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Journal of Tropical Pediatrics, 2017, 0, 1–7

doi: 10.1093/tropej/fmx023
Original Paper

Early Total Enteral Feeding in Stable Very
Low Birth Weight Infants: A Before and
After Study
by Sushma Nangia,1 Amit Bishnoi,2 Ankita Goel,2 Piali Mandal,2
Soumya Tiwari,2 and Arvind Saili1
1
Department of Neonatology, Lady Hardinge Medical College and Kalawati Saran Children Hospital, New Delhi 110001, India
2
Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children Hospital, New Delhi 110001, India
*Correspondence: Sushma Nangia, Department of Neonatology, Lady Hardinge Medical College and Kalawati Saran Children Hospital, New
Delhi 110001, India. Tel: 011-23344161-70, Ext 331, Mobile: 91-9810838181, E-mail <drsnangia@gmail.com>.

ABSTRACT
Background: Fear of necrotizing enterocolitis (NEC) has perpetuated delayed initiation and slow
advancement of enteral feeding in very low birth weight (VLBW) infants with inherent risks of par-
enteral alimentation. The objective of this study was to assess effect of early total enteral feeding
(ETEF) on day of achievement of full enteral feeds, feed intolerance, NEC and sepsis.
Methods: In total, 208 stable VLBW neonates (28–34 weeks) admitted during 6 month periods of
three consecutive years were enrolled. First phase (n ¼ 73) constituted the ‘before’ phase with
standard practice of initial intravenous fluid therapy and slow enteral feeding. The second prospect-
ive phase (n ¼ 51) consisted of implementation of ETEF with infants receiving full enteral feeds as
per day’s fluid requirement since Day 1 of life. The third phase (n ¼ 84) was chosen to assess the
sustainability of change in practice.
Results: Day of achievement of full feeds was significantly earlier in Phases 2 and 3 compared with
Phase 1 (8.97 and 5.47 vs. 14.44 days, respectively, p ¼ 0.0001). Incidence of feed intolerance was
comparable between Phases 1 and 2 (22 vs. 14%, p ¼ 0.28), with marked reduction in incidence of
NEC (14 vs. 4%, p ¼ 0.028). There was a significant decrease in sepsis, duration of parenteral fluid
and antibiotic therapy as well as hospital stay with comparable mortality.
Conclusion: In stable preterm VLBW infants, ETEF is safe and has the benefit of optimizing nutri-
tion with decrease in sepsis, NEC and hospital stay.

K E Y W O R D S : early total enteral feeding, necrotizing enterocolitis, sepsis, very low birth weight

INTRODUCTION parallel the corresponding intrauterine period [2].
Optimal nutrition has been identified as a fundamen- This goal remains elusive to best neonatal centres
tal factor in reducing mortality and long-term mor- around the world with almost 90% having growth
bidities like extrauterine growth restriction and poor delay at 36 weeks’ corrected age and 40% at 18–
neurodevelopmental outcome in preterm very 22 months of age [3]. In most centres, aggressive
low birth weight (VLBW) infants (birth weight early nutritional rehabilitation of preterms is
<1500 g) [1, 4]. According to American Academy of achieved by total parenteral nutrition (TPN) with
Pediatrics, postnatal growth of preterms should delayed initiation of enteral feeding. However,

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mortality or feed interruption [16]. Ostertag et al. Recent Cochrane review compared slow vs. These neonates also necrotizing enterocolitis (NEC) between enteral received slow incremental enteral feeding consisting feeding started on Day 1 vs. the neonate did not receive protocol. Feeding vol- before and after study was undertaken to assess the ume of this magnitude (80 ml/kg on Day 1 with feasibility. In Phase 1. it start ETEF was implemented from January 2011 has been postulated that total enteral feeding may be based on literature evidence and pilot experience. daily increments of 20 ml/kg/day to reach 150 ml/ teral feeding (ETEF) at a tertiary neonatal centre kg on Day 5/Day 6 of life) was achieved with bio- with high patient load. there was a change in feeding policy to ETEF. started safely on the first day in stable low-risk During Phase 2. this uncontrolled feeding with 80 ml/kg on Day 1 of life. studies with January and June 2010. none of these studies initiated exclusive The response was encouraging. However. [15] found no difference in trose from Day 3 onwards). were included in the study [19. With this regimen. Bolus feeds were provided This uncontrolled before and after study was con. Exclusion crite- thrombosis or bleeding and cholestasis offset the ria were documented as absence or reversal of end benefits of TPN [5]. tinal functions along with increased recognition of Study design: The study was divided into three beneficial effects of human milk has resulted in tro. related adverse events like feed intolerance or NEC. where cost and logistics of providing TPN are the day’s fluid requirement was provided as enteral usually the limiting factors. In this period. More recently. not requiring ETEF. diastolic flow in umbilical arteries and presence of Improved understanding of preterm gastrointes. of men on Day 1 (20 ml/kg/day) with successive fants. eligible babies were prospectively VLBW infants [18]. any IV fluid. of ETEF practice from January to June 2012. retrospective data were collected phic feeding along with TPN being put forth as a from case files of eligible infants. where tings. were provided ETEF (total fluid requirement for the ation within 24 h in 35% of preterm neonates when day provided as enteral feed with no IV fluid) on a gestational age (GA) was <25 weeks. admitted between feasible solution [6–8]. Hence. Recently. who were treated with stand- variable time of initiation of feeds and different feed. the unit continued with the practice of 34 weeks. phases. for all neonates was done by heel-prick method. This physiological approach included from January to June 2011. Between July of enteral feeding practices among 127 tertiary and December of 2010. gut atrophy. every 2 h through orogastric tube with prefeed ab- ducted at a tertiary care teaching institution. modynamic status (capillary refill time <3 s and Case management: Apart from hemodynamic mean arterial pressure normal for GA as per and vital monitoring.2  Early Total Enteral Feeding in VLBW Neonates complications like sepsis related to invasive catheters support (CPAP or ventilation)] admitted to NICU along with gut translocation of bacteria. feed increments of 20 ml/kg/day along with propor- fast daily increments of feed volume with no increase tionate decrease in the IV fluid volume till the baby in NEC. efficacy and sustainability of early total en. may be of greater significance in resource-limited set. During the second half of 2011 (July– Study subjects: Stable preterm infants (GA 28– December). birth weight 1000–1499 g). The dominal girth (AG) charting and abdominal assess- ethics committee of the institute approved the study ment. and unit policy to enteral feeding on the first day of life. 43% for GA pilot basis and strictly monitored for any feeding- 25–27 weeks and 71% if GA was 28–31 weeks [17]. with normal hae. ard practice of initial intravenous (IV) therapy (10% ing regimens have been conducted in preterm infants dextrose for first 2 days and N/5 saline in 10% dex- [9–14]. logical mother’s expressed breast milk predominantly along with remaining deficit fulfilled by preterm for- MATERIALS AND METHODS mula (80 kcal/100 ml). 20 stable VLBW neonates Neonatal intensive care units (NICU) revealed initi. prefeed blood sugar monitoring Zubrow’s chart) and absence of significant respira. Day 7 in sick VLBW in. Survey reached full feeds (150 ml/kg/day). The tory compromise [(no requirement of respiratory frequency of monitoring was every 4 h in the initial . Phase 3 consisted of evaluation of sustenance resuscitation beyond initial steps. 20]. gross congenital malformations.

There was no major change or revision in the unit protocols during Statistical Analysis the study period. Days to regain . fluid administration (p ¼ 0. then the feeds were omitted for 24 h.0001) Subsequent feed decisions were based on abdominal (Table 2). but if milky and crease in days required to achieve full feeds along >50%. Early Total Enteral Feeding in VLBW Neonates  3 72 h of life and thereafter every 8 h till the end of first 4. of the following: a.1 (StataCorp. Vomiting more than three times during RESULTS any 24 h period A total of 208 infants were included in the study dur- b. respectively (Fig. if the aspirate was milky and <50% of the Primary outcome previous feed volume.0005). Sepsis screen and blood culture were sent at suggestive of sepsis with positive sepsis admission and in case of any clinical deterioration. then the feeds were omitted and neonates evaluated for NEC. ETEF was not associated with assessment and girth measurement. Full feed achievement: total enteral intake Fisher’s exact test.05 was taken as significant. icus—prefeed) Demographic and baseline characteristics of study d. Moreover. inal or systemic symptoms and signs and p ¼ 0. USA). Secondary object. sepsis and Secondary outcome surgical condition. If the aspirates any increase in feed intolerance or NEC. and achievement of full enteral feeds. Gross or occult blood in stools (Table 1). Phase-wise distribution was 73. continuous variables by one-way analysis of variance 2. 2 and 3. and culture-proven sepsis and durations of antibiotic Continuous data with normal distribution were ana- therapy. were haemorrhagic or bilious. All baseline and outcome data were recorded in a predesigned pro forma. incidence of feed coded and analysed statistically using software ver- intolerance and incidence of NEC. incidence of clinical Descriptive data were analysed using means and SD. 51 and 84 in c. and known variables Outcome measures were compared between Phase 1 (before) and Phase The primary objective was to assess the feasibility 3 (after). Standard sepsis in neonate with compatible signs and management protocols as per the unit policy were symptoms followed for other clinical problems. The groups were compared for of 150 ml/kg/day sustained for 24 h. there was a statistically significant de- duced and one feed was omitted. 1). Phases 1. This was accompanied by a significant staged as per modified Bell’s classification reduction in duration of antibiotic therapy and IV [21]. and sustainability of ETEF by assessing the day of The data were entered in Excel datasheet. Prefeed aspirates were ordered if the AG increased by >2 cm. IV fluid therapy and hospital stay.or blood-stained ing the 6 month periods of consecutive years 2010– vomiting 2012.0001). ives included all-cause mortality. Abdominal wall erythema or tenderness subjects during the three phases were comparable e. Clinical sepsis: Clinical signs and symptoms week. NEC was suspected in infants with abdom.5% in Phase 3. A ‘p’ value of <0. Any episode of bile. With ETEF. College station. sion 11. screen Abdominal x-ray and ultrasound were done to look 5. AG increase >2 cm (measured at umbil. Culture-proven sepsis: Blood culture-proven for evidence of NEC in suspected cases. ETEF was associated with a marked decrease in inci- dence of both clinical and culture-proven sepsis 3. lysed by ‘t’ test and non-normally distributed data by Wilcoxon rank sum test (Mann–Whitney). Texas. then the feed was reintro. with an earlier regain of birth weight (p ¼ 0. (92 and 44% in Phase 1 to 23 and 3. Definitions Categorical data were analysed using v2 test or 1. Feed intolerance: presence of one or more test.

1 32.50 Antenatal steroids course# 48 (66%) 42 (72%) 66 (82%) 0.5 6 0.15 APGAR score§ 7 (6–8) 7 (7–7) 8 (7–8) 0.2 6 2.38 Small for gestational age# 27 (37%) 18 (35%) 33 (40%) 0.3 0. Trial flow of study. Table 1.30 Birth weight (grams)* 12436192 1341 6 182 1252 6 220 0. #Number (%).79 Note: *Mean (95% confidence interval). 1.50 Registration status in antenatal clinic—booked# 59 (77%) 43 (84%) 73 (87%) 0. .078 Male sex# 41 (56%) 21 (42%) 46 (55%) 0.561.78 32. Baseline characteristics of study subjects Parameter Phase 1 (N ¼ 73) Phase 2 (N ¼ 51) Phase 3 (N ¼ 84) p value Gestation (weeks)* 31.4  Early Total Enteral Feeding in VLBW Neonates Fig. §Median (interquartile range).

4%. 12. setting. nates at 24 months corrected age [22]. All-cause mortality remained comparable be.476 1.0001 Duration of IV therapy*(days) 12.8 0.446 6.52 vs. ment of feeds had a significantly higher rate of sepsis ated with a poorer mental outcome in preterm neo.7%. The p < 0.04 0.365.0001 Duration of antibiotic therapy* (days) 11.0 vs.2 1. shorter duration of hospital stay and no increased risk of NEC. ETEF was also associated plications. In the present study. compared with centres with rapid feed advancement. without significant gastrointestinal or infectious com.28 Incidence of NEC# 10 (14.2%) 0.5%) 0. this study included babies be- DISCUSSION tween 1200 and 1500 g with a much smaller sample This study strongly suggests the nutritional and size. p ¼ 0.0001 Incidence of culture-proven sepsis# 32 (44%) 6 (12%) 3 (3.266.4 vs.001) and antibiotics (92. Early Total Enteral Feeding in VLBW Neonates  5 Table 2. longed IV antibiotics and cannulations. 77. [26] also concluded that full feeds and faster regaining of birth weight.8 0. These results are congruous with pilot study promotion of mucosal immunity by gut-associated . In a which was particularly evident for late-onset sepsis Cochrane meta-analysis of nine studies assessing the (14.166. birth weight and duration of hospital stay were sig. Outcome parameters Parameter Phase 1 (N ¼ 73) Phase 2 (N ¼ 51) Phase 3 (N ¼ 84) p value Day of full feed achievement* (days) 14. [24]. birth weight earlier (5. thereby limiting the need for pro- benefits of total enteral feeding outweighing the un.0466.0005 Duration of hospital stay*(days) 28. In Sanghvi’s study.1%.560. 20. The results of this study when taken to. especially in a from Day 1 of life in stable preterm VLBW infants resource-poor set-up.4765.165. The possible mechanisms NEC decreased significantly along with significantly involved include prevention of gastrointestinal atro- shorter duration of hospital stay decreasing parental phy. by Sanghvi et al. it suggests ETEF as being a re- growth benefits of total enteral feeding introduced sourceful and relatively safe practice. The proven risks of NEC in stable VLBW infants.002). the incidence of risk of nosocomial sepsis.8 4.976 4. the hypoglycaemia were recorded in any of the three group started on full enteral feeds on Day 1 regained phases.4 0. [25] found that Feeding intolerance and increased length of time VLBW infants born in centres with slow advance- to reach full enteral feedings are significantly associ. However. the weighted mean difference was lower p < 0. observational study of Hartel et al.001) was seen in centres with slow advance- results of our study also show faster achievement of ment. full feeds.564. with a significant reduction in both clinical and cul- gether with other recent works suggest the potential ture-proven sepsis. 31. Nonetheless.6 14.7 6.0006 Incidence of feed intolerance# 16 (22%) 7 (14%) 12 (14%) 0.2 8.0001 Day of regaining birth weight* (days) 16.9 5.22 15. by 2. No episodes of feeding on Day 1 of life. Flidel-Rimon et al. prevention of alteration in gut flora and associ- concern and economic burden in a resource-limited ated overgrowth of enteropathogenic species.18 Note: *Mean 6 SD.55 days in the trophic feeding group [23].164. which initiated full enteral nificantly lower post-intervention. Furthermore.76 19.467.5 12.6 vs. early enteral feeding was associated with a reduced Despite introduction of full feeds.4763. #Number (%).1 2.2%) 2 (4%) 0 0. higher role of trophic feeding on number of days to reach usage of central venous lines (48.028 Incidence of clinical sepsis# 67 (92%) 24 (47%) 19 (23%) 0.0005 Mortality# 3 (4%) 1 (2%) 1 (1.7 days) with a tween the three study periods (Table 2).2 0.366.

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