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Childhood Brain Development: Is There a Critical Window for Maternal TSH Measurement?

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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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Related ObG Topics:

Does General Anesthesia Exposure in Infancy Impact Neurodevelopment?
Does Levothyroxine Increase Live Birth Rate in Women with Thyroid Peroxidase Antibodies?
Does Prophylactic rhEPO Improve Brain Development in Preterm Infants?
Does Hydrocortisone Treatment in Preterm Infants Impact Neurodevelopment?
Subclinical Hypothyroidism and Pregnancy Outcome – Is There a Relationship?

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