Saad Alhumaid, Muneera Alabdulqader, Zainab Al Alawi, Mohammed A. Al Ghamdi, Mohammed A. Alabdulmuhsin, Hassan I. Al Hassar, Hussain Ahmed Alsouaib, Hussain Ali Alhassan, Hassan Al-Helal, Sameer Ahmed Almoraihel, Mohammed Jaber Alomran, Hassan Redha AL-Tarfi, Abbas Radi Al-Makinah, Tariq T. Alghareeb, Mohammad Abdullah Alkhwaitem, Murtadha Alsuliman, Ali N. Bukhamseen, Khulood Khaled Alajmi, Ahmed Salman Al Majhad, Mariam Ali Almajhad, Ayat Hussain Alhmed, Abdulrahman A. Alnaim
University of Tasmania. King Faisal University and King Fahad Hospital. Maternity and Children Hospital. Aljafr General Hospital. Al-Ahsa Health Cluster. Rumah General Hospital. Hereditary Blood Diseases Centre. Al-Ahsa Mental Health Hospital.
Australia and Saudi Arabia
Children
Children 2024; 11:
DOI: 10.3390/children11111305
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 <37 weeks (moderate to late preterm) (36.1%). The maternal severity of COVID-19 was reported to be severe in three cases only (8.3%); however, SARS-CoV-2 infection in neonates with PPHN was either severe (44.4%) or critical (22.2%). Most of these neonates experienced acute respiratory distress syndrome (ARDS) (58.3%). Early and late multisystem inflammatory syndrome in neonates (MIS-N) were reported in 50% and 11.1%, respectively. A high proportion of neonates were admitted to the intensive care unit (ICU) (58.3%) or needed mechanical ventilation (MV) (47.2%). Neonates with concurrent PPHN and SARS-CoV-2 infection who died had worse severity of COVID-19 [i.e., severity of COVID-19 was critical in 10% (neonates with PPHN who survived group) vs. 83.3% (neonates with PPHN who died group); 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.
Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Class I. Pulmonary Hypertension Associated with Infection
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