key: cord-0801459-58vclufl
authors: Mehan, Aman; Venkatesh, Ashwin; Girish, Milind
title: COVID‐19 in pregnancy: risk of adverse neonatal outcomes
date: 2020-04-30
journal: J Med Virol
DOI: 10.1002/jmv.25959
sha: bf2c7d9dace90947f1eb116186569036bd0bcba4
doc_id: 801459
cord_uid: 58vclufl

We read with great interest the study by Siyu Chen and colleagues. The authors evaluated the clinical features and outcomes of five pregnant patients with COVID‐19 at term, whose delivery was uneventful and led to favorable perinatal outcomes for both mother and neonate. We would like to draw attention to a growing body of evidence that now points towards an under‐addressed association between preterm maternal SARS‐CoV‐2 infection, preterm delivery and adverse neonatal outcomes, which is not reflected in Chen et al.'s small cohort. We also stress that vertical transmission, which was not tested for by Chen et al., should not be excluded as a potential mechanism for viral spread. Centers should therefore be meticulous in their approach to a SARS‐CoV‐2+ pregnancy to optimize clinical outcomes for both mother and child. This article is protected by copyright. All rights reserved.

cases of infection are being reported during pregnancy. In the Journal of Medical Virology, Siyu Chen and colleagues report clinical features and outcomes of pregnant patients with COVID-19 in the Maternal and Child Hospital of Hubei Province, China. 1 The authors present 5 patients (aged 25-31) with COVID-19 at term gestation (38-41 weeks), in whom delivery was uneventful and led to favorable perinatal outcomes.

We write to highlight that the small cohort in Chen et al. is not representative of the overall literature to date. Moreover, whilst infection at term might be relatively inconsequential, a growing body of evidence now points towards an association between preterm maternal SARS-CoV-2 infection, preterm delivery and adverse neonatal outcomes, which has been under-addressed.

Although none of the patients in the study by Chen et al. delivered preterm, our review of the literature highlights several instances in which preterm delivery together with the outcomes for both mother and neonate have been documented (Table 1) . 1 For instance, Liu et al. report that 6 out of 13 (46%) hospitalized pregnant patients with COVID-19 delivered preterm (between 32-36 weeks' gestation). 2 One patient developed pneumonia and septic shock, requiring intensive care admission and emergency caesarean section, unfortunately yielding a stillbirth. In another study of 10 neonates born to mothers with COVID-19 pneumonia, 6 were preterm and of low birth weight. 3 Whilst none tested positive for SARS-CoV-2 at 72 hours post-birth, all preterm neonates had a Pediatric Critical Illness Score below 90, 1 of whom died with 4 remaining hospitalized. No underlying maternal disease or neonatal infection was reported, thus preterm maternal COVID-19 may independently predict poor neonatal outcome. A case-control study recently published by Li et al. further strengthens the evidence base for this association, highlighting a significantly increased incidence of preterm delivery in cases of COVID-19 than controls, which the authors attributed to gestational complications such as premature rupture of membranes and placental bleeding. 4 In Chen et al.'s cohort, all SARS-CoV-2+ women were asymptomatic prior to delivery, with two developing mild symptoms postpartum, and the majority delivered vaginally. 1 The greater adoption of Csection in the studies we examined was influenced by: perceived risk of vertical transmission, the lack of Accepted Article available negative pressure operating rooms, deteriorating maternal symptoms, or indeed conventional obstetric indications. We also noted that severe COVID-19 associated maternal morbidity was documented in 3 studies, which yielded adverse neonatal outcomes as one might expect. However, interestingly the majority of women generally exhibited minor symptoms or were asymptomatic -consistent with Chen et al. 1 -yet even in such cases preterm birth was reported. Thus, maternal SARS-CoV-2 infection may be an independent risk factor for preterm birth, regardless of symptom severity, though the mechanism remains to be clarified. Moreover, asymptomatic infections may present a considerable challenge for managing transmission risk in obstetric units. Thus, studies evaluating whether universal testing offers cost-effective improvements in clinical outcomes would be beneficial.

Whilst the neonates in Chen et al.'s cohort were healthy and of normal birthweight, 1 the literature highlights that in preterm deliveries, adverse neonatal outcomes can be expected. In the studies examined, this most commonly manifested as pneumonia and low birth weight and was concurrent with the death of two neonates. Follow up studies would be useful to assess whether longer-term outcomes of neonates born preterm to SARS-CoV-2+ mothers differ from preterm births without an associated maternal SARS-CoV-2 infection and may also illustrate any eventual consequences of maternal COVID infection that were absent at birth.

Despite acknowledging its possibility, Chen et al. did not test for vertical transmission 1 and we would like to emphasize that vertical transmission should not be excluded as a potential mechanism. Indeed, vertical transmission has been under-tested and sparsely reported. This may relate to the challenges of testing neonates, since only a minority are symptomatic, and both oral and nasal swab testing have low sensitivity. 3, 4, 5 However, emerging evidence of a neonate with elevated IgM antibodies to SARS-CoV-2 highlights the possibility of this phenomenon. 5 It is plausible that other existing reports of neonatal early onset infection may also represent vertical transmission. Notably, Zeng et al. report of a neonate infected with SARS-CoV-2 that developed severe clinical sequelae. 6 Although the authors attributed this outcome to prematurity, asphyxia and sepsis, the compounding pathological contributions of the virus to prematurity, and of potential vertical transmission to adverse neonatal outcomes, require further elucidation. Recent research has revealed a high expression of the SARS-CoV-2 receptor, ACE2, and the serine protease for 

Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia

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