|Year : 2022 | Volume
| Issue : 1 | Page : 12-15
Comparison of feed fortifying regimes for weight gain in preterm babies—A randomized control trial
Vinitha K Anirudhan, Preetha Remesh, M P T Vishnu, MR Anand
Department of Pediatrics, Aster MIMS, Calicut, Kerala, India
|Date of Submission||09-Mar-2022|
|Date of Acceptance||30-May-2022|
|Date of Web Publication||07-Sep-2022|
Dr. Vinitha K Anirudhan
Vineesh Bhavan, Perumpuzha P O, Kollam, Kerala
Source of Support: None, Conflict of Interest: None
Background: The fortification of human milk has been recommended for all babies <2 kg as the standard of care for rapid weight gain. The search for an ideal fortifying agent still continues. Objectives: The primary objective was to study the preterm weight gain with three different types of fortifiers (carbohydrate-rich, protein-rich, and fat-rich) with a randomized control trial. Materials and Methods: A randomized control trial in a level III Neonatal Intensive Care Unit (NICU). Preterms with < 34 weeks gestation and birth weight <2kg who were exclusively breast fed were included in the study and grouped into three groups. Feeds were fortified and the weight gain per day measured. The outcome was measured as the median weight gain in each group. Results: The median weight gain with carbohydrate-, protein-, and fat-rich fortifier was 11.8, 14.75, and 9.7 g/kg/day, respectively. It is evident that fat-rich group took more days to get discharged. No one developed feed intolerance or necrotizing enterocolitis. Conclusion: Protein-rich human milk fortifier gives higher median weight gain followed by carbohydrate-rich and fat-rich.
Keywords: Fortification, Nutrition, Prematurity
|How to cite this article:|
Anirudhan VK, Remesh P, Vishnu M P, Anand M R. Comparison of feed fortifying regimes for weight gain in preterm babies—A randomized control trial. Pediatr Companion 2022;1:12-5
| Introduction|| |
Human milk is considered the best source of nutrition for preterm babies. Growth failure in very low birth weight (VLBW) babies is due to protein deficiency rather than energy deficit. The main cause for extrauterine growth restriction is suboptimal nutrition can be prevented with human milk fortifiers (HMFs). The fortification of human milk has been recommended for all babies <2 kg. Even though there are studies showing the benefit of HMF, there are no studies comparing different fortifiers. In our study, the weight gain with three different fortifiers was compared to see which fortifier is the best to attain rapid weight gain.
| Material and methods|| |
The primary objective of our study was to compare the weight gain pattern of three cohorts of preterms with three different fortifiers. This randomized control trial was carried out in a level III neonatal intensive care unit after getting consent from parents and approval from ethical committee.
Preterms with gestation <34 weeks with birth weight <2 kg who were exclusively fed with breast milk were included in the study. Those who were top fed or having necrotizing enterocolitis and those with congenital anomalies were excluded from the study. Babies were divided into three groups. As per the unit protocol, all babies were initiated with minimal enteral nutrition within 48 h and feeds were advanced at 20–30 mL/kg/day. The fortifiers were commenced once the feeds reached 100 mL/kg/day, and this was named as study day 1 and continued till the baby was discharged. Feeds were increased 20–30 mL/kg/day for all babies. The primary investigator was blinded. Fortifiers 1 and 2 were commercially available, whereas fortifier 3 was preterm formula in the dose of 1 g–25 mL expressed breast milk (EBM) measured with appropriate weighing scales. The contents of the three fortifiers are given in [Table 1].
The baseline anthropometric measurements are as follows: weight in grams (using calibrated electronic weighing scale), length (using infantometer), and head circumference using nonstretchable tape to the nearest of 0.1 cm in centimeters (cm) were measured at the time of randomization. Babies were subsequently weighed daily before feeds or for the first 8 days of fortification.
The primary outcome measure was weight gain in g/kg/day in the three groups from the date of randomization until the baby discharged or for the first 8 days of fortification. The denominator used each day for calculating the weight gain was the previous day weight. The babies were assessed for feed intolerance. A convenient sample size of 30 in each group was chosen during the study period. Block randomization was done with computer software. Allocation concealment was ensured with the help of sealed opaque envelopes.
Data were analyzed using Microsoft Excel 2010. The statistical analysis was done using SPSS (Statistical Package for Social Sciences) version 22.0 statistical analysis Software. Quantitative variables were represented in median ± SD. Data were represented in table and boxes. Groups were compared by one-way analysis of variance (ANOVA) and Kruskal–Wallis test. P value < 0.05 was considered statistically significant.
| Results|| |
The flow diagram of the study is shown in [Figure 1].
The baseline characteristics of the three groups (gestational age, birth weight) were given in the [Table 2].
The median weight gain in the protein-rich fortified group was 14.75 g/kg/day, whereas that of the carbohydrate-rich group was 11.8 g/kg/day and that of the fat-rich group was 9.7 g/kg/day as given in the [Table 3]. No difference was found in length and head circumference. No baby developed feed intolerance or necrotizing enterocolitis.
Even though the carbohydrate-rich and protein-rich groups had similar weight gain over the first 48 h, the carbohydrate-rich group subsequently lagged behind the protein-rich group.
| Discussion|| |
The results of our study show that the protein-rich fortifier offers a better weight gain than carbohydrate- or fat-rich fortifier in the first week of fortification. This is followed by the carbohydrate-rich and then the fat-rich HMF. The median average weight gain in the protein-rich fortified group was 14.75 g/kg/day, whereas that of the carbohydrate-rich group was 11.8 g/kg/day and that of the fat-rich group was 9.7 g/kg/day. This effect is clearly evident from day 3 onward. However, upon comparing the weight pattern on individual days, although the very same difference was found among groups, this failed to reach a statistical difference. This could be because the final sample size failed to reach the expected 30 in each group. Furthermore, we had strictly excluded all babies who at any point of time had been formula fed.
In the first 2 days, the carbohydrate-rich group had a better weight gain, but from day 3, the protein-rich group started showing a better weight gain. The carbohydrate-rich group did not maintain a consistent weight gain over the first week, whereas the protein-rich group did so. Thus, although the carbohydrate-rich HMF provided an early weight gain, this is not maintained consistently. Fat-rich fortification gave the least amount of weight gain, and therefore, hospital stay was the longest in this group. The median weight gain in the three fortifier groups during the first 8 days is given in the [Figure 2]. No babies developed feed intolerance or abdominal distension.
Despite an exhaustive perusal of accessible medical literature, we could not find any study comparing different HMFs. Available studies were comparisons between the fortified and nonfortified groups only.
In a study by Verma and Yadav, 92 VLBW babies (1.1–1.5 kg, 31–34 weeks) were included. Lactodex HMF was used as the fortifier (which corresponded to our carbohydrate-rich group). On follow-up until 1.6 kg, the mean weight gain of fortifier group was 14.91 g/kg/day. The mean time to achieve targeted weight was 16.69 ± 7.19 days.
Kashyap et al. conducted prospective randomized control trial in 166 babies, 85 babies in the fortified group and 81 babies in the control group, who were <1.5 kg birth weight and <34 weeks gestational age. When the feeds reached 150 mL/kg/day, fortification of mum’s milk was done with Lactodex HMF and continued till they attained 2 kg. Gestational age and birth weight were comparable in two groups. It was found that the fortified group had a better weight gain and an increase in length and head circumference, which were statistically significant. The mean weight gain in the fortified group and control group was 15.1 and 12.9 g/kg/day, respectively.
Martins and Krebs did a prospective randomized control trial with 40 preterm babies who were <1.5 kg and <34 weeks. There were two groups, fortified and unfortified, each with 20 babies. They fortified the mother’s milk once feeds reached 100 mL/kg/day and continued till babies attained 1.8 kg. The fortifier used was fortified milk 85. The mean weight gain and an increase in length and head circumference were studied. They concluded that the mean weight gain in the fortified group was 24.4 g/day, and for the control group, it was 21.2 g/day. The increase in length and head circumference is also better in the fortified group when compared with the control group.
The above studies showed a higher weight gain of the carbohydrate-rich group in comparison with ours. This could be due to their larger sample size and longer duration of follow-up.
Kaur et al. studied the effect of human milk fortification with three different fortifiers: a preterm formula (Lactodex LBW), a term formula (Nestogen), and Lactodex HMF. Here, the control group was fed with the unfortified EBM. Each group comprised of 10 babies, all were <1.5 kg and <34 weeks gestational age and on 150 mL/kg/day feeds. This study showed a better weight gain in those babies who were on fortified feeds. Though this study showed the benefits of fortification, a comparison of fortifiers was not done.
In spite of searching literature, we could not come across any study comparing fortifiers as we did. In conclusion, the study marginally favors protein-rich fortifier over the other two. This also might reflect as lesser number of days to discharge. Preterm formula (fat rich) is not an ideal agent for fortification as it has the least weight gain and leads to extra days for weight gain as well. None of the fortifiers caused abdominal distension or feed intolerance.
The limitation of the study could be a small sample size and a lack of long-term follow-up.
What is already known
Human milk fortification is needed for all babies <2 kg.
What this study adds
Protein-rich HMF gives a higher median weight gain followed by a carbohydrate-rich and fat-rich fortifier.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Susan Carlson RD, Beth W Guidelines for the Use of Human Milk Fortifier in the Neonatal Intensive Care Unit. Iowa Neonatology Book; 2011.
Verma GK, Yadav A Role of human milk fortifier on weight gain in very low birth weight babies. Int J Contemp Pediatr 2018;5:353.
Kashyap S, Forsyth M, Zucker C, Ramakrishnan R, Dell RB, Heird WC Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants. J Pediatr 1986;108:955-63.
Martins EC, Krebs VL Effects of the use of fortified raw maternal milk on very low birth weight infants. J Pediatr (Rio J) 2009;85:157-62.
Kaur S, Sharma S, Mukhopadhyay K, Verma S Effect of different human milk fortifiers on milk composition and growth. Indian J Pediatr 2016;83:900-1.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]