Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation

Thyroid. 2009 May;19(5):511-9. doi: 10.1089/thy.2008.0341.


Background: Maternal hypothyroxinemia, due to gestational iodine deficiency, causes neurological dysfunctions in the progeny. Our aim was to determine the effects of delayed iodine supplementation (200 microg KI per day) to mildly hypothyroxinemic pregnant women at the beginning of gestation (i.e., having circulating free thyroxine [FT(4)] within the 0th-10th percentile interval and normal thyrotropin [TSH]) on the neurobehavioral development of their children.

Methods: Using the Brunet-Lézine scale, we evaluated the neurocognitive performance at 18 months of age in three groups of children. Group 1 included children of women with FT(4) above the 20th percentile at 4-6 gestational weeks and at full-term. Group 2 included children of mildly hypothyroxinemic women diagnosed during the first 12-14 gestational weeks and with FT(4) above the 20th percentile at full-term. Group 3 included children born to mildly hypothyroxinemic women at full-term, without iodine supplementation during gestation. Women of all groups were iodine supplemented from the day of enrollment until the end of lactation.

Results: Before iodine supplementation, 33.0% of the women (114 out of 345) were hypothyroxinemic, with FT(4) below normal in 28 of them (8.1%). None were found to be hypothyroxinemic at full-term after supplementation. The mean (+/-SD) developmental quotient of children was 101.8 +/- 9.7 in group 1 (n = 13) vs. 87.5 +/- 8.9 in group 3 (n = 19; p < 0.001) and 92.2 +/- 5.4 in group 2 (n = 12; p < 0.05). The difference between groups 2 and 3 was not statistically significant. Delayed neurobehavioral performance was observed in 36.8% and 25.0% of children in groups 3 and 2, respectively, compared with no children in group 1. Differences (p < 0.001) were found on gross and fine motor coordination and socialization quotients. No statistically significant differences were found on language quotients.

Conclusions: A delay of 6-10 weeks in iodine supplementation of hypothyroxinemic mothers at the beginning of gestation increases the risk of neurodevelopmental delay in the progeny. Public health programs should address the growing problem of iodine deficiency among women of gestational age in developing and industrialized nations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child Development / drug effects*
  • Deficiency Diseases / blood
  • Deficiency Diseases / drug therapy*
  • Deficiency Diseases / physiopathology
  • Dietary Supplements*
  • Drug Administration Schedule
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant Behavior / drug effects*
  • Iodine / administration & dosage*
  • Iodine / blood
  • Iodine / deficiency
  • Lactation
  • Male
  • Motor Activity / drug effects
  • Nervous System / drug effects*
  • Nervous System / growth & development
  • Nervous System / physiopathology
  • Neuropsychological Tests
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / physiopathology
  • Prenatal Care
  • Prenatal Exposure Delayed Effects
  • Severity of Illness Index
  • Social Behavior
  • Thyrotropin / blood
  • Thyroxine / blood
  • Thyroxine / deficiency*
  • Treatment Outcome


  • Thyrotropin
  • Iodine
  • Thyroxine