title: Downstream effects of maternal hypothyroxinemia in early pregnancy: nonverbal IQ and brain morphology in school-age children.
abstract: BACKGROUND
  Although maternal hypothyroxinemia is suggested to be related to various adverse consequences in a child's neurodevelopment, the underlying neurobiology is largely unknown.
  
  
  OBJECTIVE
  The objective of the study was to examine the relationship between maternal hypothyroxinemia in early pregnancy and children's nonverbal intelligence quotient (IQ). Furthermore, we explored whether global brain volumes, cortical thickness, and brain surface area differed between children exposed prenatally to hypothyroxinemia and healthy controls.
  
  
  METHODS
  The study included a large population-based prospective birth cohort in The Netherlands.
  
  
  METHODS
  A total of 3727 mother-child pairs with data on prenatal thyroid function at less than 18 weeks of gestation and nonverbal IQ at 6 years participated in the study. In 652 children, brain imaging was performed at 8 years of age.
  
  
  METHODS
  Maternal hypothyroxinemia was defined as free T4 in the lowest 5% of the sample, whereas TSH was in the normal range. At 6 years, children's IQ was assessed using a Dutch test battery. Global brain volumetric measures, cortical thickness, and surface area were assessed using high-resolution structural magnetic resonance imaging.
  
  
  RESULTS
  The children of mothers with hypothyroxinemia in early pregnancy scored 4.3 points IQ lower than the children of mothers with normal thyroid status (95% confidence interval -6.68, -1.81; P = .001). After adjustment for multiple testing, we did not find any differences in brain volumetric measures, cortical thickness, and surface area between children exposed prenatally to hypothyroxinemia and controls.
  
  
  CONCLUSIONS
  Our findings confirm a large adverse effect of maternal hypothyroxinemia on children's nonverbal IQ at school age. However, we found no evidence that maternal hypothyroxinemia is associated with differences in brain morphology in school-age children.
authors.affiliation: Departments of Child and Adolescent Psychiatry (A.G., H.E.M., F.C.V., H.T., T.W.) and Pediatrics (V.W.J.), Erasmus Medical Center-Sophia's Children Hospital, 3000 CB Rotterdam, the Netherlands; and The Generation R Study Group (A.G., H.E.M.) and Departments of Internal Medicine (R.P.P.), Epidemiology (V.W.J., A.H., H.T.), Psychiatry (H.T.), and Radiology (T.W.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Akhgar
authors.initials: A
authors.lastname: Ghassabian
authors.forename: Hanan
authors.initials: H
authors.lastname: El Marroun
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.forename: Tonya
authors.initials: T
authors.lastname: White
mesh_terms: D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002657:Child Development; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000453:epidemiology*; D007231:Infant, Newborn; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D009929:Organ Size; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000453:epidemiology*; D013974:Thyroxine / Q000097:blood*
chemical_list: D013974:Thyroxine