Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study.
Fetal growth restriction
Neonatal morbidity
Neonatal mortality
Pulmonary hypertension
Sildenafil
Journal
European journal of pediatrics
ISSN: 1432-1076
Titre abrégé: Eur J Pediatr
Pays: Germany
ID NLM: 7603873
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
16
06
2021
accepted:
16
12
2021
revised:
08
11
2021
pubmed:
13
1
2022
medline:
1
4
2022
entrez:
12
1
2022
Statut:
ppublish
Résumé
The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02). Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a "rebound" vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. • In the Dutch STRIDER trial, persistent pulmonary hypertension in the neonate (PPHN) was more frequent among infants after antenatal sildenafil exposure versus placebo. • The current analysis focuses on the distinction between PPHN and pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia and on timing of diagnosis and aims to identify the infants at risk for developing pulmonary hypertension. • The diagnosis pulmonary hypertension is complex, especially in infants born after severe early-onset fetal growth restriction. The research field could benefit from an unambiguous consensus definition and standardized screening in infants at risk is proposed.
Identifiants
pubmed: 35018508
doi: 10.1007/s00431-021-04355-x
pii: 10.1007/s00431-021-04355-x
pmc: PMC8964651
doi:
Substances chimiques
Sildenafil Citrate
BW9B0ZE037
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1709-1718Subventions
Organisme : ZonMw
ID : 836021023
Pays : Netherlands
Organisme : ZonMw
ID : 836021023
Pays : Netherlands
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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