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Updated: Sep 10, 2025

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Persistent Pulmonary Hypertension Among Infants Undergoing Therapeutic Hypothermia for Hypoxic Ischemic
Rashida Javed1, Tim J Van Hasselt2, Narasimha Rao3
1Department of Paediatrics, Northampton General Hospital, Northampton, UK.
Insights
Therapeutic hypothermia (TH) did not show an association with persistent pulmonary hypertension (PPHN) in infants with hypoxic-ischemic encephalopathy (HIE). Clinicians should remain vigilant for PPHN in both TH and non-TH groups.
Area of Science:
- Neonatal Medicine
- Pediatric Cardiology
- Critical Care Medicine
Background:
- Persistent pulmonary hypertension (PPHN) is a serious condition in neonates.
- Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity.
- Therapeutic hypothermia (TH) is a standard treatment for moderate to severe HIE.
Purpose of the Study:
- To systematically review and meta-analyze the association between PPHN and TH in infants with moderate to severe HIE.
- To compare the incidence of PPHN in infants receiving TH versus those not receiving TH.
Main Methods:
- Systematic review and meta-analysis of randomized control trials (RCTs) from 2000 to 2025.
- Searches conducted in Ovid, Medline, Embase, and Cochrane Central databases.
- Seven RCTs involving 1006 infants were included in the meta-analysis for PPHN outcomes.
Main Results:
- The relative risk of PPHN for TH versus non-TH (NT) was 1.13 (95% CI 0.81 to 1.57).
- No statistically significant association was found between TH and PPHN.
- A considerable number of infants developed PPHN in both TH and NT groups, with noted risk of bias in participant blinding.
Conclusions:
- Current evidence does not support an association between therapeutic hypothermia and an increased risk of persistent pulmonary hypertension in infants with moderate to severe HIE.
- Clinicians should maintain awareness of PPHN risk and ensure prompt investigation and management for all infants with HIE, regardless of TH status.
Abstract:
To perform a systematic review and meta-analysis to examine the association between persistent pulmonary hypertension (PPHN) and receipt of therapeutic hypothermia (TH), compared to those who did not receive TH, among infants with moderate or severe hypoxic-ischemic encephalopathy (HIE). Systematic review and meta-analysis based on Ovid, Medline, Embase and Cochrane central searches from 01/01/2000 to 31/03/2025. We included only randomized control trials for meta-analysis and followed international guidelines for conducting systematic reviews. The primary outcome of the study was PPHN in infants undergoing TH for moderate to severe HIE. Among 185 articles identified using search strategy, 19 articles were assessed for eligibility. Eight randomized control trials (RCTs) met the inclusion criteria, and seven were included in meta-analysis. A random effects model used for the outcome of PPHN, comparing TH with NT or usual care, involving a pooled population of 1006 infants across seven studies. The relative risk of PPHN for TH versus NT was 1.13 (95% confidence interval 0.81 to 1.57). We noted risk of bias in the blinding of participants across included RCTs. We assessed nine observational studies and performed a narrative review. We noted that a considerable number of infants developed PPHN across TH and NT groups. We did not find evidence of an association between TH and PPHN in infants with moderate to severe HIE, although a considerable number of infants developed PPHN across both groups. We suggest that clinicians should be aware of the risk of PPHN to allow prompt investigation and management.
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