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Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Behavior
Charlotte Hales1, Peter N Taylor1, Sue Channon2
1Centre for Endocrine and Diabetes Sciences, School of Medicine, Cardiff University, Wales, UK.
Insights
Maternal thyroid treatment during pregnancy did not impact child behavior overall. However, overtreatment was linked to increased ADHD symptoms and behavioral issues in children, highlighting the need for careful monitoring.
Area of Science:
- Obstetrics and Gynecology
- Pediatric Neurology
- Endocrinology
Background:
- Suboptimal gestational thyroid function (SGTF) is a concern during pregnancy.
- Observational studies suggest a link between SGTF and increased risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children.
- The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to examine the effects of treating SGTF on child neurodevelopment.
Purpose of the Study:
- To investigate the impact of treating maternal suboptimal gestational thyroid function (SGTF) on child behavioral outcomes, including symptoms of ASD and ADHD.
- To analyze the association between maternal thyroid hormone levels during pregnancy and neurodevelopmental outcomes in offspring.
- To assess the safety and efficacy of thyroxine supplementation in pregnant individuals with SGTF.
Main Methods:
- The CATS study enrolled 475 mothers.
- Mothers completed validated questionnaires (SDQ, Child ADHD, SCQ) regarding their children's behavior (mean age 9.5 years).
- Children were categorized into normal gestational thyroid function (GTF), treated SGTF, and untreated SGTF groups. Comparisons included total scores, clinical threshold exceedance, and effects of maternal "overtreatment" (high FT4).
Main Results:
- No significant differences in overall behavioral scores were found between normal GTF, treated SGTF, and untreated SGTF groups.
- Children of mothers who were "overtreated" (excessively high maternal FT4) showed significantly higher rates of behavioral difficulties.
- Specifically, overtreatment was associated with increased scores for conduct problems (SDQ), ASD screening (SCQ), and ADHD hyperactivity symptoms compared to normal GTF and untreated SGTF groups.
Conclusions:
- There was no overall association between treating suboptimal gestational thyroid function (SGTF) and adverse behavioral outcomes in offspring.
- Maternal "overtreatment" with thyroxine during pregnancy was linked to a significant increase in ADHD symptoms and behavioral difficulties in children.
- Thyroxine supplementation in pregnancy necessitates careful monitoring to prevent overtreatment and potential negative neurodevelopmental effects.
Context & Objectives:
The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior.
Design & Participants:
Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported.
Results:
There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children.
Conclusions:
There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment.
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