BACKGROUND AND PURPOSE:

• Fetal thyroid hormone status dependent on maternal transfer until approximately 20 weeks
• There are conflicting guidelines regarding universal TSH testing during pregnancy because data regarding treatment outcomes for subclinical hypothyroidism are inconsistent
• Jansen et al. (The Lancet Diabetes & Endocrinology, 2019) sought to determine
  • If there is an association between maternal thyroid function and child brain morphology
  • If there is an ideal time to assess maternal thyroid function

METHODS:

• Prospective cohort study
• Participants
  • Women in the Generation R Study (Netherlands)
  • Availability of TSH and free thyroxine (FT4) obtained ≤18 weeks
  • Availability of brain MRI in offspring at 10 years
• Exclusion criteria: Pre-existing thyroid disorder | Twin pregnancy | IVF pregnancy | Suboptimal-quality MRI data or major incidental finding on MRI
• Data analysis
  • Regression analyses with following covariates: GA at time maternal thyroid study | Maternal age | Ethnicity | Education level | Smoking | Thyroid peroxidase antibody positivity | Sex of child | Age at MRI | Total intracranial volume
• Primary outcome
  • Association between maternal TSH and FT4 concentrations with brain MRI outcomes of children

RESULTS:

• 1,981 mother-child pairs
  • Median gestational age at time of maternal thyroid measurements: 13.1 weeks (IQR 12.1 to 14.5)
  • Median age of offspring at time of MRI: 9.9 years (9.7 to 10.2)
• Maternal TSH, both high and low levels, had an inverted U-shaped association with MRI brain morphology in offspring for both total grey matter volume (p=0.007 and mean cortex grey matter volume (p=0.022)
  • Impact of TSH levels on grey matter was most notable before 14 weeks following which TSH was no longer associated with child brain morphology
• FT4
  • Total brain volume was associated with FT4 (p=0.023) but not TSH (p=0.45)
  • After adjusting for total intracranial volume, maternal FT4 concentrations were not associated with child total grey matter volume (p=0.75)

CONCLUSION:

• Both low and high maternal thyroid function are associated with smaller total grey matter and cortical volume in the child at 10 years of age
• There appears to be a threshold of 14 weeks, when maternal TSH levels will impact child brain development
• Studies assessing benefit of treatment of subclinical hypothyroidism may conflict if
  • Treatment started after 14 weeks
  • Risk from low TSH levels not accounted for

Learn More – Primary Sources:

Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

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