Duodenal Feeds in Very Low Birth Weight Infants

Feasibility and Safety of Duodenal Feeds in Very Low Birth Weight Infants

Premature infants have high rates of bronchopulmonary dysplasia (BPD) due to prematurity of the participants' lungs and the need for prolonged respiratory support. These infants are at increased risk for gastroesophageal reflux and aspiration which may exacerbate lung injury. Transpyloric feeds, specifically duodenal feeds, may be used to bypass the stomach and directly feed the duodenum decreasing the amount of gastric reflux contributing to aspiration. Duodenal feeds are equivalent to gastric feeds with regards to nutritional outcomes, and have been shown to decrease events of apnea and bradycardia in premature infants. This study will evaluate the feasibility and safety of duodenal feeds in premature infants. The hypothesis is that duodenal feeds may be safely and successfully performed in premature very low birth weight infants.

Study Overview

• Status: Completed
• Conditions: Premature Birth; Chronic Lung Disease of Prematurity; Feeding; Difficult, Newborn; Feeding Disorder Neonatal; BPD - Bronchopulmonary Dysplasia; VLBW - Very Low Birth Weight Infant
• Intervention / Treatment: Other: Mode of Delivery of Feeds

Detailed Description

The primary outcome of this study is the safety and feasibility of duodenal feeds in very low birth weight infants. The secondary outcomes are various measures related to growth, respiratory support, comorbidities, and hospitalization.

Eligibility of infants admitted to the Johns Hopkins All Children's Neonatal Intensive Care Unit (NICU) will be determined based on inclusion and exclusion criteria. Eligible infants will be recruited and enrolled by 14 days of life after informed consent is obtained. Randomization of the infants into two groups- investigational continuous Duodenal Feeds (DF) or standard Gastric Feeds (GF) - will occur just prior to the infants advancing beyond 50mL/kg/day of enteral feeds.

All enrolled infants will be fed per the institutional feeding protocol. Once infants advance past 50mL/kg/day of enteral feeds, at this point infants will be randomized to DF or GF groups in a 1:1 block randomization using blinded envelopes. Multiple gestation infants will be randomized individually.

Placement of gastric tubes will be per standard of practice, and insertion of duodenal tube will be per manual of operations. Continuous duodenal feeds will be provided over 24 hours as a continuous infusion through a nasoduodenal or oro-duodenal tube. Standard gastric feeds will be infused via a nasogastric or orogastric tube per the instructions of the medical team. Gastric feeds are provided as standard of care in the NICU; intermittent bolus feeds over 15-60 minutes. Feeding time may be prolonged by the medical team, for longer than 60 minutes and possibly even be given continuously, for various reasons (emesis, reflux, apnea, bradycardia, etc.) and will be monitored and recorded. Feed volume and advancement will continue to be determined by standardized institutional feeding guidelines. Decision to provide further fortification of feeds beyond institutional guidelines will be determined by the medical team and not standardized in this protocol. Once full enteral feeds are achieved (total fluid goal of at least 140mL/kg/day), patients will continue to receive feeds via the designated route.

An institutional "Infant Driven Feeding Guideline" is utilized to evaluate readiness to orally feed and to transition premature infants from enteral to oral feeds. Once an infant is eligible to receive oral feeds per this guideline (32 weeks postmenstrual age, and tolerating ≤2L flow via nasal cannula for at least 24 hours), the study will allow the medical team to transition infants in the DF group to gastric feeds. Regarding transitioning infant from duodenal to gastric feeds, infants are initially placed on continuous gastric feeds, and once the participants have demonstrated tolerance (no evidence of reflux, increased respiratory support, emesis), the participants are then transitioned to bolus gastric feeds progressively. Infants may be allowed to orally feed during this transition period if the participants meet the appropriate infant driven feeding scores per protocol.

All infants in this study will be monitored for primary and secondary outcomes through the duration of admission and up until the time of discharge. Safety events will be frequently monitored for throughout the duration of admission and addressed immediately if warranted.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Infants admitted to the Johns Hopkins All Children's NICU before 72 hours of life
• Infants with a birth weight <1251g

Exclusion Criteria:

• First obtained pH <7.0
• APGAR <5 at 5 minutes (The Apgar score is a test given to newborns soon after birth. This test checks a baby's heart rate, muscle tone, and other signs to see if extra medical care or emergency care is needed. Appearance, Pulse, Grimace, Activity, Respiration (APGAR))
• Infants on hydrocortisone for hypotension prior to randomization
• Infants with intrauterine growth restriction (IUGR) defined by birth weight ≤10th percentile for gestational age
• Infants with congenital anomalies, including but not limited to: Chromosomal abnormalities;Structural airway or pulmonary abnormalities (e.g. tracheoesophageal fistulas, cleft palate, congenital pulmonary adenomatous malformation, etc.); Abdominal anomalies requiring surgical interventions (e.g. intestinal atresia, intestinal webs, gastroschisis, omphalocele, anal atresia); Major cardiac anomalies
• Infants with a history of intestinal perforation or NEC
• Presence of gastrostomy tube
• Infants who have not been initiated on any volume of enteral feeds by 10 days of life

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Gastric Feeds; Patients in this arm will receive feeds via the standard route which is gastric feeds.
Experimental: Duodenal Feeds; Patients in this arm will receive feeds via the experimental route which is duodenal feeds.	Other: Mode of Delivery of Feeds; Eligible infants will be recruited and enrolled and randomized to either duodenal feeds (DF) or gastric feeds (GF), which will occur just prior to the infants advancing beyond 50mL/kg/day of enteral feeds. All enrolled infants will be fed per our institutional feeding protocol. Once infants advance past a volume of 50mL/kg/day of enteral feeds, at this point infants will be randomized to DF or GF groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of successful placements of duodenal tubes	Success to be measured by appropriate placement of the duodenal tube within the duodenum as confirmed by radiographic imaging.	12 months
Safety as assessed by number of intestinal perforations	Safety of duodenal feeds in very low birth weight infants as measured by the number of intestinal perforations secondary to placement of duodenal tube.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supplemental oxygen requirement	Number of days on supplemental oxygen >21% throughout duration of hospitalization	duration of hospitalization, up to 15 months
Number of participants with Bronchopulmonary Dysplasia	Mild, moderate, severe Bronchopulmonary Dysplasia (BPD) as defined by the NICHD/NHLBI/ORD Workshop published in 2001	15 months
Number of deaths during hospitalization		15 months
Number of days of mechanical ventilation	Days of invasive mechanical ventilation up until hospital discharge	15 months
Number of participants with late-onset sepsis	Number of participants diagnosed with Culture-positive sepsis after 72 hours of life	15 months
Central line days	Cumulative days of indwelling central venous catheters (peripherally inserted central catheters, tunneled venous catheters, umbilical venous catheters)	15 months
Number of participants with necrotizing enterocolitis	Number of participants with necrotizing enterocolitis (NEC) defined by Modified Bells Stage II or greater	15 months
Number of replaced enteral tubes	Number of replaced enteral tubes, gastric or duodenal, per patient	15 months
Number of Radiographs related to enteral tube placement	Number of radiographs obtained with the indication of enteral tube placement, gastric or duodenal	15 months
Weight percentile at 36 weeks postmenstrual age	Weight percentile at 36 weeks postmenstrual age	At 36 weeks
Height percentile at 36 weeks postmenstrual age	Height percentile at 36 weeks postmenstrual age	At 36 weeks
Head circumference percentile at 36 weeks postmenstrual age	Head circumference percentile at 36 weeks postmenstrual age	At 36 weeks
Z-scores for weight at 36 weeks postmenstrual age	Z-scores for weight at 36 weeks postmenstrual age calculated using PediTools	At 36 weeks
Z-scores for height at 36 weeks postmenstrual age	Z-scores for height at 36 weeks postmenstrual age calculated using PediTools	At 36 weeks
Z-scores for head circumference at 36 weeks postmenstrual age	Z-scores for head circumference at 36 weeks postmenstrual age calculated using PediTools	At 36 weeks
Daily daily weight gain	Average daily weight gain (kg/day) calculated from birth until 36 weeks postmenstrual age using the fetal-infant growth reference (FIGR) equation	At 36 weeks
Length of stay	Length of hospital stay (days)	duration of hospitalization, up to 15 months
Need for excess fortification of feeds	Number of participants requiring fortification beyond 24kcal/oz	15 months
Use of postnatal dexamethasone	Number of participants requiring use of postnatal dexamethasone for respiratory indications	15 months
Use of chronic diuretics	Number of participants requiring use of chronic diuretics including thiazide diuretics and spironolactone	15 months

Collaborators and Investigators

• Sponsor: Johns Hopkins All Children's Hospital
• Investigators: Principal Investigator: Noura Nickel, MD, Johns Hopkins All Children's Hospital

Publications and helpful links

General Publications

• Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sanchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23.
• Knight PR, Davidson BA, Nader ND, Helinski JD, Marschke CJ, Russo TA, Hutson AD, Notter RH, Holm BA. Progressive, severe lung injury secondary to the interaction of insults in gastric aspiration. Exp Lung Res. 2004 Oct-Nov;30(7):535-57. doi: 10.1080/01902140490489162.
• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.
• Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, Chan GM, Blanco CL, Abrams S, Cotten CM, Laroia N, Ehrenkranz RA, Dudell G, Cristofalo EA, Meier P, Lee ML, Rechtman DJ, Lucas A. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010 Apr;156(4):562-7.e1. doi: 10.1016/j.jpeds.2009.10.040. Epub 2009 Dec 29.
• Hsu CW, Sun SF, Lin SL, Kang SP, Chu KA, Lin CH, Huang HH. Duodenal versus gastric feeding in medical intensive care unit patients: a prospective, randomized, clinical study. Crit Care Med. 2009 Jun;37(6):1866-72. doi: 10.1097/CCM.0b013e31819ffcda.
• Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R. Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatr. 2013 Jun 11;13:92. doi: 10.1186/1471-2431-13-92.
• Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988 Oct;82(4):527-32.
• Poets CF. Gastroesophageal reflux: a critical review of its role in preterm infants. Pediatrics. 2004 Feb;113(2):e128-32. doi: 10.1542/peds.113.2.e128.
• Omari TI, Barnett CP, Benninga MA, Lontis R, Goodchild L, Haslam RR, Dent J, Davidson GP. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut. 2002 Oct;51(4):475-9. doi: 10.1136/gut.51.4.475.
• Garland JS, Alex CP, Johnston N, Yan JC, Werlin SL. Association between tracheal pepsin, a reliable marker of gastric aspiration, and head of bed elevation among ventilated neonates. J Neonatal Perinatal Med. 2014 Jan 1;7(3):185-92. doi: 10.3233/NPM-14814020.
• Peter CS, Wiechers C, Bohnhorst B, Silny J, Poets CF. Influence of nasogastric tubes on gastroesophageal reflux in preterm infants: a multiple intraluminal impedance study. J Pediatr. 2002 Aug;141(2):277-9. doi: 10.1067/mpd.2002.126298.
• Jolley SG, Halpern CT, Sterling CE, Feldman BH. The relationship of respiratory complications from gastroesophageal reflux to prematurity in infants. J Pediatr Surg. 1990 Jul;25(7):755-7. doi: 10.1016/s0022-3468(05)80012-0.
• Farhath S, Aghai ZH, Nakhla T, Saslow J, He Z, Soundar S, Mehta DI. Pepsin, a reliable marker of gastric aspiration, is frequently detected in tracheal aspirates from premature ventilated neonates: relationship with feeding and methylxanthine therapy. J Pediatr Gastroenterol Nutr. 2006 Sep;43(3):336-41. doi: 10.1097/01.mpg.0000232015.56155.03.
• Blondheim O, Abbasi S, Fox WW, Bhutani VK. Effect of enteral gavage feeding rate on pulmonary functions of very low birth weight infants. J Pediatr. 1993 May;122(5 Pt 1):751-5. doi: 10.1016/s0022-3476(06)80021-1.
• Jensen EA, Munson DA, Zhang H, Blinman TA, Kirpalani H. Anti-gastroesophageal reflux surgery in infants with severe bronchopulmonary dysplasia. Pediatr Pulmonol. 2015 Jun;50(6):584-7. doi: 10.1002/ppul.23052. Epub 2014 Apr 21.
• McGuire W, McEwan P. Transpyloric versus gastric tube feeding for preterm infants. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003487. doi: 10.1002/14651858.CD003487.pub2.
• Wells DH, Zachman RD. Nasojejunal feedings in low-birth-weight infants. J Pediatr. 1975 Aug;87(2):276-9. doi: 10.1016/s0022-3476(75)80602-0.
• Drew JH, Johnston R, Finocchiaro C, Taylor PS, Goldberg HJ. A comparison of nasojejunal witn nasogastric feedings in low-birth-weight infants. Aust Paediatr J. 1979 Jun;15(2):98-100. doi: 10.1111/j.1440-1754.1979.tb01198.x. No abstract available.
• Roy RN, Pollnitz RB, Hamilton JR, Chance GW. Impaired assimilation of nasojejunal feeds in healthy low-birth-weight newborn infants. J Pediatr. 1977 Mar;90(3):431-4. doi: 10.1016/s0022-3476(77)80710-5.
• Whitfield MF. Poor weight gain of the low birthweight infant fed nasojejunally. Arch Dis Child. 1982 Aug;57(8):597-601. doi: 10.1136/adc.57.8.597.
• Laing IA, Lang MA, Callaghan O, Hume R. Nasogastric compared with nasoduodenal feeding in low birthweight infants. Arch Dis Child. 1986 Feb;61(2):138-41. doi: 10.1136/adc.61.2.138.
• Wallenstein MB, Brooks C, Kline TA, Beck RQ, Yang W, Shaw GM, Stevenson DK. Early transpyloric vs gastric feeding in preterm infants: a retrospective cohort study. J Perinatol. 2019 Jun;39(6):837-841. doi: 10.1038/s41372-019-0372-3. Epub 2019 Apr 9.
• Macdonald PD, Skeoch CH, Carse H, Dryburgh F, Alroomi LG, Galea P, Gettinby G. Randomised trial of continuous nasogastric, bolus nasogastric, and transpyloric feeding in infants of birth weight under 1400 g. Arch Dis Child. 1992 Apr;67(4 Spec No):429-31. doi: 10.1136/adc.67.4_spec_no.429.
• Pereira GR, Lemons JA. Controlled study of transpyloric and intermittent gavage feeding in the small preterm infant. Pediatrics. 1981 Jan;67(1):68-72.
• Caillie MV, Powell GK. Nasoduodenal versus nasogastric feeding in the very low birthweight infant. Pediatrics. 1975 Dec;56(6):1065-72.
• Malcolm WF, Smith PB, Mears S, Goldberg RN, Cotten CM. Transpyloric tube feeding in very low birthweight infants with suspected gastroesophageal reflux: impact on apnea and bradycardia. J Perinatol. 2009 May;29(5):372-5. doi: 10.1038/jp.2008.234. Epub 2009 Feb 26.
• Misra S, Macwan K, Albert V. Transpyloric feeding in gastroesophageal-reflux-associated apnea in premature infants. Acta Paediatr. 2007 Oct;96(10):1426-9. doi: 10.1111/j.1651-2227.2007.00442.x. Epub 2007 Sep 10.
• Radford PJ, Stillwell PC, Blue B, Hertel G. Aspiration complicating bronchopulmonary dysplasia. Chest. 1995 Jan;107(1):185-8. doi: 10.1378/chest.107.1.185.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Actual): February 19, 2026
• Study Completion (Actual): February 19, 2026

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: BPD; Neonate; Bronchopulmonary Dysplasia; Premature infant; Duodenal feeds; Transpyloric feeds
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Bronchopulmonary Dysplasia
• Other Study ID Numbers: IRB00217658

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No