Maternal Morbidity and Mortality During the COVID-19 Pandemic

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.