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Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study.

ABSTRACT: 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.

SUBMITTER: Ghassabian A

PROVIDER: S-EPMC3271370 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study.

Ghassabian Akhgar A Bongers-Schokking Jacoba J JJ de Rijke Yolanda B YB van Mil Nina N Jaddoe Vincent W V VW de Muinck Keizer-Schrama Sabine M P F SM Hooijkaas Herbert H Hofman Albert A Visser Willy W Roman Gustavo C GC Visser Theo J TJ Verhulst Frank C FC Tiemeier Henning H

Thyroid : official journal of the American Thyroid Association 20111216 2

<h4>Background</h4>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 du ...[more]

PMID: 22175242

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Project description:ImportanceMaternal autoimmune disease has been associated with increased risk of neurodevelopmental disorders in offspring, but few studies have assessed the association with attention-deficit/hyperactivity disorder (ADHD).ObjectiveTo examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis.Design, setting, and participantsA cohort study was conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014; and a systematic review evaluated articles from the MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. A total of 12 610 children exposed to maternal autoimmune disease were propensity score matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. A child was considered to have ADHD if they had (1) an authorization or filled prescription for stimulant treatment for ADHD or (2) a hospital diagnosis of ADHD. Children linked to a first ADHD event before 3 years of age were excluded. Data were analyzed from January 13 to April 20, 2020.ExposuresOne or more maternal autoimmune diagnoses in linked hospital admission records between July 1, 2000, and December 31, 2012. Thirty-five conditions were considered together and individually.Main outcomes and measuresThe main outcome was child ADHD identified from stimulant authorization or prescription data and diagnoses in linked hospital admission records. Multivariable Cox regression was used to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. Pooled hazard ratios (HRs) were calculated using random-effects meta-analysis with inverse-variance weights for each exposure reported by 2 or more studies.ResultsIn the population-based cohort analysis, 831 718 singleton, term infants born to 831 718 mothers (mean [SD] age, 29.8 [5.6] years) were assessed. Of 12 767 infants (1.5%) who were linked to a maternal autoimmune diagnosis, 12 610 were propensity score matched to 50 440 control infants, for a total study cohort of 63 050 infants. In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was type 1 diabetes (HR, 2.23; 95% CI, 1.66-3.00), psoriasis (HR, 1.66; 95% CI, 1.02-2.70), and rheumatic fever or rheumatic carditis (HR, 1.75; 95% CI, 1.06-2.89). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR, 1.20; 95% CI, 1.03-1.38), type 1 diabetes (4 studies: HR, 1.53; 95% CI, 1.27-1.85), hyperthyroidism (3 studies: HR, 1.15; 95% CI, 1.06-1.26), and psoriasis (2 studies: HR, 1.31; 95% CI, 1.10-1.56) were associated with ADHD.Conclusions and relevanceIn this cohort study, maternal autoimmune diseases were associated with increased ADHD among children. These findings suggest possible shared genetic vulnerability between autoimmune disease and ADHD or a potential role for maternal immune activation in the expression of neurodevelopmental disorders in children. Future studies measuring disease activity, modifiers, and medication use are required to better understand the mechanisms underlying this association.

Project description:BACKGROUND:Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. OBJECTIVES:We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. METHODS:This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 ?g/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ?18 weeks and ?14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (?93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. RESULTS:UI/Creat <150 ?g/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 ?g/g in early pregnancy (i.e., ?18 weeks or ?14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status. CONCLUSIONS:There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits.

Project description:Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both within the CON and within the DMN. Full-brain behavioral associations were found for a number of between-network connections. Across both groups, more anti-correlation between DMN and occipital cortex supported better attentional control. However, in the TD group, this brain-behavior association was stronger and occurred for a more extensive set of DMN-occipital connections. Differential support for attentional control between the two groups occurred with a number of CON-DMN connections. For all CON-DMN connections identified, increased between-network anti-correlation was associated with better attentional control for the ADHD group, but worse attentional control in the TD group. A number of between-network connections with the medial frontal cortex, in particular, showed this relationship. Follow-up analyses revealed that these associations were specific to attentional control and were not due to individual differences in working memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is associated with improved attention in ADHD, other circuitry supports improved attention in TD children. Greater CON-DMN anti-correlation supported better attentional control in children with ADHD, but worse attentional control in TD children. On the other hand, greater DMN-occipital anti-correlation supported better attentional control in TD children.

Project description:IntroductionChildren with attention-deficit/hyperactivity disorder (ADHD) commonly experience behavioural sleep problems, yet these difficulties are not routinely assessed and managed in this group. Presenting with similar symptoms to ADHD itself, sleep problems are complex in children with ADHD and their aetiology is likely to be multifactorial. Common internalising and externalising comorbidities have been associated with sleep problems in children with ADHD; however, this relationship is yet to be fully elucidated. Furthermore, limited longitudinal data exist on sleep problems in children with ADHD, thus their persistence and impact remain unknown. In a diverse sample of children with ADHD, this study aims to: (1) quantify the relationship between sleep problems and internalising and externalising comorbidities; (2) examine sleep problem trajectories and risk factors; and (3) examine the longitudinal associations between sleep problems and child and family functioning over a 12-month period.Methods and analysisA prospective cohort study of 400 children with ADHD (150 with no/mild sleep problems, 250 with moderate/severe sleep problems) recruited from paediatric practices across Victoria, Australia. The children's parents and teacher provide data at baseline and 6-month and 12-month post enrolment.Key measuresParent report of child's sleep problem severity (no, mild, moderate, severe); specific sleep domain scores assessed using the Child Sleep Habits Questionnaire; internalising and externalising comorbidities assessed by the Anxiety Disorders Interview Schedule for Children IV/Parent version.AnalysesMultiple variable logistic and linear regression models examining the associations between key measures, adjusted for confounders identified a priori.Ethics and disseminationEthics approval has been granted. Findings will contribute to our understanding of behavioural sleep problems in children with ADHD. Clinically, they could improve the assessment and management of sleep problems in this group. We will seek to publish in leading paediatric journals, present at conferences and inform Australian paediatricians through the Australian Paediatric Research Network.

Dataset Information

Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study.

Publications

Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study.

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