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AIMS—To determine the effect of trophic feeding on clinical outcome in ill preterm infants.
METHODS—A randomised, controlled, prospective study of 100 preterm infants, weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition, was performed. Group TF (48infants) received trophic feeding from day 3 (0.5-1 ml/h) along with parenteral nutrition until ventilatory support finished. Group C (52 infants) received parenteral nutrition alone. "Nutritive" milk feeding was then introduced to both groups. Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks, sepsis incidence, liver function, milk tolerance, duration of respiratory support, duration of hospital stay and complication incidence.
RESULTS—Groups were well matched for birthweight, gestation and CRIB scores. Infants in group TF had significantly greater energy intake, mean difference 41.4 (95% confidence interval 9, 73.7) kcal/kg p=0.02; weight gain, 130 (CI 1, 250) g p = 0.02; head circumference gain, mean difference 0.7 (CI 0.1, 1.3) cm, p =0.04; fewer episodes of culture confirmed sepsis, mean difference −0.7 (−1.3, −0.2) episodes, p = 0.04; less parenteral nutrition, mean difference −11.5 (CI −20, −3) days, p = 0.03; tolerated full milk feeds (165 ml/kg/day) earlier, mean difference −11.2 (CI −19, −3) days, p = 0.03; reduced requirement for supplemental oxygen, mean difference −22.4 (CI−41.5, −3.3) days, p = 0.02; and were discharged home earlier, mean difference −22.1 (CI −42.1, −2.2) days, p = 0.04. There was no significant difference in the relative risk of any complication.
CONCLUSIONS—Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition.


It was reported that 30-50% of inpatients are in a malnutrition status. Measuring the prealbumin level is a sensitive and cost-effective method for assessing the severity of illness in critically or chronically ill patients. However it is uncertain whether or not the prealbumin level correlates with the level of nutrition support and outcomes in critically ill patients. The aim of this study was to evaluate serum prealbumin level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients. Forty-four patients who received total parenteral nutrition for more than 7 days at an intensive care unit (ICU) were studied. The serum prealbumin was measured at the initial time of nutrition support and at the almost seventh day since the first measurement. The patients were allocated into two groups. In Group 1 (n=31) and 2 (n=13), the prealbumin level increased and decreased, respectively. Age, APACHE II score, nutrition status, nutritional requirement and amount of supply, mortality, hospital day and ICU day in the two groups were compared. The serum prealbumin level increased in 31 out of the 44 patients. The average calorie intake was 1334 Kcal/day (83% of energy requirement) in Group 1 and 1170 kcal/day (76% of energy requirement) in Group 2 (p=0.131). The mortality was 42% in Group 1 and 54% in Group 2 (p=0.673). The average hospital day/ ICU day in Groups 1 and 2 were 80 days/38 days and 60 days/31 days respectively. In conclusion, in critically ill patients, the serum prealbumin level did not respond sensitively to nutritional support. In addition an increase in the prealbumin level dose not indicate a better prognosis for critically ill patients.

Background

Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.

Methods

We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age

Trial registration

Current controlled trials: ISRCTN76597892; EudraCT Number: 2008-008899-14

The postnatal rate of head growth in 63 infants of less than 34 weeks' gestation was examined retrospectively, together with that of 7 other infants of between 34 and 40 weeks' gestation who had severe respiratory illnesses. From the serial measurements of head circumference the timing of maximum velocity of postnatal head growth was examined and related to the infant's gestational age, nutrition, and respiratory illness during the neonatal period. Within this group of infants the longer the gestation the earlier maximum head growth velocity occurred. For infants of similar gestational ages the presence of a severe respiratory problem was associated with a delay in the time of maximum head growth. Differences in caloric intake during the first week of life did not seem to affect significantly the timing of maximum head growth velocity.

Fifty nine infants of birthweight less than 1500 g were allocated alternately to initial total parenteral nutrition or to transpyloric feeding. Mortality was similar between the two groups. Ten of the 29 infants in the transpyloric group failed to establish full enteral nutrition during the first week of life. No beneficial effects on growth were shown in infants receiving parenteral nutrition. Acquired bacterial infection was higher in the parenteral group and associated with morbidity and mortality. Conjugated hyperbilirubinaemia occurred only in the parenterally fed infants. The incidence of necrotising enterocolitis was higher in the transpyloric group. Parenteral nutrition does not confer any appreciable benefit and because of greater complexity and higher risk of complications should be reserved for those infants in whom enteral feeding is impossible.

Objective:

Premature infants, especially those born less than 1500 g, often exhibit slow overall growth after birth and lack of early nutritional support may be an important element. We tested the hypothesis that early administration of amino acids (within the first few hours of life) to infants born at less than 1500 g would be associated with fewer infants that were less than the 10th percentile at 36 weeks post-conceptual age than infants that received amino acids after the first 24 h of life.

Study Design:

A prospective intervention of early amino-acid (EAA) supplementation, began before 24 h of life, in preterm infants, <1500 g, was compared to a retrospective cohort of preterm infants receiving late amino-acid (LAA) supplementation, began after 24 h of life. The primary outcome variable was the proportion of infants at less than the 10th percentile at 36 weeks post-conceptual age.

Result:

Fewer infants fell below the 10th percentile (P<0.001) in the EAA group. Furthermore, infants in the EAA groups had significantly greater weight gains than did the LAA group (P<0.003) after adjusting for gestational age and time from birth to discharge. In addition, shorter duration of parenteral nutrition was associated with EAA supplementation (P<0.001).

Conclusion:

A prospective strategy of EAA in preterm infants <1500 g was associated with an improved weight gain, suggesting that nutrition that included amino acids may be critical during the first 24 h of life.

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

In a one year prospective study in the Trent region we examined the short term outcome (survival to discharge) of all infants who required admission to a baby care unit. Infants of less than or equal to 28 weeks' gestation who received all their perinatal care in one of five large centres (each providing more than 600 ventilator days/year) showed significantly better survival rates than infants electively treated throughout their entire course at one of the 12 smaller units (34 survivors from 65 infants (52%) compared with eight survivors from 37 infants (22%). These differences occurred despite the elective transfer of many of the sickest infants from the smaller units to the larger. Differences in survival between more mature infants were not significant. These results support the policy that there should be a more centralised neonatal service for those infants at or below 28 weeks' gestation.

Background

Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response.

Methods

VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume ≥ 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.

Critically ill patients invariably require nutritional intervention. Traditionally, enteral nutrition has not been widely employed in this patient population. This is due in part to the success of present-day parenteral nutrition, and to difficulties encountered with enteral feeding. Recent evidence has demonstrated that enteral is preferable to parenteral nutrition in terms of cost, complications, gut mucosal maintenance, and metabolic and immune function. Enterally administered nutritional support can and should be utilised as the preferred route of nourishment for the critically ill. The appropriate choice of access and formula, as well as a rational strategy for implementation, should improve the likelihood of success. This article describes the unique features of critical illness as they pertain to nutritional support, the benefits of enteral nutrition, and the obstacles to success, and offers suggestions which may improve the ability to provide nutrients adequately via the intestinal tract.

Background and the purpose of the study

It is believed that enteral nutrition (EN) support is the preferred route as compared to parenteral nutrition (PN). Critically ill patients on EN receive less than 60% of their metabolic requirements. To meet patients’ calorie goal addition of PN to EN was proposed. This study was conducted to determine whether supplemental PN have any difference with EN alone in regard to inflammatory indices.

Methods

Twenty patients were randomized to either receive EN alone or EN+PN for 7 days. Pre albumin and inflammatory indices including interleukin IL-1, IL-6 and tumor necrosis factor-α (TNF-α) were measured on days of 0, 3,7. Also Sequential Organ Failure Assessment (SOFA) score and Therapeutic Intervention Scoring System-28 (TISS-28) score were calculated on days of 0, 3 and 7.

Results and major conclusion

IL-1, IL-6 and TNF-α did not show significant difference between two interventions. Pre-albumin was increased from baseline by 9% and 81% in EN and EN+PN groups respectively but it did not reach to statistical significance. SOFA score did not show significant difference. TISS score was higher in EN+PN group on days of 3 and 7.

No difference was found between EN and EN+PN regimens in regard to inflammation, while severity of illness may not change with these regimens, nursing workload increases with implementation of supplemental PN.

Background

Early enteral nutrition is recommended in cases of critical illness. It is unclear whether this recommendation is of most benefit to extremely ill patients. We aim to determine the association between illness severity and commencement of enteral feeding.

Methods

One hundred and eight critically ill patients were grouped as “less severe” and “more severe” for this cross-sectional, retrospective observational study. The cut off value was based on Acute Physiology and Chronic Health Evaluation II score 20. Patients who received enteral feeding within 48 h of medical intensive care unit (ICU) admission were considered early feeding cases otherwise they were assessed as late feeding cases. Feeding complications (gastric retention/vomiting/diarrhea/gastrointestinal bleeding), length of ICU stay, length of hospital stay, ventilator-associated pneumonia, hospital mortality, nutritional intake, serum albumin, serum prealbumin, nitrogen balance (NB), and 24-h urinary urea nitrogen data were collected over 21 days.

Results

There were no differences in measured outcomes between early and late feedings for less severely ill patients. Among more severely ill patients, however, the early feeding group showed improved serum albumin (p = 0.036) and prealbumin (p = 0.014) but worsened NB (p = 0.01), more feeding complications (p = 0.005), and prolonged ICU stays (p = 0.005) compared to their late feeding counterparts.

Conclusions

There is a significant association between severity of illness and timing of enteral feeding initiation. In more severe illness, early feeding was associated with improved nutritional outcomes, while late feeding was associated with reduced feeding complications and length of ICU stay. However, the feeding complications of more severely ill early feeders can be handled without significantly affecting nutritional intake and there is no eventual difference in length of hospital stay or mortality between groups. Consequently, early feeding shows to be a more beneficial nutritional intervention option than late feeding in patients with more severe illness.

Insufficient nutrient supply in preterm infants and protein deprivation in particular can represent a nutritional emergency. It can cause many of the features of the starvation response, including insulin resistance and hyperglycemia, as well as growth failure and neurological injury. At Baylor University Medical Center, we began providing intravenous protein on the first day of life to extremely low birth weight infants in 2000. This has led to significant improvements in the time to regain birth weight and the rate of daily weight gain during the first month of life. While neonatologists traditionally focus first on newborns' warmth, respiratory support, and cardiovascular support, early aggressive nutrition support, in the form of intravenous amino acids at time of admission as well as glucose, is of great benefit and should be a standard element in the initial care of the extremely low birth weight infant.

No one doubts that good nutrition is an important component of neonatal intensive care, nor that this can only be accomplished by the use of intravenous fat. With regard to the effects of nutrition on bronchopulmonary dysplasia, however, we are facing a dilemma. On the one hand there is the suggestion that inadequate nutrition increases the severity of bronchopulmonary dysplasia and on the other that the use of intravenous fat predisposes to it. In an attempt to narrow the area of uncertainty we randomly allocated 129 infants of less than 1750 g birth weight to receive either early or late lipid containing parenteral nutrition. The median duration of ventilation support in the 'early' group was 8.5 days and in the 'late' group eight days; this was not significantly different.

The beneficial effects of total parenteral nutrition (TPN) in improving the nutritional status of malnourished patients during hospital stays have been well established. However, recent randomized trials and meta-analyses have reported an increased rate of TPN-associated complications and mortality in critically ill patients. The increased risk of complications during TPN therapy has been linked to the development of hyperglycemia, especially during the first few days of TPN therapy. This retrospective study was conducted to determine whether the amount of dextrose from TPN in the 1st week in the intensive care unit (ICU) was related to the development of hyperglycemia and the clinical outcome. We included 88 non-diabetic critically ill patients who stayed in the medical ICU for more than two days. The subjects were 65 ± 16 years old, and the mean APACHE (Acute Physiology and Chronic Health Evaluation) II score upon admission was 20.9 ± 7.1. The subjects received 2.3 ± 1.4 g/kg/day of dextrose intravenously. We divided the subjects into two groups according to the mean blood glucose (BG) level during the 1st week of ICU stay: < 140 mg/dl vs ≥ 140 mg/dl. Baseline BG and the amount of dextrose delivered via TPN were significantly higher in the hyperglycemia group than those in the normoglycemia group. Mortality was higher in the hyperglycemia group than in the normoglycemia group (42.4% vs 12.8%, P = 0.008). The amount of dextrose from TPN was the only significant variable in the multiple linear regression analysis, which included age, APACHE II score, baseline blood glucose concentration and dextrose delivery via TPN as independent variables. We concluded that the amount of dextrose delivered via TPN might be associated with the development of hyperglycemia in critically ill patients without a history of diabetes mellitus. The amount of dextrose in TPN should be decided and adapted carefully to maintain blood glucose within the target range.

There is a consensus that nutritional support, which must be provided to patients in intensive care, influences their clinical outcome. Malnutrition is associated in critically ill patients with impaired immune function and impaired ventilator drive, leading to prolonged ventilator dependence and increased infectious morbidity and mortality. Enteral nutrition is an active therapy that attenuates the metabolic response of the organism to stress and favorably modulates the immune system. It is less expensive than parenteral nutrition and is preferred in most cases because of less severe complications and better patient outcomes, including infections, and hospital cost and length of stay. The aim of this work was to perform a review of the use of enteral nutrition in critically ill patients.

The development of premature infants may be altered due to exposure to high cumulative doses of the perinatal corticosteroid dexamethasone during critical growth periods. To compare child behavioral development of prematurely born infants who were exposed to higher perinatal steroids (PNS; N0.2 mg/kg) with that of infants exposed to lower PNS (≤0.2 mg/kg), we used the Vineland Adaptive Behavioral Scales to assess school-age behavioral outcomes of a historical cohort of 45 prematurely born infants. Children who had received higher PNS treatment were more likely to have lower overall behavioral developmental scores, especially lower social skills (p < .05). Higher PNS plus higher severity of illness during the first day of life based on the Clinical Risk Index for Babies (p = .016) and lower birth head size (p = .015) were linked with poorer behavioral outcomes among participants. Nursing practice includes promotion of quality care and should include closer evaluation of cumulative steroid therapy, severity of illness, and promotion of long-term follow-up support for premature infants.

Critical care is in an emerging crisis of conflict between what individuals expect and the economic burden society and government are prepared to provide. The goal of critical care support is to prevent suffering and premature death by intensive therapy of reversible illnesses within a reasonable timeframe. Recently, it has become apparent that early support in an intensive care environment can improve patient outcomes. However, life support technology has advanced, allowing physicians to prolong life (and postpone death) in circumstances that were not possible in the recent past. This has been recognized by not only the medical community, but also by society at large. One corollary may be that expectations for recovery from critical illness have also become extremely high. In addition, greater numbers of patients are dying in intensive care units after having receiving prolonged durations of life-sustaining therapy. Herein lies the emerging crisis – critical care therapy must be available in a timely fashion for those who require it urgently, yet its provision is largely dependent on a finite availability of both capital and human resources. Physicians are often placed in a troubling conflict of interest by pressures to use health resources prudently while also promoting the equitable and timely access to critical care therapy. In this commentary, these issues are broadly discussed from the perspective of the individual clinician as well as that of society as a whole. The intent is to generate dialogue on the dynamic between individual clinicians navigating the complexities of how and when to use critical care support in the context of end-of-life issues, the increasing demands placed on finite critical care capacity, and the reasonable expectations of society.

Background

There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum.

Methods/Design

The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged ≤ 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective.

Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management.

Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI).

A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs.

Discussion

The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice.

Trial Registration

Current Controlled Trials ISRCTN61735247

Lipid emulsions based on soybean oil have been an integral part of parenteral nutrition supplying n-6 fatty acids, with possible negative effects in critically ill patients. Newer lipid emulsions supply less n-6 fatty acids. In addition, fish oil-based lipids may be included in the lipid component of parenteral nutrition. While clinical benefits of lipid emulsions with a reduced fraction in n-6 lipids and the addition of fish oil have been described in postoperative patients, data are less clear in critically ill or septic patients. Recent data suggest that beneficial effects may be achieved when used early but clearly more data are needed to come to a definitive conclusion. The present commentary will highlight current data in critically ill and septic patients and the use of fish oil as a part of parenteral nutrition.

The neonatal outcome of 61 infants born after pregnancies complicated by absent or reversed end diastolic flow velocities (AREDFV) in the fetal umbilical artery was compared with that of 61 controls matched for gestational age born after high risk pregnancies with documented forward end diastolic flow velocities (EDFV). The AREDFV group was significantly more growth retarded, had lower platelet counts at birth, and were more likely to become significantly thrombocytopenic in the first week after birth. Owing to concerns about the possible increased risk of necrotising enterocolitis in newborn infants after AREDFV, this group was started on enteral feeds later and was more likely to receive parenteral nutrition than the EDFV group. Seven infants with AREDFV and one control infant developed necrotising enterocolitis.

Forty one preterm infants (birth weight < 1500 g) were studied by daily Doppler echocardiography for the first week of life to examine the effect of a haemodynamically significant ductus arteriosus (HSDA) on systemic blood pressure. Hourly records of blood pressure were averaged for each infant to produce a 24 hour mean value and the infants were then allocated to groups according to whether, by echocardiographic criteria, there was a HSDA on that day. In infants from 1000 to 1500 g the differences in all parameters of blood pressure between those with and without a HSDA were not significant. In infants < 1000 g the mean blood pressure was significantly less in the infants with a HSDA throughout the first week of life. Systolic blood pressure was reduced by as much as diastolic blood pressure and as a result the pulse pressure did not differ. Infants < 1000 g with a HSDA were given more plasma and a greater number received inotropic support. Gestational age, respiratory disease severity, and complication rates did not differ between those with and without a HSDA. The possibility of a clinically silent HSDA should be considered before large amounts of plasma volume expanders are given to treat hypotension in infants < 1000 g.

Acute kidney injury (AKI) develops mostly in the context of critical illness and multiple organ failure, characterized by alterations in substrate use, insulin resistance, and hypercatabolism. Optimal nutritional support of intensive care unit patients remains a matter of debate, mainly because of a lack of adequately designed clinical trials. Most guidelines are based on expert opinion rather than on solid evidence and are not fundamentally different for critically ill patients with or without AKI. In patients with a functional gastrointestinal tract, enteral nutrition is preferred over parenteral nutrition. The optimal timing of parenteral nutrition in those patients who cannot be fed enterally remains controversial. All nutritional regimens should include tight glycemic control. The recommended energy intake is 20 to 30 kcal/kg per day with a protein intake of 1.2 to 1.5 g/kg per day. Higher protein intakes have been suggested in patients with AKI on continuous renal replacement therapy (CRRT). However, the inadequate design of the trials does not allow firm conclusions. Nutritional support during CRRT should take into account the extracorporeal losses of glucose, amino acids, and micronutrients. Immunonutrients are the subject of intensive investigation but have not been evaluated specifically in patients with AKI. We suggest a protocolized nutritional strategy delivering enteral nutrition whenever possible and providing at least the daily requirements of trace elements and vitamins.

Preterm and critically ill newborns admitted to a NICU undergo repeated skin-breaking procedures that are necessary for their survival. Sucrose is rapidly becoming the accepted clinical standard nonpharmacologic intervention for managing acute procedural pain for these infants. Although shown to be safe in single doses, only 4 studies have evaluated the effects of repeated doses of sucrose over relatively short periods of time. None has examined the use of sucrose throughout the NICU stay, and only 1 study evaluated the neurodevelopmental outcomes after repeated doses of sucrose. In that study, infants born at <31 weeks’ gestational age and exposed to >10 doses per day in the first week of life were more likely to show poorer attention and motor development in the early months after discharge from the NICU. Results of studies in animal models have suggested that the mechanism of action of sucrose is through opioid pathways; however, in human infants, little has been done to examine the physiologic mechanisms involved, and the findings reported thus far have been ambiguous. Drawing from the growing animal literature of research that has examined the effects of chronic sugar exposure, we describe alternative amine and hormone pathways that are common to the processing of sucrose, attention, and motor development. In addition, are view of the latest research to examine the effects of repeated sucrose on pain processing is presented. These 2 literatures each can inform the other and can provide an impetus to initiate research to examine not only the mechanisms involved in the calming mechanisms of sucrose but also in the long-term neurodevelopmental effects of repeated sucrose in those infants born extremely preterm or critically ill.

OBJECTIVES

The goals of this study were to describe nutritional practices in the first month of life for a large cohort of extremely low gestational age newborns and to determine the impact of these nutritional practices on growth velocity over the same period.

METHODS

The sample included 1187 infants born at 23 weeks to 27 weeks of gestation, at 14 institutions, between 2002 and 2004. Inclusion criteria included survival until day 28 and weight information for both day 7 and day 28. Growth velocity, expressed as grams per kilogram per day (g/kg/day), was calculated for the interval between days 7 and 28. Nutritional practices during the first week and on days 14, 21, and 28 were compared to current nutritional guidelines in the literature. Multivariable logistic regression models estimated the contribution of limited nutrition to limited growth velocity.

RESULTS

Protein and fat delivery approximated current nutritional recommendations while carbohydrate and total caloric delivery did not. Despite this, growth velocity of our study infants exceeded the current guideline of 15 g/kg/day. Nevertheless, we found extrauterine growth restriction (i.e., weight for gestational age below the 10th centile) in 75% of infants at 28 days, as compared to only 18% at birth. A growth velocity of 20-30 g/kg/day was associated with infants' maintaining or exceeding their birth weight Z-score, with rates in the upper range for the gestationally youngest infants. Early (day 7) nutritional practices were positively associated with growth velocity measured between days 7 and 28.

CONCLUSION

The early provision of nutrients is an important determinant of postnatal growth. Extrauterine growth restriction remains high in extremely premature infants even when they achieve a growth velocity rate within current guidelines.