio = 1.59; 95% CI, 0.82-3.08). CONCLUSIONS AND RELEVANCE To our knowledge, this is the first time a detrimental effect of high dosages of FA supplements during pregnancy on psychomotor development after the first year of life has been shown. Further research from longitudinal studies is warranted to confirm these results.

Exposure to fine particle matter, nitrogen dioxide and benzene during pregnancy and cognitive and psychomotor developments in children at 15 months of age.

BACKGROUND Prenatal exposure to air pollutants has recently been identified as a potential risk factor for neuropsychological impairment. OBJECTIVES To assess whether prenatal exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and benzene were associated with impaired development in infants during their second year of life. METHODS Regression analyses, based on 438 mother-child pairs, were performed to estimate the association between mother exposure to air pollutants during pregnancy and neurodevelopment of the child. The average exposure to PM2.5, NO2 and benzene over the whole pregnancy was calculated for each woman. During the second year of life, infant neuropsychological development was assessed using the Bayley Scales of Infant Development. Regression analyses were performed to estimate the association between exposure and outcomes, accounting for potential confounders. RESULTS We estimated that a 1 μg/m(3) increase during pregnancy in the average levels of PM2.5 was associated with a -1.14 point decrease in motor score (90% CI: -1.75; -0.53) and that a 1 μg/m(3) increase of NO2 exposure was associated with a -0.29 point decrease in mental score (90% CI: -0.47; -0.11). Benzene did not show any significant association with development. Considering women living closer (≤ 100 m) to metal processing activities, we found that motor scores decreased by -3.20 (90% CI: -5.18; -1.21) for PM2.5 and -0.51 (-0.89; -0.13) for NO2, while mental score decreased by -2.71 (90% CI: -4.69; -0.74) for PM2.5, and -0.41 (9% CI: -0.76; -0.06) for NO2. CONCLUSIONS Our findings suggest that prenatal residential exposure to PM2.5 and NO2 adversely affects infant motor and cognitive developments. This negative effect could be higher in the proximity of metal processing plants.