Ainara Andiarena

Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consumption Levels

Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype. We evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004-2008. Bayley and McCarthy scales and the Childhood Asperger Syndrome Test were used to assess neuropsychological development. Results from multivariate linear regression models were adjusted for sociodemographic characteristics and further adjusted for umbilical cord blood mercury or long-chain polyunsaturated fatty acid concentrations. Overall, consumption of seafood above the recommended limit of 340 g/week was associated with 10-g/week increments in neuropsychological scores. By subtype, in addition to lean fish, consumption of large fatty fish showed a positive association; offspring of persons within the highest quantile (>238 g/week) had an adjusted increase of 2.29 points in McCarthy general cognitive score (95% confidence interval: 0.42, 4.16). Similar findings were observed for the Childhood Asperger Syndrome Test. Beta coefficients diminished 15%-30% after adjustment for mercury or long-chain polyunsaturated fatty acid concentrations. Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits.

Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms

Background Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age. Methods This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conners Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities. Results Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38). Conclusions Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.

Vitamin D in Pregnancy and Attention Deficit Hyperactivity Disorder-like Symptoms in Childhood.

Background: Vitamin D status during prenatal brain development may influence risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. However, there are no prospective studies addressing this hypothesis. We aimed to examine whether maternal vitamin D status in pregnancy is associated with risk of ADHD-like symptoms in offspring. Methods: We conducted a prospective study analyzing data from 1,650 mother–child pairs from five birth cohorts embedded in the INMA Project (Spain, 1997–2008). Maternal vitamin D status in pregnancy was estimated by measuring plasma concentration of 25-hydroxyvitamin D3 [25(OH)D3] at 13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms at ages 4–5 years using the Diagnostic and Statistical Manual of Mental Disorders ADHD form list. Results: After adjustment, the number of total ADHD-like symptoms in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3 concentration (incidence rate ratio [IRR] = 0.89; 95% confidence interval [CI] = 0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment = 0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI = 0.78, 0.99 for the hyperactivity–impulsivity scale). Using diagnostic criteria, we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49, 1.04) in children. Conclusion: Higher maternal circulating levels of 25(OH)D3 in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood.

Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool children: The Environment and Childhood (INMA) Project

We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was associated with impaired neurodevelopment in preschool children from the Spanish Environment and Childhood (INMA) Project, using the placenta as exposure matrix. We measured metal levels in placenta tissue samples randomly selected from five of the seven population-based birth cohorts participating in the INMA Project, collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was carried through the use of the McCarthy Scales of Childrens Abilities (MSCA) at the age of 4-5years. Data on placental metal levels, MSCA scores, and relevant covariates was available for 302 children. Mn was detected in all placental samples, Cd in nearly all placentas (99%) and As, Hg, and Pb in 22%, 58%, and 17% of the placentas, respectively. After adjusting for potential confounders, detectable As levels were associated with decrements in global and verbal executive functions and quantitative abilities; detectable Hg was associated with lower scores on the verbal function of posterior cortex in a dose-response manner, and non-linearly related to poorer motor function and gross motor skills; and Mn levels were associated with decrement in perceptual-performance skills in a dose-response manner but with better memory span and quantitative skills. A synergistic interactive effect was found between As and Pb with respect to the general cognitive score, whereas an antagonistic interaction was found between Mn and Hg. Prenatal exposure to As and Hg may be a risk factor for cognitive and motor impairment in children, while the effects of Cd and Mn on neurodevelopment are less clear. Future studies should examine combined and interactive effects of exposure to multiple metals during vulnerable periods of brain development prospectively.

Evening salivary cortisol and alpha-amylase at 14 months and neurodevelopment at 4 years: Sex differences

ABSTRACT Stress system activity in early life can have long‐term effects on neurodevelopment. The main aim of this study was to assess the association of child evening salivary cortisol and alpha‐amylase basal levels at 14 months of age with longer‐term neuropsychological development at 4 years in a low‐risk population‐based birth cohort derived from the INMA (Environment and Childhood) project in Spain. We included 186 parent‐children pairs with information on both stress system activity and neurodevelopment. Both stress markers at 14 months of age showed an association with neuropsychological development at 4 years. Salivary cortisol showed a sex‐specific pattern of association. In girls, cortisol levels at 14 months were negatively associated with cognitive development [long‐term declarative memory (&bgr; = − 17.8, p = 0.028; 95% CI = − 33.2 to − 2.5); executive function (&bgr; = − 9.8, p = 0.08; 95% CI = − 21 to 1)] and gross motor development (&bgr; = − 13; p = 0.022; 95% CI = − 24 to − 2), whereas in boys cortisol levels were negatively associated with socioemotional development [autistic‐like behaviours: Incidence Rate Ratio (IRR) = 1.6, p = 0.039; 95% CI = 1.01 to 2.41]. Salivary alpha‐amylase was positively associated with socioemotional development in boys only [social competence (&bgr; = 2.11, p = 0.013; 95% CI = 0.47 to 3.72), autistic‐like behaviours (IRR = 0.93, p = 0.042; 95% CI = 0.87 to 0.99) and hyperactivity symptoms (IRR = 0.81, p = 0.021; 95% CI = 0.69 to 0.97)]. These results suggest that stress system activity in early life is associated with longer‐term neurodevelopment and that sex is an important factor in this relationship.

Neuropsychological Assessment at Preschool Age: Adaptation and Validation of the McCarthy Scales of Children’s Abilities to 4 Year-old Basque-speaking Children

Early neuropsychological assessment provides important information for clinical practice and research. As previously no tool for neuropsychological assessment has been developed in or adapted to Basque, the aim of this study was to adapt and validate the McCarthy Scales of Childrens Abilities for 4 years old children. The adaptation and validation of the original instrument followed the methodological steps established by the International Test Commission. We examined the psychometric properties of the adapted instrument in 273 Basque preschool children (aged between 4 years and 4 months and 4 years and 11 months; 52.2% boys). Confirmatory factor analysis showed satisfactory fit indexes except for the General Cognitive and Memory scales. Most scales presented adequate internal consistency (Reliability coefficients ranged between .55 and .81). The Basque version also showed evidence of validity based on the relationship between neuropsychological development and sex, parental education, attention deficit hyperactivity disorder-like behaviours and early neurodevelopment (p < .05; effect sizes ranged between Cohens d = .26 and .52 and r = .15 and 39). The Basque MSCA can be regarded as a useful tool to evaluate cognitive and psychomotor development in preschool children.