Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial.

OBJECTIVE: To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. STUDY DESIGN: This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (≤32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1, the first day of fortification, through study day 29 or until hospital discharge. RESULTS: There was no difference in the primary outcome of weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4 ± 0.4 g/kg/day; nonacidified liquid human milk fortifier, 16.9 ± 0.4 g/kg/day). However, in both the intention-to-treat and the protocol evaluable analyses, infants fed nonacidified liquid human milk fortifier had significantly greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day; P = .001). Infants fed with acidified liquid human milk fortifier received more protein (4.26 vs g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea nitrogen values (P = .010). The group fed acidified liquid human milk fortifier had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol evaluable analysis. CONCLUSIONS: Infants fed an acidified liquid human milk fortifier had higher rates of metabolic acidosis and poor feeding tolerance compared with infants fed a nonacidified liquid human milk fortifier. Initial weight gain was poorer with the acidified liquid human milk fortifier. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02307760.

Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants.

OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633.

Neonatal hypoglycemia.

PURPOSE OF REVIEW: The screening and management for neonatal hypoglycemia remains a confusing and contentious problem in neonatology. The purpose of this article is to contrast recent recommendations from the American Academy of Pediatrics and the Pediatric Endocrine Society. RECENT FINDINGS: Using different methodologies, the organizations have significant differences on whom to screen and what levels of glucose should be used for management. The identification of the first 48 h as a transitional hyperinsulinemic state is a new important concept. The neuroendocrine approach is contrasted with a neurodevelopmental strategy to find levels that exceed those associated with neuroglycopenia. SUMMARY: The questions remain the same when it comes to screening and management of neonatal low-glucose levels. Recent outcome studies with differing results continue to add to the controversy as to what to do at the bedside. It is uncertain if universal screening of glucose levels in the first hours should be applied to all newborn infants. Persistent hypoglycemic syndromes must be identified prior to discharge.

Creamatocrit analysis of human milk overestimates fat and energy content when compared to a human milk analyzer using mid-infrared spectroscopy.

BACKGROUND AND OBJECTIVE: Human milk (HM) is the preferred feeding for human infants but may be inadequate to support the rapid growth of the very-low-birth-weight infant. The creamatocrit (CMCT) has been widely used to guide health care professionals as they analyze HM fortification; however, the CMCT method is based on an equation using assumptions for protein and carbohydrate with fat as the only measured variable. The aim of the present study was to test the hypothesis that a human milk analyzer (HMA) would provide more accurate data for fat and energy content than analysis by CMCT. METHODS: Fifty-one well-mixed samples of previously frozen expressed HM were obtained after thawing. Previously assayed "control" milk samples were thawed and also run with unknowns. All milk samples were prewarmed at 40°C and then analyzed by both CMCT and HMA. CMCT fat results were substituted in the CMCT equation to reach a value for energy (kcal/oz). Fat results from HMA were entered into a computer model to reach a value for energy (kcal/oz). Fat and energy results were compared by paired t test with statistical significance set at P < 0.05. An additional 10 samples were analyzed locally by both methods and then sent to a certified laboratory for quantitative analysis. Results for fat and energy were analyzed by 1-way analysis of variance with statistical significance set at P < 0.05. RESULTS: Mean fat content by CMCT (5.8 ± 1.9 g/dL) was significantly higher than by HMA (3.2 ± 1.1 g/dL, P < 0.001). Mean energy by CMCT (21.8 ± 3.4 kcal/oz) was also significantly higher than by HMA (17.1 ± 2.9, P < 0.001). Comparison of biochemical analysis with HMA of the subset of milk samples showed no statistical difference for fat and energy, whereas CMCT was significantly higher than for both fat (P < 0.001) and energy (P = 0.002). CONCLUSIONS: The CMCT method appears to overestimate fat and energy content of HM samples when compared with HMA and biochemical methods.

Use of human milk and fortification in the NICU.

Human milk is the gold standard to provide nutritional support for all healthy and sick newborn infants including the very low birth weight (VLBW) infant (<1500 g). It has both nutritional and anti-infective properties which are especially important for these infants at risk for sepsis and necrotizing enterocolitis. Human milk alone is insufficient to meet the nutritional needs for VLBW infants, especially protein and minerals. There is a conundrum between achieving the nutritional, immunologic, developmental, psychological, social, and economic benefit with human milk vs. the inadequate growth with unfortified human milk for VLBW leading to nutritional inadequacy, growth failure and poor neurodevelopmental outcome. The use of multicomponent fortifiers to increase calories and provide additional protein, vitamins, and minerals has been associated with short-term benefits in growth. Most current fortifiers are derived from cow's milk, however there are concerns regarding a possible association between the use of cow's milk-based fortifier and NEC. There is also an exclusive human milk diet with a fortifier derived solely from human milk. There are three approaches for fortifying human milk and include fixed dosage or "blind fortification", adjustable fortification using the blood urea nitrogen as a surrogate for protein nutriture to modify dosage of fortification, and targeted, individualized fortification that is based on periodic human milk analysis.

Low blood sugar levels in the newborn infant: Do changing goal posts matter?

Glucose supply and metabolism are essential for growth and normal brain development in both the fetus and newborn. Disorders of glucose availability and metabolism can result in either hypoglycemia or hyperglycemia. The first section of this manuscript will contrast recommendations from the American Academy of Pediatrics and the Pediatric Endocrine Society on the approach to defining neonatal hypoglycemia. Recent studies will be reviewed which add to the controversy. This review aims to discuss the evidence-based guidelines, definitions, pathogenesis, outcomes and management options in this field. The current variations in practices and possibilities of future trials are also addressed.

"Extrauterine growth restriction" and "postnatal growth failure" are misnomers for preterm infants.

Preterm infants are increasingly diagnosed as having "extrauterine growth restriction" (EUGR) or "postnatal growth failure" (PGF). Usually EUGR/PGF is diagnosed when weight is <10th percentile at either discharge or 36-40 weeks postmenstrual age. The reasons why the phrases EUGR/PGF are unhelpful include, they: (i) are not predictive of adverse outcome; (ii) are based only on weight without any consideration of head or length growth, proportionality, body composition, or genetic potential; (iii) ignore normal postnatal weight loss; (iv) are usually assessed prior to growth slowing of the reference fetus, around 36-40 weeks, and (v) are usually based on an arbitrary statistical growth percentile cut-off. Focus on EUGR/PGF prevalence may benefit with better attention to nutrition but may also harm with nutrition delivery above infants' actual needs. In this paper, we highlight challenges associated with such arbitrary cut-offs and opportunities for further refinement of understanding growth and nutritional needs of preterm neonates.

Neonatal hypoglycemia.

A consistent definition for neonatal hypoglycemia in the first 48 h of life continues to elude us. Enhanced understanding of metabolic disturbances and genetic disorders that underlie alterations in postnatal glucose homeostasis has added useful information to understanding transitional hypoglycemia. This growth in knowledge still has not led to what we need to know: "How low is too low and for how long?" This article reviews the current state of understanding of neonatal hypoglycemia and how different approaches reach different "expert" opinions.

Fortification of human milk for preterm infants.

Human milk is the preferred feeding for all infants, including those of very low birth weight (<1500 g). It has both nutritional and anti-infective properties which are especially important for infants at risk for sepsis and necrotizing enterocolitis. When maternal milk is not available or the amount produced is not sufficient to meet daily needs, donor human milk may (should) be used in its place. However, donor human milk is generally term in quality and likely has insufficient protein to promote appropriate growth. Whether donor or mother's own milk, fortification of human milk is required to meet nutrient requirements for growth and development for these preterm infants who are at high risk for growth faltering during the hospital stay. There are multiple strategies and products that may be employed to support desired growth rates. The advent of human milk analyzers may be helpful in a more customized approach to fortification.

Feeding problems in the late preterm infant.

Much of the neonatal nutrition literature has focused on the management of very low birth weight infants, a group of infants usually less than 33 weeks gestation. Much less attention has been paid to nutritional management issues in preterm infants at higher gestations. This article reviews nutritional issues that exist from the 239th day (34 0/7 weeks gestation) and ending on the 259th day (36 6/7 weeks gestation) since the first day of the mother's last normal menstrual period.

Pragmatic approach to in-hospital nutrition in high-risk neonates.

Extremely low birth weight infants may experience periods of moderate to severe undernutrition during the acute phase of their respiratory problems. This undernutrition contributes to early growth deficits in these patients and may have long-lasting effects, including poor neurodevelopmental outcome. Early postnatal intravenous amino-acid administration and early enteral feeding strategies will minimize the interruption of nutrient intake that occurs with premature birth. These two strategies will prevent intracellular energy failure, allow the administration of more non-protein energy, as well as enhance overall nutritional health, as evidenced by less postnatal weight loss and earlier return to birth weight, and improved overall postnatal growth and outcome.

Metabolic screening and postnatal glucose homeostasis in the newborn.

Although individual metabolic diseases are relatively uncommon, inherited metabolic diseases collectively represent a more common cause of disease in the neonatal period than is generally appreciated. Newborn screening is among the most successful public health programs today. Every day, newborns considered to be at risk for hypoglycemia are screened. The definition of clinically significant hypoglycemia remains among the most confused and contentious issues in neonatology. There are 2 "competing" methods of defining hypoglycemia that suggest very different levels for management: one based on metabolic-endocrinologic hormones and another that uses outcome data to determine threshold levels of risk.

Hidden morbidity with "successful" early discharge.

OBJECTIVE: This study was conducted to determine if early postnatal discharge (EDC; < or =48 hours) in well newborns had an effect on the rate of hospital readmission within the first week after hospital discharge when compared to infants who remained >48 hours after birth (later discharge, LDC). STUDY DESIGN: This was a retrospective medical chart review. Charts of infants born between January 1994 and December 1998, discharged as "well newborns" and treated subsequently at a primary children's hospital within 7 days of neonatal discharge, were reviewed. Infants were categorized by length of neonatal hospital stay, level of medical intervention (emergency department treatment or hospital admission), and final diagnosis. RESULTS: There was a significant increase in hospital readmission rate for LDC infants when compared to EDC infants. When considering jaundice alone as an admitting diagnosis, EDC infants were admitted at a higher rate than LDC infants and with higher serum bilirubin concentrations. Readmitted, jaundiced infants had been almost always breast-fed. CONCLUSION: Overall, EDC of well newborns appears to be a safe and reasonable practice. However, the risk for severe jaundice is an unresolved issue that requires a discharge strategy and early follow-up to prevent serious morbidity.

Postnatal malnutrition of extremely low birth-weight infants with catch-up growth postdischarge.

OBJECTIVE: To assess nutritional intakes and subsequent growth of extremely low birth-weight (BW) infants. STUDY DESIGN: Chart review of 69 extremely low BW infants stratified into two groups by BW: < or =750 g (group 1; n=27) or 751 to 1000 g (group 2; n=42). Dietary intakes, weights, and head circumferences (HC) were collected through discharge and at 1 month postdischarge. The differences between goals and intakes were calculated weekly during hospitalization. Descriptive comparisons were made between growth parameters at birth, discharge, and follow-up. RESULTS: Total energy and protein deficits were inversely related to BW. Both groups exhibited extrauterine growth retardation while hospitalized. After discharge, the rates of weight gain and HC growth increased, leading to some growth recovery at follow-up. CONCLUSIONS: Existing feeding methods resulted in sizeable deficits in energy and protein, particularly for the smallest infants. Changing current practices to limit these deficits is essential to improving postnatal growth.

Prediction of extrauterine growth retardation (EUGR) in VVLBW infants.

BACKGROUND: Long-term growth failure in very very low birth weight (VVLBW) infants is a common complication of extreme prematurity. Critical illnesses create challenges to adequate nutriture. PURPOSE: To identify predictors of extrauterine growth retardation (EUGR) in VVLBW infants and to evaluate their nutritional intake and subsequent growth. STUDY DESIGN: A 4-year retrospective chart review of 221 infants