Clinical Characteristics and Outcomes of SARS-CoV-2 Infection in Neonates with Persistent Pulmonary Hypertension of the Newborn (PPHN): A Systematic Review

Abstract

PPHN is a common cause of neonatal respiratory failure and is still a serious condition that is associated with high mortality. Objectives: To analyze the clinical characteristics and outcomes of SARS-CoV-2 infection in neonates with PPHN to identify neonatal cases at risk to develop severe illness. Methods: For this systematic review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, Embase, CINAHL, and PubMed for studies on the development of COVID-19 in neonates with PPHN, published from 1 December 2019 to 29 February 2024, with an English language restriction. Results: Of the 2406 papers that were identified, 21 articles were included in the systematic review. Studies involving thirty-six neonates with PPHN and infected with SARS-CoV-2 were analyzed (twenty-nine survived, six died, and one is still hospitalized). The main causes of PPHN in neonates who had COVID-19 were neonatal respiratory distress syndrome (NRDS) (41.7%), meconium-stained amniotic fluid (MSAF) (16.7%), preterm premature rupture of membranes (PPROM) (11.1%), hypoxic ischemic encephalopathy (HIE) (5.5%), pneumonia (5.5%), and idiopathic (2.8%). Most of those neonates were male (33.3%), belonged to Indian ethnicity (50%), and were delivered via caesarean section (44.4%). COVID-19 in cases with PPHN commonly occurred in neonates born with a pregnancy range from 32 to p = 0.026]. Neonates with PPHN and COVID-19 had a higher relative risk of death if they received more antibiotics (RR 4.14, 95% CI 0.64–6.88) and if their COVID-19 was defined as critical (RR 2.84, 95% CI 0.86–9.39). Male neonates with PPHN and COVID-19 (RR 2.60, 95% CI 0.30–1.17) and those requiring prolonged invasive positive pressure ventilation (RR 2.22, 95% CI 0.64–7.73) also showed an increased relative risk for death. Conclusions: COVID-19 in neonates with PPHN is challenging and may be associated with increased mortality, severity, ICU admission, ARDS, MIS-N, and MV usage. The results should be interpreted with caution owing to the small number of studies and substantial heterogeneity and indicate a need for future research in this area. Due to its benefits, testing for SARS-CoV-2 should be encouraged for newborns with symptoms consistent with COVID-19, especially in neonates with a history of SARS-CoV-2 exposure. Effective protection measures should be implemented during delivery and post-delivery care as necessary.

Keywords

• COVID-19
• persistent fetal circulation
• patent ductus arteriosus
• patent foramen ovale
• persistent pulmonary hypertension
• PPHN