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.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review

“…Based on the title screening, 850 records were eligible for abstract screening, of which 60 articles met the criteria for full article review. Following thorough review of the articles, 13 (26,27,28,29,30,31,32,33,34,35,36,37,38) remained eligible ( Fig. 1).…”

“…As shown in (Table 1), maternal thyroid status was measured during the first trimester and early second trimester in six studies (26,27,28,29,34,35,38); in one study it was measured during late second trimester (32) and in four studies timing was not reported (30,31,33,36). Offspring outcomes were measured between 3 and 8 years of age in most studies (26,27,29,31,32,33,34,35), except for some studies where outcomes were measured in young adulthood (28,36) and from age 15 through to 31 years (30).…”

“…Offspring outcomes were measured between 3 and 8 years of age in most studies (26,27,29,31,32,33,34,35), except for some studies where outcomes were measured in young adulthood (28,36) and from age 15 through to 31 years (30).…”

“…Across these studies, ADHD was assessed using different instruments, including the Conners' Parent Rating Scale-Revised Short Form reported by mothers (27), teachers evaluation using Rutter Scale B2 (34), and Child Behaviour Checklist (CBCL) reported by parents (29,32,35), although one study used hospital diagnosis and dispensed prescriptions of medications as indicators of ADHD which is more reliable given that appropriate recording and data extraction are applied (31).…”

“…In a study of 3139 mother-child pairs (35), the odds of offspring externalising behaviour at age 3 were higher among children exposed to maternal prenatal autoimmune thyroiditis (OR = 1.64 (1.17, 2.29)) at mean gestational age of 13.5 (s.d. = 1.8) weeks compared with those who were not.…”