Effect of early total enteral feeding vs incremental feeding in small for gestational age very low birth weight infants: A randomized controlled trial

Abstract

1 Introduction

Early aggressive postnatal nutrition in very low birth weight infants (VLBWI) not only leads to reduction in several neonatal morbidities and extra-uterine growth retardation but also facilitates improved neurodevelopmental outcomes [1]. However, concerns about feed intolerance and necrotizing enterocolitis (NEC) often lead to a delay in early initiation and rapid increment of enteral feeds. This delay is more profound if there is growth restriction in this population necessitating prolonged parenteral nutrition. Delay in time to reach full feeds might increase the risk of metabolic and infectious morbidities leading to a prolonged hospital stay.

A growth restricted fetus tries to preserve cerebral blood flow at the expense of blood flow to the splanchnic circulation and visceral organs. As a consequence of the brain sparing effect, small for gestational age (SGA) preterm infants are likely to have suboptimal gut perfusion and function which may preclude early total enteral feeding [2]. On the other hand, delay in feed initiation reduces functional adaptation of the gastrointestinal tract that could eventually result in mucosal atrophy [3]. Evidence suggests that early feed initiation and rapid feed advancement does not necessarily increase the risk of NEC in VLBW babies [4].

Though there is evidence advocating early enteral feeding in preterm VLBW infants who are appropriate for gestational age (AGA), the same is lacking in preterm SGA infants, especially regarding early total enteral feeding [5, 6]. With this background we conducted this study in SGA VLBW infants≥32 weeks gestation comparing the effect of early total enteral feeding (ETEF) with incremental feeding (IF) at birth on duration of hospital stay.

2 Subjects and methods

2.1 Settings

This was an open label parallel group randomized controlled trial conducted from March 2021 to February 2022 in a tertiary NICU in a major teaching hospital in Western India, after approval of institutional ethics committee (IEC/93/20) and trial registration CTRI/2021/03/031643.

2.2 Randomization and intervention

Infants were randomized into two groups. ETEF (Early total enteral feeding) group, where total enteral feeding was started within first two hours of life and the IF (Incremental feeding) group, where feeds were started on an incremental basis as per a standardized feeding protocol as shown in Table 1 [5]. The infants were randomized using block randomization of block sizes of 2 and 4 into two groups. Allocation concealment was done using serially numbered opaque sealed envelopes.

Table 1
Standardized feeding protocol

Day of Life Early Total Enteral Feeding (ETEF) Volume of feed in ml/kg/day Incremental Feeding (IF) Volume of feed in ml/kg/day

D1 80 20

D2 100 40

D3 120 60

D4 150 90

D5 150 120

D6 150 150

D7 150

D8 150

Day of Life	Early Total Enteral Feeding (ETEF) Volume of feed in ml/kg/day	Incremental Feeding (IF) Volume of feed in ml/kg/day
D1	80	20
D2	100	40
D3	120	60
D4	150	90
D5	150	120
D6	150	150
D7	150
D8	150

2.3 Sample size

Based on the observations in the preceding year, the average duration of hospital stay for stable, SGA VLBW infants≥32 weeks of gestation on incremental feeds was 21.1±7.1 days. Assuming a reduction in the mean duration of hospital stay by 25% with early total enteral feeding since birth, with α of 0.05, power of 80% and a loss to follow up rate of 10%, a final sample size of 62 was calculated, with 31 infants in each group.

2.4 Inclusion and exclusion criteria

We included all SGA infants as follows:

Intramural infants≥32 weeks of gestation (preterm and term infants).

Birth weight between 1000 to 1499 gm (VLBW).

Birth weight < 10th centile as per Fenton growth chart, 2013 [7].

Maternal Doppler abnormalities including any one of the following [8]:

iii.
Cerebro-placental Ratio (CPR) <p5 (centile).

Umbilical artery Pulsatility Index (PI)>p95.

Middle cerebral artery (MCA) PI < p5.

Uterine artery PI > p95.

Stable cardiopulmonary and neurological status.

Age at enrolment ≤2 hours.

We excluded infants with: a.
Major congenital anomalies.

Maternal umbilical artery doppler suggestive of absent or reversed end diastolic flow and/or ductus venosus changes.

Infants requiring resuscitation with positive pressure ventilation (PPV) for≥30 seconds.

2.5 Outcomes

The primary outcome of interest was duration of hospital stay (in days). Secondary outcomes studied included incidence of shock requiring≥2 inotropes, incidence of feed intolerance, NEC Bell’s stage≥2, symptomatic hypoglycemia, culture positive sepsis, time taken to achieve full enteral feeds defined as a feed volume of 150 ml/kg/d tolerated for three consecutive days, time to regain birth weight in days and mortality.

2.6 Methods

We approached the families of women expected to deliver SGA infants admitted before or during labour. All eligible infants satisfying the inclusion criteria were enrolled after obtaining a written informed consent from the parents soon after birth. Gestational age assessment was done based on the first trimester dating scan or last menstrual period if known, or the Expanded New Ballard score if both were unavailable. Infants were classified as small for gestational age (SGA), if the birth weight was below 10th centile and severe SGA if below 3rd centile as per Fenton’s growth chart, 2013 [7]. Cardiopulmonary stability was assessed by monitoring of vital signs on admission to NICU. Stable infants satisfying the inclusion criteria were randomized within first two hours of life.

Infants allocated to the ETEF group received early total enteral feeding with mother’s own milk (MOM) and/or pasteurized donor human milk (PDHM) if MOM is not available. Feeding was initiated within 2 hours of birth and continued every 3 hourly by gavage. Daily increments in feeds were made as per the standardized feeding protocol as shown in Table 1 [5]. In the IF group, enteral feeds were initiated at 20 mL/kg/day of MOM/PDHM on day 1, and increments were made as shown in Table 1. The remaining fluid requirement for the day was provided as intravenous nutrition. Fortification was started once the infant tolerated 150 ml.kg/day for 3 days as per the standard feeding protocol in the study. Further increment in feed volume beyond 150 ml/kg/day was provided as per the tolerance of the infant and as per unit protocol. Infants received vitamin D, calcium and/or phosphate supplements in addition to HMF supplementation only if needed if their biochemical profile done during hospital stay showed any abnormality.

All babies were monitored for hypoglycemia prior to the first feed and pre-feed every 6th hourly for first 48 hours, and twice daily thereafter till first week of life. In case of documented low blood sugar, monitoring was done as per standard hypoglycemia protocol [10]. Asymptomatic hypoglycemia in ETEF group was managed by giving an additional feed and in the IF group by increasing the glucose infusion rate (GIR). Low sugar on repeat testing post feeding or need for increased GIR≥8 mg/kg/min or symptomatic hypoglycemia was managed by withholding feeds and starting parenteral therapy as per standard hypoglycemia protocol [10, 11]. Feeding was reintroduced once normoglycemia was achieved as incremental feeds in both groups as shown in Table 1.

Feeds were interrupted if infants had features of feed intolerance, NEC≥Stage 2 as per the Modified Bell’s criteria or shock requiring≥2 inotrope. Feed intolerance was defined as presence of any one of the following a) Increase in abdominal girth (AG) of more than 2 cm with gastric residuals > 50% of the previous feed volume. b) Any episode of bile or blood-stained vomiting [12]. Necrotizing enterocolitis (NEC) was defined as≥stage 2 by modified Bell’s staging [13].

Infants with feed intolerance were kept nil per oral for 12 hours and reassessed for feed initiation. Feeds were restarted with the same feed volume as at the time of stoppage. Infants diagnosed to have shock requiring≥2 inotropes or NEC≥Stage 2, were kept nil per oral until the resolution of the acute pathology. Feeds were restarted as per incremental feeding group protocol in both groups once infant was ascertained to be clinically stable by the treating physician. Infants were also screened for hyperbilirubinemia, polycythemia and sepsis whenever indicated and managed as per standard protocols [14 –17].

Daily weight, weekly head circumference and length were monitored in all infants. All mothers were encouraged for early participation in infant care, frequent breastmilk expression and kangaroo mother care (KMC). All infants received oro-motor intervention and breastfeeding was initiated when the infants had favorable oro-motor activity and coordinated suck-swallow-breathe pattern.

All infants were followed up till discharge or death. Infants were discharged once they were able to maintain normothermia, weighed≥1500 gms with consistent weight gain for 3 consecutive days on full oral feeds, achieved total or partial breastfeeding, were not on any medications other than fortification / supplements, had received vaccination as per schedule and newborn screening reports were available. It was ensured that parents were confident of taking care of the baby and were aware of the danger signs and follow-up plans.

2.7 Statistical analysis

Statistical analysis was carried out using the SPSS software, version 24.0 for Windows (SPSS, Chicago, IL, USA). We analyzed the data with intention to treat (ITT). Data was summarized by routine descriptive statistics, namely mean and standard deviation for numerical variables that were normally distributed, median and interquartile range for skewed numerical variables, and counts and percentages for categorical variables. Numerical variables were compared by Student’s independent samples t test, if normally distributed, or by Mann-Whitney U test, if otherwise. Fisher’s exact test or Pearson’s chi-square test was employed for intergroup comparison of categorical variables. Analyses were two-tailed and statistical significance level was set at p < 0.05 for all comparisons.

3 Results

We assessed 77 infants for eligibility, out of which 15 infants were excluded for various reasons (Fig. 1). Out of the 62 infants (53 preterm VLBWI and 9 Term VLBWI) enrolled in the study, 31 infants were randomized to ETEF group and 31 to the IF group (Fig. 1). Baseline demographic characteristics were comparable between the groups except the APGAR at 5 minutes (Table 2). Median (IQR) gestational age was 35 (33, 36) weeks in ETEF group and 35 (33, 37) weeks in IF group. Median (IQR) birth weight was 1460 (1390, 1495) gm in ETEF group and 1420 (1320, 1490) gm in IF group. The incidence of pre-eclampsia, maternal anemia and abnormal antenatal doppler studies in the ETEF group was 35.4%, 25.8% and 35.4% compared to 35.4%, 19.3% and 38.7% in the IF group respectively.

Fig. 1

CONSORT flow diagram.

Table 2

Baseline characteristics

Variables	ETEF (n = 31)	IF (n = 31)
Maternal Age in years, Mean (SD)	26.90 (3.41)	26.06 (3.63)
Male, n (%)	19 (61.2)	18 (58.0)
Gestational age in weeks, Mean (SD)	35 (33, 36)	35 (33, 37)
Birth weight in gm, Median (IQR)	1460 (1390,1495)	1420 (1320,1490)
Pregnancy weight gain in kg, Mean (SD)	8.25 (1.06)	8.29 (1.13)
Twins^#, n (%)	2 (6.4)	5 (16.1)
Primigravida, n (%)	8 (25.8)	14 (45.1)
Antenatal visits≥4, n (%)	19 (61.2)	16 (51.6)
Small for Gestational Age < 3^rd centile, n (%)	15 (48.3)	16 (51.6)
Pre-gestational hypertension, n (%)	1(3.2)	1(3.2)
Pre-gestational diabetes, n (%)	0(0)	2(6.4)
Gestational Diabetes Mellitus, n (%)	0(0)	1(3.2)
Pre-eclampsia, n (%)	11(35.4)	11(35.4)
Eclampsia, n (%)	5(16.1)	1(3.2)
Chronic medical illness, n (%)	2(6.4)	3(9.6)
Anemia in mother, n (%)	8(25.8)	6(19.3)
Preterm Premature Rupture of Membranes, n (%)	3(9.6)	5(16.1)
Intrapartum fever, n (%)	3(9.6)	3(9.6)
Meconium stained amniotic fluid, n (%)	2(6.4)	3(9.6)
Received complete course of antenatal corticosteroids, n (%)	11(35.4)	6(19.3)
Oligohydramnious, n (%)	6(19.3)	13(41.9)
Abnormal Dopplers (Except A/REDF*), n (%)	11(35.4)	12(38.7)
LSCS**, n (%)	18(58.0)	21(67.7)
APGAR,1 min, Median (IQR)	8 (8,9)	8(8,9)
APGAR,5 min, Median (IQR)	9(8,9)	8(8,9)
Head circumference-z score, Mean (SD)	–1.51 (0.96)	–1.53 (1.04)
Length-z score (Mean (SD)	–1.75 (1.05)	–1.64 (1.08)
Ponderal Index, Mean (SD)	1.975 (0.216)	1.954 (0.254)

#Twins were randomised as independent infants and analysed as per their group allocation; *A/REDF –Absent/ Reversed End Diastolic Flow; **LSCS –Lower Segment Caeserean Section.

The median (IQR) duration of hospital stay in the ETEF group was significantly lower than that in the IF group (12 (9, 21.5) vs 20.5 (15, 25.5) days, p = 0.004, Table 3). On analyzing the subgroup of severe SGA infants, we found that median (IQR) duration of hospital stay in the ETEF group was significantly lower than that in the IF group (10 (9, 22) vs 22 (16.5, 27.5) days, p = 0.035, Table 3). We did not analyse the data for term VLBW SGA infants separately since the numbers were very small. The time taken to reach full feeds (7.69±3.84 days in ETEF group vs 11.86±5.42 days in IF group, Mean difference, MD= -4.16 days, 95% CI –6.67 to –1.65, p = 0.002), the time to regain birth weight (9.38±3.13 days in ETEF group vs 13.39±3.48 days in IF group, MD = –4.01 days, 95% CI –5.77 to –2.25, p = 0.001), the incidence of feed intolerance (RR 0.50, 95% CI 0.26–0.98, p = 0.031), the incidence of culture positive LOS (RR 0.16, 95% CI 0.02–1.09, p = 0.005) and incidence of shock requiring≥2 inotrope (RR 0.23,CI (0.06–0.83), p = 0.002) were significantly lower in the ETEF group. There was no difference in the incidence of NEC≥stage 2 (RR 0.64, 95% CI 0.12–3.25, p = 0.611), hypoglycemia (RR 0.70, 95% CI 0.27–1.79, p = 0.470) and polycythemia (RR 1.52 (0.81–2.86), p = 0.611).

Table 3

Primary and secondary outcomes

Variables	ETEF (n = 29)	IF (n = 27)	MD/RR (95% CI)	p value
Duration of Hospital stay in days, Median (IQR, N = 57)	12 (9,21.5)	20.5 (15,25.5)		0.004
Duration of Hospital stay in severe SGA infants in days, Median (IQR, N = 31)	10 (9,22)	22(16.5,27.5)		0.035
Time to reach full feeds of 150 ml/kg/day for 3 days, (Mean±SD, Mean difference, 95% CI)	7.69±3.84	11.86±5.42	–4.167 (–6.67 to –1.65)	0.002
Time to regain birth weight in days, Mean±SD (Mean difference, 95% CI)	9.38±3.13	13.39±3.48	–4.01 (–5.77 to –2.25)	0.001
Feed intolerance, n (%)	7 (24.1)	15 (53.6)	0.50 (0.26–0.98)	0.031
NEC* stage≥2, n (%)	1 (3.4)	2 (7.1)	0.64 (0.12–3.25)	0.611
Culture positive late onset sepsis, n (%)	1 (3.4)	9 (32.1)	0.16 (0.02–1.09)	0.005
Culture negative CRP**+sepsis, n (%)	7 (24.1)	20 (71.4)	0.35(0.18–0.69)	0.001
Asymptomatic hypoglycemia, n (%)	4 (13.8)	6 (21.4)	0.75 (0.33–1.68)	0.504
Symptomatic hypoglycemia, n (%)	3 (10.3)	5 (17.9)	0.70 (0.27–1.79)	0.470
Mortality, n (%)	0(0)	1 (3.6)	–	0.491
Neonatal Jaundice requiring phototherapy, n (%)	5 (17.2)	17 (60.7)	0.33 (0.15–0.73)	0.001
PRBC^# transfusion, n (%)	1 (3.4)	5 (17.9)	0.30 (0.05–1.84)	0.102
Polycythemia, n (%)	3 (10.3)	1 (3.6)	1.52 (0.81–2.86)	0.611
Shock requiring inotropes, n (%)	2 (6.9)	12 (42.9)	0.23 (0.06–0.83)	0.002
Osteopenia of prematurity, n (%)	4 (13.8)	4 (14.3)	0.98 (0.46–2.06)	1.0
hsPDA^# #, n (%)	0(0)	2 (7.1)	–	–
Discharge weight in gm, (Mean (SD)	1628.62 (193.23)	1687.50 (205.43)	–58.87 (–164.85 to 47.09)	0.270
Growth velocity in gm/kg/day, Median (IQR)	11.4 (4.9,13.3)	13.05 (9.62,15.7)		0.164
Head circumference z score at discharge, Mean (SD)	–1.52 (0.81)	–1.84 (1.07)		0.21
Length z score at discharge, Mean (SD)	–2.16 (1.15)	–2.32 (1.34)		0.64
Delta z head circumference, Mean (SD)	–0.09 (0.81)	0.13 (0.85)		0.30
Delta z Length, Mean (SD)	0.28 (0.87)	0.46 (1.04)		0.46

NEC*- Necrotising enterocolitis, CRP**- C-reactive protein, PRBC#- Packed Red blood Cells, hsPDA##- Hemodynamically significant patent ductus arteriosus.

4 Discussion

Fear of NEC or feed intolerance in VLBW infants, especially when they are SGA, often causes delayed initiation and slower increments in enteral feeds. This leads to increased duration of parenteral nutrition, risk of hospital acquired infections and prolonged hospital stay.

The multicentric ADEPT study demonstrated that introduction of enteral feeding as early as second day in preterm infants with abnormal antenatal doppler studies resulted in full feeds being achieved earlier without increase in the incidence of NEC [18]. The SIFT trial showed that larger increments in feed volumes of 30 ml/kg/day vs 18 ml/kg/day in VLBW infants did not increase the risk of NEC. SGA babies accounted for 21% of the SIFT cohort [19]. However, neither of these studies looked at early full enteral feeds in SGA-VLBW infants. Our study demonstrated that early total enteral feeding in stable SGA-VLBWI≥32 weeks gestation lead to a significant reduction in duration of hospital stay by a median of 8 days (p = 0.004) without increase in the incidence of NEC. Zecca et al used proactive feeding regimen and reported a reduction in the length of hospital stay by a mean of 2.1 days (p = 0.029) in a population of moderate and late preterm SGA infants [20]. Similar findings were reported by Nangia et al who found a significant reduction in the duration of hospital stay in ETEF group with a mean difference (MD) of 4.1 days; however only 30% of the study infants were SGA-VLBWI [5].

In our study, median time to reach full enteral feeds was significantly lesser in the ETEF group by median of 4 days compared to the IF group (p = 0.002). Nangia et al found that the time to achieve full enteral feeds was significantly shorter in their ETEF group with a mean difference (MD) of –3.6 days [5]. In our study, the time to regain birth weight was 4 days earlier in the ETEF group. Similarly, Sanghvi et al. looked at feasibility of exclusive enteral feeds from birth in VLBW babies > 1200 gms and reported a significant reduction in time to regain birth weight by 7.2 days [6].

In our study the incidence of culture positive sepsis was significantly lower in the ETEF group (p = 0.005). Study by Patole et al on preterm infants reported sepsis as an important factor in delaying the time to reach full feeds [21]. Increased incidence of sepsis leads to continued parenteral access for antibiotics and intravenous fluids, ultimately prolonging the duration of hospital stay. Patwardhan et al reported similar decrease in late onset sepsis in early feeding group (p = < 0.0001) [22]. In contrast to our study, Nangia et al reported no significant reduction in the incidence of culture positive sepsis in ETEF group (3.3% vs 7.8%, p = 0.19) [5]. The incidence of feed intolerance in our study was significantly lower in the ETEF group, p = 0.03 similar to the study by Nangia et al that reported a statistically lower incidence of feed intolerance in ETEF group (15.9% vs 30.2%, p = 0.002) [5].

There was no significant difference in the incidence of symptomatic hypoglycemia between the groups in our study, in contrast to the study by Zecca et al, where the incidence of hypoglycemia was significantly higher in the slower feeding regimen group, p = 0.0002 [20]. There was a significant decrease in the incidence of neonatal hyperbilirubinemia in the ETEF group probably related to frequent breast milk feeding helping elimination of bilirubin by early passage of meconium.

In our study there was a significantly higher change in weight ‘z’ scores (delta ‘z’ score) in the incremental feeding group (p = 0.01) similar to the study by Zecca et al. This implies faster weight gain in the ETEF group, which can be attributed to higher caloric intake due to early introduction of higher enteral feed volumes in the ETEF group compared to the IF group. However, there was no significant difference in the change in length and head circumference ‘z’ score in our study, in contrast to the study by Zecca et al that showed a significantly lower change length z scores in the proactive enteral feeding group [20].

This is one of the first studies to have looked at early total enteral feeding in SGA VLBWI. The other strength of our study is the presence of a donor milk bank attached to our unit that ensured that every infant receieved PDHM till MOM was available. The ongoing FEED1 (Fluids exclusively enteral from day one) trial comparing effect of full versus gradual feeding in very preterm infants on length of hospital stay shall provide more evidence on aggressive feeding practices [23]. The limitation of our study was the inability to blind the feeding intervention since the presence of an intravenous cannula running intravenous fluids made the group allocation obvious. However, the data analyst was blinded to the intervention. To minimize any bias, we developed a standardized feed advancement protocol and a feed intolerance guideline. Decisions about management of feed intolerance were left to the clinical care team, rather than to the study physicians. Our study results are encouraging. In low- and middle-income countries with a high SGA birth rate coupled with resource limitation, being able to shorten hospital stay, reduce sepsis, improve weight gain are important factors to generate cost effective models of neonatal care. The findings of our study are of particular importance for LMICs given a higher incidence of SGA births on one hand and the resource limitations on the other. More studies from LMICs focussing on early total enteral feeds for the group of stable VLBW, SGA infants are needed in units having access to PDHM to confirm the findings of our study.

5 Conclusions

We conclude that early total enteral feeding as compared to incremental feeding in stable SGA VLBWI≥32 weeks gestation leads to significant reduction in the duration of hospital stay. ETEF also leads to significantly lesser time to reach full enteral feeds and regain birth weight. There is a significant decrease in the incidence of late onset sepsis and feed intolerance in the ETEF group. Also there is no difference in the incidence of NEC irrespective of the feeding regimen.

Ethics statement

Institutional Ethics Committee, Lokmanya Tilak Municipal medical College & General Hospital, Mumbai (IEC 93/20). The study was performed in accordance with the Declaration of Helsinki.

Footnotes

Acknowledgments

We are thankful to the Dean of the institution for allowing us to conduct the study and publish our data. We also wish to thank Dr. Nandkishor Kabra for critical review of the manuscript.

Author contributions

SM conceived the study. TS, SM, JM, PK, TK, SK and SP developed study protocol. TS, PK, TK, SK and SP implemented the study and SM and JM supervised implementation. TS, PK, TK, SK and SP contributed to data collection and analysis. SM and JM contributed to data interpretation. TS, PK, TK, SK and SP wrote the initial draft while SM and JM edited the final manuscript. All authors have reviewed the manuscript and approve the submitted version. All authors meet the criteria for authorship.

Conflict of interest

The authors have no conflicts of interest to disclose.

Funding

None.

References

Thoene

, Anderson-Berry

. Early enteral feeding in preterm infants: A narrative review of the nutritional, metabolic, and developmental benefits. Nutrients. 2021;13(7):2289.

Miller

, Huppi

, Mallard

. The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome: Fetal growth restriction: Brain structure and function. J Physiol. 2016;594(4):807–23.

Morgan

, Young

, McGuire

. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Neonatal Group, editor. Cochrane Database Syst Rev. 2022;1, CD001970.

Rayyis

, Ambalavanan

, Wright

, Carlo

. Randomized trial of “slow” versus “fast” feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. J Pediatr. 1999)134(3).

Nangia

, Vadivel

, Thukral

, Saili

. Early total enteral feeding versus conventional enteral feeding in stable very-low-birth-weight infants: A randomized controlled trial. Neonatology. 2019;115(3):256–62.

Sanghvi

, Joshi

, Nabi

, Kabra

. Feasibility of exclusive enteral feeds from birth in VLBW infants >g –an RCT. Acta Paediatr. 2013;102(7):e299–304.

Fenton

, Kim

. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13(1):59.

Figueras

, Gratacós

. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther. 2014;36(2):86–98.

Banait

, Basu

, Desai

, et al Feeding of low birth weight neonates. Journal of Neonatology. 2020;34(1-2):28–51.

10.

Adamkin

. Neonatal hypoglycemia. Semin Fetal Neonatal Med. 2017;22(1):36–41.

11.

Narvey

, Marks

. The screening and management of newborns at risk for low blood glucose. Paediatr Child Health. 2019;24(8):536–44.

12.

Dutta

, Singh

, Chessell

, Wilson

, Janes

, McDonald

, et al Guidelines for feeding very low birth weight infants. Nutrients. 2015;7(1):423–42.

13.

Walsh

, Kliegman

, Fanaroff

. Necrotizing enterocolitis: A practitioner’s perspective. Pediatr Rev. 1988;9, 219–26.

14.

Kemper

, Newman

, Slaughter

, Maisels

, Watchko

, Downs

, et al Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.(2022)150(3).

15.

Rennie

, Burman-Roy

, Murphy

. Neonatal jaundice: Summary of NICE guidance. BMJ. 2010;340(May19 3):c2409–c2409.

16.

Prasad

, Rameshbabu

, Dutta

, Kabra

N. NNF clinical practice guidelines-diagnosis and management of neonatal sepsis. 2021.

17.

Oski

, Naiman

Polycythemia and hyperviscosity in the neonatal period. In: Hematologic Problems in the Newborn, 3 ed, Oski FA (Ed), WB Saunders, New York 1982. p.87

18.

Leaf

, Dorling

, Kempley

, McCormick

, Mannix

, Brocklehurst

. ADEPT –Abnormal Doppler Enteral Prescription Trial. BMC Pediatr. 2009;9(1):63.

19.

Dorling

, Abbott

, Berrington

, Bosiak

, Bowler

, Boyle

, et al Controlled trial of two incremental milk-feeding rates in preterm infants. N Engl J Med. 2019;381(15):1434–43.

20.

Zecca

, Costa

, Barone

, Giordano

, Zecca

, Maggio

. Proactive enteral nutrition in moderately preterm small for gestational age infants: A randomized clinical trial. J Pediatr. 2014;165(6):1135–1139.e1.

21.

Patole

, Kumaran

, Travadi

, Brooks

, Doherty

. Does patent ductus arteriosus affect feed tolerance in preterm neonates? Arch Dis Child - Fetal Neonatal Ed. 2007;92(1):F53–5.

22.

Patwardhan

, Soni

, Rachwani

, Kadam

, Patole

, Pandit

. Factors associated with time to full feeds in preterm very low birth weight infants. J Trop Pediatr. 2018;64(6):495–500.

23.

Mitchell

, Meakin

, Anderson