Increased incidence of Persistent Pulmonary Hypertension of the Newborn following third trimester maternal COVID-19 infection

Abstract Background Novel coronavirus (COVID-19) has been a world concern since December 2019. The knowledge about vertical transmission and fetal morbidity and mortality from maternal COVID-19 infection is limited. We detected an increase in the number of cases of term and near-term neonates with persistent pulmonary hypertension (PPHN) during the COVID-19 pandemic in 2020. Methods and results We collected data on all newborns with PPHN born between 2018 and 2020. We excluded premature infants (<34+0 weeks) and infants with other significant pathology or genetic syndromes. Compared to 5 cases of PPHN of 22930 live births in 2018, and 6 cases of PPHN of 22270 live births in 2019 (2-year average 0.02%, 95% CI 0.013%-0.043%), there were 16 PPHN cases from 22323 live births in 2020 (0.07%, 95% CI 0.044%-0.12%), a 3 fold increase (p<0.01). We report 5 cases of term and near-term neonates born to mothers who had highly suspected (2) and PCR proven (3) COVID-19 infection during the third trimester of pregnancy, who presented with PPHN during COVID-19 pandemic in 2020. All had otherwise unexplained pulmonary hypertension, right ventricular hypertrophy (RVH) and dilatation. Two patients needed endotracheal intubation, one was supported by nasal continuous positive airway pressure (CPAP) without intubation, two needed O2 support by nasal cannula only ant two newborns (one of them was intubated) needed Nitric oxide (NO) as pulmonary vasodilator therapy. No patient required Extracorporeal membrane oxygenation (ECMO) or died, and no prolonged residual cardiovascular or pulmonary morbidity was recorded during a median follow up of 4.8 months (range 4–6 months). Conclusions The increase in the incidence of PPHN during the COVID-19 pandemic, and the cases presented, suggest an intrauterine effect of maternal COVID-19 infection on the fetal pulmonary circulation. It is possible that the maternal infection affected the fetal pulmonary vascular resistance, or altered the normal decline in the resistance after birth. The right ventricular hypertrophy and dilatation with reduced function may be secondary to this hypothetical increased afterload or a direct effect of the infection. Further studies are warranted to elucidate the pathogenesis and clinical implications of this phenomenon. Funding Acknowledgement Type of funding sources: None.