Peter J. Porcelli

Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: A randomized trial

OBJECTIVE To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes. STUDY DESIGN We conducted a two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 neonatal intensive care units. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, neonatal intensive care unit stay, and antibiotic use. RESULTS The mortality rate was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (hazard ratio, 0.78; 95% CI, 0.61-0.99; P = .04; number needed to monitor = 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared with 93.6 in control subjects, P = .08). The mortality benefit was concentrated in infants with a birth weight <1000 g (hazard ratio, 0.74; 95% CI, 0.57-0.95; P = .02; number needed to monitor = 23). There were no significant differences in the other outcomes. CONCLUSION HRC monitoring can reduce the mortality rate in very low birth weight infants.

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age

BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Increased parenteral amino acid administration to extremely low-birth-weight infants during early postnatal life.

Background Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight ≤1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit. Methods The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g · kg−1 · d−1 in the standard group and 4 g · kg−1 · d−1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid–base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome. Results The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 ± 0.83 g · kg−1 · d−1; mean, ±1 SD) and 18% greater (3.86 ± 0.94 g · kg−1 · d−1) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 ± 1.8 mEq/dL at week 1 and 23.9 ± 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 ± 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 (P < 0.03) in both groups. Conclusions Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g · kg−1 · d−1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.

Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial

Background:Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality.Methods:This is a secondary analysis of clinical and HRC data from 2,989 VLBW infants enrolled in a randomized clinical trial of HRC monitoring in nine NICUs from 2004 to 2010.Results:LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and nondisplay groups. Mortality within 30 d of LOS was lower in the HRC display as compared with the nondisplay group (11.8 vs. 19.6%; relative risk: 0.61; 95% confidence interval: 0.43, 0.87; P < 0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed.Conclusion:Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants

BACKGROUND Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. OBJECTIVE Evaluate relationship between early postnatal nutriture and ROP surgery. DESIGN/METHODS Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). RESULTS BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. CONCLUSIONS Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates.

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

Background/Aims: Human milk fortification has been advocated to enhance premature infants’ growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. Methods: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. Results: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 ± 2.1 vs. 144.4 ± 2.5 ml/kg/day, mean ± SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 ± 1.3 and 20.4 ± 1.2 g/day, p < 0.05; head circumference 1.0 ± 0.1 and 0.8 ± 0.1 cm/week; length 0.9 ± 0.1 and 0.8 ± 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. Conclusions: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Plasma and urine riboflavin and pyridoxine concentrations in enterally fed very-low-birth-weight neonates

Preterm infant formulas (PIFs) for very-low-birth-weight (VLBW) infants (birth weight, < 1,500 g) are augmented to provide daily riboflavin and pyridoxine at levels up to five-fold greater than in term infant formula and 18-fold greater than in human milk. We evaluated plasma riboflavin and pyridoxine concentrations in VLBW infants who received PIF during their first postnatal month. Eighty-eight plasma and 124 urine samples were collected for riboflavin- and pyridoxine-concentration measurements from 57 clinically healthy VLBW infants weekly during their first postnatal month. Concentrations were measured using high-performance liquid chromatography. At the time of the sample, patients were receiving > or = 80% of their total calories via enteral feedings. Plasma riboflavin concentrations rose from 45.3 +/- 7.3 ng/ml at baseline (mean +/- SEM) to 173.5 +/- 20.3 ng/ml by 1 week of age and remained at 177.3-199.7 ng/ml during the following three weekly measurements; values were up to 14-fold above baseline concentration. Urine riboflavin concentration increased from 534 +/- 137 ng/ml at baseline to 3,521 +/- 423 ng/ml by 1 week of age and remained at 4,451-5,216 ng/ml during the next 3 weeks. In a similar pattern, baseline plasma (69.4 +/- 10.4 ng/ml) and urine (145 +/- 30 ng/ml) pyridoxine concentrations were significantly increased by 1 week postnatal age; they remained at 163-248 ng/ml (plasma) and 1,573-2,394 ng/ml (urine) through the first postnatal month. Plasma and urine riboflavin and pyridoxine concentrations in enterally fed VLBW infants increased from baseline concentrations by 1 week of postnatal age and remained elevated for the first postnatal month. High daily intake and immature renal development are probable contributing causes of the elevated plasma riboflavin and pyridoxine concentrations. We suggest that lower daily enteral administration of riboflavin and pyridoxine should maintain adequate blood concentrations and minimize potential toxicity.

A Survey of Neonatal Parenteral Nutrition Design Practices in North Carolina

BACKGROUND: Parenteral nutrition is an important component of postnatal hospital care for very-low-birth-weight infants (VLBW; birth weight ≤1500 g). Designing and preparing parenteral nutrition for VLBW infants is a complicated process requiring many nutrition decisions and mathematical computations, a process most medical centers have developed independently. The goal of this project was to examine the nutrition design practices and resources of regional neonatal intensive care units (NICUs).METHODS: In depth interviews were conducted with neonatal nutrition health-care providers at eight medium to large NICUs in North Carolina to describe the patient population, the nutrition support staff, nutrition decision-making procedures and resources, the design of parenteral nutrition, and problems with parenteral nutrition design and preparation.RESULTS: The eight centers reported an average of 182 VLBW infant admissions and prepared 4810 parenteral nutrition orders per year. Five centers employed experienced neonatal nutrition staff to offer decision support. Six centers used paper parenteral nutrition order forms, all of which provided some decision guidance such as a recommended ordering dose range. Self-reported medical mistakes included incorrect parenteral nutrition additive dilutions and incorrect supplementation of parenteral nutrition additives.CONCLUSIONS: Most NICUs offered nutrition resource personnel and used paper parenteral nutrition order forms, which offered a wide range of decision guidance. About half the reported medical errors could be addressed using electronic parenteral nutrition design; however, a broader, more general approach to the entire design and administration system would reduce more errors. Last, as development of electronic neonatal nutrition resources in the clinical arena progresses, standards for recording neonatal nutrition content, and evaluating the effect of decision support need to be identified.

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants.

Introduction: Very-low–birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. Methods: Preterm infants with birth weight ≤1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid®. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, χ2, and analysis of variance. Results: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 ± 29 g and 25.5 ± 0.3 weeks (mean ± SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 ± 0.009 mg/kg/day), 35% more vitamin A (318.3 ± 11.4 μg/kg/day), and 14% more vitamin E (3.17 ± 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 ± 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 ± 0.022 μg/mL) and vitamin E (22.26 ± 1.61 /mL) concentrations were greater in the modified group. Conclusions: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.

A New Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) Supplemented Preterm Formula: Growth and Safety Assessment. † 1440

A New Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) Supplemented Preterm Formula: Growth and Safety Assessment. † 1440