Enteral Feeding In Preterm Infants Research Articles

Influence of Early Total Enteral Feeding in Preterm Infants with Respiratory Distress Syndrome

Plain Language SummaryThe objective of this secondary analysis of data from the randomized trial comparing less invasive surfactant therapy (LISA) with InSurE method of surfactant administration among preterm infants with respiratory distress syndrome (RDS) is to demonstrate the feasibility of ETEF in hemodynamically stable preterm neonates on respiratory support.In this randomized control trial comparing LISA versus InSurE among preterm infants with RDS between 26 and 34 weeks of gestation, 150 infants were enrolled with 117 being hemodynamically stable. In 33 patients, early total enteral feeding could not be started due to various reasons – 7 babies had absence/reversal of end-diastolic flow (A/REDF) on antenatal Doppler, 15 babies had shock and required inotropic support on day 1 of life, 8 babies had higher ventilatory settings at the time of admission, and in the 3 babies, the abdomen was not soft to start total enteral feeding. Full-volume enteral feeding without any parenteral supplementation was started on day 1 of life using the mother’s own milk (MoM) or donor human milk (≤32 weeks of GA) and MoM or preterm formula (33–34 weeks of GA). The data were analyzed to assess the proportion of babies developing feed intolerance and/or NEC and factors associated with failure of ETEF. Out of these 117 babies, 102 tolerated ETEF, and 15 had one or more episodes of FI requiring parenteral supplementation, but none developed NEC. There was a statistically significantly increased incidence of culture-positive sepsis as well as the requirement of antibiotic therapy for possible sepsis in babies with failure of ETEF. There was no difference in the morbidities noted such as intraventricular hemorrhage grade 2 or more, patent ductus arteriosus requiring medical or surgical management, retinopathy of prematurity requiring treatment, and NEC stage II or more. Our study suggests that hemodynamically stable preterm infants with RDS on respiratory support can be successfully fed with exclusive enteral feeds started immediately post-birth. ETEF results in early attainment of full feeding and reduces the incidence of sepsis and the duration of hospital stay without increasing the risk of NEC.

Breast Milk Enema and Meconium Evacuation Among Preterm Infants

Delayed meconium evacuation and delayed achievement of full enteral feeding among premature infants are associated with poor short- and long-term outcomes. Identifying a more effective and safer enema for meconium evacuation is imperative for improving neonatal care. To examine whether breast milk enemas can shorten the time to complete meconium evacuation and achievement of full enteral feeding for preterm infants. This randomized, open-label, parallel-group, single-center clinical trial was conducted from September 1, 2019, to September 30, 2022, among 286 preterm infants with a gestational age of 23 to 30 weeks in the neonatal ward of the Shengjing Hospital of China Medical University in Shenyang. Preterm infants were randomly assigned to receive either breast milk enemas or normal saline enemas 48 hours after birth. The primary outcomes were time to complete meconium evacuation and time to achieve full enteral feeding. Secondary outcomes were duration of hospitalization, weight at discharge, and duration of total parenteral nutrition. Intention-to-treat and per-protocol analyses were conducted. In total, 286 preterm infants (mean [SD] gestational age, 198.8 [7.9] days; 166 boys [58.0%]) were eligible and included in this study. A total of 145 infants were randomized to the normal saline group, and 141 were randomized to the breast milk group. The time to achieve complete meconium evacuation was significantly shorter in the breast milk group than in the normal saline group (-2.2 days; 95% CI, -3.2 to -1.2 days). The time to achieve full enteral feeding was also significantly shorter in the breast milk group than in the normal saline group (-4.6 days; 95% CI, -8.0 to -1.2 days). The duration of total parenteral nutrition was significantly shorter in the breast milk group than in the normal saline group (-4.6 days; 95% CI, -8.6 to -1.0 days). There were no clinically notable differences in any other secondary or safety outcomes between the 2 groups. In this randomized clinical trial testing the effects of breast milk enema on meconium evacuation, breast milk reduced the time to achieve complete meconium evacuation and achieve full enteral feeding for preterm infants with a gestational age of 23 to 30 weeks. Subgroup analyses highlight the need for tailored interventions based on gestational age considerations. isrctn.org Identifier: ISRCTN17847514.

A Comparison of Slow Infusion Intermittent Feeding versus Gravity Feeding in Preterm Infants: A Randomized Controlled Trial.

The transition to full enteral feeding is important for ensuring adequate growth in preterm infants. The aim of this study was to investigate the effects of two different intermittent feeding methods on the transition to full enteral feeding in preterm infants. A prospective, randomized controlled study was conducted in a neonatology and perinatology center. Preterm infants with a gestational age between 24 + 0/7 and 31 + 6/7 were included in this study. They were divided into two groups: the SIF (slow infusion feeding) group and the IBF (intermittent bolus feeding) group. In the SIF group, feed volumes were administered over one hour using an infusion pump through an orogastric tube, with feeding occurring every three hours. The IBF group received enteral feeding using a gravity-based technique with a syringe through an orogastric tube, completed within 10 to 30 min. The primary outcome was the achievement of full enteral feeding and the occurrence of feeding intolerance. A total of 103 infants were enrolled in the study (50 in SIF and 53 in IBF). The time to achieve full enteral feeding did not differ significantly between the two groups (p = 0.20). The SIF group had significantly fewer occurrences in which gastric residual volume exceeded 50% (p = 0.01). Moreover, the SIF group had a significantly shorter duration of non-per-oral (NPO) status than the IBF group (p = 0.03). It is our contention that the use of the SIF method as an alternative feeding method is appropriate for infants with feeding intolerance and those at high risk of feeding intolerance.

Efficacy and Safety of Enteral Human Recombinant Insulin to Reduce the Time to Full Enteral Feeding in Preterm Infants: A Meta-Analytical Study.

Recombinant human insulin plays an important role in the gut maturation of preterm infants. This meta-analysis was carried out to assess the efficacy and safety of enteral recombinant human insulin in decreasing the time to full enteral feeding in preterm infants. The pooling of data from four clinical trials yielded a significant decrease in the time to full enteral feeding in preterm infants under both low (Mean difference [MD] -3.43 days; 95% CI: -6.18 to -0.69 days; I2 = 48%) and high doses of insulin (MD -7.10 days; 95% CI: -10.02 to -4.18 days; I2 = 0%). These findings require confirmation by further large trials that evaluate the efficacy and safety of enteral insulin, especially at supraphysiological doses.

Survey of Enteral Feeding of Preterm Infants and the Human Milk Bank in Japan.

In Japan, the first human milk bank (HMB) was established in 2017, which changed the practice of enteral feeding in neonatal care. This study investigated the practice of enteral feeding of preterm infants after the establishment of the HMB in Japan and examine future issues. A survey was conducted in 251 neonatal intensive care units (NICUs) from December 2020 to February 2021. The response rate was 61%. Although approximately 59% and 62% NICUs responded for ELBWI and VLBWI, only 30% and 46% could achieve this, respectively. Artificial nutrition was used to initiate enteral feeding for ELBWI in 24% and VLBWI in 56% of NICUs. Of the NICUs, 92% considered HMBs necessary or rather necessary and 55% wanted to use the HMB but could not. The major reasons for the same were (1) paying the annual membership fee of the HMB is troublesome, (2) obtaining approval from the facility is difficult, and (3) using the HMB is complicated. The indication and discontinuation for using donor milk vary among NICUs. Only in 17%, milk expression started within 1h delivery. Compared with before the establishment of the HMB, more NICUs are currently willing to start enteral feeding for preterm infants earlier. However, the implementation of enteral feeding appears to be challenging. Issues related to the HMB highlighted by the responses need to be addressed. Additionally, guidelines for using donor milk need to be established.

Проградиентное форсированное наращивание объема энтерального питания у глубоконедоношенных детей: результаты мультицентрового проспективного рандомизированного исследования

Проградиентное форсированное наращивание объема энтерального питания у глубоконедоношенных детей: результаты мультицентрового проспективного рандомизированного исследования

The Physiologic Significance of Early Urinary Intestinal Fatty Acid Binding Protein Levels in Preterm Infants: A Prospective Cohort Study.

Intestinal fatty acid binding protein (I-FABP) is released from mature enterocytes when cell membrane integrity is disrupted. This study aimed to prospectively investigate the physiologic significance of early urinary I-FABP and whether it might reflect intestinal compromise in preterm infants. We conducted a prospective cohort study of 100 preterm infants weighing <1250 g and collected serial urine samples at 12, 24, and 48 h after birth. The correlations between initial urinary I-FABP/urinary creatinine (creatinineu) levels and associated factors were analyzed. Among 100 patients, 15 were diagnosed with meconium obstruction of prematurity, and five were diagnosed with necrotizing enterocolitis during the hospital stay. Early urinary I-FABP/creatinineu levels were inversely correlated with both gestational age (Spearman’s rank correlation coefficient (Rs) −0.381, p < 0.01) and birth weight ((Rs) −0.424, p < 0.01). Early urinary I-FABP/creatinineu levels were associated with cord pH ((Rs) −0.436, p < 0.01) and base excess ((Rs) −0.258, p = 0.021). There were significantly positive correlations between early urinary I-FABP/creatinineu levels and the time to full enteral feeding in preterm infants without specific intestinal morbidities. Therefore, a more premature gut with acute perinatal ischemia is expected to exhibit increased I-FABP levels shortly after birth. Because of small sample size, further large-scale studies are needed.

Oropharyngeal administration of colostrum for preventing necrotizing enterocolitis and late-onset sepsis in preterm infants with gestational age\u2009\u2264\u200932\u2009weeks: a pilot single-center randomized controlled trial

BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis and improve short-term outcomes. Our objective was to evaluate the role of OAC in the early prevention of NEC and late-onset sepsis in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA pilot, single-center, 1:1 parallel randomized controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China from 1 January 2019 to 30 September 2020. Preterm infants were randomly divided into two groups with GA ≤ 32 weeks. The OAC group included preterm infants who received 0.4 ml of maternal colostrum via the oropharyngeal route every 3 h for 10 days beginning within the first 48 h after birth, and the control group included preterm infants who received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 infants in the OAC group and 125 infants in the control group were enrolled. The incidence of NEC (Bell stage 2 or 3) and late-onset sepsis were lower in the OAC group [2.36% vs. 10.40%, relative risk (RR) 0.23 (95% confidence interval (CI) 0.07, 0.78), adjusted RR 0.23 (95% CI 0.06, 0.84); 4.72% vs. 13.60%, RR 0.35 (95% CI 0.14, 0.85), adjusted RR 0.36 (95% CI 0.14, 0.95)]. In addition, the incidence of proven sepsis and intraventricular hemorrhage (IVH) (stage 3 or 4) were lower in the OAC group [2.36% vs. 8.80%, RR 0.27 (95% CI 0.08, 0.94); 1.57% vs. 7.20%, RR 0.22 (95% CI 0.05, 0.99)], and the time to achieve full enteral feeding was shorter (23.13 ± 9.45 days vs. 28.50 ± 14.80 days). No adverse reactions were observed in either group.ConclusionsOropharyngeal administration of colostrum is a safe and simple NICU procedure that may yield a potential effect in decreasing the incidences of NEC, late-onset sepsis, and severe IVH and shorten the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry, ChiCTR1900023697, Registered 8 June 2019, retrospectively registered.

Early Enteral Feeding in Preterm Infants: A Narrative Review of the Nutritional, Metabolic, and Developmental Benefits.

Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants with subsequent outcomes. The findings support the early initiation and advancement of enteral feeding impact preterm infant health by enhancing micronutrient delivery, promoting intestinal development and maturation, stimulating microbiome development, reducing inflammation, and enhancing brain growth and neurodevelopment. Clinicians must consider these short- and long-term implications when caring for preterm infants.

Erratum: Nasogastric versus Orogastric Bolus Tube Feeding in Preterm Infants: Pilot Randomized Clinical Trial.

Objective According to the most recent metanalysis, the best way to establish safe enteral feeding in preterm babies using nasogastric or orogastric tubes is still not well understood. This study aimed to determine the effects of bolus nasal tubes versus bolus orogastric tubes on the time required to reach full enteral feeding in preterm infants, as well as to compare the incidence rates of adverse events including nonintentional removal or displacement of the feeding tube, aspiration pneumonia/pneumonitis, apnea, necrotizing enterocolitis, gastric residual, and growth parameters between the studied cohort of preterm infants. Study Design We conducted an unblinded pilot randomized clinical trial on hemodynamically stable preterm infants (>28 weeks) recruited from level 2 neonatal intensive care unit at Mansoura University Children's Hospital from June 2015 to May 2017. Results Our study included 98 stable preterm infants with mean gestational age (orogastric group: 33.27 ± 1.08, nasogastric group: 33.32 ± 1.57) and mean birthweight (orogastric group: 1,753.3 ± 414.51, nasogastric group: 1,859.6 ± 307.05). Preterm infants who were fed via bolus nasogastric tube achieved full enteral feeding in a significantly shorter duration compared with the infants fed via bolus orogastric tube. The incidence rates of aspiration and feeding tube displacement were significantly higher in the bolus orogastric tube group compared with the bolus nasogastric tube group. There was no difference in the incidence rates of apnea, necrotizing enterocolitis, bradycardia, oxygen desaturation, and gastric residual in both groups. Conclusion Preterm infants without any respiratory support receiving bolus nasogastric tube feeding achieved full enteral feeding significantly sooner than those receiving bolus orogastric tube feeding. Additionally, bolus nasogastric tube feeding had a lower incidence of aspiration, tube displacement, and the infants regained birthweight more quickly than those receiving orogastric tube feeding. Key Points

Effect of Different Positions on Arterial Oxygen Saturation during Enteral Feeding of Preterm Infants Admitted to Neonatal Intensive Care Units

Background: This study aimed to determine the effects of various positions on the arterial oxygen saturation during enteral feeding of preterm infants admitted to Neonatal Intensive Care Units (NICUs). It is assumed that different body positions influence arterial oxygen saturation during enteral feeding.Methods: This crossover clinical trial included 88 infants. The inclusion criteria were gestation age of fewer than 32 weeks, a weight of 1001-1500 gr, age of fewer than one month, 5-minute Apgar score of at least 5, exclusive breast-feeding, absence of any underlying illness, no oxygen therapy, and a minimum feed volume of 10cc for two h. The subjects were selected from the infants admitted to NICUs at Alzahra, Shahid Beheshti, and Amin hospitals, Isfahan, Iran, using a convenience sampling method. Subsequently, they were randomly assigned to four groups of 22 cases per group. The four groups were A, B, C, and D who were initially positioned on the left side, supine, prone, and right side, respectively. The arterial oxygen saturation was recorded on a minute-by-minute basis 5 min before, during, and 5 min after enteral feeding. Data were analyzed in STATA software (version 14) using a one-way analysis of variance, (ANOVA), linear mixed model, and the Chi-square test.Results: According to the results of the one-way ANOVA and Chi-square test, no significant difference was observed among the four groups regarding the demographic characteristics. Moreover, the linear mixed model revealed no significant difference among the four groups of intervention, the four periods of the study, and carryover effect in terms of the mean oxygen saturation before, during, and after enteral feeding.Conclusion: The results revealed that variations in infant positions during feeding had no effects on the arterial oxygen saturation. Therefore, neonatal nurses are advised to carry out enteral feeding without unnecessary changing of the infant position, which leads to lower manipulation, and improved sleep and awakening cycle of the infants.

Breastfeeding promotion strategies study on preterm infants in the neonatal intensive care unit

To explore the effect of breastfeeding promotion strategies on neonatal clinical outcomes of preterm infants during hospitalization in the neonatal intensive care unit (NICU). We developed breastfeeding promotion strategies, including the establishment of a multidisciplinary breastfeeding steering team, breastfeeding support of families and society, family-integrated care, kangaroo mother care, donor human milk bank, and so on. Preterm infants meeting the inclusion standard, less than 32 weeks gestational age, who were admitted to NICU from November 2015 to February 2017 were enrolled, and the eligible infants were divided into two groups (control group and intervention group) before and after policy implementation. The data of preterm infants including breastfeeding related outcomes (time to initiation of enteral feeding, time to initiation of breastfeeding, time to achieve full breastfeeding, time to achieve full enteral feeding and rate of breastfeeding), growth (extrauterine growth restriction) and complications were compared between the two groups. One hundred and twenty-three preterm infants were enrolled, including 61 in the control group and 62 in the intervention group. There were no significant differences in gender, gestational age, birth weight, intrauterine growth retardation (IUGR) and admission disease status between the two groups (P>0.05). Compared with the control group, there were significantly earlier time to initiation of enteral feeding [15.37 (10.00, 22.13) h vs. 20.25 (12.88, 26.33) h, P<0.01], time to achieve full breastfeeding [91.00 (69.75, 103.00) h vs. 94.00 (80.37, 118.75) h, P=0.04], and time to achieve full enteral feeding [12 (11, 15) d vs. 14 (12, 18) d, P<0.01] in the intervention group. Otherwise, there were no significant differences in time to initiation of breastfeeding, hospital stay, extrauterine growth restriction (EUGR) occurance rate of weight, the rate of breastfeeding, motality, and the incidence of complications including feeding intolerance, neonatal necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) (P>0.05). The breastfeeding promotion strategie was a quality improvement of ordinary breastfeeding protocol. It had significantly reduced time to initiation of enteral feeding, time to achieve full breastfeeding and time to achieve full enteral feeding for preterm infants in NICU. Further research is needed to confirm whether the strategies can improve the breastfeeding rate and reduce the occurrence of the complications, such as NEC, BPD, and ROP.

USING OF A PARTIALLY HYDROLYZED PROTEIN TO FEEDING PRETERM INFANTS. CLINICAL TRIAL RESULTS

Early enteral feeding is extremely important aspect for the care of a premature baby, maintaining the normal functioning of organs andsystems in the neonatal period, and for the longterm prognosis. Features of the digestive tract, often accompanied by severe pathology affect toleranceto enteral feeding in preterm infants, particularly in children with ELBW and VLBW. In the absence or insufficient amount of breast milk you must choosea substrate for a premature infant feeding, which will enable faster to adapt the gastrointestinal tract enteral nutrition and will provide the growth rate, the approximate for the fetal growth.

A Fortified Donor Milk Policy is Associated With Improved In-Hospital Head Growth and Weight Gain in Very Low-Birth-Weight Infants.

Previous research has reported that infants fed donor milk grow slower than those fed formula. However, most of the trials used unfortified donor milk, which limits the ability to generalize the results to current clinical practice. To evaluate the impact of early human milk feeding (donor milk and/or mother's own milk) with standard fortification on in-hospital growth of very low-birth-weight infants. This pre-/postretrospective study included selected newborn infants less than 1500 g admitted to a level IV neonatal intensive care unit before and after the introduction of a policy providing donor milk when mother's own milk was not available in sufficient quantity to meet her infant's need. When enteral feeds reached 80 mL/kg per day, all human milk was fortified. Seventy-two "before" (any formula-fed) and 114 "after" (human milk-fed) infants were enrolled in this study. Infant characteristics and neonatal morbidity were similar in both groups. Outcomes revealed that an initial human milk diet with standard fortification was associated with significantly higher early extrauterine weight gain and head growth in very low-birth-weight infants than a formula-fed diet. Very early initiation of fortified breast and/or donor milk feeding can help promote in-hospital head growth and weight gain of preterm infants. Formula may not be appropriate for early use among preterm infants. Further large-scale clinical trials are needed to determine the best initiation and composition of enteral feeding for preterm infants.

The Impact of Routine Evaluation of Gastric Residual Volumes on the Time to Achieve Full Enteral Feeding in Preterm Infants

To evaluate the time to full enteral feedings in preterm infants after a practice change from routine evaluation of gastric residual volume before each feeding to selective evaluation of gastric residual volume , and to evaluate the impact of this change on the incidence of necrotizing enterocolitis (NEC). Data were collected on all gavage-fed infants born at ≤34 weeks gestational age (GA) for 2 years before (n = 239) and 2 years after the change (n = 233). The median GA was 32.0 (IQR: 29.7-33.0) weeks before and 32.4 (30.4-33.4) weeks after the change (P = .02). Compared with historic controls, infants with selective evaluations of gastric residual volumes weaned from parenteral nutrition 1 day earlier (P < .001) and achieved full enteral feedings (150 cc/kg/day) 1 day earlier (P = .002). The time to full oral feedings and lengths of stay were similar. The rate of NEC (stage ≥ 2) was 1.7% in the selective gastric residual volume evaluation group compared with 3.3% in the historic control group (P = .4). Multiple regression analyses showed that the strongest predictor of time to full enteral feedings was GA. Routine evaluation of gastric residual volume and increasing time on noninvasive ventilation both prolonged the attainment of full enteral feedings. Findings were consistent in the subgroup with birth weights of <1500 g. Increased weight at discharge was most strongly associated with advancing postmenstrual, age but avoidance of routine evaluations of gastric residual volume also was a significant factor. Avoiding routine evaluation of gastric residual volume before every feeding was associated with earlier attainment of full enteral feedings without increasing risk for NEC.

Starting enteral nutrition with preterm single donor milk instead of formula affects time to full enteral feeding in very low birthweight infants.

This study compared the impact of using either single donor breastmilk or formula to start enteral feeding in preterm infants, on the time to full enteral feeding, growth and morbidity. The milk was provided by other preterm mothers. This was an observational prospective study, carried out from June 2012 to March 2013 at the Medical University of Vienna, Austria, on the effects of preterm single donor milk on 133 very low birthweight infants with a birthweight <1500 g and a gestational age <32 weeks until they were on full enteral feeding. They were compared to a retrospective group of 150 infants from March 2011 to May 2012 who received preterm formula. The time to full enteral feeding, defined as 140 mL/kg, was significantly shorter in the donor milk group than in the formula group (18 vs. 22 days, p = 0.01). Feeding donor milk was also associated with a lower incidence for retinopathy of prematurity (4% vs. 13%, p < 0.01) and culture-proven sepsis (11% vs. 23%, p < 0.01). Feeding preterm infants breastmilk from a single donor rather using formula was associated with a shorter time to full enteral feeding and lower incidences of retinopathy of prematurity and sepsis.

Splanchnic Oxygenation at First Enteral Feeding in Preterm Infants: Correlation With Feeding Intolerance.

Preterm infants are at risk of developing gastrointestinal complications such as feeding intolerance and necrotizing enterocolitis. Near-infrared spectroscopy (NIRS) provides continuous monitoring of abdominal oxygenation (ArSO2) and could help to predict gastrointestinal complications in preterm neonates. In this prospective observational study, ArSO2 patterns at first enteral feed were evaluated by NIRS in 61 clinically stable preterm infants. Splanchnic-cerebral oxygenation ratio, which is a marker of gut hypoxia, was also calculated. ArSO2 and splanchnic-cerebral oxygenation ratio were significantly lower both at baseline and after feeding administration in infants who later developed feeding intolerance (n = 23). NIRS could help the early prediction of gastrointestinal complications in high-risk preterm infants.

A Stepwise, Pilot Study of Bovine Colostrum to Supplement the First Enteral Feeding in Preterm Infants (Precolos): Study Protocol and Initial Results.

The optimal feeding for preterm infants during the first weeks is still debated, especially when mother's own milk is lacking or limited. Intact bovine colostrum (BC) contains high amounts of protein, growth factors, and immuno-regulatory components that may benefit protein intake and gut maturation. We designed a pilot study to investigate the feasibility and tolerability of BC as the first nutrition for preterm infants. The study was designed into three phases (A, B, and C) and recruited infants with birth weights of 1,000-1,800 g (China) or gestational ages (GAs) of 27 + 0 to 32 + 6 weeks (Denmark). In phase A, three infants were recruited consecutively to receive BC as a supplement to standard feeding. In phase B, seven infants were recruited in parallel. In phase C (not yet complete), 40 infants will be randomized to BC or standard feeding. Feeding intolerance, growth, time to full enteral feeding, serious infections/NEC, plasma amino acid profile, blood biochemistry, and intestinal functions are assessed. This paper presents the study protocol and results from phases A and B. Seven Danish and five Chinese infants received 22 ± 11 and 22 ± 6 ml·kg-1·day-1 BC for a mean of 7 ± 3 and 7 ± 1 days which provided 1.81 ± 0.89 and 1.83 ± 0.52 g·kg-1·day-1 protein, respectively. Growth rates until 37 weeks or discharge were in the normal range (11.8 ± 0.9 and 12.9 ± 2.7 g·kg-1·day-1 in Denmark and China, respectively). No clinical adverse effects were observed. Five infants showed a transient hypertyrosinemia on day 7 of life. The three-phased study design was used to proceed with caution as this is the first trial to investigate intact BC as the first feed for preterm infants. BC supplementation appeared well tolerated and resulted in high enteral protein intake. Based on the safety evaluation of phases A and B, the randomized phase C has been initiated. When complete, the Precolos trial will document whether it is feasible to use BC as a novel, bioactive milk diet for preterm infants. Our trial paves the way for a larger randomized controlled trial on using BC as the first feed for preterm infants with insufficient access to mother's own milk.

Medications That Increase Osmolality and Compromise the Safety of Enteral Feeding in Preterm Infants

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis. Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined. Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF. Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF. Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM.

Comparison of enteral feeding of preterm infants between two hospitals in China and United States

Aim: To compare the details of preterm infants enteral feeding between the two hospitals in China and in the United States, and to analyze the reason of the differences.Methods: A retrospective cohort study was conducted. Infants < 32 weeks were enrolled from Cincinnati University Hospital (CUH) during January 2011 to January 2012 and Peking Union Medical College Hospital (PUMCH) during January 2011 to May 2012. Basic data and enteral feeding data of the two groups were compared.Results: Eighty-two infants in CUH group and 74 infants in PUMCH group were enrolled, infants in CUH group were much smaller than PUMCH group (gestational age (29.1 ± 2.0) versus (30.6 ± 1.3) weeks, p = 0.000, birth weight (1204 ± 328) versus (1406 ± 320) g, p = 0.000). Significantly more infants in CUH group received human milk as the first enteral feeding (78/82 versus 7/74, p = 0.000). Human milk feeding rate in first 28 days in CUH group was much higher (77/82 versus 7/74, p = 0.000). The initial milk volume, and the milk volume on the 7th, 14th, 21st and 27th day of CUH group were significant larger [(15.9 versus 9.3 ml/kg·d, p = 0.000), (79.8 versus 35.2 ml/kg·d, p = 0.000), (133.2 versus 76.4 ml/kg·d, p = 0.000), (140.6 versus 108.6 ml/kg·d, p = 0.000), (142.2 versus 121.5 ml/kg·d, p = 0.002)]. CUH group achieved full enteral feeding sooner (12.0 versus 22.4 d, p = 0.000).Conclusion: Preterm infants achieved full enteral feeding sooner at CUH compared to PUMCH. Human milk feeding may improve enteral feeding tolerance. We need more aggressive enteral feeding proposal in PUMCH.