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Cytokines and posthemorrhagic ventricular dilation in premature infants
Namasivayam Ambalavanan1, Waldemar A Carlo, Scott A McDonald
1Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35249, USA. ambal@uab.edu
Insights
Cytokine levels in extremely low-birth-weight infants showed links to brain injury, but did not reliably predict the need for shunts or ventricular dilation after intraventricular hemorrhage (IVH). These biomarkers may not be clinically useful for white matter damage.
Area of Science:
- Neonatal research
- Immunology
- Pediatric neurology
Background:
- Severe intraventricular hemorrhage (IVH) is a significant complication in extremely low-birth-weight (ELBW) infants.
- The need for shunt surgery or ventricular dilation following IVH can impact long-term neurodevelopmental outcomes.
- Cytokines play a role in inflammatory responses and brain injury, but their specific role in IVH complications is not fully understood.
Purpose of the Study:
- To investigate the association between specific blood cytokines and the need for shunt placement in ELBW infants with severe IVH.
- To examine the relationship between blood cytokines and ventricular dilation in ELBW infants with milder or no IVH.
- To assess the potential of cytokines as clinical biomarkers for white matter damage in this population.
Main Methods:
- Whole blood cytokine levels (interferon-γ, interleukin-1β, IL-18, tumor necrosis factor-α, transforming growth factor-β) were measured on multiple postnatal days (1, 3, 7, 14, 21).
- Infants were monitored for maximum IVH grade within 28 days and for shunt surgery or ventricular dilation up to 36 weeks' postmenstrual age via ultrasound.
- Data from 902 ELBW infants in a Neonatal Research Network Cytokine study were analyzed.
Main Results:
- 3.1% of infants required shunt surgery, primarily those with severe IVH (grade III-IV), associated with elevated tumor necrosis factor-α (TNF-α).
- No shunts were needed for infants without IVH or with grades I-II IVH; however, 8.4% developed ventricular dilation, linked to lower interferon-γ (IFN-γ) and higher IL-18.
- While statistically significant cytokine alterations were observed, they were not clinically discriminatory for predicting shunt need or dilation.
Conclusions:
- Elevated TNF-α was associated with shunts in severe IVH cases, and altered IFN-γ/IL-18 with dilation in milder/no IVH cases.
- Blood cytokines appear related to brain injury in ELBW infants but lack clinical utility as biomarkers for white matter damage.
- Further research may be needed to identify reliable biomarkers for predicting IVH complications and guiding treatment.
Objective:
To determine in extremely low-birth-weight infants if elevated blood interferon-γ (IFN-γ), interleukin (IL)-1β, IL-18, tumor necrosis factor-α (TNF-α), and transforming growth factor-β are associated with need for shunt following severe intraventricular hemorrhage (IVH) or with ventricular dilation following milder grades/no IVH.
Study Design:
Whole blood cytokines were measured on postnatal days 1, 3, 7, 14, and 21. Maximum IVH grade in the first 28 days, and shunt surgery or ventricular dilation on subsequent ultrasound (28 days' to 36 weeks' postmenstrual age) were determined.
Results:
Of 902 infants in the National Institute of Child Health and Human Development Neonatal Research Network Cytokine study who survived to 36 weeks or discharge, 3.1% had shunts. Of the 12% of infants with severe (grade III to IV) IVH, 26% had a shunt associated with elevated TNF-α. None of the infants without IVH (69%) or with grade I (12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-γ and higher IL-18.
Conclusion:
Statistically significant but clinically nondiscriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage.
