A Randomized Controlled Trial of Early Exclusive Enteral Nutrition vs. Conventional Nutrition in 28-31 + 6 Weeks of Gestation Preterm Neonates and Its Effects on Growth and Body Composition at Discharge

We shall be screening all very preterm babies (28-31+6 weeks gestation) born in PGIMER and admitted consecutively in the neonatal unit of PGIMER, and will be enrolled after meeting the inclusion and exclusion criteria, within 2 hours of birth. Parental or guardian written consent will be obtained after explaining the need for the study and a written PIS will be provided in local languages. For the calculation of gestational age, it will be assigned as per LMP, and postnatally will be confirmed by using New Ballard scoring. By using Intergrowth-21 at birth charts, we will allocate the newborn as SGA or AGA and SES will be assessed by the Modified Kuppuswamy SES scale.

Randomization process: On day 1 of life, at 2 hours of life, neonates will be randomized to receive either early exclusive enteral nutrition (group A) or they will be initiated on conventional nutrition (group B) based on eligibility. Random numbers will be computer-generated and placed in sealed, opaque envelopes, and a non-PI person will generate these numbers. As this is an open trial, the PI could not be blinded. There will be 2 subgroups, decided a priori, consisting of an 80% sample size in the AGA group and 20% in the SGA group.

Mothers and newborns will have their demographic and clinical information documented. Birth anthropometry (weight, length, and head circumference) and a thorough clinical examination will also be performed as per the procedure described below.

Type of milk to be used: Mother’s own milk (MOM) will be the preferred feed; however, if MOM is not available, pasteurized donor human milk (DHM) will be used till full volume EBM is not available or for a minimum of 2 weeks, whichever is earlier.

Babies enrolled in both groups will be given feeds or fluids as per the institutional protocol as described. Time to attain full enteral feeds (150 ml per kg per day and sustaining it for more than 24 hours) will be noted. The number of episodes of feed intolerance during hospital stay is noted in each patient. The feed intolerance will be defined as the presence of any two of these criteria: gastric residuals more than 33% of total feeds on 2 consecutive occasions (if total feed volume more than 8 ml) or greater than 50% on a single occasion (if total feed volume was less than 8 ml), abdominal distension (increase in abdominal girth by more than 2 cm from baseline), brown, bilious, or blood stained gastric aspirates, vomiting for which feeds were withheld for more than 12 hours, and absent bowel sounds on auscultation in two different quadrants for two minutes.

Incidence of sepsis and number of antibiotic days in both groups is compared. All-cause mortality is compared in both groups. If any baby later on develops a surgical abdomen or is not being given significant feeds for more than 5 days due to any cause, they will be excluded from the final comparison. Number of babies being given Total Parenteral Nutrition (TPN) (clinician’s judgement) in the hospital course in both groups will also be noted. Babies in both groups will be given feed fortification as per institute protocol (if inadequate weight gain despite feed volume of 180-200 ml per kg per day), Kangaroo Mother Care (KMC), and supplements will be started as per protocol in babies in both groups. Weekly anthropometry will be collected and noted. Babies will be monitored for Osteopenia of Prematurity (OOP) and anemia as per protocol during the hospital stay. Babies will be assessed for fitness to discharge (clinician’s judgement), and before discharge, growth and body composition will be assessed using bioelectrical impedance analysis.

WEIGHT - It will be recorded on an electronic weighing scale with an accuracy of 5 grams, with the neonate in nude or minimal light clothing, and the child will be placed in the middle of the weighing pan. LENGTH - Child will be placed in supine position on an infantometer. The head will be held firmly by one person. Legs will be straightened, keeping feet at right angles to legs with toes pointing upward. The free footboard will be brought into firm contact with the child’s heels. The accuracy should be 0.5 cm. HEAD CIRCUMFERENCE - Using non-stretchable tape, the maximum circumference of the head from the occipital protuberance to the supraorbital ridges will be recorded. The accuracy should be 0.1 cm.

All these parameters will be recorded weekly and at discharge. All the above anthropometric measurements will be plotted in the Intergrowth chart, and centiles will be calculated.

BODY COMPOSITION: Maltron Bioscan Touch i8-Nano will be used to measure neonatal body composition.