Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants Does the Enteral Feeding Advancement Affect Short-term Outcomes in Very Low Birth Weight Infants? Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. ADEPT - Abnormal Doppler Enteral Prescription Trial Early enteral feeding and nosocomial sepsis in very low birthweight infants
Background : Most preterm infants who develop necrotising enterocolitis ( NEC )  have received enteral feeds . Uncertainty exists about which aspects of the feeding regimen affect the risk of NEC . Aim : To examine associations between various enteral feeding practice s and the development of  NEC  in preterm infants . Methods : Multicentre case – control study . 53 preterm infants with NEC were enrolled together with a gestational age frequency-matched control without NEC from a r and omly selected neonatal unit . Clinical and feeding data were extracted and compared between the groups . Results : Significantly fewer cases than controls had received human breast milk ( 75 % vs 91 % ; OR 0.32 , 95 % CI 0.11 to 0.98 ) . The day on which enteral feeding was started did not differ significantly ( mean ( SD ) days after birth : cases 2.9 ( 2.8 ) and controls 2.8 ( 1.8 ) ) . The mean ( SD ) duration of trophic feeding ( < 1 ml/kg/h ) was significantly shorter in the cases ( 3.3 ( 3.1 ) days ) than controls ( 6.2 ( 6.7 ) days ) ( mean difference ( MD ) −2.9 , 95 % CI −4.9 to −0.9 ) days . Cases were fully fed significantly earlier than controls ( mean ( SD ) days after birth : cases 9.9 ( 4.2 ) and controls 14.3 ( 9.8 ) ; MD −4.4 , 95 % CI −7.3 to −1.5 ) . Conclusions : These data suggest that the duration of trophic feeding and rate of advancement of feed volumes may be modifiable risk factors for NEC in preterm infants . Further r and omised controlled trials are warranted to assess the effect of different rates of feed advancement on the incidence of NEC , as well as other outcomes AIMS To improve energy intake in sick very low birthweight ( VLBW ) infants ; to decrease growth problems , lessen pulmonary morbidity , shorten hospital stay , and avoid possible feeding related morbidity . Morbidity in VLBW infants thought to be associated with parenteral and enteral feeding includes bronchopulmonary dysplasia , necrotising enterocolitis , septicaemia , cholestasis and osteopenia of prematurity . METHODS A prospect i ve r and omised controlled trial ( RCT ) comparing two types of nutritional intervention was performed involving 125 sick VLBW infants in the setting of a regional neonatal intensive care unit . Babies were r and omly allocated to either an aggressive nutritional regimen ( group A ) or a control group ( group B ) . Babies in group B received a conservative nutritional regimen while group A received a package of more aggressive parenteral and enteral nutrition . Statistical analysis was done using Student’st test , the Mann-Whitney U test , the χ2 test and logistic regression . RESULTS There was an excess of sicker babies in group A , as measured by initial disease severity ( P < 0.01 ) , but mean total energy intakes were significantly higher ( P < 0.001 ) in group A at days 3 to 42 while receiving total or partial parenteral nutrition . Survival and the incidences of bronchopulmonary dysplasia , septicaemia , cholestasis , osteopenia and necrotising enterocolitis were similar in both groups . Growth in early life and at discharge from hospital was significantly better in babies in group A. There were no decreases in pulmonary morbidity or hospital stay . CONCLUSION Nutritional intake in sick VLBW infants can be improved without increasing the risk of adverse clinical or metabolic sequelae . Improved nutritional intake result ed in better growth , both in the early neonatal period and at hospital discharge , but did not decrease pulmonary morbidity or shorten hospital stay Background and Objectives : Controversy exists regarding the optimal enteral feeding regimen of very low birth weight infants ( VLBW ) . Rapid advancement of enteral feeding has been associated with an increased rate of necrotizing enterocolitis . In contrast , delaying enteral feeding may have unfavorable effects on nutrition , growth , and neurodevelopment . The aim is to compare the short-term outcomes of VLBW infants in tertiary care centers according to their enteral feeding advancement . Patients and Methods : We prospect ively studied the influence of center-specific enteral feeding advancement in 1430 VLBW infants recruited from 13 tertiary neonatal intensive care units in Germany on short-term outcome parameters . The centers were post hoc stratified to “ rapid advancement to full enteral feeds ” ( median duration of advancement to full enteral feeds ≤12.5 days ; 6 centers ) , that is , rapid advancement ( RA ) , or “ slow advancement to full enteral feeds ” ( median duration of advancement to full enteral feeds > 12.5 days ; 7 centers ) , that is , slow advancement ( SA ) . Results : VLBW infants born in centers with SA ( n = 713 ) had a significantly higher rate of sepsis compared with VLBW infants born in centers with RA ( n = 717 ) , which was particularly evident for late-onset sepsis ( 14.0 % vs 20.4 % ; P = 0.002 ) . Furthermore , more central venous lines ( 48.6 % vs 31.1 % , P < 0.001 ) and antibiotics ( 92.4 % vs 77.7 % , P < 0.001 ) were used in centers with SA . Conclusions : Center differences in enteral feeding advancement occur and may have a significant impact on short-term outcomes such as nosocomial sepsis . Large , multicenter , prospect i ve trials are required to further eluci date the optimal feeding strategy for VLBW infants OBJECTIVE To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750 - 1250 g birth weight . STUDY DESIGN A total of 92 stable neonates 750 - 1250 g and gestational age < 32 weeks were r and omly allocated to enteral feeding advancement of 20 mL/kg/d ( n = 46 ) or 30 mL/kg/d ( n = 46 ) . The primary outcome was days to reach full enteral feeding , defined as 180 mL/kg/d . Secondary outcomes included rates of necrotizing enterocolitis ( NEC ) and culture-proven sepsis , days of parenteral nutrition ( PN ) , length of hospital stay , and growth end points . RESULTS Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group . They received significantly fewer days of PN , exhibited a shorter time to regain birth weight , and had a shorter duration of hospital stay . The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups , whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement . Excluding infants who were small for gestational age at birth , the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge . CONCLUSION Rapid enteral feeding advancements in 750 - 1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration . Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants Background Pregnancies complicated by abnormal umbilical artery Doppler blood flow patterns often result in the baby being born both preterm and growth-restricted . These babies are at high risk of milk intolerance and necrotising enterocolitis , as well as post-natal growth failure , and there is no clinical consensus about how best to feed them . Policies of both early milk feeding and late milk feeding are widely used . This r and omised controlled trial aims to determine whether a policy of early initiation of milk feeds is beneficial compared with late initiation . Optimising neonatal feeding for this group of babies may have long-term health implication s and if either of these policies is shown to be beneficial it can be immediately adopted into clinical practice . Methods and Design Babies with gestational age below 35 weeks , and with birth weight below 10th centile for gestational age , will be r and omly allocated to an " early " or " late " enteral feeding regimen , commencing milk feeds on day 2 and day 6 after birth , respectively . Feeds will be gradually increased over 9 - 13 days ( depending on gestational age ) using a schedule derived from those used in hospitals in the Eastern and South Western Regions of Engl and , based on surveys of feeding practice . Primary outcome measures are time to establish full enteral feeding and necrotising enterocolitis ; secondary outcomes include sepsis and growth .  The target sample size is 400 babies . This sample size is large enough to detect a clinical ly meaningful difference of 3 days in time to establish full enteral feeds between the two feeding policies , with 90 % power and a 5 % 2-sided significance level . Initial recruitment period was 24 months , subsequently extended to 38 months . Discussion There is limited evidence from r and omised controlled trials on which to base decisions regarding feeding policy in high risk preterm infants . This multicentre trial will help to guide clinical practice and may also provide pointers for future research .Trial registration Current Controlled Trials IS RCT N : Background : The interrelations between early enteral feeding , necrotising enterocolitis ( NEC ) , and nosocomial sepsis ( NS ) remain unclear . Objective : To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight ( VLBW < 1500 g ) infants . Methods : Data were collected on the pattern of enteral feeding  and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995–2001 .  Enteral feeding was compared between infants with and without NS and /or NEC . Results : The study sample included 385 infants . Of these , 163 ( 42 % ) developed NS and 35 ( 9 % ) developed NEC .  Enteral feeding was started at a significantly earlier mean ( SD ) age in infants who did not develop nosocomial sepsis ( 2.8 ( 2.6 ) v 4.8 ( 3.7 ) days , p = 0.0001 ) . Enteral feeding was introduced at the same age in babies who did or did not develop NEC ( 3.1 ( 2 ) v 3.7 ( 3 ) days , p = 0.28 ) . Over the study period , the mean annual age at the start of enteral feeding fell consistently , and this correlated with the mean annual incidence of NS ( r2 = 0.891 , p = 0.007 ) . Multiple logistic regression analysis showed age at start of enteral feeding , respiratory distress syndrome , and birth weight to be the most significant predictors of risk of NS ( p = 0.0005 , p = 0.024 , p = 0.011 ) . Conclusions : Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC  in VLBW infants . These findings support the use of early enteral feeding in this high risk population , but this needs to be confirmed in a large r and omised controlled trial
The available trial data suggest that advancing enteral feed volumes at daily increments of 30 ml/kg to 35 ml/kg does not increase the risk of necrotising enterocolitis in very preterm or VLBW infants .
Advancing the volume of enteral feeds at slow rates result ed in several days delay in regaining birth weight and establishing full enteral feeds .
The applicability of these findings to extremely preterm , extremely low birth weight , or growth-restricted infants is limited .
BACKGROUND Early enteral feeding practice s are potentially modifiable risk factors for necrotising enterocolitis  in very preterm or very low birth weight ( VLBW ) infants .
Observational studies suggest that conservative feeding regimens , including slowly advancing enteral feed volumes , reduce the risk of necrotising enterocolitis .
However , slow feed advancement may delay establishment of full enteral feeding and be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition .
OBJECTIVES To determine the effect of slow rates of enteral feed advancement on the incidence of necrotising enterocolitis , mortality , and other morbidities in very preterm or VLBW infants .