Covid-19 in Pregnancy: a French Population-based Cohort of Women and Newborns

In the overall context of uncertainty about the morbidity associated with COVID-19 infection
and its optimal management, knowledge is urgently required on infection during pregnancy.

First, pregnant women and newborns can have specific and severe reactions to infectious
diseases, as seen in previous pandemics which justifies targeted surveillance. Second,
optimal management must minimize the health risks of transmission to the newborn. While
initial studies did not provide evidence for transmission in utero or during delivery, more
recent data suggest that transmission is possible. The virus is present in vaginal secretions
and stool, making vertical contamination possible during vaginal delivery. Similarly,
transmission may occur during breastfeeding. These risks, which remain theoretical, must be
weighed against known harmful consequences of mitigating strategies such as systematic
caesarean (increase in maternal morbidity) and separating the child from the mother and
contraindicating breastfeeding (negative impact on maternal-child bonding and optimal
nutrition). In the absence of reliable data, some maternity hospitals have adopted a maximum
precautionary principle, recommending caesarean for all COVID-19 positive women and imposing
immediate mother-child separation after childbirth. These approaches are strongly debated in
France. Third, optimal management of COVID-19 during pregnancy requires balancing maternal
and newborn risks. Risks of maternal deterioration in the event of continuing pregnancy must
be weighed against those to the child resulting from indicated preterm birth. This tradeoff
is even more complex as evidence-based interventions to protect preterm infants, such as
antenatal corticosteroid, may aggravate maternal infection. Finally, childbirth is not an
elective procedure and requires managing large numbers of healthy women and newborns in a
hospital setting where they are exposed to risks of infection.

Population-based research that captures the diversity of organizational structures and
practices within maternity units is needed to guide management during the current epidemic
and draw lessons for future infectious pandemics.

Principal innovative features are:

- A population-based approach: Current data systems will include a limited number of
pregnant women, principally from university hospitals with specific patient populations
and management strategies. Because all maternity hospitals care for COVID-19+ pregnant
women, a population-based approach is needed to calculate reliable incidence rates,
assess practice variability and measure the impact of differences in management on
maternal and newborn infection rates and health.

- The inclusion of infected pregnant women who are not hospitalized and who recover before
delivery will provide comprehensive data and measure early fetal in-utero exposure.

- Immediate feedback to clinicians on their practices will inform current controversies
about optimal management.

- Joint follow-up of mother and child to 12 weeks after delivery, and longer if indicated,
will document the medium-term impact of infection.

- Inclusion of regions with time-varying exposure to the epidemic will provide information
to evaluate public health policies.

The results of this study will make it possible to:

1. guide care for COVID-19 + mothers and their newborns in real time, through a targeted
analysis of key minimum data items, on a bimonthly basis during the epidemic. To achieve
this objective, rapid deployment of the data collection system is necessary.

2. generate knowledge on the morbidity profile of maternal COVID-19 infection for mother
and child, the subgroups at risk, and the impact of management options in real life
settings;

3. document risks of intrapartum, peri-partum and postpartum transmission based on viral
tests performed in the course of routine care; this approach is complementary to the
biological collections set up in other projects, which aim to determine the infectious
status of pregnant women from specialized centers that are not representative of the
general population of pregnant women.

4. carry out comparative international research through collaboration with the
international INOSS network which is coordinating similar data collection protocols and
designs worldwide. The investigators are French INOSS partners.

5. evaluate the impact of the epidemic on the organization of care for all pregnant women
and newborns. Major and rapid changes to prenatal and childbirth care have been made in
response to the epidemic, including spacing out consultations, using teleconsultation
instead of in-person visits, restricting the presence of relatives and early discharge.
These changes may induce negative consequences, notably delays in the diagnosis of
obstetrical complications. It is therefore crucial to document the impact of the
epidemic and the resulting measures on the health of all women and newborns. For all
pregnant women and newborns monitored in participating maternity hospitals, we will
extract routinely collected data from the computerized records of the maternity
hospitals and/or via the SNDS-PMSI databases. These data will also be collected for
periods before the epidemic to enable comparisons with overall pregnancy outcomes
between the two periods. These results can be placed in an international context through
collaboration with the European Euro-Peristat network, coordinated by the investigators'
research team.

The objective of this multi-regional population-based cohort is to assess the impact of
COVID-19 infection during pregnancy on maternal and neonatal health, including rates of
perinatal transmission and the influence of diverse management practices on morbidity. The
study's focus on this specific population and its population-based coverage complement other
facility-based surveillance systems on all cases in France.