To Determine the Best Feeding Practice in Preterm Infants on Non-invasive Ventilation.

Study Overview
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Brief Summary
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To evaluate the duration to reach full feeds by comparing continuous gavage feeds versus bolus feeds in preterm infants who are on non-invasive respiratory support (RAM cannula - short binasal prongs).

Detailed Description
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Methods: The study will be a randomized control trial at our NICU (Neonatal Intensive Care Unit) (Level III). Preterm infants on non -invasive ventilation (nasal intermittent positive pressure ventilation (NIPPV)/ continuous positive airway pressure (CPAP)) will be randomly assigned into either continuous feeds or bolus feeds groups. Baby will be fed enterally through a nasogastric tube via continuous or bolus feeds using either maternal milk or formula, according to parental choice. Feeds will be advanced as per the feeding guidelines or per treating physician. Currently we use both bolus and continuous feeding practice in our NICU, as per physician's discretion. Intervention: Infants will be randomized into 2 groups; one will receive continuous nasogastric feeding and the other group will receive intermittent bolus feeds. Continuous feeds will be delivered via an indwelling nasogastric/orogastric tube with a continuous infusion pump. Intermittent bolus feedings will be given by gravity every 3 hours over 15- 30 minutes. Parents' consent will be taken when the infant is qualified for the study. The consent will be taken by one of the coinvestigators. Each coinvestigator will be trained to consent for standardization. Non-English-speaking parents will be consented using the medical video interpreter (Voyce). Accent will not be obtained as neonates aren't mature to give accent. Patients will be randomized into each group by pulling a sealed envelope. Monitoring for complications: During the study, infants will be monitored for any complications due to either feeding protocol like feeding intolerance, reflux, abdominal distension, poor weight gain, any risk of aspiration pneumonia or necrotizing enterocolitis (NEC). Such symptoms are usually monitored by our NICU team as per our guidelines. These feeding issues can be encountered in either group. If such problems are encountered, feeding protocol will be changed as per the physician's clinical decision. Parents will be informed of the changes. Intention to treat protocol will be used while calculating the statistical analysis. Guidelines for withholding the feeds (bolus or intermittent) or changing either group will be: Excessive gastric residual (> 50% of the volume fed) Increase in abdominal girth (>1.5-2.5 cm along with other signs and symptoms of intolerance to feeds) Poor/slow weight gain (rate of weight gain is significantly below that expected for age and sex, or if weight has dropped ≥2 major percentile lines) Occult blood positive in stools/visible blood in the stools Concerns for neonatal sepsis clinically as per attending's discretion Apnea pertaining for more than 20 secs alone or apnea for > 10 seconds along with bradycardia (<80) or desaturations (hypoxemia as per gestational age); and occurring more than 2 or 3 times a day and requiring intervention Abnormal Abdominal X rays concerning for suspected NEC or NEC as per Bell's criteria Infants who need to be on invasive ventilation Treating physician's clinical decision Feeding protocol: BW: 500 -1000 grams: Initiate: When baby is stable. Start with trophic feeds, that is, 5 -10 ml/kg/day. Advance: If tolerating trophic feeds for 2-3 days, advance feeds by 10 ml/kg/day. Initial choice of milk: Breast Milk/Donor Breast Milk / Formula (Enfamil) - 20Kcal/Oz. Fortify: When 60-80 ml/kg/day feeds are reached, fortify to 22Kcal/Oz and within next few days to 24 Kcal/Oz. BW 1000 - 1500 grams: Initiate: When baby is stable. Trophic feeds 5-10 ml/kg/day. Advance: 15-20 ml/kg/day Initial choice of milk, fortifying and full feeds as above. BW 1500 grams and above: Initiate: 30 ml/kg/day. Advance: 20 -35 ml/kg/day Initial choice of milk, fortifying and full feeds as above.

Official Title
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To Determine the Best Feeding Practice in Preterm Infants on Non-invasive Ventilation.

Conditions
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Prematurity; Extreme, Feeding Patterns, Ventilator Lung; Newborn

Intervention / Treatment
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* Other: Continuous Feeds
* Other: Intermittent Bolus Feeds


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm Infants 24- 34 weeks of gestation On Non-invasive ventilation (NIPPV/CPAP/HFNC) Nothing by mouth (NPO) or on trophic feeds (<20 ml/kg/day) at the time of randomization. Exclusion Criteria: Gestational Age > 34 weeks Infants on invasive ventilation or low flow nasal cannula and on feeding volume more than trophic feeds. Major congenital anomalies.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Infants will be randomized into 2 groups; one will receive continuous nasogastric feeding and the other group will receive intermittent bolus feeds. Each group will be stratified as per weight, thus (<1000 g, 1000-1500 g, and > 1500 g). It will be 1-1 randomization and will be randomized into each group by pulling a sealed envelope. Protected Health Information (PHI) will be de-identified by assigning a study code. Sample size: A sample size of at least 23 in each arm was calculated using the SAS system. A power of 80% and a mean difference of 40% decrease in the length of time to achieve full feeds; and an SD of 8.5 was considered while calculating the number of patients. The mean length of time to achieve full feeds in our NICU as per chart review was 17 +/- 8.5 days.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bolus Feeding<br>Intermittent bolus feeding will be defined as delivering enteral nutrition multiple times, usually every 2-3 hours over 15 - 30 minutes by gravity or an electric pump. It will be further stratified as per weight ( less than 1000 g, 1000-1500 g, >1500 g). | Other: Intermittent Bolus Feeds<br>* Intermittent bolus feedings will be given by gravity every 3 hours over 15- 30 minutes.<br>|
| Experimental: Continuous Feeding<br>Continuous feeding will be defined as delivering enteral nutrition with constant speed for 24 hours via a nutritional pump. It will be further stratified as per weight ( less than 1000 g, 1000-1500 g, >1500 g). | Other: Continuous Feeds<br>* Continuous feeds will be delivered via an indwelling nasogastric/orogastric tube with a continuous infusion pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day of life to reach full feeds | the day of life to reach full feed, that is, 120 ml/kg/day. | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feeding interruptions | Interruptions while feeding, which includes NPO days, Lab usage and Radiological evaluation. | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 
| Time to reach (day of life) first oral feed | Day of life when infant was taking oral feeds (no feeds by nasogastric tube) | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 
| Weight gain, head circumference (HC) and Length. | Anthropometric parameters | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 
| Length of hospital stay | Total duration of hospital stay | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 
| Use of investigative medicine for feeding intolerance | Use of radiographic imaging or blood work-up to rule out any feeding intolerance | From the date of randomization until the date of NICU discharge/death, assessed up to 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm infants, Feeding methods, bolus feeds, continuous feeds, non-invasive ventilation, RAM cannula