Maternal Morbidity and Mortality During the COVID-19 Pandemic
Maternal Morbidity and Mortality During the COVID-19 Pandemic
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.
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.
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