<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/NCT04431869</url>
  </required_header>
  <id_info>
    <org_study_id>20-1399</org_study_id>
    <nct_id>NCT04431869</nct_id>
  </id_info>
  <brief_title>In-Utero Vascular Accidents in Neonates From COVID-19 Infected Mothers</brief_title>
  <official_title>In-Utero Vascular Accidents in Neonates From COVID-19 Infected Mothers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</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 pregnancy related pro-thrombotic state, in addition to the COVID-19 associated&#xD;
      hypercoagulability may have unknown consequences to the developing fetus. Hence, this&#xD;
      proposal seeks to address this question that may have important implications for women that&#xD;
      contract this virus during gestation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypercoagulability and increased risk for venous thromboembolism (VTE) in severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are well documented in the&#xD;
      growing body of literature, leading to institutional recommendations for daily pharmacologic&#xD;
      anticoagulation while hospitalized and after discharge for some. While some of these&#xD;
      hospitalized patients with COVID-19 infections have included pregnant women that also require&#xD;
      inpatient pharmacologic anticoagulation and occasionally extended anticoagulation after&#xD;
      discharge, little is known about the effects of the hypercoagulable COVID-19 induced state on&#xD;
      the developing embryo, nor the necessary anticoagulation recommendation guidelines for these&#xD;
      expecting mothers.&#xD;
&#xD;
      The pregnancy related pro-thrombotic state, in addition to the COVID-19 associated&#xD;
      hypercoagulability may have unknown consequences to the developing fetus. Hence, this&#xD;
      proposal seeks to address this question that may have important implications for women that&#xD;
      contract this virus during gestation through the following specific aims.&#xD;
&#xD;
      Specific Aim 1: To evaluate evidence for in-utero vascular accidents that may manifest as&#xD;
      intestinal atresias and limb abnormalities in the first 30 days of life as well as rates of&#xD;
      preterm labor, fetal growth restriction and spontaneous abortions in pregnant females that&#xD;
      contract the SARS-CoV-2 virus during gestation.&#xD;
&#xD;
      Rationale: Pregnancy produces a hypercoagulable state, this study intends to expand on the&#xD;
      body of literature for COVID-19 manifestations by evaluating the additional virus-induced&#xD;
      hypercoagulability on the developing embryo.&#xD;
&#xD;
      Methods: A multidisciplinary approach in conjunction with maternal fetal medicine (MFM),&#xD;
      neonatology, and pathology, the study will identify, and recruit infants whom were exposed to&#xD;
      COVID-19 while in-utereo. This project will run in parallel with the institution's COVID-19&#xD;
      in Pregnancy Biobank that intends to obtain needed epidemiological and clinical data linked&#xD;
      to biosamples to provide insight into SARS-CoV-2 in pregnant women and their infants.&#xD;
&#xD;
      Specific Aim 2: To evaluate children identified in the neonatal intensive care unit (NICU) as&#xD;
      having evidence of intestinal atresias or limb anomalies for potential asymptomatic carriers&#xD;
      of COVID-19 that could have contracted the disease during the pregnancy.&#xD;
&#xD;
      Rationale: As high as 81% of patients that contract SARS-CoV-2 are asymptomatic or minimally&#xD;
      symptomatic during the infection period. The long-term manifestation of the virus in these&#xD;
      asymptomatic carriers, especially in pregnant women and their developing embryos, are&#xD;
      presently unknown.&#xD;
&#xD;
      Methods: Mothers of children identified will undergo SARS-CoV-2 antibody testing to identify&#xD;
      the possibility of asymptomatic carriers which may have occurred during the pregnancy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">September 1, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>Rates of intestinal atresias and limb abnormalities</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluate rates of intestinal atresias and limb anomalies in neonates born to women that contract SARS-CoV-2 during pregnancy in the first 30 days of life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rates of preterm labor, fetal growth restriction and spontaneous abortions</measure>
    <time_frame>12 months</time_frame>
    <description>Rates of preterm labor, fetal growth restriction and spontaneous abortions for women that are known to be infected with SARS-CoV-2 during gestation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rates of maternal SARS-CoV-2 infection among mothers to infants born with intestinal atresias or limb anomalies</measure>
    <time_frame>12 months</time_frame>
    <description>For neonates identified in the NICU with intestinal atresias and limb anomalies, we will test the mothers for the presence of SARS-CoV-2 antibodies that may represent an asymptomatic carrier during gestation</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">215</enrollment>
  <condition>Pregnancy Related</condition>
  <condition>COVID</condition>
  <condition>Intestinal Atresia</condition>
  <condition>Limb Anomaly</condition>
  <arm_group>
    <arm_group_label>Mothers that contract SARS-CoV-2 during pregnancy</arm_group_label>
    <description>To evaluate evidence for in-utero vascular accidents that may manifest as intestinal atresias and limb abnormalities in the first 30 days of life as well as rates of preterm labor, fetal growth restriction and spontaneous abortions in pregnant females that contract the SARS-CoV-2 virus during gestation.&#xD;
A multidisciplinary approach in conjunction with maternal fetal medicine (MFM), neonatology, and pathology will identify, and recruit infants whom were exposed to COVID-19 while in-utereo. This project will run in parallel with the institution's COVID-19 in Pregnancy Biobank that intends to obtain needed epidemiological and clinical data linked to biosamples to provide insight into SARS-CoV-2 in pregnant women and their infants. This study will request access to enrolled women infected during gestation and their neonates to assess for the conditions suggestive of in-utero vascular accidents such as intestinal atresias or limb anomalies.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Infants noted to have intestinal atresias or limb anomalies</arm_group_label>
    <description>To evaluate children identified in the neonatal intensive care unit (NICU) as having evidence of intestinal atresias or limb anomalies for potential asymptomatic carriers of COVID-19 that could have contracted the disease during the pregnancy.&#xD;
Mothers of children identified will undergo SARS-CoV-2 antibody testing to identify the possibility of asymptomatic carriers which may have occurred during the pregnancy.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Mothers of children enrolled in the study with intestinal atresias or limb anomalies will&#xD;
      undergo SARS-CoV-2 antibody testing to identify the possibility of asymptomatic carriers&#xD;
      which may have occurred during the pregnancy.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant females with documented COVID-19 gestational infections and their infants will be&#xD;
        enrolled. Additionally, neonates with limb anomalies and intestinal atresias will be&#xD;
        identified in the NICU and both infant and mother enrolled to identify if maternal&#xD;
        SARS-CoV-2 infection occurred during the pregnancy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant females, 18 years and higher, with documented COVID-19 infection (antigen,&#xD;
             PRC, or antibodies in a biologic sample) during gestation who received medical care at&#xD;
             the University of Colorado Hospital (UCH) or Children's Hospital Colorado (CHCO)&#xD;
&#xD;
          -  Neonates born to COVID-19 infected mothers&#xD;
&#xD;
          -  Neonates ages 1-60 days of life with documented limb anomalies and intestinal atresias&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mothers with a history of vasoactive drug usage during pregnancy&#xD;
&#xD;
          -  Mothers taking known teratogens during pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>September 24, 2021</last_update_submitted>
  <last_update_submitted_qc>September 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Atresia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>This study seeks to find a correlation between maternal COVID-19 infection and in-utero vascular accidents affecting the developing fetus. The knowledge gained from this multidisciplinary study may serve as the foundation for larger epidemiological studies that may query the longitudinal effects of this infection in mothers who contract the disease during pregnancy, as well as for their neonates. On a larger scale, if the study hypothesis is supported by the data, this may provide the foundation for future anticoagulation guidelines that may be enacted on certain women during gestation.</ipd_description>
  </patient_data>
  <!-- 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/NCT04431869
org study id: 20-1399
nct id: NCT04431869
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The pregnancy related pro-thrombotic state, in addition to the COVID-19 associated
      hypercoagulability may have unknown consequences to the developing fetus. Hence, this
      proposal seeks to address this question that may have important implications for women that
      contract this virus during gestation.
Hypercoagulability and increased risk for venous thromboembolism (VTE) in severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are well documented in the
      growing body of literature, leading to institutional recommendations for daily pharmacologic
      anticoagulation while hospitalized and after discharge for some. While some of these
      hospitalized patients with COVID-19 infections have included pregnant women that also require
      inpatient pharmacologic anticoagulation and occasionally extended anticoagulation after
      discharge, little is known about the effects of the hypercoagulable COVID-19 induced state on
      the developing embryo, nor the necessary anticoagulation recommendation guidelines for these
      expecting mothers.

      The pregnancy related pro-thrombotic state, in addition to the COVID-19 associated
      hypercoagulability may have unknown consequences to the developing fetus. Hence, this
      proposal seeks to address this question that may have important implications for women that
      contract this virus during gestation through the following specific aims.

      Specific Aim 1: To evaluate evidence for in-utero vascular accidents that may manifest as
      intestinal atresias and limb abnormalities in the first 30 days of life as well as rates of
      preterm labor, fetal growth restriction and spontaneous abortions in pregnant females that
      contract the SARS-CoV-2 virus during gestation.

      Rationale: Pregnancy produces a hypercoagulable state, this study intends to expand on the
      body of literature for COVID-19 manifestations by evaluating the additional virus-induced
      hypercoagulability on the developing embryo.

      Methods: A multidisciplinary approach in conjunction with maternal fetal medicine (MFM),
      neonatology, and pathology, the study will identify, and recruit infants whom were exposed to
      COVID-19 while in-utereo. This project will run in parallel with the institution's COVID-19
      in Pregnancy Biobank that intends to obtain needed epidemiological and clinical data linked
      to biosamples to provide insight into SARS-CoV-2 in pregnant women and their infants.

      Specific Aim 2: To evaluate children identified in the neonatal intensive care unit (NICU) as
      having evidence of intestinal atresias or limb anomalies for potential asymptomatic carriers
      of COVID-19 that could have contracted the disease during the pregnancy.

      Rationale: As high as 81% of patients that contract SARS-CoV-2 are asymptomatic or minimally
      symptomatic during the infection period. The long-term manifestation of the virus in these
      asymptomatic carriers, especially in pregnant women and their developing embryos, are
      presently unknown.

      Methods: Mothers of children identified will undergo SARS-CoV-2 antibody testing to identify
      the possibility of asymptomatic carriers which may have occurred during the pregnancy.
observational model: Cohort
time perspective: Prospective
measure: Rates of intestinal atresias and limb abnormalities
time frame: 12 months
description: Evaluate rates of intestinal atresias and limb anomalies in neonates born to women that contract SARS-CoV-2 during pregnancy in the first 30 days of life
measure: Rates of preterm labor, fetal growth restriction and spontaneous abortions
time frame: 12 months
description: Rates of preterm labor, fetal growth restriction and spontaneous abortions for women that are known to be infected with SARS-CoV-2 during gestation
measure: Rates of maternal SARS-CoV-2 infection among mothers to infants born with intestinal atresias or limb anomalies
time frame: 12 months
description: For neonates identified in the NICU with intestinal atresias and limb anomalies, we will test the mothers for the presence of SARS-CoV-2 antibodies that may represent an asymptomatic carrier during gestation
arm group label: Mothers that contract SARS-CoV-2 during pregnancy
description: To evaluate evidence for in-utero vascular accidents that may manifest as intestinal atresias and limb abnormalities in the first 30 days of life as well as rates of preterm labor, fetal growth restriction and spontaneous abortions in pregnant females that contract the SARS-CoV-2 virus during gestation.
A multidisciplinary approach in conjunction with maternal fetal medicine (MFM), neonatology, and pathology will identify, and recruit infants whom were exposed to COVID-19 while in-utereo. This project will run in parallel with the institution's COVID-19 in Pregnancy Biobank that intends to obtain needed epidemiological and clinical data linked to biosamples to provide insight into SARS-CoV-2 in pregnant women and their infants. This study will request access to enrolled women infected during gestation and their neonates to assess for the conditions suggestive of in-utero vascular accidents such as intestinal atresias or limb anomalies.
arm group label: Infants noted to have intestinal atresias or limb anomalies
description: To evaluate children identified in the neonatal intensive care unit (NICU) as having evidence of intestinal atresias or limb anomalies for potential asymptomatic carriers of COVID-19 that could have contracted the disease during the pregnancy.
Mothers of children identified will undergo SARS-CoV-2 antibody testing to identify the possibility of asymptomatic carriers which may have occurred during the pregnancy.
Mothers of children enrolled in the study with intestinal atresias or limb anomalies will
      undergo SARS-CoV-2 antibody testing to identify the possibility of asymptomatic carriers
      which may have occurred during the pregnancy.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Intestinal Atresia
sharing ipd: Undecided
ipd description: This study seeks to find a correlation between maternal COVID-19 infection and in-utero vascular accidents affecting the developing fetus. The knowledge gained from this multidisciplinary study may serve as the foundation for larger epidemiological studies that may query the longitudinal effects of this infection in mothers who contract the disease during pregnancy, as well as for their neonates. On a larger scale, if the study hypothesis is supported by the data, this may provide the foundation for future anticoagulation guidelines that may be enacted on certain women during gestation.