Researchers at Karolinska Institutet and the Public Health Agency of Sweden have studied newborn babies whose mothers tested positive for SARS-CoV-2 during pregnancy or childbirth.
The results show that although babies born of test-positive mothers are more likely to be born early, extremely few were infected with COVID-19.
The study, which is published in the esteemed journal JAMA, supports the Swedish recommendation not to separate mother and baby after delivery.
The population-based study comprised 92 per cent of all neonates – almost 90,000 births – in Sweden during the first year of the pandemic (11 March 2020 to 31 January 2021), making it one of the largest datasets in the field to date.
The results show a slightly higher level of morbidity in neonates whose mothers tested positive for SARS-CoV-2, including an increased risk of respiratory disorders, which were largely due to the higher number of preterm births in this group. No direct correlation between maternal infection and neonatal respiratory infection or pneumonia could be observed.
A total of 2,323 babies were born to SARS-CoV-2-positive mothers, of whom about one third were tested close to or just after childbirth.
Only 21 (0.9 per cent) of the babies of these women tested positive for the virus at some point during the newborn period (the first 28 days), the majority without displaying any symptoms; a few babies were treated for other reasons than COVID-19.
The study supports the Swedish recommendation that babies born of women who have tested positive for SARS-CoV-2 while pregnant or during delivery do not need to be routinely separated from their mothers at birth.
In many countries such a precautionary measure is taken despite the lack of supporting evidence.
“Separating a newborn baby from its mother is a serious intervention with negative consequences for the health of both mother and baby that must be weighed against the possible benefits,” says Mikael Norman, professor of pediatrics at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and one of the researchers leading the study.
“Our study suggests that mother and baby can be cared for together and that nursing can be recommended without danger to the baby’s health. This is good news for all pregnant women, their babies and postnatal and neonatal staff.”
The study was made possible through daily reports to three Swedish registries: the National Quality Register for Pregnancy, the National Quality Register for Neonatal Care, and the Communicable Diseases Register (SmiNet).
SmiNet is a system for reporting communicable diseases used jointly by the Public Health Agency of Sweden and the regional communicable diseases units to surveille the 60-plus notifiable diseases that must be reported in accordance with the Communicable Diseases Act.
“By cross-referencing the three registries we’ve been able to monitor and report outcomes for the neonates in real time during both the first and second waves of COVID-19,” says Professor Norman.
COVID-19 (coronavirus disease 2019), which has been declared a pandemic in March 2020, has caused an unprecedented uncertainty within the scientific community. Contradictory scientific evidences are released almost every day, on every aspect of the pandemic from its pathogenesis, to the methods of transmission, and to the possible compassionate use of medications to combat it.
Transplacental transmission of COVID-19 is one of the topics that have raised conflicting evidences across the globe. The dilemma about transplacental transmission of Coronaviridae is not exclusive to the current outbreak. To our knowledge, nine studies [1–9] from SARS-1 (Severe Acute Respiratory syndrome) and HKCoV (Hong Kong Coronavirus) and MERS (Middle East Respiratory syndrome) outbreaks were reported, ranging from case reports to retrospective case reviews, comprising 71 mother-infant pairs.
Table 1 summarizes the findings of the nine studies. Two cases only have shown vertical transmission, a remarkable finding was the strong evidence in those reports of intrauterine fetal hypoxia possibly due to placental damage or even direct evidence of placental infarctions. Gagneur et al.  reported two cases of still birth that was preceded by fetal heart deceleration, whereas Wong et al.  and Jeong et al.  demonstrated placental infarction in three cases.
Analysis of placental outcomes was largely lacking in the studies performed in the previous outbreaks; however, all studies that mentioned the presence of placental vascular compromise namely Wong et al.  and Jeong et al.  excluded the presence of any maternal co-morbidity that can cause such finding (Table (Table1).1).
The latter finding might signify that CoV are mainly implicated in the thrombotic injury observed in such case reports. The vascular tropism of COVID-19 has recently gained so much interest, and many of its multi-organ manifestations has been attributed to its endothelial tropism. Such endothelial tropism is accounted for by the high load of Angiotensin Converting Enzyme 2 (ACE2) and Furin [10, 11], which are important viral checkpoints, in the endothelium.
The placenta is a vascular organ, in which Furin plays an important role in its differentiation; moreover, ACE2 and angiotensin 1-7 are heavily expressed in it, making the placenta an important target for the vascular tropic effect of COVID-19. As mentioned earlier, the conflicting evidence regarding vertical transmission of COVID-19 and the effect of maternal COVID-19 on newborns and their placenta, render systematic review of the clustered cases available of utmost importance to build stronger evidence for the neonatal outcomes of COVID-19.
The primary outcome parameter of this systematic review is the percentage of newborns testing positive to COVID-19 mothers, while secondary outcome parameters included the assessment of laboratory abnormalities among COVID-19 newborns, and the placental abnormalities encountered in COVID-19 mothers.
Reported cases of vertical transmission, clinical manifestations and placental abnormalities in SARS-1, HKCoV, and MERS
|Paper||Jeong et al ||Payne et al ||Wong et al ||Yudin et al ||Stockman et al ||Gagneur et al ||Li et al ||Shek et al ||Robertson et al ||Totals|
|Number of studied mother-infant pairs||1||1||12||1||2||7||41||5||1||71|
|Number of neonates with vertical transmission||0||0||0||0||0||2||0||0||0||2/71 (2.8%)|
|Reported complications in neonates(whether with positive or negative swabs)||0||1: Still birth||2: NEC1: RDS||0||0||2: Still birth with fetal deceleration||0||2: NEC||0||RDS: 1/71 (1.4%)Still birth:Mar-71− 4.20%NEC: 4/71 (5.6%)|
|Reported placental abnormalities||2: Placental infarction||Not reported||1: Placental infarction||Not reported||Placenta negative for SARS-CoV, no pathological examination||Not reported||Not reported||Not reported||Not reported||3/25 (12%)|
|Maternal co-morbidities||None||None||None||None||Gestational diabetes in the third trimester||One mother developed eclampsia||None||None|
The aggregated data in this systematic review are by far the largest to date regarding neonatal outcomes of COVID-19. Results suggest that vertical transmission of COVID-19 is unlikely as it occurred in 2.8% of neonates but underlines an important and underestimated risk, which is the possible placental insufficiency due to the prothrombotic tendency created by COVID-19.
These findings should warrant more case/control studies to compare placental abnormalities with the duration and degree of viremia. Also thorough antenatal care should be offered to COVID-19-positive mothers to evaluate their prothrombotic tendency and to monitor their need for anticoagulation. Finally, yet importantly, complications such as meconium aspiration and PPHN should be compared in COVID-19-positive vs. COVID-19-negative mothers and should be anticipated by neonatologists in the delivery room and during follow-up after delivery.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047589/
More information: Mikael Norman et al. Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. JAMA, online 29 April 2021, DOI: 10.1001/jama.2021.5775.
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