Enteral Feeding Volume Research Articles

Clinical Outcomes of Surgical Treatment of Hypertrophic Pyloric Stenosis 
 with Application of Various Operational Access

Introduction. Treatment options of congenital hypertrophic pyloric stenosis (HPS) appear to be an acute issue nowadays due to the fact that this pathology is often detected in children of the first year of life - according to statistics, the incidence rate of congenital hypertrophic pyloric stenosis in children is 3:1000 live newborns. Since there are various treatment options of the given congenital pathology, there is no general consensus in the opinions of surgeons regarding the superiority of different treatment methods. Therefore, it is necessary to search for a single most relevant treatment technique for this pathology.The aim of the study was to analyze clinical outcomes for treatment of congenital hypertrophic pyloric stenosis in children with application of various surgical techniques: open pylorotomy (transverse, circumbilical incision) and laparoscopic pylorotomy.Materials and methods. The study included 67 patients, who received treatment in Kursk Regional Pediatric Hospital №2 in 2014-2018. Patients with congenital HPS were divided into 3 groups, depending on the performed surgical interventions. Group 1 included patients who underwent an open pylorotomy with transverse access, group 2 included patients who underwent an open pylorotomy with circumbilical access, and group 3 included patients who underwent laparoscopic pylorotomy. The following parameters were used to assess the efficiency of the treatment performed: the duration of the operative intervention, the duration of stay of a child in the ICU, the duration of stay of a child in the hospital, extubation time, initiation of enteral feeding, recovery rate of enteral feeding volume. The data were statistically performed using the Mann-Whitney test to determine the significance of differences between the mean values (p0.05).Results. The study results demonstrated that the shortest duration of operational intervention was observed in patients of group 3, it constituted 41,4 3,5 minutes. In addition, patients of this group spent the shortest average time in the ICU - 4,2 0,3 days - and in the hospital in general - 12,1 0,8 days; initiation of enteral feeding in patients of this group was registered in 10,8 1,2 hours and the recovery rate of enteral feeding volume was 4,8 0,5 days.Conclusions. Having analyzed clinical outcomes for treatment of pilorostenosis in the studied groups of children, it is possible to conclude that laparoscopic pyloromyotomy is preferred to open surgical interventions not only for reasons of cosmetic result, but also according to the criteria of the postoperative course of the disease in patients.

Can Use of Cerebral Oxygenation Predict Developmental Outcomes in Preterm Infants With NEC?

* Abbreviations: NEC — : necrotizing enterocolitis NIRS — : near-infrared spectroscopy In this issue of Pediatrics, Howarth et al1 report on a completed longitudinal study of 46 preterm infants born at <30 weeks’ gestational age in which they recorded cerebral oxygenation using near-infrared spectroscopy (NIRS) for 1 hour per week until hospital discharge or transfer. The 6 infants who developed necrotizing enterocolitis (NEC) had consistently lower levels of cerebral oxygenation (mean −6.6%) and small increases in cerebral fractional tissue oxygen extraction (mean 0.08) throughout the study. Using multilevel mixed-effects linear models nested within each infant, the authors adjusted for a large number of confounding variables, including patent ductus arteriosus, sex, ethnicity, volume of enteral feeding, hemoglobin, and gestational age. Although the small number of infants who developed NEC limited the study, the study provides preliminary evidence that lowered cerebral oxygenation may underpin the worse neurodevelopmental outcomes that have been reported in preterm infants with NEC.2–4 Worldwide, >15 million infants are born preterm (<37 weeks’ gestation) each year, and these rates are increasing. Improvements in the care of these infants have dramatically improved survival. However, contrary to expectations, recent data, in which outcomes in … Address correspondence to Rosemary S.C. Horne, PhD, DSc, Department of Paediatrics, Level 5, Monash Children’s Hospital, 246 Clayton Rd, Melbourne, VIC 3168, Australia. E-mail: rosemary.horne{at}monash.edu

Early fortification of human milk versus late fortification to promote growth in preterm infants.

Uncertainty exists about the optimal point at which multi-component fortifier should be added to human milk for promoting growth in preterm infants. The most common practice is to start fortification when the infant's daily enteral feed volume reaches 100 mL/kg body weight. Another approach is to commence fortification earlier, in some cases as early as the first enteral feed. Early fortification of human milk could increase nutrient intake and growth rates but may increase the risk of feed intolerance and necrotising enterocolitis (NEC). To assess effects on growth and safety of early fortification of human milk versus late fortification in preterm infants To assess whether effects vary based upon gestational age (≤ 27 weeks; 28 to 31 weeks; ≥ 32 weeks), birth weight (< 1000 g; 1000 to 1499 g; ≥ 1500 g), small or appropriate for gestational age, or type of fortifier (bovine milk-based human milk fortifier (HMF); human milk-based HMF; formula powder) SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8); OVID MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions (R) (1946 to 15 August 2019); MEDLINE via PubMed (1 August 2018 to 15 August 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL) (1981 to 15 August 2019). We searched clinical trials databases and reference lists of included studies. We included randomised controlled trials that compared early versus late fortification of human milk in preterm infants. We defined early fortification as fortification started at < 100 mL/kg/d enteral feed volume or < 7 days postnatal age, and late fortification as fortification started at ≥ 100 mL/kg/d feeds or ≥ 7 days postnatal age. Both review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials, and we reported risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. We included two trials with a total of 237 infants. All participants were very low birth weight infants (birth weight < 1500 g). Early fortification was started at 20 mL/kg/d enteral feeds in one study and 40 mL/kg/d in the other study. Late fortification was started at 100 mL/kg/d feeds in both studies. One study used bovine milk-based fortifier, and the other used human milk-based fortifier. Meta-analysis showed that early fortification may have little or no effect on growth outcomes including time to regain birth weight (MD -0.06 days, 95% CI -1.32 to 1.20 days), linear growth (MD 0.10 cm/week, 95% CI -0.03 to 0.22 cm/week), or head growth (MD -0.01 cm/week, 95% CI -0.07 to 0.06 cm/week) during the initial hospitalisation period. Early fortification may have little or no effect on the risk of NEC (MD -0.01, 95% CI -0.07 to 0.06). The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). Early fortification may have little or no effect on incidence of surgical NEC, time to reach full enteral feeds, extrauterine growth restriction at discharge, proportion of infants with feed interruption episodes, duration of total parenteral nutrition (TPN), duration of central venous line usage, or incidence of invasive infection, all-cause mortality, and duration of hospital stay. The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). We did not have data for other outcomes such as subsequent weight gain after birth weight is regained, parenteral nutrition-associated liver disease, postdischarge growth, and neurodevelopmental outcomes. Available evidence is insufficient to support or refute early fortification of human milk in preterm infants. Further large trials would be needed to provide data of sufficient quality and precision to inform policy and practice.

FEEding DURing red cell transfusion (FEEDUR RCT): a multi-arm randomised controlled trial

BackgroundNecrotising Enterocolitis (NEC) is a devastating neonatal disease. A temporal association between red cell transfusion and NEC has been recognized and there have been concerns about the effects of feeding during transfusion. We aimed to assess the effect of different enteral feeding regimens on splanchnic oxygenation in preterm infants receiving red cell transfusions.MethodsThis was an open, multi-arm, parallel-group, randomised controlled trial conducted in a single centre in Australia. We compared three different enteral feeding regimes during a single red cell transfusion in preterm infants < 35 weeks gestational age at birth. Infants were randomised to either: (1) Withholding enteral feeds for 12 h from the start of transfusion or; (2) Continuing enteral feeds or; (3) Restriction of enteral feed volume to 120 ml/kg/day (maximum 20 kcal/30 ml) for 12 h. The primary outcome was mean splanchnic-cerebral oxygenation ratio (SCOR) and mean splanchnic fractional oxygen extraction (FOE) before (1 h prior), during (1 h into transfusion) and after (end of transfusion; 12 and 24 h post) transfusion.ResultsThere were 60 transfusion episodes (20 transfusion episodes in each group) included in the analysis. 41 infants with a median gestational age at birth of 27 weeks (range 23–32 weeks) were enrolled. The median postnatal age was 43 days (range 19–94 days) and the median pre-transfusion haematocrit was 0.27 (range 0.22–0.32). All three groups were similar at baseline. There were no differences in mean SCOR and mean splanchnic FOE at any of the pre-specified time points. There were also no differences in clinical outcomes. There were no episodes of NEC in any infant. Across all groups the mean SCOR increased from the start to the end of each transfusion (0.97 [CI95% 0.96–0.98] vs 1.00 [CI95% 0.99–1.01]; p = 0.04) and the mean FOE decreased from the start to the end of each transfusion (0.22 [CI95% 0.21–0.23] vs 0.17 [CI95% 0.16–0.18]; p < 0.001).ConclusionsThere were no differences in splanchnic oxygenation when enteral feeds were either withheld, continued or restricted during a transfusion. However, the successful conduct of this study supports the feasibility of a large trial powered to assess clinical outcomes.Trial registrationANZCTR, ACTRN12616000160437. Registered 10 February 2016, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370069

Early fortification of enteral feedings for infants

BACKGROUND:An exclusive human milk diet (EHM) including fortification with a human milk-based fortifier has been shown to decrease the occurrence of necrotizing enterocolitis (NEC) but growth velocity may be less for infants receiving EHM compared to a bovine diet.OBJECTIVE:The objective of this study was to determine if growth is improved by earlier fortification of breast milk for preterm infants supported with a human milk based fortifier.STUDY DESIGN:A multi-center retrospective cohort study of the outcomes of infants of 500– 1250 g birth weight whose breast milk feedings were fortified at >60 mL/kg/day (late) versus <60 mL/kg/day (early) of enteral feeding volume.RESULTS:Median±IQR range for gestational age (27.6±3.4 vs 27.0±2.9 weeks, p = 0.03) and chronic lung disease (CLD: 42.6 vs 27.6%, p = 0.008) were higher, and weight gain (12.9±2.6 vs 13.3±2.6 g/kg/day, p = 0.03) was lower in the late (N = 102) vs the early (N = 292) group. Adjusted multiple linear regression analysis found that early fortification was associated with improved growth velocity for weight (p = 0.007) and head circumference (HC) (p = 0.021) and less negative changes in z-scores for weight (p = 0.022) and HC (p = 0.046) from birth to discharge. Adjusted multiple logistic regression found that early fortification was associated with decreased occurrence of CLD (p = 0.004). No other outcomes, including NEC, were associated with early versus late fortification.CONCLUSION:The study results suggested that early HM fortification appears to positively affect growth for infants whose human milk feedings are fortified with a human milk based fortifier without adverse effects. The incidence of CLD was also reduced in the early fortification group.

Effect of 100% human milk-derived fortifier on growth of premature infants with birth weight of 1000–1500 g

Background: Preterm birth has the highest risk of perinatal morbidity and mortality. Nutrition plays a key role in the growth and development of a preterm infant. Fortification of expressed breast milk is followed to provide an optimal nutrition and a faster catch up growth. The new 100% human milk-derived fortifier (HMDF) can help in providing a safe nutritional option for a premature infant. Objective: The objective of the study was to assess the feed tolerance and impact of a new 100% HMDF on growth outcomes of preterm infants. Materials and Methods: In a single-center study, exclusively human milk-fed preterm infants (1000–1500 g birth weight) were chosen to receive human milk fortified with a new 100% HMDF. The fortifier was initiated when the enteral feed volume reached 100 ml/kg/day and was administered until discharge. The primary outcome of the study was to assess feed tolerance and the secondary endpoints included growth parameters. Results: The cohort study comprised 13 infants with a mean gestational age of 31.64±2.2 weeks and birth weight of 1314.62±110.1 g. During the study period, feed interruptions were nil and none of the infants showed any adverse events of clinical significance. Growth outcomes recorded at the end of the study period showed a mean weight gain of 25.97±7.7 g/day, mean length gain of 0.32±0.23 cm/week, and mean head circumference gain of 0.39±0.20 cm/week. The mean weight growth velocity of the infants was 18.37±5.1 g/kg/day. Conclusion: Preterm infants who received a new 100% HMDF demonstrated feed tolerance and weight gain without any clinically significant record of adverse events. The findings indicate that the new HMDF is a safe option for providing an exclusive human milk-based diet. However, a study with a larger study population may be required to reinforce the findings of this study.

The Influence of Donor Milk Supplementation on Duration of Parenteral Nutrition in Preterm Infants.

Data are limited on the association between the use of donor human milk and improvements in feeding tolerance. To determine the influence of the duration of parenteral nutrition on the growth and morbidity of the breastfed newborn when using donated human milk in the absence of mother's own milk. We conducted a retrospective study before and after the intervention that compared two groups of newborns (N = 284; each group n = 142). We used a convenience sample of all newborns ≤32 weeks gestation consecutively admitted in a single unit before (Group 1 between December 2012 and May 2014) or after (Group 2 between October 2014 and December 2016) the availability of donor human milk. In Group 2, donor human milk was administered at least 3 to 4 weeks or until the baby weighed 1,500 g. Weight was recorded daily and length and head circumference weekly. Parenteral nutrition was continued until enteral feeding volume reached 120 ml/kg/day. Additional variables measured were the number of days with a central venous catheter, age that the enteral feeding volume reached 150 ml/kg/day, and duration of stay. The duration of parenteral feeding was the same before and after: 12 (8.23) and 11 (7.19) days (p = .822). The z scores for weight and height of newborns was lower in Group 2 = -1.8 (1.0) and -2.3 (1.1) and Group 1 = -1.2 (1.1) (p < .001) and -1.8 (1.4) (p = .005). We did not find an association between the administration of donor human milk as a supplement to mother's own milk and reduced number of days of parenteral nutrition. Back translation by Laurence Grummer-Strawn.

Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants

BackgroundObservational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited.MethodsWe randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy.ResultsAmong 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P=0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16).ConclusionsThere was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.)

For preterm or very low birth weight infants, how does slow advancement compare with fast advancement of enteral feed volumes in improving outcomes?

For preterm or very low birth weight infants, how does slow advancement compare with fast advancement of enteral feed volumes in improving outcomes?

Gastric Residual Volume Measurement in U.K. PICUs: A Survey of Practice*

Despite little evidence, the practice of routine measurement of gastric residual volume to guide both the initiation and delivery of enteral feeding in PICUs is widespread internationally. In light of increased scrutiny of the evidence surrounding this practice, and as part of a trial feasibility study, we aimed to determine enteral feeding and gastric residual volume measurement practices in U.K. PICUs. An online survey to 27 U.K. PICUs. U.K. PICUs. A clinical nurse, senior doctor, and dietician were invited to collaboratively complete one survey per PICU and send a copy of their unit guidelines on enteral feeding and gastric residual volume. None. Twenty-four of 27 units (89%) approached completed the survey. Twenty-three units (95.8%; 23/24) had written feeding guidelines, and 19 units (19/23; 83%) sent their guidelines for review. More units fed continuously (15/24; 62%) than intermittently (9/24; 37%) via the gastric route as their primary feeding method. All but one PICU routinely measured gastric residual volume, regardless of the method of feeding. Eighteen units had an agreed definition of feed tolerance, and all these included gastric residual volume. Gastric residual volume thresholds for feed tolerance were either volume based (mL/kg body weight) (11/21; 52%) or a percentage of the volume of feed administered (6/21; 29%). Yet only a third of units provided guidance about the technique of gastric residual volume measurement. Routine gastric residual volume measurement is part of standard practice in U.K. PICUs, with little guidance provided about the technique which may impact the accuracy of gastric residual volume. All PICUs that defined feed tolerance included gastric residual volume in the definition. This is important to know when proposing a standard practice arm of any future trial of no-routine gastric residual volume measurement in critically ill children.

Individualized Human Milk Fortification to Improve the Growth of Hospitalized Preterm Infants

Human milk (HM) is the first choice for preterm infants, but exclusive HM feeding is inadequate for the growth of very preterm infants. The hypothesis of this trial is that infants fed according to an individualized fortification regimen will have higher protein intake and improved weight gain velocity (WGV). A prospective, randomized, controlled study was conducted. Infants <34 weeks of gestational age were enrolled when enteral feeding volume reached 60 mL/kg/d and were randomly allocated to the individualized fortification (IF) group or the standard fortification group. The IF group was fed using a regimen that featured modifying HM fortifier and supplemental protein powder based on the protein concentration in HM, current body weight of infants, and blood urea nitrogen (fortification level was set as L-1, L0, L1, L2, L3; the amount of HM fortifier and protein powder were determined accordingly). Between September 2012 and August 2016, 51 preterm infants completed the study. In the IF group, 62.5% (15/24) of preterm infants were fed with HM fortified to level 1, 29.2% (7/24) to level 2, and 12.5% (3/24) to level 3. The WGV of the third week in the IF group was greater than the standard group (20.8 ± 7.9 vs 14.9 ± 4.5 g/kg/d, P = 0.022). About two-thirds of preterm infants needed to adjust the HM fortification to a higher level. The WGV of infants in the IF group was better than that of the standard group in the third week of this study.

Effect of Early Parenteral Nutrition Discontinuation on Time to Regain Birth Weight in Very Low Birth Weight Infants: A Randomized Controlled Trial.

Peripherally inserted central catheters (PICCs) are used to administer parenteral nutrition (PN) in very low birth weight infants (VLBW; <1500 g). Clinicians try to optimize early nutrition but also minimize the risks associated with intravascular devices. The objective of this study was to examine the early nutrition impact of discontinuing PN at different enteral feed volumes in VLBW infants. In this unmasked, multicenter, randomized controlled trial, patients were randomly assigned to PICC removal and PN discontinuation at an enteral feed volume of 100mL/kg/day (intervention) or 140mL/kg/day (control). Clinically stable VLBW infants with a PICC in situ who were receiving PN were eligible for inclusion. Infants with major congenital anomalies were excluded. A total of 139 patients were enrolled; 69 and 70 patients were randomized to the intervention and control groups, respectively. The primary outcome measure was the mean difference in time (days) to regain birth weight. The groups were well matched at study entry. Patients in the intervention group regained birth weight more slowly (mean difference 1.5 days CI: 0.3-2.7 days, P = 0.01). The mean difference in time to regain birth weight for infants <1000g was 2.8 days (95% CI: 0.8-4.8 days, P = 0.008). In VLBW infants, early PICC removal at an enteral feed volume of 100mL/kg/day compared with later removal at 140mL/kg/day resulted in a significant delay in time to regain birth weight, and this delay was more pronounced in infants <1000 g.

Commencing Nutrient Supplements before Full Enteral Feed Volume Achievement Is Beneficial for Moderately Preterm to Late Preterm Low Birth Weight Babies: A Prospective, Observational Study

The aim of this study was to observe after following a routine change in the feeding protocol whether the earlier introduction of nutrient supplements improved nutritional outcomes in moderately preterm to late preterm low birth weight (LBW) babies. In this prospective observational study, LBW babies between 31 and 39 weeks’ gestation admitted to a Special Care Nursery were assigned to two groups (F80, n = 45, F160, n = 42) upon commencing nutrient supplement at total fluid intake achievement of 80 or 160 mL/kg/day. Outcomes included weight, protein intake, biochemical markers, feeding intolerance, and length of stay (LOS). F80 nutrient supplements commenced before F160 (2.8 vs. 6.7 days, p < 0.0001) and lasted longer (15.2 vs. 12.2 days, p < 0.03). Weight gain velocity and LOS were similar. F80 mean protein intake during the first 10 days was higher (3.38 vs. 2.74 g/kg/day, p < 0.0001). There were fewer infants with protein intake <3 g/kg/day in the F80 group (8% vs. 65%, p < 0001). F80 babies regained birthweight almost two days earlier (7.5 vs. 9.4 days, p < 0.01). Weight gain Z-scores revealed an attenuation of the trend towards lower weight percentiles in the F80 group. Feeding intolerance was decreased for F80 (24.4% vs. 47.6%, p < 0.03). There were no adverse outcomes. Earlier nutrient supplementation for LBW babies lifts mean protein intake to above 3 g/kg/day and reduces both the duration of post-birth weight loss and incidence of feeding intolerance.

The Relationship Between Early Weight Z-Score Changes and Nutritional Differences in Very Low Birth Weight Infants During Hospital Stay

Background: Advances in neonatal care have resulted in improved survival for very low birth weight infants (VLBWIs). However, the main factors that lead to early weight Z-score [standard deviation score (SDS)] changes during hospital stay in VLBWIs still need to be studied more. Objectives: In this study we aimed to investigate the differences in specific factors that relate to VLBWIs’ early weight Z-score changes as the scientific basis for clinical practice of VLBWIs during the entire hospital stay. Methods: We retrospectively reviewed baseline characteristics, nutrition management, clinical outcomes, and complications between non-catch-down (NCD) (Δ weight SDS ≥ -0.67) and catch-down (CD) groups (Δ weight SDS < -0.67) in VLBWIs during hospital stay. Results: A total of 227 infants (NCD group = 117, CD group = 110) met the inclusion criteria. No significant differences were found in baseline characteristics between the two groups. The NCD group received higher parenteral lipids (g/kg/d) from day 5 to day 7 and higher enteral feeding volume (mL/kg/d) from day 5 to week 5. The NCD group had higher protein:energy ratios at day 2 to day 4 and day 7 and higher total energy (kcal/kg/d) during the first six weeks. The NCD group had lower incidence of bronchopulmonary dysplasia (BPD) and parenteral nutrition-associated cholestasis (PNAC). Conclusions: This study showed that adequate parenteral lipid and energy at the first week of life and earlier enhanced enteral feeding volume might significantly improve the VLBWIs’ weight Z-scores during hospital stay. The VLBWIs with catch-down growth might be more prone to developing BPD and PNAC.

Growth and neurodevelopment in very preterm infants receiving a high enteral volume-feeding regimen – a population-based cohort study

Aim: The aim of this study is to evaluate a feeding regimen routinely providing >180 ml/kg/d fortified human milk to very preterm infants and impact on in-hospital growth, osteopenia, and neurodevelopment.Method: Retrospective population-based descriptive study of infants <30-week gestation admitted within 24 h of birth and discharged during the 6-year period 2005–2010. Growth and neurodevelopment was assessed until 2 years corrected age, and cerebral palsy up to 4 years corrected ageResults: Ninety-nine infants below 30-week gestation were admitted within 24 h of birth during the 6-year period, of which 84 (85%) survived to discharge. Two infants had surgical necrotizing enterocolitis, both survived to 2 years follow up. Seventy-eight infants (mean 27 weeks) had complete growth data until discharge. Full enteral feeds were tolerated after mean 10 d. Average milk volumes were 193 ml/kg/d from 15 to 42 d of life. Rates of weight below 10th centile were 10% at birth and 14% at discharge. Head circumference Z-scores were stable from birth to discharge. Blood values did not indicate osteopenia. Increasing head circumference Z-scores were associated with improved language development.Conclusions: This high enteral feeding volume regimen was associated with low rates of in-hospital growth restriction and good head growth. High enteral volume intake seems safe and may improve nutritional status of very preterm infants.

A retrospective study on the effects of exclusive donor human milk feeding in a short period after birth on morbidity and growth of preterm infants during hospitalization.

The risks and benefits of feeding preterm formula (PF) versus donor human milk (DHM) in preterm infants are uncertain, and studies evaluating the efficacy of DHM to the morbidities and growth of preterm infants in the neonatal intensive care unit are confused by the need for milk fortification. We aimed to determine and compare the outcome of short-term morbidities in neonatal intensive care unit and growth between premature infants fed exclusively DHM only until a volume of 130 mL/kg/d of enteral feeding was achieved and infants fed with a PF mix after birth. The data of 132 infants with low birth weight of <1500 g and gestational age of less than 32 weeks were considered. Ninety infants were analyzed, of which 86 were discharged alive. The DHM group (n = 36) was made up of infants who were fed exclusively with DHM, whereas the PF group (n = 54) consisted of infants who were fed with a combination of PF and either DHM or human milk, until a volume of 130 mL/kg/d of enteral feeding was achieved. Once feeding in the DHM group progressed to volumes greater than 130 mL/kg/d, infants were fed fortified DHM and PF alternately. One infant (2.8%) in the DHM group had late-onset sepsis or necrotizing enterocolitis compared with 21 (38.9%) in the PF group (adjusted odds ratio 0.05, 95% confidence interval 0.01–0.41); 13 (36.1%) infants in the DHM group had bronchopulmonary dysplasia compared with 38 (70.4%) in the PF group (odds ratio 0.18, 95% confidence interval 0.05–0.41). Although the DHM group demonstrated a comparatively lower rate of weight gain, head circumference increment, and height increment from birth to the age at which an enteral feeding volume of 130 mL/kg/d was achieved, there were no significant differences in these values at 36 weeks’ postmenstrual age between both groups.

Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants.

Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) 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 NEC. However, slow feed advancement may delay establishment of full enteral feeding and may be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition. To determine effects of slow rates of enteral feed advancement on the incidence of NEC, mortality, and other morbidities in very preterm or VLBW infants. We used the standard Cochrane Neonatal search strategy to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to June 2017), Embase (1980 to June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2017). We searched clinical trials databases, conference proceedings, previous reviews, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes upon the incidence of NEC in very preterm or VLBW infants. Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model for meta-analyses and explored potential causes of heterogeneity via sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We identified 10 RCTs in which a total of 3753 infants participated (2804 infants participated in one large trial). Most participants were stable very preterm infants of birth weight appropriate for gestation. About one-third of all participants were extremely preterm or extremely low birth weight (ELBW), and about one-fifth were small for gestational age (SGA), growth-restricted, or compromised in utero, as indicated by absent or reversed end-diastolic flow velocity (AREDFV) in the fetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 20 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Trials generally were of good methodological quality, although none was blinded.Meta-analyses did not show effects on risk of NEC (typical RR 1.07, 95% CI 0.83 to 1.39; RD 0.0, 95% CI -0.01 to 0.02) or all-cause mortality (typical RR 1.15, 95% CI 0.93 to 1.42; typical RD 0.01, 95% CI -0.01 to 0.03). Subgroup analyses of extremely preterm or ELBW infants, or of SGA or growth-restricted or growth-compromised infants, showed no evidence of an effect on risk of NEC or death. Slow feed advancement delayed establishment of full enteral nutrition by between about one and five days. Meta-analysis showed borderline increased risk of invasive infection (typical RR 1.15, 95% CI 1.00 to 1.32; typical RD 0.03, 95% CI 0.00 to 0.05). The GRADE quality of evidence for primary outcomes was "moderate", downgraded from "high" because of lack of blinding in the included trials. Available trial data do not provide evidence that advancing enteral feed volumes at daily increments of 15 to 20 mL/kg (compared with 30 to 40 mL/kg) reduces the risk of NEC or death in very preterm or VLBW infants, extremely preterm or ELBW infants, SGA or growth-restricted infants, or infants with antenatal AREDFV. Advancing the volume of enteral feeds at a slow rate results in several days of delay in establishing full enteral feeds and may increase the risk of invasive infection.

Refeeding gastric residuals in extremely preterm infants.

Commentary on: Salas AA, Cuna A, Bhat R, McGwin G Jr, Carlo WA, Ambalavanan N. A randomised trial of refeeding gastric residuals in preterm infants. Arch Dis Child Fetal Neonatal Ed 2015; 100: F224–8. doi:10.1136/archdischild-2014-307067. Salas et al. 1 tackle a common clinical problem: what should you do when significant gastric contents are aspirated before feeding an extremely preterm infant? Gastric residuals could be an early sign of NEC and may call for caution on refeeding. On the other hand, discarding gastric residuals may impair digestion and delay full enteral feeds. There is no evidence to support either approach, especially in the high-risk (for both NEC and undernutrition) group of extremely preterm infants. Although Salas et al. 1 is to be congratulated for their attempt to resolve this issue, the most important drawback is that conclusions – regarding both efficacy and safety – suffer from some limitations. For the primary question ‘Does refeeding of gastric residuals reduce time needed to achieve full enteral feedings?’, the authors conclude that the answer is no. However, although intention-to-treat analysis was used, the primary efficacy end point was only possible to assess in 59 infants, as the estimated sample size (n = 72) was not reached. Therefore, there are two possibilities: either the study may have been underpowered (p = 0.11 for a group difference in primary outcome) or the results rightly disprove the hypothesis for an effect size of 2-day difference or more to achieve full feeds (whether this desired group difference was based on pilot data or represents a consensual view of what would be the minimal clinically significant difference is not known). Also, and as pointed out by the authors, numbers were too small to draw any firm conclusions about safety. Information on the volumes of gastric residuals was lacking, and such information would have helped interpretation. Finally, donor milk 2 was not offered, possibly contributing to quite high rates of intestinal perforation, surgical necrotising enterocolitis or death. So what should the clinician do? Previous studies in ELBW infants (<1000 g) have demonstrated that disregarding of gastric residuals up to 2–3 mL (even if they were greenish) did not increase the risk for NEC 3. Other than that, there seems to be very little evidence. Given the findings by Salas et al. 1, this reviewer agrees with the conclusion that refeeding gastric residual volumes in extremely preterm infants does not seem to reduce time to achieve full enteral feeding and is likely to be safe. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) suggest that minimal enteral nutrition is initiated within the first 2 days of life and advanced by 30 mL/kg/day in infants ≥1000 g 4. A recent systematic review of studies in VLBW infants (1000–1500 g) came to a similar conclusion: advancing enteral feed volumes at daily increments of 30–40 mL/kg did not increase the risk of NEC, whereas advancing the enteral feeds at slower rates resulted in several days delay in regaining birthweight and establishing full enteral feeds 5. For ELBW infants below 1000 g BW, recommendations are more scarce, most likely reflecting the lack of solid evidence. In Sweden, minimal enteral feeding with breastmilk is – right or wrong – initiated within hours after birth, also in extremely preterm infants. https://ebneo.org/2015/05/re-feeding-gastric-residuals-in-extremely-preterm-infants/ None. None.

Effect of Increased Enteral Protein Intake on Growth in Human Milk–Fed Preterm Infants

Protein, supplied in currently available commercial fortifiers, may be inadequate to meet the requirements of very preterm infants; in addition, intraindividual and interindividual variability of human milk protein and energy content potentially contribute to unsatisfactory early postnatal growth. To determine effects on growth of different levels of enteral protein supplementation in predominantly human milk-fed preterm infants. This randomized clinical and partially blinded single-center trial was conducted in a neonatal tertiary referral center in Germany. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2) weeks. All analyses were conducted in an intention-to-treat population. Infants were randomly assigned to either a lower-protein (adding 1 g of bovine protein/100 mL of breast milk through a commercial human milk fortifier; n = 30) or a higher-protein group at a median (IQR) postnatal age of 7 (6-8) days. The higher-protein group (n = 30) received either standardized higher-protein supplementation (study fortifier adding 1.8 g of bovine protein/100 mL of breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventions were continued for a median (IQR) of 41 (30-57) days and until definite discharge planning. Primary outcome was weight gain (g/kg/d) from birth to the end of intervention. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth), 33 girls, were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (IQR) gestational age at birth was 29.9 (28.7-31.2) weeks. Demographic characteristics and hospital courses were similar in both groups, and birth weights ranged from 580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein group. Weight gain was similar in the lower- and higher-protein groups: mean (95% CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lower-protein group vs 16.0 g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head circumference and lower leg longitudinal growth were also similar, as was the proportion of cumulative total enteral feeding volume provided as breast milk: median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group vs 94% (62%-99%) in the higher-protein group (P = .89). An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3 g/kg/d did not further enhance growth of very preterm infants with a median birth weight of 1200 g, who achieved near-fetal growth rates. This might point to a ceiling effect for enteral protein intake with respect to its influence on growth. clinicaltrials.gov Identifier: NCT01773902.

Validation of Test Weighing Protocol to Estimate Enteral Feeding Volumes in Preterm Infants

To evaluate the accuracy of pre- and postfeeding weights to estimate enteral feeding volumes in preterm infants. Single-center prospective cohort study of infants 28-36 weeks' corrected age receiving gavage feedings. For each test weight, 3 pre- and 3 postgavage feeding weights were obtained by study personnel, blinded to feeding volume, via a specific protocol. The correlation between test weight difference and actual volume ingested was assessed by the use of summary statistics, Spearman rho, and graphical analyses. The relationship between categorical predictive variables and a predefined acceptable difference (±5 mL) was assessed with the χ2 or Fisher exact test. A total of 101 test weights were performed in 68 infants. Estimated and actual feeding volumes were highly correlated (r = 0.94, P < .001), with a mean absolute difference of 2.95 mL (SD: 2.70; range: 0, 12.3 mL; 5th, 95th percentile: 0, 9.3); 85% of test weights were within ±5 mL of actual feeding volume and did not vary significantly by corrected age, feeding tube or respiratory support type, feeding duration or volume, formula vs breast milk, or caloric density. With adherence to study protocol, 89% of test weights (66/74) were within ±5 mL of actual volume, compared with 71% (19/27, P = .04) when concerns about protocol adherence were noted (eg, difficulty securing oxygen tubing). Via the use of a standard protocol, feeding volumes can be estimated accurately by pre- and postfeeding weights. Test weighing could be a valuable tool to support direct breastfeeding in the neonatal intensive care unit.