title: 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.
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Akhgar
authors.initials: A
authors.lastname: Ghassabian
authors.forename: Jacoba J
authors.initials: JJ
authors.lastname: Bongers-Schokking
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Nina
authors.initials: N
authors.lastname: van Mil
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: Sabine M P F
authors.initials: SM
authors.lastname: de Muinck Keizer-Schrama
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Willy
authors.initials: W
authors.lastname: Visser
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Roman
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D000328:Adult; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000453:epidemiology* / Q000209:etiology* / Q000523:psychology; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology / Q000523:psychology; D013959:Thyroid Diseases / Q000150:complications* / Q000453:epidemiology* / Q000523:psychology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine
chemical_list: D001323:Autoantibodies; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine