title: Severe maternal hypothyroidism corrected prior to the third trimester is associated with normal cognitive outcome in the offspring.
abstract: BACKGROUND
  Concern about potential harmful effects of early maternal hypothyroidism (MH) on fetal brain development has led to calls for universal screening early in, or even before, pregnancy. However, evidence in humans that adverse effects are irreversible if thyroid hormone replacement is initiated after the first trimester is limited. Severe MH due to thyrotropin (TSH) receptor blocking antibodies (Abs) is associated with profound cognitive delay in the offspring if MH is untreated or inadequately treated; here, we sought to determine the outcome if treatment is given in early pregnancy.
  
  
  METHODS
  We identified three women who had TSH receptor blocking Ab-induced MH during pregnancy and were treated with L-thyroxine (L-T4), starting at 27 weeks, 5 weeks, and the first month of gestation. The corresponding pretreatment serum TSH levels in the two women in whom data were available were 68 and 65 mU/L, falling to 6 mU/L at 25 and 24 weeks of gestation, respectively. The third woman with MH required 0.5 mg of L-T4 to normalize her thyroid hormone levels by 4 months of gestation. Their infants were also treated with L-T4 after neonatal screening that identified congenital hypothyroidism (CH). Neuropsychological tests to assess intelligence, language, memory, and visual-motor performance were administered to these three infants at 5.4 years of age (range 5.1-6.1) and to three sibling controls at 6.8 years (range 9.1-3.0).
  
  
  RESULTS
  Children born after MH had average or above average results on all parameters. Comparative scores of the neuropsychological tests in sibling pairs for full-scale intelligence quotient (IQ) and performance IQ were variable; some scores were higher and some were lower in CH children.
  
  
  CONCLUSIONS
  Although the findings do not exclude a subtle impact of MH during early gestation on intellectual function, the normal cognitive outcome despite overt MH should provide data with which to counsel mothers who have overt hypothyroidism early in pregnancy. Aggressive thyroid hormone replacement as soon as possible is important, but early termination of the pregnancy because of fear that the baby will have significant cognitive delay is not warranted.
authors.affiliation: UMass Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Downing
authors.forename: Leslie
authors.initials: L
authors.lastname: Halpern
authors.forename: Jeremi
authors.initials: J
authors.lastname: Carswell
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D003071:Cognition; D003072:Cognition Disorders / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D008297:Male; D008429:Maternal Welfare; D009483:Neuropsychological Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; C094372:thyrotropin-binding inhibitory immunoglobulin; D013972:Thyrotropin; D013974:Thyroxine