Associations between newborn thyroid-stimulating hormone concentration and neurodevelopment and growth of children at 18 months

Iodine is an integral part of thyroid hormone, which in turn is required for normal brain development and physical growth during the early critical periods of life⁽¹⁾. Insufficient maternal iodine intake in pregnancy has been linked to poor growth^(2,3) and impaired neurodevelopment in children^(3–5) and can result in cretinism if iodine deficiency in pregnancy is severe⁽³⁾. Because of the concern of potential adverse effects on offspring, iodine supplementation in pregnancy has been recommended in many countries, including countries with sustained programmes to combat iodine deficiency like Australia with mandatory iodine fortification of bread⁽⁶⁾. However, the WHO technical consultation does not recommend iodine supplementation during pregnancy in iodine-sufficient populations with sustained programmes to combat iodine deficiency⁽⁷⁾. Evidence from randomised controlled trials suggested that iodine supplementation during pregnancy improved child neurodevelopment and growth in severe iodine deficiency settings^(2,8), but there is lack of benefit in mild iodine deficiency to iodine sufficiency settings based on limited data^(2,9,10). There is a concern of excess iodine intake in pregnant women from iodine-sufficient settings⁽¹¹⁾. Excessive iodine intake in pregnancy has been linked with subclinical hypothyroidism and isolated hypothyroxinaemia^(11,12).

Both iodine deficiency^(13–15) and excess^(16–18) in pregnancy were associated with elevated newborn thyroid-stimulating hormone (TSH) concentration. Newborn TSH has been suggested as a marker of iodine nutrition in pregnancy⁽¹⁹⁾, and it may be useful to identify children at risk of neurodevelopmental or growth delay in countries where newborn screening is routinely practiced.

There are several studies that assessed the association between newborn TSH concentration and childhood neurodevelopment. Studies in iodine-deficient populations showed that newborns with higher TSH concentrations of ≥5 mIU/l^(20–22) had an increased risk of developmental delay, but the association between newborn TSH and neurodevelopmental scores was inconsistent in iodine-sufficient populations^(23–26). Most published studies had methodological limitations like inadequate adjustment for potential confounders^(20,22), small sample sizes of <30 participants⁽²⁷⁾ or subjective assessment of the outcome^(23,24). Only a few studies have examined the association between newborn TSH concentration and childhood growth^(23,28,29).

The quality of the studies examining the relationship between newborn TSH concentration and neurodevelopment or growth of children was limited,...