Omega-3 Fatty Acid Intake during Pregnancy and Child Neuropsychological Development: A Multi-Centre Population-Based Birth Cohort Study in Spain.

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child's neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children's Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings.

Serum metal levels in a population of Spanish pregnant women.

OBJECTIVE: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD: Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain).

We assessed whether prenatal selenium (Se) exposure is associated with anthropometry at birth, placental weight and gestational age. Study subjects were 1249 mother-child pairs from the Valencia and Gipuzkoa cohorts of the Spanish Childhood and Environment Project (INMA, 2003-2008). Se was determined in serum samples taken at the first trimester of pregnancy. Socio-demographic and dietary characteristics were also collected by questionnaires. Mean (SD) serum Se concentration was 79.57 (9.64) µg/L. Se showed weak associations with both head circumference and gestational age. The association between serum Se concentration and birth weight and length was negative, and direct for placental weight and probability of preterm birth, although the coefficients did not reach statistical significance. Individuals with total mercury (THg) levels >15 µg/L reversed the serum Se concentration effect on head circumference. Significant interactions were found between sex and both gestational age and prematurity. Spontaneous birth gestational ages were estimated to be lower for males and their probability of prematurity was higher. In conclusion, prenatal Se exposure may be associated with lower head circumference and lower gestational ages at spontaneous birth. Interactions with THg exposure and gender should be considered when assessing these relationships.

Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data.

CONTEXT: Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. OBJECTIVE: To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. DESIGN: Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. SETTING: General community. PARTICIPANTS: 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease. MAIN OUTCOME MEASURE: Child nonverbal and verbal IQ assessed at 1.5 to 8 years of age. RESULTS: There was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (-0.6 point; 95% CI: -1.7 to 0.4 points; P = 0.246) or lower verbal IQ (-0.6 point; 95% CI: -1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. CONCLUSIONS: Fetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.

Maternal selenium status and neuropsychological development in Spanish preschool children.

BACKGROUND: The relationship between maternal selenium (Se) status and child neurodevelopment has been scarcely assessed. In a previous study we observed an inverse U-shaped association between maternal Se concentrations and infant neurodevelopment at 12 months of age. In this study, this non-linear association was explored at preschool age. The effect modification by breastfeeding, child's sex and cord blood mercury was also evaluated. METHODS: Study subjects were 490 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2012). Child neuropsychological development was assessed at around 5 years of age by the McCarthy Scales of Children's Abilities (MSCA). Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation and at 5 years of age. Se was measured in serum samples by ICP-MS at the end of the first trimester of pregnancy (mean ±â€¯standard deviation (SD) = 12.4 ±â€¯0.6 weeks of gestation). RESULTS: The mean ±â€¯SD of maternal serum Se concentrations was 79.9 ±â€¯8.1 µg/L. In multivariate analysis, no linear association was found between Se concentrations and the nine MSCA scales. Generalized additive models indicated inverted U-shaped relationships between Se concentrations and the verbal and global memory scales. When assessing the influence of effect modifiers, breastfeeding played a role: the association between Se and neuropsychological development was inverted U-shaped for the quantitative, general cognitive, working memory, fine motor, global motor and executive function scales only for non-breastfed children. CONCLUSION: Low and high maternal Se concentrations seem to be harmful for child neuropsychological development, however further studies should explore this non-linear relationship.

Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA Mother and Child Cohort Study.

BACKGROUND: The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years. METHODS: We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr). RESULTS: Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI -6.18 to -1.69) general cognitive scores lower than the reference (150-249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: -1.36; 95% CI -2.12 to -0.61; per one daily milk serving). CONCLUSIONS: We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child's neurodevelopment at 4-5 years.

Selenium status during pregnancy: Influential factors and effects on neuropsychological development among Spanish infants.

Selenium (Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT. Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2005). Infant neuropsychological development was assessed around 12months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation. Se was measured in serum samples at the first trimester. The mean serum Se concentration was 79.7 (standard deviation=7.9) µg/L. In multivariate analysis, nonsignificant inverse linear associations were found between Se concentrations and standardized mental and psychomotor development scores (ß (95% CI)=-0.13 (-0.29, 0.03) and ß (95% CI)=-0.08 (-0.24, 0.07), respectively). Generalized additive models indicated inverted U-shaped relationships between Se concentrations and both scales. Using segmented regression, the turning point for the associations was estimated at 86µg/L for both scales. The association between Se and neuropsychological development was inverted U-shaped for children with the AG+AA genotype for rs6970396 INMT but a descending curve was suggested for the GG genotype. Further studies would be necessary in order to disentangle the complex equilibrium between the toxicity and benefits of Se exposure during the prenatal period.

The INMA-INfancia y Medio Ambiente-(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research.

BACKGROUND: In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. RESULTS: The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. CONCLUSIONS: INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children.

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women.

OBJECTIVE: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. METHODS: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. RESULTS: The geometric means of TSH, TT3, FT4 and mercury were 1.1µU/L, 2.4nmol/L, 10.5pmol/L and 7.7µg/L, respectively. Mercury levels were marginally significantly associated with TT3 (ß: -0.05; 95%CI: -0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (-0.08; 95%CI: -0.15, -0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. CONCLUSION: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed.

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.