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.