Delayed Neurobehavioral Development in Children Born to Pregnant Women with Mild Hypothyroxinemia During the First Month of Gestation: The Importance of Early Iodine Supplementation

Abstract

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 mg 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 (AESD) developmental quotient of children was 101.8 AE 9.7 in group 1 (n ¼ 13) vs. 87.5 AE 8.9 in group 3 (n ¼ 19; p < 0.001) and 92.2 AE 5.4 in group 2 (n ¼ 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.

11 Hypothyroidism in Pregnancy

“…Interestingly, in a very recent study by Henrichs et al [44] carried out in The Netherlands on a cohort of 3659 women, the prevalence of mild hypothyroxinemia (FT4 < 10th percentile) was 8.5% and that of severe hypothyroxinemia (FT4 < 5th percentile) 4.3%. These figures are significantly higher than those reported in previous studies conducted in iodine sufficient regions [40,42].…”

“…Indeed, in regions where iodine intake is sufficient, as is the case in the United States, the prevalence of isolated hypothyroxinemia ranges between 1.3% [40] and 2.3% [41]. In contrast, in mildly to moderately iodine deficient regions, isolated hypothyroxinemia affects a much higher percentage of women, reaching values up to 25-30% [42,43]. Interestingly, in a very recent study by Henrichs et al [44] carried out in The Netherlands on a cohort of 3659 women, the prevalence of mild hypothyroxinemia (FT4 < 10th percentile) was 8.5% and that of severe hypothyroxinemia (FT4 < 5th percentile) 4.3%.…”

“…Berbel P et al [94] recruited three groups of pregnant women living in Spain at different phases of gestation; the first group of women had T4 concentrations >20th percentile at recruitment (>0.92 ng/dL at 4-6 weeks gestation), while the second and third groups of women had T4 concentrations <10th percentile (<0.83 ng/dL) at 12-14 weeks gestation and near term, respectively. All three groups of women were supplemented with 200 μg of iodine until the end of lactation.…”

Iodine intake in Portuguese pregnant women: results of a countrywide study

“…Moreover, there is evidence that these neurocognitive problems may appear in children born to mothers with mild to moderate iodineinsufficient intake (20)(21)(22).…”

Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project

“…It has also been observed repeatedly that, aside from dietary iodine insufficiency, prolonged elevation of thyroid autoantibodies-especially those to thyroid peroxidase (TPO)-may lead to a gamut of neurodevelopmental delays, including cognitive deficits (3)(4)(5)(6)(7)(8)(9). The presence of circulating thyroid autoantibodies does not necessarily presage clinical disease, and affordable technological advances are changing our understanding of the prevalence and possible implications of subclinical autoantibody elevation (10).…”