<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04463758</url>
  </required_header>
  <id_info>
    <org_study_id>APHP200513</org_study_id>
    <nct_id>NCT04463758</nct_id>
  </id_info>
  <brief_title>Covid-19 in Pregnancy: a French Population-based Cohort of Women and Newborns</brief_title>
  <acronym>Coropreg</acronym>
  <official_title>Covid-19 in Pregnancy: a French Population-based Cohort of Women and Newborns</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM, Epopé team</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to characterize the incidence and clinical features of the&#xD;
      maternal COVID 19 infection, as well as the associated morbidity of the mother and the child,&#xD;
      in the French context&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the overall context of uncertainty about the morbidity associated with COVID-19 infection&#xD;
      and its optimal management, knowledge is urgently required on infection during pregnancy.&#xD;
&#xD;
      First, pregnant women and newborns can have specific and severe reactions to infectious&#xD;
      diseases, as seen in previous pandemics which justifies targeted surveillance. Second,&#xD;
      optimal management must minimize the health risks of transmission to the newborn. While&#xD;
      initial studies did not provide evidence for transmission in utero or during delivery, more&#xD;
      recent data suggest that transmission is possible. The virus is present in vaginal secretions&#xD;
      and stool, making vertical contamination possible during vaginal delivery. Similarly,&#xD;
      transmission may occur during breastfeeding. These risks, which remain theoretical, must be&#xD;
      weighed against known harmful consequences of mitigating strategies such as systematic&#xD;
      caesarean (increase in maternal morbidity) and separating the child from the mother and&#xD;
      contraindicating breastfeeding (negative impact on maternal-child bonding and optimal&#xD;
      nutrition). In the absence of reliable data, some maternity hospitals have adopted a maximum&#xD;
      precautionary principle, recommending caesarean for all COVID-19 positive women and imposing&#xD;
      immediate mother-child separation after childbirth. These approaches are strongly debated in&#xD;
      France. Third, optimal management of COVID-19 during pregnancy requires balancing maternal&#xD;
      and newborn risks. Risks of maternal deterioration in the event of continuing pregnancy must&#xD;
      be weighed against those to the child resulting from indicated preterm birth. This tradeoff&#xD;
      is even more complex as evidence-based interventions to protect preterm infants, such as&#xD;
      antenatal corticosteroid, may aggravate maternal infection. Finally, childbirth is not an&#xD;
      elective procedure and requires managing large numbers of healthy women and newborns in a&#xD;
      hospital setting where they are exposed to risks of infection.&#xD;
&#xD;
      Population-based research that captures the diversity of organizational structures and&#xD;
      practices within maternity units is needed to guide management during the current epidemic&#xD;
      and draw lessons for future infectious pandemics.&#xD;
&#xD;
      Principal innovative features are:&#xD;
&#xD;
        -  A population-based approach: Current data systems will include a limited number of&#xD;
           pregnant women, principally from university hospitals with specific patient populations&#xD;
           and management strategies. Because all maternity hospitals care for COVID-19+ pregnant&#xD;
           women, a population-based approach is needed to calculate reliable incidence rates,&#xD;
           assess practice variability and measure the impact of differences in management on&#xD;
           maternal and newborn infection rates and health.&#xD;
&#xD;
        -  The inclusion of infected pregnant women who are not hospitalized and who recover before&#xD;
           delivery will provide comprehensive data and measure early fetal in-utero exposure.&#xD;
&#xD;
        -  Immediate feedback to clinicians on their practices will inform current controversies&#xD;
           about optimal management.&#xD;
&#xD;
        -  Joint follow-up of mother and child to 12 weeks after delivery, and longer if indicated,&#xD;
           will document the medium-term impact of infection.&#xD;
&#xD;
        -  Inclusion of regions with time-varying exposure to the epidemic will provide information&#xD;
           to evaluate public health policies.&#xD;
&#xD;
      The results of this study will make it possible to:&#xD;
&#xD;
        1. guide care for COVID-19 + mothers and their newborns in real time, through a targeted&#xD;
           analysis of key minimum data items, on a bimonthly basis during the epidemic. To achieve&#xD;
           this objective, rapid deployment of the data collection system is necessary.&#xD;
&#xD;
        2. generate knowledge on the morbidity profile of maternal COVID-19 infection for mother&#xD;
           and child, the subgroups at risk, and the impact of management options in real life&#xD;
           settings;&#xD;
&#xD;
        3. document risks of intrapartum, peri-partum and postpartum transmission based on viral&#xD;
           tests performed in the course of routine care; this approach is complementary to the&#xD;
           biological collections set up in other projects, which aim to determine the infectious&#xD;
           status of pregnant women from specialized centers that are not representative of the&#xD;
           general population of pregnant women.&#xD;
&#xD;
        4. carry out comparative international research through collaboration with the&#xD;
           international INOSS network which is coordinating similar data collection protocols and&#xD;
           designs worldwide. The investigators are French INOSS partners.&#xD;
&#xD;
        5. evaluate the impact of the epidemic on the organization of care for all pregnant women&#xD;
           and newborns. Major and rapid changes to prenatal and childbirth care have been made in&#xD;
           response to the epidemic, including spacing out consultations, using teleconsultation&#xD;
           instead of in-person visits, restricting the presence of relatives and early discharge.&#xD;
           These changes may induce negative consequences, notably delays in the diagnosis of&#xD;
           obstetrical complications. It is therefore crucial to document the impact of the&#xD;
           epidemic and the resulting measures on the health of all women and newborns. For all&#xD;
           pregnant women and newborns monitored in participating maternity hospitals, we will&#xD;
           extract routinely collected data from the computerized records of the maternity&#xD;
           hospitals and/or via the SNDS-PMSI databases. These data will also be collected for&#xD;
           periods before the epidemic to enable comparisons with overall pregnancy outcomes&#xD;
           between the two periods. These results can be placed in an international context through&#xD;
           collaboration with the European Euro-Peristat network, coordinated by the investigators'&#xD;
           research team.&#xD;
&#xD;
      The objective of this multi-regional population-based cohort is to assess the impact of&#xD;
      COVID-19 infection during pregnancy on maternal and neonatal health, including rates of&#xD;
      perinatal transmission and the influence of diverse management practices on morbidity. The&#xD;
      study's focus on this specific population and its population-based coverage complement other&#xD;
      facility-based surveillance systems on all cases in France.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 11, 2020</start_date>
  <completion_date type="Anticipated">October 2022</completion_date>
  <primary_completion_date type="Anticipated">February 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Joint evaluation of morbi-mortality for mother and child up to 12 weeks postpartum</measure>
    <time_frame>At12 weeks after delivery</time_frame>
    <description>Maternal Criterion: Validated Composite Criterion of Severe Maternal Morbidity (Epimoms study ref 7).&#xD;
Neonatal Criterion: Mortality and Composite Criterion of Severe Neonatal Morbidity Perinatal asphyxia (arterial pH to cord-7.15 and/or an excess base - 10mmol/L and/or lactates-6 mmol/L, Apgar score at 5 minutes -7), neonatal encephalopathy, seizures, intraventricular hemorrhage, cerebral infarction, periventricular leucomalacia, ulcerative enterocolite, sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, central catheter, ventilatory support, transfusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of women infection COVID-19</measure>
    <time_frame>During pregnancy and up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe forms of COVID-19 infection in the mother</measure>
    <time_frame>Until 12 weeks after delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe neonatal morbidity</measure>
    <time_frame>Until 12 weeks after delivery</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">3060</enrollment>
  <condition>covid19 Infection</condition>
  <condition>Pregnancy Complications</condition>
  <condition>Neonatal Complications</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>An auto-questionnaire comprising three psychometric scales</intervention_name>
    <description>three psychometric scales validated in French: _depression (Edinburgh Postpartum Depression Scale (EPDS)), anxiety (State-Trait Anxiety Inventory (STAI)&#xD;
- and Impact of Event Scale (Revised) (IES-R)</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All pregnant or recently pregnant women managed in one maternity unit of the 16&#xD;
        participating perinatal networks&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any woman with :&#xD;
&#xD;
        either proven COVID-19 infection= positive PCR test, OR probable COVID-19 infection =&#xD;
        typical clinical symptoms AND typical pulmonary radiology&#xD;
&#xD;
          -  during pregnancy or within 42 days postpartum,&#xD;
&#xD;
          -  whether or not this diagnosis is followed by hospitalization,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate&#xD;
&#xD;
          -  Major protected (curator, trusteeship)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierre Yv Ancel, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Catherine Deneux-Tharaux, MD, PhD</last_name>
    <phone>+33 1 42 34 55 79</phone>
    <email>catherine.deneux-tharaux@inserm.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laurence Lecomte, PhD</last_name>
    <phone>+33 1 58 41 34 78</phone>
    <email>laurence.lecomte@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>AP-HP Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Marc Treluyer, M.D., PhD</last_name>
      <phone>+ 00 1 58 41 28 85</phone>
      <email>jean-marc.treluyer@parisdescartes.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>October 1, 2021</last_update_submitted>
  <last_update_submitted_qc>October 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Covid19</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Maternal morbidity</keyword>
  <keyword>Perinatal mortality</keyword>
  <keyword>Neonatal morbidity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pregnancy Complications</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04463758
org study id: APHP200513
nct id: NCT04463758
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to characterize the incidence and clinical features of the
      maternal COVID 19 infection, as well as the associated morbidity of the mother and the child,
      in the French context
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.
observational model: Cohort
time perspective: Prospective
measure: Joint evaluation of morbi-mortality for mother and child up to 12 weeks postpartum
time frame: At12 weeks after delivery
description: Maternal Criterion: Validated Composite Criterion of Severe Maternal Morbidity (Epimoms study ref 7).
Neonatal Criterion: Mortality and Composite Criterion of Severe Neonatal Morbidity Perinatal asphyxia (arterial pH to cord-7.15 and/or an excess base - 10mmol/L and/or lactates-6 mmol/L, Apgar score at 5 minutes -7), neonatal encephalopathy, seizures, intraventricular hemorrhage, cerebral infarction, periventricular leucomalacia, ulcerative enterocolite, sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, central catheter, ventilatory support, transfusion
measure: Number of women infection COVID-19
time frame: During pregnancy and up to 12 weeks
measure: Severe forms of COVID-19 infection in the mother
time frame: Until 12 weeks after delivery
measure: Severe neonatal morbidity
time frame: Until 12 weeks after delivery
intervention type: Other
intervention name: An auto-questionnaire comprising three psychometric scales
description: three psychometric scales validated in French: _depression (Edinburgh Postpartum Depression Scale (EPDS)), anxiety (State-Trait Anxiety Inventory (STAI)
- and Impact of Event Scale (Revised) (IES-R)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Pierre Yv Ancel, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Catherine Deneux-Tharaux, MD, PhD
phone: +33 1 42 34 55 79
email: catherine.deneux-tharaux@inserm.fr
last name: Laurence Lecomte, PhD
phone: +33 1 58 41 34 78
email: laurence.lecomte@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pregnancy Complications