Mild thyroid dysfunction at birth does not predict mid-childhood IQ
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Children with mildly elevated thyroid-stimulating hormone levels at birth have normal thyroid function in mid-childhood and have neurocognitive abilities similar to their sibling controls, study data show.
"Although no-one would question the benefit from detecting severe congenital hypothyroidism on newborn screening, TSH cutoffs in many parts of the world have dropped and now detect increasingly mild and subclinical disease,” Natasha L. Heather, MD, FRACP, MBChB, pediatric endocrinologist and clinical fellow to the national Newborn Metabolic Screening Programme of the Auckland District Health Board, New Zealand, told Healio. “The long-term benefit from treating these children remains unclear, yet their diagnosis and management causes anxiety and stress for families.”
Heather and colleagues analyzed data from 67 children aged 7 to 13 years born in the Auckland region with data from a newborn TSH screening that showed a TSH level between 8 mIU/L and 14 mIU/L, as well as 75 sibling controls. Researchers assessed thyroid function and neurocognitive function, including intelligence quotient via the Wechsler Intelligence Scale for Children, Fourth Edition.
“In New Zealand, we have maintained a conservative TSH screening cutoff of 15 mIU/L blood,” Heather said. “In this study, we followed 96 children with mild TSH elevation in their newborn screen, which had been below cutoff and therefore reported as normal. Children with similar TSH levels in other international centers would have been diagnosed and treated as having congenital hypothyroidism. A small number of the children had mild subclinical hypothyroidism; however, the majority had normal thyroid biochemistry.”
Mean TSH level at the time of newborn screening was 10.1 mIU/L, which fell to a mean of 2.4 mIU/L at the mid-childhood assessment. Although higher newborn TSH levels among children in the elevated TSH group correlated with lower full-scale IQ scores (P = .04), they were not associated with the magnitude of the IQ difference within sibling pairs, according to researchers.
There were no between-group differences in cognitive scores for children with an elevated TSH screening at birth vs. controls (full-scale IQ, 107 vs. 109; P = .36); however, researchers noted a minor isolated difference in motor coordination scores.
“Although each 1 IU/mL increase in TSH was associated with a 2.3-point decline in Wechsler Intelligence Scale for Children full-scale IQ score among children with mild TSH elevation, we did not observe a corresponding difference in IQ between these children and their sibling controls,” the researchers wrote. “Furthermore, [children with] mild TSH elevation and sibling groups performed similarly across a wide range of neurocognitive parameters. Together, our findings suggest that lower mid-childhood IQ levels are unlikely to be a consequence of untreated mild TSH elevation, but that the apparent correlation occurs due to familial and other environmental confounders.”
The researchers noted the data support the New Zealand newborn screening TSH cutoff of at least 15 mIU/L whole blood as being sufficient to detect congenital hypothyroidism cases requiring treatment.
“We caution against the practice of reducing congenital hypothyroid screening cutoffs to levels where the diagnosis may not offer long-term benefit to those detected,” Heather said. “Further studies in large, well-defined cohorts of children with treated and untreated mild TSH elevation are needed to help characterize subtle differences and demonstrate whether there is true benefit from early detection and treatment."
Untreated congenital hypothyroidism can result in cognitive impairment and growth complications, and newborn screening for primary congenital hypothyroidism is part of the U.S. Recommended Uniform Screening Panel. As Healio previously reported, a 2018 analysis published in the CDC’s Morbidity and Mortality Weekly Report demonstrated that a two-screen approach to diagnostic testing for congenital hypothyroidism, performed in newborns during the first 48 hours after birth and again at age 7 to 28 days, better identified missed cases of the disease vs. lowering the diagnostic threshold for a single test.
Perspective
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This is an interesting study which leverages the epidemiological advantages of sibling controls to remove major socioeconomic confounding factors to show that mildly elevated TSH at birth is not associated with IQ during later life. I fully support the conclusions of the authors and particularly their opinion that a conservative approach to changing reference ranges should be maintained.
Among children with congenital hypothyroidism, it has been shown that early overtreatment is also associated with suboptimal neurocognitive outcomes. Similarly, in the thyroid and pregnancy field, progressive decision making strategies for reference ranges for pregnant women based on limited evidence has likely led to long-term systematic overtreatment of pregnant women.
I hope the authors will be able to perform additional studies in which they obtain maternal data as well, as this could be key to assessing if certain subgroups of newborns with a mildly elevated TSH — for example, those with inadequate iodine intake or abnormal maternal thyroid function tests — do have suboptimal neurocognitive development.
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