Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study.

This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i) <400 µg/d, (ii) ≥400 to 999 µg/d, (iii) ≥1000 to 4999 µg/d, and (iv) ≥5000 µg/d. Leucocyte TL at age four was measured using quantitative PCR methods. Multiple robust linear log-level regression models were used to report the % difference among FA categories. During the first period, and compared with children whose mothers were classified in the reference group (<400 µg/d), children whose mothers took higher dosages of FAs showed shorter TL at age four (≥5000 µg/d). When the first and the second periods were mutually adjusted, children whose mothers self-reported ≥5000 µg/d during the first period of pregnancy had a statistically significant shorter TL than their counterparts (% difference: -7.28% [95% CI: -14.42 to -0.13]). Similar trends were observed for the whole period of pregnancy. When the analysis was stratified by sex, the association was more evident in boys (% difference: -13.5% [95% CI: -23.0 to -4.04]), whereas no association was observed in girls. This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys. Further studies should confirm these results.

Early life tobacco exposure and children's telomere length: The HELIX project.

Telomere length and mitochondrial DNA content are considered biomarkers of cellular aging, oxidative stress, and inflammation, but there is almost no information on their association with tobacco smoke exposure in fetal and early life. The aim of this study was to assess whether prenatal and childhood tobacco exposure were associated with leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in children. As part of a multi-centre European birth cohort study HELIX (Human Early-Life Exposome) (n = 1396) we assessed maternal smoking status during pregnancy through questionnaires, and through urinary cotinine levels that were then used to classify women as not exposed to smoking (<10 µg/L), exposed to secondhand smoke (SHS) (10-50 µg/L) and active smokers (>50 µg/L). When the children were around 8 years of age (range: 5.4-12.0 years), childhood SHS tobacco smoke exposure was assessed through an extensive questionnaire and through measurements of urinary cotinine (<3.03 µg/L non-detected, >3.03 µg/L detected). Leukocyte mtDNA content and LTL were measured in the children at 8 years employing real time polymerase chain reaction (qPCR). Effect estimates were calculated using multivariate linear regression models for prenatal and childhood exposures adjusted for potential confounders. Maternal cotinine levels indicative of SHS exposure during pregnancy were associated with a decrease of 3.90% in LTL in children (95% CI: -6.68, -0.91), compared with non-smoking, whereas the association for maternal cotinine levels indicative of active smoking did not reach statistical significance (-3.24%; 95% CI: -6.59, 0.21). Childhood SHS tobacco exposure was not associated with LTL in children. Global SHS exposure during childhood was associated with an increase of 3.51% (95% CI: 0.78, 6.27) in mtDNA content. Our findings suggest that tobacco smoke exposure during pregnancy, even at SHS levels, may accelerate telomere shortening in children and thus induce biological aging from an early age.

Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms.

OBJECTIVE: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. STUDY DESIGN: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. RESULTS: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. CONCLUSIONS: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring.

The Association of Mediterranean Diet during Pregnancy with Longitudinal Body Mass Index Trajectories and Cardiometabolic Risk in Early Childhood.

OBJECTIVE: To evaluate the associations between maternal adherence to the Mediterranean diet during pregnancy and their offspring's longitudinal body mass index (BMI) trajectories and cardiometabolic risk in early childhood. STUDY DESIGN: We included mother-child pairs from the Infancia y Medio Ambiente (INMA) longitudinal cohort study in Spain. We measured dietary intake during pregnancy using a validated food frequency questionnaire and calculated the relative Mediterranean diet score (rMED). We estimated offspring's BMI z score trajectories from birth to age 4 years using latent class growth analyses (n = 2195 mother-child pairs). We measured blood pressure, waist circumference, and cardiometabolic biomarkers to construct a cardiometabolic risk score at 4 years (n = 697 mother-child pairs). We used multivariable adjusted linear and multinomial regression models. RESULTS: A higher maternal rMED in pregnancy was associated with a lower risk in offspring of larger birth size, followed by accelerated BMI gain (reference trajectory group: children with average birth size and subsequent slower BMI gain) (relative risk of high vs low rMED score, 0.68; 95% CI, 0.47-0.99). rMED score during pregnancy was not associated with the cardiometabolic risk score, its components, or related biomarkers. CONCLUSIONS: Higher adherence to the Mediterranean diet in pregnancy was associated with lower risk of having offspring with an accelerated growth pattern. This dietary pattern was not associated with the offspring's cardiometabolic risk at 4 years.

Are Early Physical Activity and Sedentary Behaviors Related to Working Memory at 7 and 14 Years of Age?

OBJECTIVE: To evaluate the role of extracurricular physical activity and sedentary behavior at preschool and primary school age on working memory at primary school age and adolescence, respectively. STUDY DESIGN: This prospective study was based on a birth cohort across 4 Spanish regions. In the 3 younger subcohorts (n = 1093), parents reported lifestyle habits of child at age 4 years of age on a questionnaire, and children performed a computerized working memory task at 7 years of age. In the older subcohort (n = 307), the questionnaire was completed at 6 years of age and working memory was tested at 14 years of age. Adjusted regression models were developed to investigate the associations between lifestyle habits and working memory. RESULTS: Low extracurricular physical activity levels at 4 years of age were associated with a nonsignificant 0.95% (95% CI -2.81 to 0.92) reduction of correct responses in the working memory task at age 7 years of age. Low extracurricular physical activity levels at 6 years of age were associated with a 4.22% (95% CI -8.05 to -0.39) reduction of correct responses at age 14 years. Television watching was not associated with working memory. Other sedentary behaviors at 6 year of age were associated with a 5.07% (95% CI -9.68 to -0.46) reduction of correct responses in boys at 14 years of age. CONCLUSION: Low extracurricular physical activity levels at preschool and primary school ages were associated with poorer working memory performance at primary school age and adolescence, respectively. High sedentary behavior levels at primary school age were related negatively to working memory in adolescent boys.

Child patterns of growth delay and cognitive development in a Bolivian mining city.

OBJECTIVES: This study aims to (1) follow up and characterize infant growth patterns during the first year of life in Bolivia, and (2) determine whether there exists an association between weight gain and cognitive development in children living near contaminated mining industries. METHODS: Data on 175 children participating to the ToxBol (Toxicity in Bolivia) birth cohort were analyzed. Rapid-growth during the first 6 months was defined as a change in weight z-score > 0.67 while slow-growth was defined as a weight z-score change of < -0.67. Neurodevelopment was evaluated using the Bayley Scales of Infant Development at 10.5-12.5 months of age. Mixed models were used to examine the association between cognitive development and weight gain. RESULTS: Rapid growers weighed less at birth (P < 0.01). However, they revealed a higher body mass index at 12 months of age (0.70 ± 0.73, P < 0.01). After adjustment for confounding, rapid growth was not associated with cognitive development (coef = 0.49, 95% confidence interval = -4.10, 5.08). CONCLUSIONS: In this Bolivian cohort, children born smaller were more likely to grow/develop faster and attain greater weight and length. Their cognitive development was not affected by their growth patterns.

Child neurodevelopment in a Bolivian mining city.

This study evaluates the neurodevelopment of children living near contaminated mining industries during their first year of life. Participants from the city of Oruro (Bolivia) were prospectively recruited during pregnancy. Follow-up occurred between May 2007 and November 2009. Information about the socioeconomic status and medical history of the pregnant women were collected using questionnaires. Neurodevelopment was evaluated for 246 children using the Bayley Scales of Infant Development (BSID) at 10.5-12.5 months of age. Exposure to trace elements (Pb, As, Cd, Sb, Cs, Zn, Fe, Cu, Se, Rb, and Sr) during prenatal life was evaluated by testing maternal blood concentrations before delivery. Almost all measured levels were lower than the control limits. The blood lead concentration of pregnant women was low, considering the contaminated environmental context. The geometric mean was 1.76 µg/dL (95% CI: 1.68-1.84), a level comparable with those observed in non-contaminated areas. The only element found to be relatively elevated was antimony, with a geometric mean of 1.03 µg/dL (95% CI: 0.96-1.11). Our results suggest that women from this mining area were not highly exposed. The Bayley Scales of Infant Development (BSID) did not reveal mental or psychomotor abnormalities. Surprisingly, at the observed low levels, lead was positively associated with the children's BSID performance.

Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.

BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. RESULTS: An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.