http://repub.eur.nl/res/aut/36364/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/38257/ 2012-02-01T00:00:00Z Background: Maternal thyroid status and autoimmunity during pregnancy have been associated with impaired development of the offspring in animal and human studies. Our objective was to examine whether elevated titers of maternal thyroid peroxidase antibodies (TPOAbs) in early pregnancy increased the risk of cognitive impairment and problem behavior in preschool children. Second, we aimed at exploring to what extent any effect on child behavior was mediated by maternal thyroid parameters during pregnancy. Methods: In the Generation R Study, a population-based cohort of 3139 children and their mothers, we measured maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) at 13.5±1.8 weeks of gestation. Children's verbal and nonverbal cognitive functioning was measured at 2.5 years using the Language Development Survey and the Parent Report of Children Abilities. At 3 years, children's behavior was assessed using the Child Behavior Checklist. Results: Elevated titers of TPOAbs during pregnancy did not predict the verbal and nonverbal cognitive functioning of the children. However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17-2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15-2.72, p=0.01). To explore whether the effect of maternal TPOAbs on child problem behavior was mediated by maternal thyroid parameters, we added maternal TSH to the model. After correcting for TSH, the effect of TPOAbs on externalizing problems was attenuated slightly but remained significant (OR=1.56, 95% CI: 1.14, 2.14, p=0.005). Conclusions: Our findings imply that the elevated titers of TPOAbs during pregnancy impact children's risk of problem behavior, in particular, attention deficit/hyperactivity. The observed effect is only partially explained by maternal TSH levels. These findings may point to a specific mechanism of Attention Deficit/Hyperactivity Disorder in children. Nevertheless, we can only speculate about public health implication of the study, as there is no specific treatment for TPOAb-positive pregnant women with normal thyroid function. Further investigation is needed to explore whether TPOAb-positive pregnant women and their children can benefit from close monitoring and early detection of developmental delay in populations at risk. http://repub.eur.nl/res/pub/26472/ 2011-05-01T00:00:00Z Maternal thyroid function during pregnancy is implicated in the neurodevelopment of the offspring, yet little is known about the effect of maternal thyroid parameters on the behavior of children. We investigated the association of maternal thyroid function during the first half of pregnancy with parent-reported problem behavior of the offspring up to age of 3 y. In the Generation R study, a population-based cohort of 3736 children and their mothers, data on maternal thyroid function and child's behavior were examined. The degree of internalizing and externalizing problems in the children were assessed with the Child Behavior Checklist at ages 11/2 and 3 y. Higher levels of maternal TSH during pregnancy predicted a higher externalizing scores in children at 11/2 and 3 y (B = 0.22 per SD of TSH; 95% CI: 0.04, 0.40; B = 0.10 per SD for internalizing scores; 95% CI:-0.01, 0.21). Maternal free thyroxine (T4) and total T4 were not associated with internalizing or externalizing scores of children. The linear relationship with more externalizing scores was across the range of TSH; this implies that subtle impairments of maternal thyroid function may affect the child. The results suggest that thyroid function is crucial for fetal brain development, which determines problem behavior later in life. Copyright http://repub.eur.nl/res/pub/27484/ 2010-09-01T00:00:00Z Context: Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and children's cognitive development are sparse. Objective: Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T4(FT4) levels across the entire range with cognitive functioning in early childhood. Design and Setting: We conducted a population-based cohort in The Netherlands. Participants: Participants included 3659 children and their mothers. Main Measures: In pregnant women with normal TSH levels at 13 wk gestation (SD = 1.7), mild and severe maternal hypothyroxinemia were defined as FT4concentrations below the 10th and 5th percentile, respectively. Children's expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Report of Children's Abilities measuring verbal and nonverbal cognitive functioning. Results: Maternal TSH was not related to the cognitive outcomes. An increase in maternal FT4predicted a lower risk of expressive language delay at 30 months only. However, both mild and severe maternal hypothyroxinemia was associated with a higher risk of expressive language delay across all ages [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.09-1.91; P = 0.010 and OR = 1.80; 95% CI = 1.24-2.61; P = 0.002, respectively]. Severe maternal hypothyroxinemia also predicted a higher risk of nonverbal cognitive delay (OR = 2.03; 95% CI = 1.22-3.39; P = 0.007). Conclusions: Maternal hypothyroxinemia is a risk factor for cognitive delay in early childhood. Copyright