<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/NCT02245815</url>
  </required_header>
  <id_info>
    <org_study_id>R-2013-1002-7</org_study_id>
    <nct_id>NCT02245815</nct_id>
  </id_info>
  <brief_title>Prevention of Necrotizing Enterocolitis of Premature Newborns Under Less Than 1500 g Using Probiotics</brief_title>
  <acronym>(PEPP)</acronym>
  <official_title>The Use of Probiotics (L. Acidophilus Boucardii vs. Multi-species) in the Prevention of Necrotizing Enterocolitis and Their Effect on Secreting IgA in the Feces of Premature Newborns Under Less Than 1500 g</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Coordinación de Investigación en Salud, Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Coordinación de Investigación en Salud, Mexico</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the incidence of necrotizing enterocolitis and its&#xD;
      effect over the secreting immunoglobulin A in the feces with the use of probiotics of the&#xD;
      strain Lactobacillus acidophilus boucardii vs. Multispecies in premature newborns weighting&#xD;
      less than 1500 g.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized controlled trial, in the Neonatal department of Highly Specialized Medical Unit&#xD;
      (UMAE) of Hospital Pediatric - Gynecology No. 48 of Mexican Institute of Social Security&#xD;
      (IMSS ) on Leon, Mexico, between 15th of December 2013 and 30th of October 2014, on premature&#xD;
      newborns of less than 1500 g. They were two groups of patients:&#xD;
&#xD;
      Group A: was given Lacteol fort, which contains 1x10⁹(CFU) of Lactobacillus acidophilus&#xD;
      strain boucardii every 24 hours during 3 weeks. Its presentation is a powder of 160 mg. It's&#xD;
      manufactured by (Carnot ® laboratories), scientific products .&#xD;
&#xD;
      Group B: was given multispecies probiotic, which contains 1x10⁹ (CFU) of Lactobacillus&#xD;
      acidophilus, rhamnosus, casei, plantarum, Bifidobacterium infantis, Streptococcus&#xD;
      thermophilus , every 24 hours during 3 weeks. Its presentation is a powder with 1. (ITALMEX&#xD;
      laboratories), scientific products .&#xD;
&#xD;
      All patients received trophic enteral stimulation for 5 days, then an increasing amount of&#xD;
      12-20 ml/kg of breast milk on a daily basis, according to the Clinical Practice Guidelines of&#xD;
      feeding premature newborns of the investigators hospital.&#xD;
&#xD;
      The envelops containing the probiotic they were labeled with patient data and handled to the&#xD;
      nurse in charge of the feeding so that it can be added preferably to the prescribed breast&#xD;
      milk, and administered at12 o´clock every day with the feeding.&#xD;
&#xD;
      The diagnosis of Necrotizing Enterocolitis (NEC) was made by the attending physician using&#xD;
      Bell criteria. Moreover the attending physician did the adjustments in the amount of breast&#xD;
      milk consumed by the patient.&#xD;
&#xD;
      Gastric tolerance will be observed through: the presence of vomit, abdominal distention,&#xD;
      presence of blood or bile juice on the gastric tube, and the pattern and characteristics of&#xD;
      the feces using a daily record.Stool samples were taken between 9 am. and 21:00., before the&#xD;
      first administration of probiotics and at the end of the third week of probiotic treatment.&#xD;
      The samples were processed and frozen at -70'C. Quantifying secrete immunoglobulin A (IgA s)&#xD;
      was made by immunodiagnostic assay K8870, Benshein, Germany ELISA.&#xD;
&#xD;
      was monitored the clinical evolution of Necrotizing Enterocolitis (NEC), medical or surgical&#xD;
      treatment and the complications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With (NEC)</measure>
    <time_frame>3 weeks</time_frame>
    <description>(NEC) was evaluated according to Bell's criteria and only considered in case of stage II-III</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Infectious Diseases</condition>
  <arm_group>
    <arm_group_label>use probiotics boucardii</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>was administered the probiotic 1x10⁹ colonies forming units per day for 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>use probiotics Multi-species</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>was administered the probiotic 1x10⁹ colonies forming units per day for 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>use probiotics boucardii</intervention_name>
    <description>group A was administered the lactobacillus acidophilus boucardii probiotic (1x10⁹ colonies forming units (UFC) per day for 3 weeks). The diagnosis of (NEC) was made using the Bell criteria by the attending physician. Gastric tolerance was measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) was measured at the beginning and at the end of treatment.</description>
    <arm_group_label>use probiotics boucardii</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>use probiotics Multi-species</intervention_name>
    <description>Group B was administered multi-species probiotic (1x10⁹colonies forming units (UFC) per day for 3 weeks). The diagnosis of (NEC) was made using the Bell criteria by the attending physician. Gastric tolerance was measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) was measured at the beginning and at the end of treatment.</description>
    <arm_group_label>use probiotics Multi-species</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All of the premature newborns of 34 weeks of gestational age, and with a weight&#xD;
             between 700 to 1500 g. that are admitted in the Neonatal Intensive Care Unit or the&#xD;
             Neonatology Department that have no contraindication for oral intake in the first 7&#xD;
             days of life. Must not have been diagnosed of sepsis of early onset, prenatal&#xD;
             asphyxia, patent ductus arterious with hemodynamic repercussion, major congenital&#xD;
             malformations. In all cases the parents or legal guardian must sign the informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All preterm newborns younger than 34 weeks of gestational age that develop any disease&#xD;
             different of (NEC) that require to stop the enteral feeding for more than seven days&#xD;
             or whose parents or legal guardians revoke the informed consent form.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>27 Weeks</minimum_age>
    <maximum_age>34 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guadalupe Gómez Rodríguez, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Guanjuato</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Guanajuato School of Medicine</name>
      <address>
        <city>Leon</city>
        <state>Guanajuato</state>
        <zip>37000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <results_first_submitted>July 31, 2015</results_first_submitted>
  <results_first_submitted_qc>January 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 28, 2021</results_first_posted>
  <last_update_submitted>January 27, 2021</last_update_submitted>
  <last_update_submitted_qc>January 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Coordinación de Investigación en Salud, Mexico</investigator_affiliation>
    <investigator_full_name>Guadalupe Gómez Rodríguez</investigator_full_name>
    <investigator_title>neonatologist</investigator_title>
  </responsible_party>
  <keyword>Necrotizing enterocolitis</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Secreting IgA</keyword>
  <keyword>Preterm newborns</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Infections</mesh_term>
    <mesh_term>Enterocolitis</mesh_term>
    <mesh_term>Enterocolitis, Necrotizing</mesh_term>
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>clinic</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Use Probiotics Boucardii</title>
          <description>group A will be administered the lactobacillus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Boucardii: group A will be administered the lactobacillus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
        <group group_id="P2">
          <title>Use Probiotics Multi-species</title>
          <description>Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Multi-species: Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Use Probiotics Boucardii</title>
          <description>group A will be administered the lactobacillus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Boucardii: group A will be administered the lactobacillus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
        <group group_id="B2">
          <title>Use Probiotics Multi-species</title>
          <description>Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Multi-species: Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
            <count group_id="B2" value="45"/>
            <count group_id="B3" value="90"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>weeks of gestation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.3" spread="1.83"/>
                    <measurement group_id="B2" value="31.1" spread="2.3"/>
                    <measurement group_id="B3" value="30.7" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Mexico</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With (NEC)</title>
        <description>(NEC) was evaluated according to Bell's criteria and only considered in case of stage II-III</description>
        <time_frame>3 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Probiotics Lactobacillus Acidophilus Boucardii</title>
            <description>group A will be administered the Lactobacillus acidophilus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Use Probiotics Multi-species</title>
            <description>Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With (NEC)</title>
          <description>(NEC) was evaluated according to Bell's criteria and only considered in case of stage II-III</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Change in Fecal Secretory IgA Levels From Baseline to 3 Weeks of Probiotics Use.</title>
        <description>The change was calculated from two time points (at 3 weeks of treatment minus baseline).</description>
        <time_frame>3 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Probiotics Lactobacillus Acidophilus Boucardii</title>
            <description>Group A will be administered the Lactobacillus acidophilus boucardii probiotic</description>
          </group>
          <group group_id="O2">
            <title>Use Probiotics Multi-species</title>
            <description>Group B will be administered multi-species probiotics</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fecal Secretory IgA Levels From Baseline to 3 Weeks of Probiotics Use.</title>
          <description>The change was calculated from two time points (at 3 weeks of treatment minus baseline).</description>
          <units>mg/10g</units>
          <param>Geometric Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" lower_limit="0.15" upper_limit="0.45"/>
                    <measurement group_id="O2" value="0.56" lower_limit="0.24" upper_limit="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>11 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Use Probiotics Lactobacillus Acidophilus Boucardii</title>
          <description>group A will be administered the lactobacillus acidophilus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Lactobacillus acidophilus boucardii: group A will be administered the Lactobacillus acidophilus boucardii probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
        <group group_id="E2">
          <title>Use Probiotics Multi-species</title>
          <description>Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks).&#xD;
use probiotics Multi-species: Group B will be administered multi-species probiotic (1x109 colonies forming units (UFC) per day for 3 weeks). The diagnosis of NEC will be made using the Bell criteria by the attending physician. Gastric tolerance will be measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) will be measured at the beginning and at the end of treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The quantification of the amount of breast milk administered was imprecise because in the Unit there is no Milk Bank, and the visits from the mothers are restricted, however we acknowledge the crucial role of breast milk in the prevention of (NEC).</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dra. Guadalupe Gómez Rodríguez</name_or_title>
      <organization>Instituto Mexicano del Seguro Social</organization>
      <phone>477 75 23 166</phone>
      <email>lupitaneonato@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02245815
org study id: R-2013-1002-7
nct id: NCT02245815
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the incidence of necrotizing enterocolitis and its
      effect over the secreting immunoglobulin A in the feces with the use of probiotics of the
      strain Lactobacillus acidophilus boucardii vs. Multispecies in premature newborns weighting
      less than 1500 g.
Randomized controlled trial, in the Neonatal department of Highly Specialized Medical Unit
      (UMAE) of Hospital Pediatric - Gynecology No. 48 of Mexican Institute of Social Security
      (IMSS ) on Leon, Mexico, between 15th of December 2013 and 30th of October 2014, on premature
      newborns of less than 1500 g. They were two groups of patients:

      Group A: was given Lacteol fort, which contains 1x10⁹(CFU) of Lactobacillus acidophilus
      strain boucardii every 24 hours during 3 weeks. Its presentation is a powder of 160 mg. It's
      manufactured by (Carnot ® laboratories), scientific products .

      Group B: was given multispecies probiotic, which contains 1x10⁹ (CFU) of Lactobacillus
      acidophilus, rhamnosus, casei, plantarum, Bifidobacterium infantis, Streptococcus
      thermophilus , every 24 hours during 3 weeks. Its presentation is a powder with 1. (ITALMEX
      laboratories), scientific products .

      All patients received trophic enteral stimulation for 5 days, then an increasing amount of
      12-20 ml/kg of breast milk on a daily basis, according to the Clinical Practice Guidelines of
      feeding premature newborns of the investigators hospital.

      The envelops containing the probiotic they were labeled with patient data and handled to the
      nurse in charge of the feeding so that it can be added preferably to the prescribed breast
      milk, and administered at12 o´clock every day with the feeding.

      The diagnosis of Necrotizing Enterocolitis (NEC) was made by the attending physician using
      Bell criteria. Moreover the attending physician did the adjustments in the amount of breast
      milk consumed by the patient.

      Gastric tolerance will be observed through: the presence of vomit, abdominal distention,
      presence of blood or bile juice on the gastric tube, and the pattern and characteristics of
      the feces using a daily record.Stool samples were taken between 9 am. and 21:00., before the
      first administration of probiotics and at the end of the third week of probiotic treatment.
      The samples were processed and frozen at -70'C. Quantifying secrete immunoglobulin A (IgA s)
      was made by immunodiagnostic assay K8870, Benshein, Germany ELISA.

      was monitored the clinical evolution of Necrotizing Enterocolitis (NEC), medical or surgical
      treatment and the complications.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Number of Patients With (NEC)
time frame: 3 weeks
description: (NEC) was evaluated according to Bell's criteria and only considered in case of stage II-III
arm group label: use probiotics boucardii
arm group type: Experimental
description: was administered the probiotic 1x10⁹ colonies forming units per day for 3 weeks
arm group label: use probiotics Multi-species
arm group type: Experimental
description: was administered the probiotic 1x10⁹ colonies forming units per day for 3 weeks
intervention type: Dietary Supplement
intervention name: use probiotics boucardii
description: group A was administered the lactobacillus acidophilus boucardii probiotic (1x10⁹ colonies forming units (UFC) per day for 3 weeks). The diagnosis of (NEC) was made using the Bell criteria by the attending physician. Gastric tolerance was measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) was measured at the beginning and at the end of treatment.
arm group label: use probiotics boucardii
intervention type: Dietary Supplement
intervention name: use probiotics Multi-species
description: Group B was administered multi-species probiotic (1x10⁹colonies forming units (UFC) per day for 3 weeks). The diagnosis of (NEC) was made using the Bell criteria by the attending physician. Gastric tolerance was measured, the number and the characteristics of the feces before and after the administration of the probiotic, and also the levels of (IgA s) was measured at the beginning and at the end of treatment.
arm group label: use probiotics Multi-species
criteria: 
gender: All
minimum age: 27 Weeks
maximum age: 34 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: Guadalupe Gómez Rodríguez, M.D.
role: Principal Investigator
affiliation: University of Guanjuato
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Coordinación de Investigación en Salud, Mexico
investigator full name: Guadalupe Gómez Rodríguez
investigator title: neonatologist
mesh term: Communicable Diseases
mesh term: Infections
mesh term: Enterocolitis
mesh term: Enterocolitis, Necrotizing
mesh term: Premature Birth
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The quantification of the amount of breast milk administered was imprecise because in the Unit there is no Milk Bank, and the visits from the mothers are restricted, however we acknowledge the crucial role of breast milk in the prevention of (NEC).
point of contact: 