Safety, Testing/Transmission, and Outcomes in Pregnancies With COVID-19 (STOPCOVID19)

Pregnant women are a vulnerable and high-risk population, as COVID-19 is associated with an increased risk preterm birth, cesarean section, and maternal critical care. This study will examine the factors that impede testing for SARS-CoV-2 (the causative virus among pregnant women), help determine optimal testing strategies by evaluating the necessity of testing for asymptomatic disease in pregnancy, inform prenatal care plans by assessing the full impact of infection, and contribute to a provider's ability to counsel women and create prenatal care plans if they are pregnant or considering pregnancy.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19; Preterm Birth; Pregnancy Related; Coronavirus; Neonatal Infection; Prenatal Stress; Maternal Complication of Pregnancy
• Intervention / Treatment: Diagnostic test: Antibody testing for SARS-CoV-2 IgG; Diagnostic test: Testing for SARS-CoV-2 RNA; Diagnostic test: Testing for SARS-CoV-2 IgM/IgG

Detailed Description

Pregnant women are a vulnerable and high-risk population, as COVID-19 is associated with an increased risk of preterm birth, cesarean section, and maternal intensive care. The objectives of this study are to: (a) evaluate the full impact of SARS-CoV-2 in pregnancy to inform testing strategies, (b) examine the factors that impede testing during pregnancy, and (c) use study data to devise implementation strategies that improve SARS-CoV-2 testing in pregnancy and prenatal care during the pandemic. Investigators will prospectively enroll two cohorts of pregnant women: 1) exposed (SARS-CoV-2 positive), and 2) unexposed (SARS-CoV-2 negative as defined by antibody testing at the beginning of pregnancy, every trimester, and at delivery). Women who initially enroll as unexposed but later test positive for SARS-CoV-2 antibodies will cross over to the exposed cohort. In Aim 1, investigators will evaluate patients' and providers' perceptions of SARS-CoV-2 testing during pregnancy and the influence of COVID-19 on maternal care-seeking behavior and anxiety via surveys and semi-structured interviews. In Aim 2, investigators will determine the effect of SARS-CoV-2 infection during pregnancy on the risk of preterm birth and other adverse pregnancy outcomes in symptomatic and asymptomatic disease. It is hypothesized that SARS-CoV-2 infection will increase the risk of preterm birth by 12%. In Aim 3, investigators will estimate the risk of mother-to-fetus SARS-CoV-2 transmission and viral presence in umbilical cord blood, placenta, and amniotic fluid by assaying for viral RNA in the neonate, cord blood, and placenta. Collectively, Aims 1-3 will be interpreted by investigators, the Scientific Advisory Board and the Community Advisory Board who will apply data to devising targeted implementation strategies designed for rapid community dissemination to improve testing and prenatal care.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Megan E Foeller, MD; Phone Number: 314-747-1380; Email: mfoeller@wustl.edu
• Study Contact Backup: Name: Indira Mysorekar, PhD; Email: imysorekar@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for exposed (SARS-CoV-2 positive) cohort:

• Viable intrauterine pregnancy
• Seroconversion or SARS-CoV-2 IgG antibodies or positive RT-PCR for SARS-CoV-2 during current pregnancy

Exclusion Criteria for exposed (SARS-CoV-2 positive) cohort:

• No viable intrauterine pregnancy
• No history of SARS-CoV-2 infection during pregnancy

Inclusion Criteria for unexposed (SARS-CoV-2 negative) cohort:

• Viable intrauterine pregnancy
• No history of SARS-CoV-2 infection prior to pregnancy

Exclusion Criteria for unexposed (SARS-CoV-2 negative) cohort:

• No viable intrauterine pregnancy
• Detection of SARS-CoV-2 IgG antibodies at enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Unexposed (SARS-CoV-2 negative) cohort; Women who do not experience laboratory-confirmed SARS-CoV-2 infection during pregnancy.	Diagnostic test: Antibody testing for SARS-CoV-2 IgG; Women enrolled into the unexposed (SARS-CoV-2 negative) cohort will undergo testing for SARS-CoV-2 IgG antibodies at enrollment, every trimester of pregnancy, and during delivery hospitalization.
Active Comparator: Exposed (SARS-CoV-2 positive) cohort; Women who experience laboratory-confirmed SARS-CoV-2 infection during pregnancy.	Diagnostic test: Testing for SARS-CoV-2 RNA; Women in the exposed (SARS-CoV-2 positive) cohort will undergo testing of placental tissue, umbilical cord blood, amniotic tissue, and neonates for SARS-CoV-2 RNA, as available.; Diagnostic test: Testing for SARS-CoV-2 IgM/IgG; Women in the exposed (SARS-CoV-2 positive) cohort will undergo testing of umbilical cord blood for SARS-CoV-2 IgG and IgM antibodies, as available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of preterm delivery	Childbirth prior to 37 weeks of pregnancy, to be determined in accordance to standard pregnancy dating and the established estimated due date.	20 weeks gestation until childbirth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of preeclampsia	Standard definitions will be used (new-onset presence of elevated blood pressure > 140 systolic or > 90 diastolic separated by >4 hours and new onset proteinuria after 20 weeks of pregnancy or evidence of severe features of preeclampsia).	After 20 weeks gestation and up to 6 weeks postpartum
Rate of gestational hypertension	Standard definitions of gestational hypertension will be used (new-onset presence of elevated blood pressure > 140 systolic or > 90 diastolic separated by >4 hours without proteinuria after 20 weeks of pregnancy).	After 20 weeks gestation and up to 6 weeks postpartum
Rate of cesarean section	Delivery via a cesarean section operation.	Time of delivery
Rate of stillbirth	Fetal demise in utero after 20 weeks gestation.	Between 20 weeks gestation and childbirth
Rate of fetal growth restriction	Estimated fetal weight by sonographic assessment less than the 10th percentile for gestational age.	Between conception and childbirth
Rate of fetal hydrops	The presence of abnormally located fluid collections in two or more areas in the fetal body (i.e., fetal ascites and pericardial effusion) or one abnormal fluid collection plus fetal skin thickening.	Between conception and childbirth
Rate of oligohydramnios	Estimated amniotic fluid index less than 5 or estimated deepest vertical pocket (no presence of umbilical cord) less than 2 by sonographic assessment.	Between conception and childbirth
Perinatal death	Fetal or neonatal death occurring after 20 weeks gestation and up to 21 days of life.	During the pregnancy after 20 weeks of pregnancy to 21 days after delivery
Rate of premature preterm rupture of membranes	Rupture of membranes prior to 37 weeks gestation.	Between conception and 36 weeks 6 days of pregnancy
Rate of neonatal intensive care unit (NICU) admission	Admission of the newborn to the NICU after delivery during delivery hospitalization.	After delivery of newborn during delivery hospitalization
Rate of neonatal sepsis	Clinical syndrome that includes systemic signs of infection and bacteremia.	After delivery of newborn during delivery hospitalization up to 6 weeks of life
Rate of oxygen therapy	Use of oxygen therapy for the newborn after delivery during delivery hospitalization.	After delivery of newborn during delivery hospitalization up to 6 weeks of life
Percentage of infants with low 5-minute Apgar	Five minute Apgar less than 7. Maximum 10, minimum 0. Higher scores typically have improved outcomes.	At time of delivery
Percentage of infants with abnormal umbilical cord gas	pH of arterial blood of umbilical cord blood less than 7 and/or base excess greater than -12.	At time of delivery
Low birth weight	Weight at birth less than 2,500 grams.	At time of delivery
Confirmed congenital infection	SARS-CoV-2 RNA detection in the umbilical cord blood, in amniotic fluid if collected before rupture of membranes or in neonatal nasopharyngeal swabs collected both immediately after birth (and after cleaning of the infant).	Testing will be conducted at time of delivery.
Probable congenital infection	SARS-CoV-2 RNA detection in the neonatal nasopharyngeal swabs collected immediately after birth (after cleaning of infant) and in the fetal side of the placenta.	At time of delivery
Possible congenital infection	Anti-SARS-CoV-2 IgM antibodies detection in the umbilical cord blood but no SARS-CoV-2 RNA detected in the neonate.	At time of delivery

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Mercy Research
• Investigators: Principal Investigator: Megan E Foeller, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: January 16, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; pregnancy; stress; prenatal; social determinants of health; antibody testing; pregnancy complication; maternal complication; neonatal complication; mother-to-fetal transmission; placental pathology; SARS-CoV-2 testing
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; COVID-19; Premature Birth; Pregnancy Complications; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: 202012075

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No