Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?

Abstract

Background We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage. Methods We measured the concentrations of TSH on day 14, and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on two separate days a week apart during the first two postnatal weeks. We first assessed the risk of brain damage indicators comparing 1) neonates who had HTT to those without (regardless of ISSI), and 2) neonates with HTT only, ISSI only, or HTT+ ISSI, to those who were exposed to neither HTT nor ISSI. HTT was defined as a TSH concentration in the highest quartile for gestational age on postnatal day 14. Results In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI, to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (OR) ranged from 2–6], while those with HTT only were at significantly reduced risk of a hypoechoic lesion [ORs ranged from 0.2–0.4]. Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis [ORs ranged from 1.6–2.4]. Elevated risk of a very low mental development score was associated with both ISSI only and with HTT+ISSI while a very low motor development score and microcephaly were associated with HTT+ISSI. Conclusions The association of HTT with increased or decreased risk of indicators of brain damage depends upon the presence or absence of ISSI.

Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

“…In some cases, elevated TSH level at NBS results from other factors than CH – such as preterm birth – that are also associated with poor developmental outcomes (23). Providing thyroxine treatment to preterm infant is not associated with improvement of their developmental outcomes (39).…”

“…Infants with mild increase in TSH at birth may have poorer neurodevelopmental outcomes for a number of reasons (23). Information about the long-term cognitive outcomes for neonates with mildly elevated TSH at birth is critical for any debate regarding the lowering of NBS cutoffs.…”

Systemic endogenous erythropoietin and associated disorders in extremely preterm newborns

“…The second is that an EPO blood concentration in the lowest quartile for gestational age is not associated with any postnatal disorder. These hypotheses were generated by previous findings in the ELGAN sample when we explored the relationship of EPO concentrations with those of inflammation-related proteins,11 and between thyrotropin concentrations and inflammation-related proteins and dysfunctions at age 2 years 20 21…”

Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns

“…Elevated concentrations of presumed anti-inflammatory protectors of the brain and retina, [55–58] such as erythropoietin and thyroid stimulating hormone, accompany systemic inflammation,[15, 59, 60] which contributes to brain damage. [59–61] Consequently, our second null hypothesis postulates that postnatal systemic inflammation is not associated with top quartile concentrations of NT-4, BDNF, or bFGF.…”