Assessing the Mother-to-infant Transmission Capabilities of COVID-19 Infection Among Pregnant Women in Ontario, Canada

Completed

Conditions: SARS-CoV-2
Corona Virus Infection
Covid19
Pregnancy
Infectious Disease Transmission, Vertical

Interventions: Other: No intervention

Registration Number: NCT04913948

Lead Sponsor: Ottawa Hospital Research Institute

Brief Summary: In order to assess the mother-to-infant and potential vertical transmission of SARS-CoV-2 infection in pregnant women, maternal and neonatal biological samples were prospectively collected from women with confirmed or suspected COVID-19 at participating hospitals. Samples were be tested for the SARS-CoV-2 serology and presence of SARS-CoV-2 RNA.

Outcomes for the study objective will be ascertained through the collection and testing of biological samples from the mother and/or infant. Specifically the investigators will:

1. Assess maternal nasopharyngeal or oropharyngeal swab, vaginal mucosa, ano-rectal swab, amniotic fluid, placenta (including subamniotic swab), breastmilk, cord blood and neonatal nasopharyngeal swab for RNA particles of coronavirus, by ddPCR.

2. Assess maternal serum for anti-coronavirus antibodies, by immunoassay.

3. Examine the impact of coronavirus on the neonate with respect to serology and viral load, in addition to placenta pathology findings and ddPCR.

4. Assess vertical transmission and the effect of coronavirus through placental pathology examination using placental pathology synoptic report.

Detailed Description: Pregnant individuals with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were more likely to experience greater disease severity and higher rates of hospitalization, intensive care unit (ICU) admission and death compared to their non-pregnant counterparts. Early pandemic data were limited to a few small case series and reports that failed to provide a clear understanding of the timing and likelihood of fetal/neonatal infection. Data now suggest that in utero, intrapartum and early postnatal transmission of SARS-CoV-2 to the fetus/neonate is rare (\<5%) and predominantly associated with third trimester infections and severe disease presentation. A living systematic review and meta-analysis of 144 cohort studies found that the rate neonates/fetuses testing positive for SARS-CoV-2 by RT-PCR, having anti-SARS-CoV-2 IgM antibodies or both was 1.94% (95%CI 1.31%, 2.66%). However, tests for SARS-CoV-2 and anti-SARS-CoV-2 antibodies were limited during the earliest stages of the pandemic and relatively few of the included studies provided sufficient data on the timing of fetal/neonatal exposure, and the type and timing of tests performed.

Derivation of reliable risk estimates for perinatal transmission remains challenging due to significant heterogeneity across published studies regarding the types of tissues profiled, diagnostic methods used and availability of essential COVID-19 disease characteristics such as timing and severity of maternal infection. As variants of concern continue to emerge, more data are required to elucidate the circumstances in which SARS-CoV-2 infection is likely to be transmitted to the developing fetus/neonate. We sought to evaluate the rate of SARS-CoV-2 transmission from mother-to-neonate in a large multicenter cohort from Ontario and Quebec, Canada.

To address early pandemic challenges in characterizing perinatal infections, a prospective cohort study was conducted across 14 sites in Ontario and Quebec, Canada. Pregnant individuals who had received a diagnosis of SARS-CoV-2 infection in pregnancy were eligible. Sample collection at delivery included maternal samples (nasopharyngeal/oropharyngeal, vaginal and anorectal swabs; blood; breastmilk), newborn samples (nasopharyngeal swabs, cord blood, amniotic fluid), and placental samples (sub-amniotic swab, placental biopsies). Swab, amniotic fluid, placenta and breastmilk samples were analyzed for SARS-CoV-2 RNA by RT-qPCR. Blood, breastmilk and amniotic fluid were assessed for anti-SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid (N) IgG, IgM and IgA.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 246

Inclusion Criteria

Pregnant women with confirmed COVID-19 at any point during pregnancy or suspected COVID-19 at time of delivery (as identified at local hospital) , who will be delivering at a participating hospital in Ontario or Quebec

Exclusion Criteria

None

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pregnant	No intervention	Pregnant women with confirmed COVID-19 at any point during pregnancy or suspected (as identified at local hospital) of COVID-19 at time of delivery, who will be delivering at a participating hospital within Ontario

Primary Outcome Measures

Name	Time	Method
Rate of Perinatal Transmission of SARS-CoV-2	During the delivery admission	Evidence of SARS-CoV-2 RNA or antibodies against SARS-CoV-2 from a sterile (amniotic fluid) or non-sterile sample (nasopharyngeal swab sample, placental tissue, subamniotic swab or by cord blood serology \[for IgM or IgA\]) collected during the maternal hospital admission for delivery (specific time frame varied per participant).
Rate of Intrauterine Transmission of SARS-CoV-2	During the delivery admission	Evidence of SARS-CoV-2 RNA or antibodies against SARS-CoV-2 in fetal tissues (i.e., amniotic fluid, placental tissue, sub-amniotic swab, cord blood) collected during maternal hospital admission for delivery (specific time frame varied per participant). Evidence of intrauterine transmission was determined using RT-PCR and serological analysis.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (12): The Ottawa Hospital - General Campus
🇨🇦
Ottawa, Ontario, Canada
Hamilton Health Sciences Corporation
🇨🇦
Hamilton, Ontario, Canada
Humber River Hospital
🇨🇦
North York, Ontario, Canada
Grand River Hospital
🇨🇦
Kitchener, Ontario, Canada
Hôpital Montfort
🇨🇦
Ottawa, Ontario, Canada
North York General Hospital
🇨🇦
North York, Ontario, Canada
The Ottawa Hospital - Civic Campus
🇨🇦
Ottawa, Ontario, Canada
St. Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
London Health Sciences
🇨🇦
London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Mount Sinai Hospital
🇨🇦
Toronto, Ontario, Canada