SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis
Authors: Allotey John , Kew Tania , Fernández-García Silvia , Gaetano-Gil Andrea , Yap Magnus , Sheikh Jameela , Littmoden Megan , Akande Oluwadamilola , Khalil Halimah , Kumaran Maurie , Barry Kathryn , Attarde Shruti , Sambamoorthi Dharshini , Ramkumar Anoushka , Lawson Heidi , Manning Millie , Maddock Sophie , Gupta Ankita , Hebbar Meghnaa , Khashaba Alya , Ansari Kehkashan , Banjoko Adeolu , Walker Kate , O’Donoghue Keelin , van Wely Madelon , van Leeuwen Elizabeth , Kostova Elena , Kunst Heinke , Khalil Asma , Brizuela Vanessa , Kara Edna , Kim Caron Rahn , Thorson Anna , Oladapo Olufemi T , Zamora Javier , Bonet Mercedes , Mofenson Lynne , Thangaratinam Shakila 
Published: March 2022

Abstract

Objectives
To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring.

Design
Living systematic review and meta-analysis.

Data sources
Major databases between 1 December 2019 and 25 April 2022.

Study selection
Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies.

Data extraction
Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal).

Results
643 studies (343 cohort studies, 300 case series and case reports; 44 552 mothers, 30 822 babies) were included. Overall, 2.7% (95% confidence interval 2.1% to 3.5%; 210 studies, 24 040 babies) born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 1107 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 32 had confirmed mother-to-child transmission: 20 in utero (857 assessed), three intrapartum (35 assessed), and nine during the early postnatal period (144 assessed). Of the 1213 SARS-CoV-2 positive babies with outcome data, 64 were stillbirths, 36 were neonatal deaths, and nine were early pregnancy losses; 1104 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 3.5, 95% confidence interval 1.5 to 8.1), maternal death (14.1, 4.1 to 48.0), maternal postnatal infection (5.0, 1.2 to 20.1), caesarean section (1.4, 1.1 to 1.8), and preterm delivery (1.5, 1.2 to 1.9) were associated with SARS-CoV-2 positivity in offspring. Positivity rates in offspring using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.5%) in studies from North America to 8.5% (4.6% to 13.3%) in studies from Latin America and the Caribbean.

Conclusion
SARS-CoV-2 positivity rates are low in babies born to mothers with SARS-CoV-2 infection. Evidence confirms vertical transmission of SARS-CoV-2, although this is rare. Severity of maternal covid-19 is associated with SARS-CoV-2 positivity in offspring.

Systematic review registration
PROSPERO CRD42020178076.

Readers’ note

This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 16 March 2022 (
BMJ
2022;376:e067696), and previous updates can be found as data supplements (
https://www.bmj.com/content/376/bmj-2021-067696/related#datasupp
).