Tamara M. Hundscheid, Ilaria Amodeo, Giacomo Cavallaro, Carlijn R. Hooijmans, František Bartoš, Eduardo Villamor
MosaKids Children’s Hospital and Maastricht University Medical Center. Clínica Universidad de Navarra. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. Radboud University Medical Center. University of Amsterdam.
Netherlands, Spain and Italy
Biomedicines
Biomed 2025; 13:
DOI: 10.3390/biomedicines13092274
Abstract
Background: In congenital diaphragmatic hernia (CDH), pulmonary hypoplasia and pulmonary hypertension are major causes of morbidity and mortality. Antenatal treatment with sildenafil has shown some promising protective effects in experimental CDH, but no systematic review has yet evaluated the preclinical evidence on this topic.
Methods: PubMed and EMBASE databases were searched for studies using antenatal sildenafil in animal models of CDH. Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (presence of effect) over the probability of the data under the null hypothesis (absence of effect). Risk of bias was assessed by the SYRCLE tool.
Results: We included 18 studies (14 nitrofen and 4 surgical CDH). The BMA analysis showed inconclusive evidence (BF10 between 0.33 and 3) for the presence of an effect of sildenafil in fetal survival (7 studies, BF10 = 1.25) or in lung hypoplasia as assessed by the lung-to-body weight ratio (16 studies, BF10 = 2.04). In contrast, the BMA analysis showed conclusive evidence (BF10 > 3) in favor of a positive effect of sildenafil on small pulmonary arteries medial wall thickness (12 studies, BF10 = 1499), radial alveolar count (6 studies, BF10 = 167.57), interalveolar septa thickness (4 studies, BF10 = 56.86), distal airway complexity (3 studies, BF10 = 7.95), mean saccular airspace diameter (2 studies, BF10 = 7.61), total lung capacity (2 studies, BF10 = 6.91), lung compliance (2 studies, BF10 = 5.19), and VEGF expression (5 studies, BF10 = 10.62).
Conclusions: In preclinical models of CDH, antenatal sildenafil rescues pulmonary vascular remodeling and airway/airspace morphometric alterations.
Category
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia
Medical Therapy. Efficacy or Lack of Efficacy
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes