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Published on: November 20, 2015
Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?
Insights
Hyperthyrotropinemia (HTT) and inflammation (ISSI) impact brain damage differently. HTT alone may reduce some risks, but combined with ISSI, it elevates risks for developmental delays and microcephaly in preterm infants.
Area of Science:
- Neonatal neurology
- Endocrinology
- Immunology
Background:
- Investigating factors contributing to brain damage in preterm infants.
- Disentangling the roles of thyroid dysfunction and systemic inflammation.
- Assessing hyperthyrotropinemia (HTT) and intermittent or sustained systemic inflammation (ISSI) as potential contributors.
Purpose of the Study:
- To determine the independent and combined effects of HTT and ISSI on brain injury indicators.
- To analyze the association between HTT, ISSI, and structural/functional brain damage in very preterm neonates.
- To differentiate the impact of HTT and ISSI on neonatal brain development.
Main Methods:
- Measured TSH and 25 inflammation markers in 786 preterm infants.
- Defined HTT by TSH in the highest quartile on day 14.
- Defined ISSI by inflammatory protein levels in the top quartile on two separate days.
Main Results:
- ISSI alone or combined with HTT increased ventriculomegaly risk.
- HTT alone was associated with reduced hypoechoic lesions but increased quadriparesis risk.
- HTT+ISSI elevated risks for poor mental/motor scores and microcephaly.
Conclusions:
- The effect of HTT on brain damage indicators is modulated by the presence or absence of ISSI.
- ISSI plays a significant role in adverse brain outcomes, particularly when co-occurring with HTT.
- Understanding these interactions is crucial for targeted interventions in preterm infants.
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 thyroid-stimulating hormone (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 2 separate days a week apart during the first 2 postnatal weeks. We first assessed the risk of brain damage indicators by 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.
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 (ORs) 2-6], whereas those with HTT only were at significantly reduced risk of a hypoechoic lesion (ORs 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 1.6-2.4). Elevated risk of a very low mental development score was associated with both ISSI only and HTT+ISSI, whereas 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 on the presence or absence of ISSI.
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