Clinical trial NCT04519502: Maternal Morbidity and Mortality During the COVID-19 Pandemic
Official title: Maternal Morbidity and Mortality During the COVID-19 Pandemic
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Pregnancy Complications
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2020-08-19
Enrollment: 25604
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Approximately 24,400 deliveries on randomly selected days in 2019 and 2020, and an additional 1000-2100 confirmed COVID-19 infections among pregnant women or immediately postpartum

Brief summary: A cohort study of women who deliver at select sites on randomly selected days in 2019 and 2020, and all confirmed COVID-19 infections among pregnant or immediately postpartum women in 2020. The study population includes approximately 24,400 deliveries on randomly selected days in 2019 and 2020, and an additional 1000-2100 confirmed COVID-19 infections among pregnant women or immediately postpartum.

Detailed description: This cohort study includes women who deliver at one of the MFMU Network hospitals on randomly selected days between March 1 and December 31, 2019 and March 1 and December 31, 2020 to evaluate the effect of a major public health crisis (COVID-19 pandemic) on maternal morbidity and mortality among pregnant and immediately postpartum women. This time period allows for calendar months in 2020 representing the key time period of the pandemic - after testing became available and changes were implemented in healthcare. Inclusion of the same months from 2019 represent the time period prior to the pandemic.

In addition to the cohort of women delivering at the selected MFMU Network sites on randomly selected days, all pregnant and immediately postpartum (within 6 weeks of delivery) with confirmed COVID-19 infection will be included in this study. Both women who were managed in-patient and those managed out-patient with COVID-19 infection will be included. All pregnant women with confirmed COVID-19 infection between March 1, 2020 and December 31, 2020 will be followed for maternal and neonatal outcomes through 6 weeks after delivery or surgical removal of the pregnancy.

Trained research staff will abstract data from the hospital's electronic medical records that meet eligibility criteria. Measures of healthcare and community-based modifications in response to the pandemic will be recorded by research staff. Individual participant data will include baseline data, COVID-19 exposure data, and maternal and neonatal outcome data.

The three primary objectives are 1) to evaluate whether pregnant or immediately postpartum women experience higher maternal morbidity and mortality during the COVID-19 pandemic than before the pandemic, 2) to evaluate whether women with COVID-19 infection, both in- and out-patient, have higher maternal morbidity and mortality than pregnant women without COVID-19 infection, and 3) to describe maternal and neonatal outcome data for all pregnant and immediately postpartum women with a confirmed COVID infection and contribute these data to an NICHD COVID-19 pregnancy registry. The primary endpoint, maternal morbidity and mortality, is defined as morbidity related to hypertensive disorders of pregnancy, morbidity related to postpartum hemorrhage, or morbidity related to infection during pregnancy or within six weeks (42 days) postpartum. For primary objective 1, the study has more than 90% power to show a 30% increase in the rate of the primary endpoint assuming the rate is at least 3% in calendar year 2019 and an alpha of 0.05 two-sided. For primary objective 2, the study will have more than 85% power to detect a 50% increase in the primary composite maternal morbidity endpoint, from 5% to 7.5% with an alpha=0.05 two sided if only 1,000 confirmed COVID-19 people are enrolled (80% power to detect a 30% increase in the primary composite if 2,200 confirmed COVID-19 people are enrolled).

For objective 1, analyses of the primary endpoint will consist of summarizing the proportions of participants with the primary endpoint for each calendar year cohort and calculating the corresponding relative risks with 95% confidence intervals. Individual morbidity composites (hypertensive disorders, postpartum hemorrhage, and infection) will also be compared by calendar year cohort. Outcome rates within 2019 will be graphically displayed and tested over time to ensure changes are not evident during the year that may explain differences between calendar years 2019 and 2020. For objective 2, analyses of the primary endpoint will consist of summarizing the proportions of participants with the primary endpoint among women with confirmed COVID-19 infection and those without confirmed infection, and calculating the corresponding relative risk with 95% confidence intervals.

Eligibility criteria: Inclusion Criteria:

* Women who deliver at a selected hospital participating in the MFMU Network on selected dates sent by the Data Coordinating Center from March 1, 2019, through Dec, 31, 2019. Women delivered in the calendar year 2019 will serve as the controls (before pandemic).
* Women who deliver at a selected hospital participating in the MFMU Network on selected dates sent by the Data Coordinating Center from March 1, 2020, through Dec, 31, 2020. Women delivered in the calendar year 2020 will be considered as deliveries during the pandemic (research question 1) and non-confirmed positives as controls (research question 2).
* Pregnant and postpartum (within 6 weeks of delivery) women with confirmed COVID-19 infection from March 1, 2020, through Dec, 31, 2020 and who deliver on or before December 31, 2020. Both those with COVID-19 infection requiring in-patient management and those managed as out-patients will be included. Confirmed COVID-19 infection is defined as a positive COVID-19 viral (i.e., nucleic acid or antigen tests) test during pregnancy through 42 days postpartum.

Exclusion Criteria:

* Multifetal gestation higher than twins

Primary outcomes:
measure: Maternal Mortality and Morbidity Composite
timeFrame: During pregnancy through 6 weeks postpartum
Secondary outcomes:
measure: Cesarean Delivery
timeFrame: Delivery
measure: Severe maternal morbidity or mortality
timeFrame: During pregnancy through 6 weeks postpartum
measure: Adverse maternal outcomes
timeFrame: During pregnancy through 6 weeks postpartum
measure: Adverse neonatal outcomes
timeFrame: Delivery through hospital discharge up to 120 days
measure: Neonatal infection
timeFrame: Delivery through hospital discharge up to 120 days
measure: Maternal in-patient hospitalization days
timeFrame: During pregnancy through 6 weeks postpartum
measure: Maternal ICU admission
timeFrame: During pregnancy through 6 weeks postpartum
measure: Duration of labor and delivery
timeFrame: During pregnancy through delivery
measure: Neonatal length of stay
timeFrame: Delivery through hospital discharge up to 120 days
measure: Neonatal ICU length of stay
timeFrame: Delivery through hospital discharge up to 120 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Columbia University-St. Luke's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina-Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Women's Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown Univeristy
state: Rhode Island
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Monica Longo, MD
role: STUDY_DIRECTOR
affiliation: University of Utah Medical Center
name: Torri Metz, MD
role: STUDY_CHAIR
References:
citation: Metz TD, Clifton RG, Hughes BL, Sandoval GJ, Grobman WA, Saade GR, Manuck TA, Longo M, Sowles A, Clark K, Simhan HN, Rouse DJ, Mendez-Figueroa H, Gyamfi-Bannerman C, Bailit JL, Costantine MM, Sehdev HM, Tita ATN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Association Between Giving Birth During the Early Coronavirus Disease 2019 (COVID-19) Pandemic and Serious Maternal Morbidity. Obstet Gynecol. 2023 Jan 1;141(1):109-118. doi: 10.1097/AOG.0000000000004982. Epub 2022 Oct 27.