<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/NCT04400175</url>
  </required_header>
  <id_info>
    <org_study_id>SOFT-study</org_study_id>
    <nct_id>NCT04400175</nct_id>
  </id_info>
  <brief_title>Effects of a Valved Feeding System in Late-preterm Newborns: the Safe Oral Feeding Trial</brief_title>
  <acronym>SOFT</acronym>
  <official_title>Effects on Coordination of Sucking, Swallowing and Breathing Process of a Valved Feeding System in Late-preterm Newborns. The Safe Oral Feeding Trial (SOFT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Turin, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Turin, Italy</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Comparing with a randomized controlled trial two different feeding systems in two groups of&#xD;
      late-preterm newborns for evaluating which is more efficient in promoting the coordination in&#xD;
      the process of sucking-swallowing-breathing and better cardiorespiratory stability.&#xD;
&#xD;
      The B-ESP group will be fed with a feeding system with a valved ergonomic teat; the B-STD&#xD;
      with a standard feeding system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The swallowing patterns are still immature in the newborn, especially if preterm. An&#xD;
      incomplete synchronization in the process of sucking, swallowing and breathing could lead to&#xD;
      some difficulty during feedings with desaturations and risk of milk inhalation in the upper&#xD;
      airway tract. Moreover, a dysfunctional or immature pattern of sucking, swallowing and&#xD;
      breathing also affect the post-prandial period, tiring the newborn and increasing the&#xD;
      cardio-respiratory instability.&#xD;
&#xD;
      Breastfeeding promote the development of a physiological coordination of the process of&#xD;
      sucking, swallowing and breathing, guaranteeing high and stable values of oxygenation during&#xD;
      feedings. On the other hand, bottle-feeding could be responsible of a difficult coordination&#xD;
      among the phases of swallowing and breathing. In an healthy, at term, brestfed newborn is&#xD;
      observed a typical pattern of sucking-swallowing-expiration with a ratio of 1:1:1. In a&#xD;
      bottlefed newborn this ratio is 2-12:1:4, with a relative increase of the period of sucking&#xD;
      compared to the swallowing one, that could lead to apnoeas and desaturations.&#xD;
&#xD;
      The differences between the two feedings modality are more accentuated in the late-preterm&#xD;
      newborn, which is more prone to cardio-respiratory instability compared to the healthy at&#xD;
      term newborn, because of the immaturity of the respiratory centers in the brainstem, and of&#xD;
      the processes responsible for the coordination of the sucking, swallowing and breathing .&#xD;
&#xD;
      However breastfeeding, in spite of the fact that is crucial for the development of the&#xD;
      correct process of sucking, can be challenging in the premature infant because it requires a&#xD;
      considerable physical effort.&#xD;
&#xD;
      Therefore, disposing of devices for nutrition able to facilitate oral feeding, simulating the&#xD;
      physiologic breastfeeding, is necessary. In this way, we can contribute to the development of&#xD;
      the proper sucking-swallowing-breathing pattern and to improve cardio-respiratory stability.&#xD;
&#xD;
      In literature there are multiple studies carried out on term newborns demonstrating the&#xD;
      importance of the negative pressure or air vacuum created in the oral cavity, in order to&#xD;
      promote the emptying of the lactiferous ducts and/or of the teat and simultaneously promote&#xD;
      the maintainance of the right respiratory pattern. An ergonomic feeding system with a valve&#xD;
      able to create vacuum could be able to respond to the demands of late preterm newborns.&#xD;
&#xD;
      Aim of the study is to evaluate the effects of a trial with an experimental feeding system&#xD;
      with a teat with a valve able to facilitate the vacuum in the oral cavity on the pattern of&#xD;
      sucking-swallowing and breathing in late preterm newborns.&#xD;
&#xD;
      NUMBER OF PATIENTS Precise data regarding swallowing/respiration rate in bottle-fed late&#xD;
      preterm infants in the first 3 days of life are lacking in the literature. Considering a mean&#xD;
      swallow/respiration ratio of 1.5 and a variance of 0.5, obtained from surveys performed at&#xD;
      our center prior to the study, a sample size of 38 infants per arm was estimated to achieve&#xD;
      80% power to detect a 30% difference on the primary outcome with a significance level of&#xD;
      0.05.&#xD;
&#xD;
      STUDY DESIGN Late preterm newborns eligible to enter in the study, prior obtaining the&#xD;
      informed consent from parents, will be assigned in the &quot;B-ESP&quot; or &quot;B-STD&quot; group through a&#xD;
      process of block randomisation, controlled by a software.&#xD;
&#xD;
      Newborns included in the randomisation, after a training of 3 meals with the feeding bottle&#xD;
      assigned from the randomisation, can be entered in the study.&#xD;
&#xD;
      Newborns included in the study will be monitored for the entire duration of a meal and the&#xD;
      subsequent 3-hours period. This monitoring will be collected in two different times (T1 and&#xD;
      T2): in the second day of life (24-48 hours of life) and in the fourth day of life (72-96&#xD;
      hours of life). The study includes an audio recording of the swallowings through a microphone&#xD;
      in the room and the recordings of the process of sucking and swallowing through a cutaneous&#xD;
      sensor.&#xD;
&#xD;
      In addition, a cardiorespiratory monitoring with a poligraph will be made, considering oxygen&#xD;
      saturation, cardiac and respiratory frequency and electrocardiography. The meal's video&#xD;
      recording will permit a subsequent classification of the sucking movements and the evaluation&#xD;
      of any possible interference in the polygraphic recording.&#xD;
&#xD;
      FEEDING DEVICES&#xD;
&#xD;
      Newborns of the B-STD group will be fed using a classic disposable feeding device, which is&#xD;
      actually in use in our centre and provided by our hospital, composed of:&#xD;
&#xD;
        -  a 150 mL feeding bottle in polypropylene, devoid of BPA;&#xD;
&#xD;
        -  a silicon teat, devoid of BPA, available in two types, (a slow graduated flow and a&#xD;
           standard flow) depending on the necessities and suction abilities of the baby;&#xD;
&#xD;
        -  a protective plug.&#xD;
&#xD;
      Newborns of the B-ESP group will be fed using a feeding system with a valved ergonomic teat,&#xD;
      composed of:&#xD;
&#xD;
        -  a slow-flow ergonomic silicon teat&#xD;
&#xD;
        -  polipropilene bottle with a capacity of 150 mL, with a ventilation valve on the bottom&#xD;
&#xD;
        -  silicon valve&#xD;
&#xD;
      Newborns will be fed with defined quantities of maternal milk or bank donated milk, based on&#xD;
      weight and gestational age.&#xD;
&#xD;
      The meal will be administered by the caregiver (a parent or a nurse) previously trained. The&#xD;
      meal's administration will be performed keeping the baby in the caregivers's arms in the ESL&#xD;
      position (semielevated side-lying). At the end of the feeding process the newborn will be&#xD;
      repositioned in his cradle in the supine position.&#xD;
&#xD;
      The cardiosaturimetric evaluation will be performed using a system of polygraphic monitoring,&#xD;
      which allows a simultaneous non-invasive recording of cardiorespiratory parameters, noises&#xD;
      and movements associated to the sucking and swallowing processes combined to video&#xD;
      recordings.&#xD;
&#xD;
      The evaluation of the sucking process will be carried out using a structured questionnaire&#xD;
      composed by 31 items, which allows to distinguish normal suction (mature) from disorganized&#xD;
      and dysfunctional ones.&#xD;
&#xD;
      Considering simultaneously the cardiosaturimetric parameters, video, audio and cutaneous&#xD;
      sensor's recordings, it is possible to obtain a more accurate evaluation of the processes of&#xD;
      swallowing, sucking and breathing of the newborn during meal administration. It is also&#xD;
      possible to identify the exact moment of the breathing process assigned to the newborn's&#xD;
      swallowing.&#xD;
&#xD;
      CLINICAL DATA&#xD;
&#xD;
      At birth:&#xD;
&#xD;
        -  gestational age;&#xD;
&#xD;
        -  weight in grams;&#xD;
&#xD;
        -  z-score;&#xD;
&#xD;
        -  sex;&#xD;
&#xD;
        -  type of delivery;&#xD;
&#xD;
        -  peri-partum condition, including possible administration of prenatal corticosteroids;&#xD;
&#xD;
        -  type of support provided at birth;&#xD;
&#xD;
      At T1 and T2:&#xD;
&#xD;
        -  hours from birth;&#xD;
&#xD;
        -  weight;&#xD;
&#xD;
        -  z-score;&#xD;
&#xD;
        -  number of meals in a day;&#xD;
&#xD;
        -  type of milk administered;&#xD;
&#xD;
        -  overall volume administered expressed in mL in a day;&#xD;
&#xD;
        -  duration of a meal expressed in minutes;&#xD;
&#xD;
        -  number of regurgitation or vomit during the administration of a meal;&#xD;
&#xD;
        -  number of regurgitation or vomit after the admninistration of a meal;&#xD;
&#xD;
      At discharge:&#xD;
&#xD;
        -  weight;&#xD;
&#xD;
        -  z-score;&#xD;
&#xD;
        -  number of meals in a day;&#xD;
&#xD;
        -  type of feeding (exclusive breastfeeding; exckusive bottlefeeding or mixed)&#xD;
&#xD;
        -  overall volume administered expressed in mL in a day;&#xD;
&#xD;
      INSTRUMENTAL DATA&#xD;
&#xD;
        -  Number of suctions;&#xD;
&#xD;
        -  Number of swallowings;&#xD;
&#xD;
        -  Number of apnoeas;&#xD;
&#xD;
        -  Average duration of apnoeas;&#xD;
&#xD;
        -  Number of oxygen desaturations&#xD;
&#xD;
        -  Minimal oxygen saturation;&#xD;
&#xD;
        -  Number of reduction of cardiac frequency (bradycardia);&#xD;
&#xD;
        -  Minimal cardiac frequency. The definition of apnoea, oxygen desaturation and bradycardia&#xD;
           applied in this study are the ones defined by literature (Di Fiore JM, Arko MK, Miller&#xD;
           MJ, et al. Cardiorespiratory Events in Preterm Infants Referred for Apnea Monitoring&#xD;
           Studies. PEDIATRICS. 2001;108(6):1304-1308.)&#xD;
&#xD;
        -  APNOEA: arrest of the breathing acts for a period of at least 20 seconds or arrest of&#xD;
           the breathing acts for a period of at least 5 seconds associated with bradycardia and/or&#xD;
           desaturations;&#xD;
&#xD;
        -  OXYGEN DESATURATIONS: reduction of the oxygen saturation (SpO2) &lt;80% or of at least 5%&#xD;
           compared to the baseline, for at least 4 seconds.&#xD;
&#xD;
        -  BRADYCARDIA: reduction of the cardiac frequency under 80 bpm for at least 4 seconds&#xD;
&#xD;
      STATISTICAL ANALYSIS&#xD;
&#xD;
      Statistical analysis will be carried out using the STATISTICA software package for Windows&#xD;
      (StatSoft, Inc., Tulsa, Oklahoma, USA). Every newborn in the experimental group will be&#xD;
      matched with a newborn of the control group similar for gestational age and weight. For the&#xD;
      normal distribution, data will be tested with the Kolmogorov-Smirnov test and with the&#xD;
      exploratory data analysis. Data will be expressed as statistical mean and standard deviation&#xD;
      (SD) or as median and interquantile range depending on the relative distribution. The&#xD;
      differences between the polisonnographic data will be evaluated with the Student's T test or&#xD;
      through a similar non-parametric test depending on the distribution: Fisher test for&#xD;
      comparison between categorical data and regression tests (linear and non-linear) for&#xD;
      comparison between continuous variables. Statistical significance is set as p&lt;0.05.&#xD;
&#xD;
      EXPECTED RESULTS&#xD;
&#xD;
      The more physiological administration of milk with a feeding system with a valved ergonomic&#xD;
      teat, could better promote the development of coordination in the process of&#xD;
      sucking-swallowing-breathing. Therefore inhalation and cardiosaturimetric events during a&#xD;
      meal and immediately after will be reduced and therefore the newborn's oral feeding tolerance&#xD;
      will increase, making it more similar to physiological breastfeeding.&#xD;
&#xD;
      Bottle-feeding milk administration with a feeding system with a valved ergonomic teat in the&#xD;
      first days of life, the period when exclusive breastfeeding is more difficult, could also&#xD;
      promote the transition between bottle-feeding to breastfeeding, because this mechanism is&#xD;
      more similar to the physiological one.&#xD;
&#xD;
      If the results of this study will support this hypotesis, feeding system with a valved&#xD;
      ergonomic teat could be chosen as a non-pharmacological treatment for late-preterm newborns&#xD;
      who encounter difficulty in the oral feeding, such as cardio-respiratory instability during&#xD;
      the sucking process and risk of milk inhalation when the breastfeeding is not possible.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Actual">May 31, 2023</completion_date>
  <primary_completion_date type="Actual">May 31, 2023</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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluating the level of coordination in the sucking-swallowing-breathing pattern in the B-ESP group compared with the B-STD</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This evaluation will be recorded at 24 and 72 hours of life and defined from the suckings/swallowings ratio.&#xD;
The literature describes this parameter as strongly associated to a higher maturity of the sucking-swallowing-breathing pattern; in fact, a ratio of sucking-swallowing-breathing of 1:1:1 describes the mature pattern, typical of the breastfeeding and considered the optimum for a newborn.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Coefficient of variation of time between sucking and swallowing</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This coefficient is expressed in seconds. a lower coefficient corresponds to breastfeeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean percentage of incidence of breaths that precede and follow the swallowings</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This percentage is classified by Lau et al. (the average interval between two breathing acts monitored during a meal of an healthy at term newborn varies between 1.2-2 seconds)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the sucking processes</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This evaluation is made through the a structured questionnaire composed by 31 items</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of cardiorespiratory stability</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This evaluation is made considering frequency and characteristics of cardiorespiratory events (during and after meal administration)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of meal tolerance</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
    <description>This evaluation is carried out considering the number of vomiting and regurgitations during and after the meal, volume in mL per meal, number of meals per day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of breastfed newborns at the time of dimission</measure>
    <time_frame>Calculated throughout 72 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Premature Birth</condition>
  <condition>Feeding; Difficult, Newborn</condition>
  <condition>Feeding, Bottle</condition>
  <arm_group>
    <arm_group_label>B-ESP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>B-ESP group will be fed with a feeding system with a valved ergonomic teat.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-STD</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>B-STD will be fed with a standard feeding system.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Valved ergonomic teat</intervention_name>
    <description>Administration of milk with a feeding system with a valved ergonomic teat in late preterm newborns.</description>
    <arm_group_label>B-ESP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Standard silicon teat</intervention_name>
    <description>Administration of milk with a feeding system with a standard silicon teat</description>
    <arm_group_label>B-STD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Gestational age 34+0 - 36+6 weeks at birth;&#xD;
&#xD;
          -  Exclusive oral feeding;&#xD;
&#xD;
          -  Bottle-feeding for at least a meal a day;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Newborns with exclusive breastfeeding;&#xD;
&#xD;
          -  Newborns with congenital anomalies, perinatal asphyxia, respiratory or neurological&#xD;
             issues, genetic syndromes, infections, metabolic diseases;&#xD;
&#xD;
          -  Ongoing administration of medication able to interfere with esophageal or respiratory&#xD;
             function;&#xD;
&#xD;
          -  Newborns who require respiratory support, including oxygen-therapy via nasal-cannula;&#xD;
&#xD;
          -  Newborns who require oral or nasal feeding tube;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>5 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Cresi, MD; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Città della Salute e della Scienza - Ospedale S.Anna - University of Turin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Città della Salute e della Scienza - Ospedale S.Anna - University of Turin</name>
      <address>
        <city>Turin</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Joshi R, van Pul C, Sanders A, Weda H, Bikker JW, Feijs L, Andriessen P. A Strategy to Reduce Critical Cardiorespiratory Alarms due to Intermittent Enteral Feeding of Preterm Neonates in Intensive Care. Interact J Med Res. 2017 Oct 20;6(2):e20. doi: 10.2196/ijmr.7756.</citation>
    <PMID>29054835</PMID>
  </reference>
  <reference>
    <citation>Poets CF, Langner MU, Bohnhorst B. Effects of bottle feeding and two different methods of gavage feeding on oxygenation and breathing patterns in preterm infants. Acta Paediatr. 1997 Apr;86(4):419-23. doi: 10.1111/j.1651-2227.1997.tb09034.x.</citation>
    <PMID>9174231</PMID>
  </reference>
  <reference>
    <citation>Gross RD, Trapani-Hanasewych M. Breathing and Swallowing: The Next Frontier. Semin Speech Lang. 2017 Apr;38(2):87-95. doi: 10.1055/s-0037-1599106. Epub 2017 Mar 21.</citation>
    <PMID>28324898</PMID>
  </reference>
  <reference>
    <citation>Chen CH, Wang TM, Chang HM, Chi CS. The effect of breast- and bottle-feeding on oxygen saturation and body temperature in preterm infants. J Hum Lact. 2000 Feb;16(1):21-7. doi: 10.1177/089033440001600105.</citation>
    <PMID>11138220</PMID>
  </reference>
  <reference>
    <citation>Goldfield EC, Richardson MJ, Lee KG, Margetts S. Coordination of sucking, swallowing, and breathing and oxygen saturation during early infant breast-feeding and bottle-feeding. Pediatr Res. 2006 Oct;60(4):450-5. doi: 10.1203/01.pdr.0000238378.24238.9d. Epub 2006 Aug 28.</citation>
    <PMID>16940236</PMID>
  </reference>
  <reference>
    <citation>Simmer K, Kok C, Nancarrow K, Hepworth AR, Geddes DT. Novel feeding system to promote establishment of breastfeeds after preterm birth: a randomized controlled trial. J Perinatol. 2016 Mar;36(3):210-5. doi: 10.1038/jp.2015.184. Epub 2015 Dec 10.</citation>
    <PMID>26658121</PMID>
  </reference>
  <reference>
    <citation>Mizuno K, Ueda A. Changes in sucking performance from nonnutritive sucking to nutritive sucking during breast- and bottle-feeding. Pediatr Res. 2006 May;59(5):728-31. doi: 10.1203/01.pdr.0000214993.82214.1c.</citation>
    <PMID>16627890</PMID>
  </reference>
  <reference>
    <citation>Mathew OP. Respiratory control during nipple feeding in preterm infants. Pediatr Pulmonol. 1988;5(4):220-4. doi: 10.1002/ppul.1950050408.</citation>
    <PMID>3237449</PMID>
  </reference>
  <reference>
    <citation>Ward, N. Feeding and Swallowing Disorders in Infancy: Assessment and Management. J. Hum. Lact. 11, 147-147 (1995)</citation>
  </reference>
  <reference>
    <citation>Sakalidis VS, Geddes DT. Suck-Swallow-Breathe Dynamics in Breastfed Infants. J Hum Lact. 2016 May;32(2):201-11; quiz 393-5. doi: 10.1177/0890334415601093. Epub 2015 Aug 28.</citation>
    <PMID>26319112</PMID>
  </reference>
  <reference>
    <citation>Dalgleish SR, Kostecky LL, Blachly N. Eating in &quot;SINC&quot;: Safe Individualized Nipple-Feeding Competence, a Quality Improvement Project to Explore Infant-Driven Oral Feeding for Very Premature Infants Requiring Noninvasive Respiratory Support. Neonatal Netw. 2016;35(4):217-27. doi: 10.1891/0730-0832.35.4.217.</citation>
    <PMID>27461200</PMID>
  </reference>
  <reference>
    <citation>Whyte R. Safe discharge of the late preterm infant. Paediatr Child Health. 2010 Dec;15(10):655-66. doi: 10.1093/pch/15.10.655.</citation>
    <PMID>22131865</PMID>
  </reference>
  <reference>
    <citation>Meier P, Patel AL, Wright K, Engstrom JL. Management of breastfeeding during and after the maternity hospitalization for late preterm infants. Clin Perinatol. 2013 Dec;40(4):689-705. doi: 10.1016/j.clp.2013.07.014. Epub 2013 Sep 21.</citation>
    <PMID>24182956</PMID>
  </reference>
  <reference>
    <citation>Lau C. Development of infant oral feeding skills: what do we know? Am J Clin Nutr. 2016 Feb;103(2):616S-21S. doi: 10.3945/ajcn.115.109603. Epub 2016 Jan 20.</citation>
    <PMID>26791183</PMID>
  </reference>
  <reference>
    <citation>Geddes DT, Sakalidis VS, Hepworth AR, McClellan HL, Kent JC, Lai CT, Hartmann PE. Tongue movement and intra-oral vacuum of term infants during breastfeeding and feeding from an experimental teat that released milk under vacuum only. Early Hum Dev. 2012 Jun;88(6):443-9. doi: 10.1016/j.earlhumdev.2011.10.012. Epub 2011 Nov 26.</citation>
    <PMID>22119233</PMID>
  </reference>
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    <citation>Cannon AM, Sakalidis VS, Lai CT, Perrella SL, Geddes DT. Vacuum characteristics of the sucking cycle and relationships with milk removal from the breast in term infants. Early Hum Dev. 2016 May;96:1-6. doi: 10.1016/j.earlhumdev.2016.02.003. Epub 2016 Mar 8.</citation>
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  </reference>
  <reference>
    <citation>da Costa SP, van der Schans CP, Zweens MJ, Boelema SR, van der Meij E, Boerman MA, Bos AF. The development of sucking patterns in preterm, small-for-gestational age infants. J Pediatr. 2010 Oct;157(4):603-9, 609.e1-3. doi: 10.1016/j.jpeds.2010.04.037. Epub 2010 Jun 14.</citation>
    <PMID>20542296</PMID>
  </reference>
  <reference>
    <citation>Fucile S, McFarland DH, Gisel EG, Lau C. Oral and nonoral sensorimotor interventions facilitate suck-swallow-respiration functions and their coordination in preterm infants. Early Hum Dev. 2012 Jun;88(6):345-50. doi: 10.1016/j.earlhumdev.2011.09.007. Epub 2011 Sep 29.</citation>
    <PMID>21962771</PMID>
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  <reference>
    <citation>Lau C, Smith EO, Schanler RJ. Coordination of suck-swallow and swallow respiration in preterm infants. Acta Paediatr. 2003 Jun;92(6):721-7.</citation>
    <PMID>12856985</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>April 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>August 15, 2023</last_update_submitted>
  <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Turin, Italy</investigator_affiliation>
    <investigator_full_name>Francesco Cresi, MD, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>late-preterm newborns, valved feeding system</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Silicon</mesh_term>
  </intervention_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/NCT04400175
org study id: SOFT-study
nct id: NCT04400175
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Comparing with a randomized controlled trial two different feeding systems in two groups of
      late-preterm newborns for evaluating which is more efficient in promoting the coordination in
      the process of sucking-swallowing-breathing and better cardiorespiratory stability.

      The B-ESP group will be fed with a feeding system with a valved ergonomic teat; the B-STD
      with a standard feeding system.
The swallowing patterns are still immature in the newborn, especially if preterm. An
      incomplete synchronization in the process of sucking, swallowing and breathing could lead to
      some difficulty during feedings with desaturations and risk of milk inhalation in the upper
      airway tract. Moreover, a dysfunctional or immature pattern of sucking, swallowing and
      breathing also affect the post-prandial period, tiring the newborn and increasing the
      cardio-respiratory instability.

      Breastfeeding promote the development of a physiological coordination of the process of
      sucking, swallowing and breathing, guaranteeing high and stable values of oxygenation during
      feedings. On the other hand, bottle-feeding could be responsible of a difficult coordination
      among the phases of swallowing and breathing. In an healthy, at term, brestfed newborn is
      observed a typical pattern of sucking-swallowing-expiration with a ratio of 1:1:1. In a
      bottlefed newborn this ratio is 2-12:1:4, with a relative increase of the period of sucking
      compared to the swallowing one, that could lead to apnoeas and desaturations.

      The differences between the two feedings modality are more accentuated in the late-preterm
      newborn, which is more prone to cardio-respiratory instability compared to the healthy at
      term newborn, because of the immaturity of the respiratory centers in the brainstem, and of
      the processes responsible for the coordination of the sucking, swallowing and breathing .

      However breastfeeding, in spite of the fact that is crucial for the development of the
      correct process of sucking, can be challenging in the premature infant because it requires a
      considerable physical effort.

      Therefore, disposing of devices for nutrition able to facilitate oral feeding, simulating the
      physiologic breastfeeding, is necessary. In this way, we can contribute to the development of
      the proper sucking-swallowing-breathing pattern and to improve cardio-respiratory stability.

      In literature there are multiple studies carried out on term newborns demonstrating the
      importance of the negative pressure or air vacuum created in the oral cavity, in order to
      promote the emptying of the lactiferous ducts and/or of the teat and simultaneously promote
      the maintainance of the right respiratory pattern. An ergonomic feeding system with a valve
      able to create vacuum could be able to respond to the demands of late preterm newborns.

      Aim of the study is to evaluate the effects of a trial with an experimental feeding system
      with a teat with a valve able to facilitate the vacuum in the oral cavity on the pattern of
      sucking-swallowing and breathing in late preterm newborns.

      NUMBER OF PATIENTS Precise data regarding swallowing/respiration rate in bottle-fed late
      preterm infants in the first 3 days of life are lacking in the literature. Considering a mean
      swallow/respiration ratio of 1.5 and a variance of 0.5, obtained from surveys performed at
      our center prior to the study, a sample size of 38 infants per arm was estimated to achieve
      80% power to detect a 30% difference on the primary outcome with a significance level of
      0.05.

      STUDY DESIGN Late preterm newborns eligible to enter in the study, prior obtaining the
      informed consent from parents, will be assigned in the "B-ESP" or "B-STD" group through a
      process of block randomisation, controlled by a software.

      Newborns included in the randomisation, after a training of 3 meals with the feeding bottle
      assigned from the randomisation, can be entered in the study.

      Newborns included in the study will be monitored for the entire duration of a meal and the
      subsequent 3-hours period. This monitoring will be collected in two different times (T1 and
      T2): in the second day of life (24-48 hours of life) and in the fourth day of life (72-96
      hours of life). The study includes an audio recording of the swallowings through a microphone
      in the room and the recordings of the process of sucking and swallowing through a cutaneous
      sensor.

      In addition, a cardiorespiratory monitoring with a poligraph will be made, considering oxygen
      saturation, cardiac and respiratory frequency and electrocardiography. The meal's video
      recording will permit a subsequent classification of the sucking movements and the evaluation
      of any possible interference in the polygraphic recording.

      FEEDING DEVICES

      Newborns of the B-STD group will be fed using a classic disposable feeding device, which is
      actually in use in our centre and provided by our hospital, composed of:

        -  a 150 mL feeding bottle in polypropylene, devoid of BPA;

        -  a silicon teat, devoid of BPA, available in two types, (a slow graduated flow and a
           standard flow) depending on the necessities and suction abilities of the baby;

        -  a protective plug.

      Newborns of the B-ESP group will be fed using a feeding system with a valved ergonomic teat,
      composed of:

        -  a slow-flow ergonomic silicon teat

        -  polipropilene bottle with a capacity of 150 mL, with a ventilation valve on the bottom

        -  silicon valve

      Newborns will be fed with defined quantities of maternal milk or bank donated milk, based on
      weight and gestational age.

      The meal will be administered by the caregiver (a parent or a nurse) previously trained. The
      meal's administration will be performed keeping the baby in the caregivers's arms in the ESL
      position (semielevated side-lying). At the end of the feeding process the newborn will be
      repositioned in his cradle in the supine position.

      The cardiosaturimetric evaluation will be performed using a system of polygraphic monitoring,
      which allows a simultaneous non-invasive recording of cardiorespiratory parameters, noises
      and movements associated to the sucking and swallowing processes combined to video
      recordings.

      The evaluation of the sucking process will be carried out using a structured questionnaire
      composed by 31 items, which allows to distinguish normal suction (mature) from disorganized
      and dysfunctional ones.

      Considering simultaneously the cardiosaturimetric parameters, video, audio and cutaneous
      sensor's recordings, it is possible to obtain a more accurate evaluation of the processes of
      swallowing, sucking and breathing of the newborn during meal administration. It is also
      possible to identify the exact moment of the breathing process assigned to the newborn's
      swallowing.

      CLINICAL DATA

      At birth:

        -  gestational age;

        -  weight in grams;

        -  z-score;

        -  sex;

        -  type of delivery;

        -  peri-partum condition, including possible administration of prenatal corticosteroids;

        -  type of support provided at birth;

      At T1 and T2:

        -  hours from birth;

        -  weight;

        -  z-score;

        -  number of meals in a day;

        -  type of milk administered;

        -  overall volume administered expressed in mL in a day;

        -  duration of a meal expressed in minutes;

        -  number of regurgitation or vomit during the administration of a meal;

        -  number of regurgitation or vomit after the admninistration of a meal;

      At discharge:

        -  weight;

        -  z-score;

        -  number of meals in a day;

        -  type of feeding (exclusive breastfeeding; exckusive bottlefeeding or mixed)

        -  overall volume administered expressed in mL in a day;

      INSTRUMENTAL DATA

        -  Number of suctions;

        -  Number of swallowings;

        -  Number of apnoeas;

        -  Average duration of apnoeas;

        -  Number of oxygen desaturations

        -  Minimal oxygen saturation;

        -  Number of reduction of cardiac frequency (bradycardia);

        -  Minimal cardiac frequency. The definition of apnoea, oxygen desaturation and bradycardia
           applied in this study are the ones defined by literature (Di Fiore JM, Arko MK, Miller
           MJ, et al. Cardiorespiratory Events in Preterm Infants Referred for Apnea Monitoring
           Studies. PEDIATRICS. 2001;108(6):1304-1308.)

        -  APNOEA: arrest of the breathing acts for a period of at least 20 seconds or arrest of
           the breathing acts for a period of at least 5 seconds associated with bradycardia and/or
           desaturations;

        -  OXYGEN DESATURATIONS: reduction of the oxygen saturation (SpO2) <80% or of at least 5%
           compared to the baseline, for at least 4 seconds.

        -  BRADYCARDIA: reduction of the cardiac frequency under 80 bpm for at least 4 seconds

      STATISTICAL ANALYSIS

      Statistical analysis will be carried out using the STATISTICA software package for Windows
      (StatSoft, Inc., Tulsa, Oklahoma, USA). Every newborn in the experimental group will be
      matched with a newborn of the control group similar for gestational age and weight. For the
      normal distribution, data will be tested with the Kolmogorov-Smirnov test and with the
      exploratory data analysis. Data will be expressed as statistical mean and standard deviation
      (SD) or as median and interquantile range depending on the relative distribution. The
      differences between the polisonnographic data will be evaluated with the Student's T test or
      through a similar non-parametric test depending on the distribution: Fisher test for
      comparison between categorical data and regression tests (linear and non-linear) for
      comparison between continuous variables. Statistical significance is set as p<0.05.

      EXPECTED RESULTS

      The more physiological administration of milk with a feeding system with a valved ergonomic
      teat, could better promote the development of coordination in the process of
      sucking-swallowing-breathing. Therefore inhalation and cardiosaturimetric events during a
      meal and immediately after will be reduced and therefore the newborn's oral feeding tolerance
      will increase, making it more similar to physiological breastfeeding.

      Bottle-feeding milk administration with a feeding system with a valved ergonomic teat in the
      first days of life, the period when exclusive breastfeeding is more difficult, could also
      promote the transition between bottle-feeding to breastfeeding, because this mechanism is
      more similar to the physiological one.

      If the results of this study will support this hypotesis, feeding system with a valved
      ergonomic teat could be chosen as a non-pharmacological treatment for late-preterm newborns
      who encounter difficulty in the oral feeding, such as cardio-respiratory instability during
      the sucking process and risk of milk inhalation when the breastfeeding is not possible.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Evaluating the level of coordination in the sucking-swallowing-breathing pattern in the B-ESP group compared with the B-STD
time frame: Calculated throughout 72 hours
description: This evaluation will be recorded at 24 and 72 hours of life and defined from the suckings/swallowings ratio.
The literature describes this parameter as strongly associated to a higher maturity of the sucking-swallowing-breathing pattern; in fact, a ratio of sucking-swallowing-breathing of 1:1:1 describes the mature pattern, typical of the breastfeeding and considered the optimum for a newborn.
measure: Coefficient of variation of time between sucking and swallowing
time frame: Calculated throughout 72 hours
description: This coefficient is expressed in seconds. a lower coefficient corresponds to breastfeeding
measure: Mean percentage of incidence of breaths that precede and follow the swallowings
time frame: Calculated throughout 72 hours
description: This percentage is classified by Lau et al. (the average interval between two breathing acts monitored during a meal of an healthy at term newborn varies between 1.2-2 seconds)
measure: Evaluation of the sucking processes
time frame: Calculated throughout 72 hours
description: This evaluation is made through the a structured questionnaire composed by 31 items
measure: Evaluation of cardiorespiratory stability
time frame: Calculated throughout 72 hours
description: This evaluation is made considering frequency and characteristics of cardiorespiratory events (during and after meal administration)
measure: Evaluation of meal tolerance
time frame: Calculated throughout 72 hours
description: This evaluation is carried out considering the number of vomiting and regurgitations during and after the meal, volume in mL per meal, number of meals per day
measure: Number of breastfed newborns at the time of dimission
time frame: Calculated throughout 72 hours
arm group label: B-ESP
arm group type: Experimental
description: B-ESP group will be fed with a feeding system with a valved ergonomic teat.
arm group label: B-STD
arm group type: Sham Comparator
description: B-STD will be fed with a standard feeding system.
intervention type: Device
intervention name: Valved ergonomic teat
description: Administration of milk with a feeding system with a valved ergonomic teat in late preterm newborns.
arm group label: B-ESP
intervention type: Device
intervention name: Standard silicon teat
description: Administration of milk with a feeding system with a standard silicon teat
arm group label: B-STD
criteria: 
gender: All
minimum age: 1 Day
maximum age: 5 Days
healthy volunteers: No
last name: Francesco Cresi, MD; PhD
role: Principal Investigator
affiliation: Città della Salute e della Scienza - Ospedale S.Anna - University of Turin
facility: 
country: Italy
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PMID: 16940236
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responsible party type: Principal Investigator
investigator affiliation: University of Turin, Italy
investigator full name: Francesco Cresi, MD, PhD
investigator title: Principal Investigator
mesh term: Premature Birth
mesh term: Silicon