• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• Q. What are the exact anatomical effects of maternal Hypothyroidism on the fetal brain?

  • Reduced neuronal differentiation
  • Reduced synapse formation
  • Reduced myelin formation
  • Reduced axonal and dendritic growth
  • Reduced astrocyte development

• Q. Which is more critical for fetal development- T4 or TSH?

  • Free T4 and T3 are essential for fetal development
  • TSH is essential for maternal well being

• Q. Does high T4 affect the fetal brain?

  • Both high and low T4 has an adverse effect on fetal brain development

• Q. What is a complete form of the CATS study?

  • Controlled antenatal thyroid screening

• Q. What was the design for the CATS study?

  • Women <15 weeks of gestation  TFT was done
  • Women with Free t4 <2.5 th percentile and TSH >97.5 percentile were treated with 150 mcg of LT4
  • IQ of the child was studied at 3 years
  • In the control group- TFT sample was taken and stored and analyzed after delivery

• Q. What were the results of the CATS study?

  • Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for Hypothyroidism did not improve cognitive function in children at 3 years of age.

• Q. Summarize the intrauterine timings in relation to the thyroid and neurological development?

  • Neurological development – starts at 5 weeks
  • Thyroid receptor present by 8 weeks
  • Thyroid gland development – 12 weeks
  • Thyroid hormone production – 16-18 weeks of gestation
  • Hence from 5 weeks to 18 weeks – the fetus is dependent on the maternal thyroid

• Q. What are the neurological manifestation of fetal Hypothyroidism?

  • Mental retardation and low IQ
  • Developmental delay
  • Spasticity
  • Deafness

• Q. How is the fetus protected from an excessive amount of maternal T4?

  • By type 3 deiodinase present in the placenta

• #Clinicalpearl

  • Thyroid is essential for brain development in the first 1000 days of life, including the antenatal period

• Q. Which affects the fetal brain- T4 or T3?

  • T3
  • Fetal neurological tissue has local deiodinase 2, which converts T4 to T3

• Q. Which are the various thyroid hormone transporters in the fetus?

  • MCT8 and 10
  • OATP2 and OATp3
  • LAT1 and LAT2

• Q. Describe with diagram the transport process of thyroid hormone in the fetus?

  • 

• Q. What is the importance of MCT8?

  • MCT8 is critical for T3 to enter the neurons
  • Hence MCT8 deficiency produces a neurological disorder called Allan-Herndon Dudley syndrome

• Q. What neurological outcomes are studied in various studies in relation to fetal brain and thyroid?

  • IQ
  • Risk of ADHD
  • Risk of Autism
  • Risk of schizophrenia
  • Gray matter volume and morphology

• Q. What is the Generation R study?

  • Study published in Lancet
  • Showed that both high and low T4 is associated with lower IQ in children
  • This was the population-based prospective cohort study

• Q. How much is IQ reduction seen in infants of mothers having untreated Hypothyroidism?

  • 7 point reduction in IQ
  • This is from a study by Haddow et al

• Q. Is lower maternal T4 associated with poor brain outcomes?

  • Prolonged low T4 is in mother is associated with poor neurological outcomes

• **Iodine nutrition and pregnancy **

• Q. What is the recommended intake of iodine during pregnancy?

  • 250 mcg/day

• Q. How is iodine deficiency assessed?

  • Using urinary iodine concentration
  • Sufficient iodine status is determined by UIC of 150-250 mcg/l

• Q. How much gap must be there between thyroid supplementation and iron supplementation?

  • At least 4 hours

• Q. What should be the iodine intake during breastfeeding?

  • 250 mcg/day (some recommend 290 mcg/day)

• Q. Why is iodine deficiency during pregnancy so important?

  • Because it is the leading cause of preventable brain damage

• Q. When does iodine deficiency produce neurological cretinism, and when does it produce myxomatous cretinism in infants?

  • Iodine deficiency in early pregnancy – neurological cretinism
  • Iodine deficiency later in pregnancy – myxomatous cretinism

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