Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

Abstract 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, an... Mehr ...

Verfasser: Pels, Anouk
Onland, Wes
Berger, Rolf M. F.
van Heijst, Arno F. J.
Lopriore, Enrico
Reiss, Irwin K. M.
Limpens, Jacqueline
Gordijn, Sanne J.
Ganzevoort, Wessel
Dokumenttyp: Artikel
Erscheinungsdatum: 2022
Reihe/Periodikum: European Journal of Pediatrics ; volume 181, issue 4, page 1709-1718 ; ISSN 1432-1076
Verlag/Hrsg.: Springer Science and Business Media LLC
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29035407
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://dx.doi.org/10.1007/s00431-021-04355-x

Abstract 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). Conclusion: 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. What is Known: • In the Dutch STRIDER trial, persistent pulmonary hypertension in the neonate (PPHN) was more frequent among infants after antenatal sildenafil exposure versus placebo. What is New: • The current analysis focuses on the distinction between PPHN and pulmonary hypertension associated with sepsis or ...