Anouk Pels, Wes Onland, Rolf M. F. Berger, Arno F. J. van Heijst, Enrico Lopriore, Irwin K. M. Reiss, Jacqueline Limpens, Sanne J. Gordijn, Wessel Ganzevoort
University of Amsterdam and Emma Children’s Hospital. University of Groningen, University Medical Center Groningen and Beatrix Children’s Hospital. Radboud University Medical Center and Amalia Children’s Hospital. Leiden University Medical Center. Erasmus University Medical Center.
Netherlands
European Journal of Pediatrics
Eur J Pediatr 2022; 181: 1709-1718
DOI: 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.
Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Class III. Pulmonary Hypertension Associated with Lung Disease
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes