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CTRI Number  CTRI/2025/02/079878 [Registered on: 03/02/2025] Trial Registered Prospectively
Last Modified On: 04/08/2026
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Nutraceutical 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Time of starting fortification of feeds in preterm neonates admitted to neonatal intensive care unit. 
Scientific Title of Study   Early versus late fortification of feeds in preterm neonates admitted to neonatal intensive care unit-A randomized controlled study 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Saikat Patra 
Designation  Associate Professor 
Affiliation  Himalayan Institute of Medical Sciences 
Address  Department of Neonatology HIMS SRHU

Dehradun
UTTARANCHAL
248140
India 
Phone  9780317739  
Fax    
Email  dr.saikatpatra@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ravleen Kaur 
Designation  Senior Resident Neonatology 
Affiliation  Himalayan Institute of Medical Sciences 
Address  Department of Neonatology Himalayan Institute of Medical Sciences SRHU, Jolly Grant, Swami Ram Nagar

Dehradun
UTTARANCHAL
248016
India 
Phone  9646753450  
Fax    
Email  ravleen135@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Saikat Patra 
Designation  Associate Professor 
Affiliation  Himalayan Institute of Medical Sciences 
Address  Department of Neonatology HIMS SRHU

Dehradun
UTTARANCHAL
248140
India 
Phone  9780317739  
Fax    
Email  dr.saikatpatra@gmail.com  
 
Source of Monetary or Material Support  
Himalayan Institute of Medical Sciences, SRHU, Jolly Grant, Swami Ram Nagar, Beside Jolly Grant Airport, Dehradun, Uttarakhand 248016, India 
 
Primary Sponsor  
Name  Himalayan Institute of Medical Sciences 
Address  Department of Neonatology Himalayan Institute of Medical Sciences, SRHU, Jolly Grant, Swami Ram Nagar, Beside Jolly Grant Airport, Dehradun, Uttarakhand 248016, India 
Type of Sponsor  Private medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Saikat Patra  Himalayan Institute of Medical Sciences  NICU-Ward No. 110,First Floor Hospital building;Neurodevelopmental OPD-Room No.14, Ground Floor, Hospital building, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Swami Ram Nagar, 248016
Dehradun
UTTARANCHAL 
9780317739

dr.saikatpatra@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Ethics Committee,Swami Rama Himalayan University.  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: P073||Preterm [premature] newborn [other],  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Early Fortification with Human Milk Fortifier (HMF)  Done at feed volume of 80 mL/kg/day.1 HMF sachet will be added in 25 mL breast milk and required volume will be given every 2 hourly. Number of HMF sachets received by the patient will be calculated daily. 
Comparator Agent  Late Fortification with Human Milk Fortifier(HMF)  Done at feed volume of 150 mL/kg/day.1 HMF sachet will be added in 25 mL breast milk and required volume will be given every 2 hourly. Number of HMF sachets received by the patient will be calculated daily. 
 
Inclusion Criteria  
Age From  1.00 Day(s)
Age To  28.00 Day(s)
Gender  Both 
Details  Preterm neonates born at gestational age 26-34 weeks and birth weight 600 g-1800 g on enteral feeds of 80mL /kg/day.
 
 
ExclusionCriteria 
Details  1. Neonates with gross congenital anomalies.
2. Those with NEC stage 2 or worse (Modified Bell’s staging) prior to enrollment.
3. Those with genetic or metabolic syndromes.
4. Those with surgical gastro-intestinal condition.
5. Those on formula feed.
6. Outborn neonates already on feed more than 80mL/kg/day.
7. More than two episodes of feed intolerance prior to enrollment.
8. Parents who don’t give written informed consent.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Rate of weight gain after regaining birth weight (g/kg/day) during NICU stay.  At discharge 
 
Secondary Outcome  
Outcome  TimePoints 
Linear growth (cm/week) and increase in head circumference (cm/week) during NICU stay.  At discharge 
Day of regaining birth weight.  During NICU stay 
Gross weight gain after regaining birth weight.  At discharge 
Rate of weight gain since addition of HMF.  At discharge 
Rate of weight gain from birth weight.  At discharge 
Rate of weight gain from nadir weight.  At discharge 
Total number of HMF days.  At discharge 
Incidence of extra-uterine growth restriction.  At discharge 
Incidence of necrotising enterocolitis (NEC) stage 2 or worse (Modified Bell’s staging)  At discharge 
Incidence of invasive infection as determined as confirmed by positive culture of bacteria or fungus from blood, cerebrospinal fluid, urine or a normally sterile body space.  At discharge 
Duration of parenteral nutrition (PN) (days).  At discharge 
Duration of central venous line (CVL) usage (days).  At discharge 
Number of infants with retinopathy of prematurity requiring treatment, intraventricular hemorrhage, bronchopulmonary dysplasia, metabolic bone disease, anemia  At discharge 
Duration of hospital stay (days).  At discharge 
All-cause mortality   At discharge 
Rate of weight gain after regaining birth weight (g/kg/day), linear growth (cm/week), and increase in head circumference (cm/week)   At 1, 3 and 6 months’ corrected age and at latest follow-up. 
Hearing evaluation by BERA.  Before 3 months age 
Visual assessment
 
At 6 months corrected age 
Neurodevelopmental assessment  At 6 months corrected age 
 
Target Sample Size   Total Sample Size="66"
Sample Size from India="66" 
Final Enrollment numbers achieved (Total)= "66"
Final Enrollment numbers achieved (India)="66" 
Phase of Trial   N/A 
Date of First Enrollment (India)   10/02/2025 
Date of Study Completion (India) 19/01/2026 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) 19/01/2026 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
Sent for publication in Indian Journal of Pediatrics. 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary
Modification(s)  

This study was done to analyse effect of early (80 mL/kg/day) versus late fortification (150 mL/kg/day) in preterm neonates on anthropometry at discharge, anthropometry and neurodevelopment at 6 months’ corrected age.Sixty-six preterm neonates (gestational age-26-24 weeks and birth weight 600-1800 grams) were randomized. Primary outcome was rate of weight gain (g/kg/day) after regaining birth weight during NICU stay; which was analysed by three different methods as secondary outcome. Various morbidities, side effects of fortification, anthropometry, neurodevelopment by Trivandrum Development Screening Chart (TDSC) at 1, 3, and 6 months’ corrected age were also studied. In results, baseline neonatal and maternal characteristics were comparable. Median birth weight [1430 g (IQR:1192–1675) vs 1436 g (IQR:1242–1622); p=0.980] and gestational age [31 weeks (IQR:30–33) vs 32 weeks (IQR:30–33); p=0.571] were similar. Early fortification showed higher median weight gain velocity (18.3 vs 14 g/kg/day; p=0.062) though not statistically significant. Subgroup analysis and analysis of rate of weight gain by three different methods showed uniform trend favouring early fortification. Linear and head growth were similar. Rates of necrotising enterocolitis, feed intolerance, extra-uterine growth restriction, mortality, post-discharge growth and neurodevelopment were also similar. It was concluded that early fortification of feeds at around 80 mL/kg/day appears feasible and safe in preterm neonates, with consistent trends toward improved growth velocity but post-discharge growth and short-term neurodevelopmental outcomes are similar.

 


 
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