Gilberto R. Pereira

Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes.

Objective. Necrotizing enterocolitis (NEC) is primarily a disease of the premature infant. Among children born at term, however, congenital heart disease may be an important predisposing factor for this condition. To determine risk factors for NEC in patients with congenital heart disease, we conducted a case–control study of neonates with cardiac disease admitted to the cardiac intensive care unit at our center during the 4-year period from January 1995 to December 1998. Methods. Cardiac diagnosis and age at admission were analyzed for association with NEC among the 643-patient inception cohort. Demographic, preoperative, and operative variables were recorded retrospectively in 21 neonates with congenital heart disease who developed NEC and 70 control neonates matched by diagnosis and age at admission. Using parametric and nonparametric analysis, cases and controls were compared with respect to previously identified risk factors for NEC. Results. Among the entire cohort of 643 neonates with heart disease admitted to the cardiac intensive care unit, diagnoses of hypoplastic left heart syndrome (odds ratio [OR] = 3.8 [1.6–9.1]) and truncus arteriosus or aortopulmonary window (OR = 6.3 [1.7–23.6]) were independently associated with development of NEC by multivariable analysis. In the case–control analysis, earlier gestational age at birth (36.7 ± 2.7 weeks vs 38.1 ± 2.3 weeks), prematurity (OR = 3.9 [1.2–12.5]), highest dose of prostaglandin >0.05 μg/kg/minute (OR = 3.9 [1.2–12.5]), and episodes of low cardiac output (meeting specific laboratory criteria) or clinical shock (OR = 6.5 [1.8–23.5]) correlated with the development of NEC. Earlier gestational age and episodes of low output were the only factors that remained significantly associated with NEC by multivariable analysis. Although there was no difference in hospital mortality between patients with and without NEC, mean hospital stay was significantly longer in those who developed NEC (36 ± 22 days vs 19 ± 14 days). Conclusions. The risk of NEC in neonates with congenital heart disease is substantial. Factors associated with an elevated risk of NEC in infants with heart disease include premature birth, hypoplastic left heart syndrome, truncus arteriosus, and episodes of poor systemic perfusion or shock. Heightened suspicion is warranted in newborns with these risk factors.

Effect of neonatal caloric deprivation on head growth and 1-year developmental status in preterm infants

The effects of neonatal illness and caloric intake on head growth velocity and on 1-year developmental outcome were studied in 73 appropriate (AGA) and small for gestational age (SGA) premature infants of (mean +/- SD) 30 +/- 2 weeks gestation who received intensive care during the neonatal period. Head growth from birth to 1 year of corrected age was characterized by a triphasic curve initiated by a period of growth arrest or suboptimal growth followed by a period of catch-up growth and terminated by a period of growth along standard curves. Head growth arrest or suboptimal head growth were directly related to the duration of the initial period of caloric deprivation (less than 85 kcal/kg/day) and to the duration of mechanical ventilation. Catch-up head growth was influenced by the duration of the preceding period of caloric deprivation in all infants and by the caloric intake during that phase only in SGA infants; catch-up growth was unrelated to the duration of mechanical ventilation. Head growth along standard curves occurred in all infants by 3 months of corrected age and persisted up to 1 year of corrected age. Infants calorically deprived the longest (AGA 4 to 6 weeks, SGA 2 to 3 weeks) had head growth along standards at curves below -1 SD on the growth chart; all other groups had this phase of head growth at curves between the mean and -1 SD. Infants calorically deprived for more than 4 weeks had developmental scores below normal ranges by 1 year of corrected age.

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.

Mid-arm circumference and mid-arm/head circumference ratios: standard curves for anthropometric assessment of neonatal nutritional status.

Two hundred four neonates, 25 to 42 weeks estimated gestational age (EGA), were measured on day 2 or 3 of life for upper mid-arm circumference (MAC) and head circumference. Regression analysis was used to construct standard curves for MAC versus EGA and mid-arm circumference/head circumference ratio (MAC/HC) versus EGA. Correlation coefficients were 0.93 for MAC versus EGA, and 0.84 for MAC/HC versus EGA. MAC, MAC/HC, and head circumference were also highly correlated with birth weight. These measurements may more accurately assess intrauterine growth and body proportionality at birth than weight, length, and head circumference.

Taurine deficiency in the severe hepatic dysfunction complicating total parenteral nutrition

The etiology of the severe hepatic dysfunction associated with total parenteral nutrition (TPN) remains unknown, but recent studies suggest that taurine deficiency may be associated with the development of cholestasis in experimental animals. That taurine deficiency might also play a role in the development of the severe hepatic dysfunction in human infants receiving TPN as their sole nutritional intake is the subject of the present report. Serial plasma aminograms were obtained from three children with severe hepatic dysfunction associated with TPN, in whom progressive disease led to death after 20, 13, and 14 months. All three children underwent massive intestinal resection for necrotizing enterocolitis, leaving 30, 44, and 17 cm of viable small bowel, respectively. Balanced TPN was given as 20 to 25 g/kg/d dextrose, 1.5 to 2.5 g/kg/d crystalline amino acids, and 2 to 3 g/kg/d fat emulsion; enteral feedings were attempted but were poorly tolerated. Mild cholestasis progressed to severe hepatic dysfunction manifested by hyperbilirubinemia, increased serum transaminases, hypoproteinemia, and abnormal coagulation profiles. Liver histology revealed extensive fibrosis, fatty replacement, and coarse cholestasis, necrosis not being prominent. Serial plasma aminograms revealed markedly elevated plasma levels of methionine (1353, 1168, and 113 nm/mL), low levels of 1/2 cystine (68.4, trace, and 17 nm/dL), and undetectable levels of taurine; plasma levels of branched-chain amino acids were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Mid-arm circumference/head circumference ratios for identification of symptomatic LGA, AGA, and SGA newborn infants

Mid-arm circumference/head circumference ratios (MAC/HC) and birth weights obtained in 73 neonates were studied to compare which of these growth measurements could more accurately predict risk of metabolic complications resulting from either acceleration or retardation of fetal growth. The MAC/HC ratio was more sensitive than birth weight in distinguishing symptomatic large for gestational age (LGA) infants who were born to diabetic mothers from other LGA infants who were asymptomatic, and symptomatic from asymptomatic small for gestational age infants. In addition, the MAC/HC ratio identified symptomatic appropriate for gestational age (AGA) infants born to diabetic mothers and AGA infants with signs and symptoms of growth retardation. The MAC/HC is more useful than birth weight in assessing newborn infants at risk for the metabolic complications associated with fetal growth disorders.

A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth.

ABSTRACT. We studied the accuracy of the ponderal index and the mid‐arm circumference/head circumference ratio for detecting newborn infants who were likely to be symptomatic because of aberrant intrauterine growth. Sixty infants were evaluated because of suspected intrauterine growth retardation; both the mean ponderal index and mid‐arm circumference/head circumference ratio were significantly lower in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants (p<0.05). However, the mid‐arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (80% vs. 47%; p=0.007). An additional 60 infants were evaluated because of suspected abnormal intrauterine growth acceleration. The mean mid‐arm circumference/head circumference ratio, but not the ponderal index, was significantly higher in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants (p<0.005). Again, the mid‐arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (79% vs. 33%; p<0.001). The mid‐arm circumference/head circumference ratio is more accurate than the ponderal index for the evaluation of potentially symptomatic newborn infants who suffered abnormal fetal growth. The ponderal index is not useful for the detection of symptomatic large‐for‐dates infants.

Prealbumin as a biochemical marker of nutritionaladequacy in premature infants

To determine whether serum prealbumin would be useful in identifying adequacy of protein and calorie intake in premature infants, 17 infants between 26 and 33 weeks gestational age were studied throughout hospitalization. Serial anthropometric measurements, nutritional intake, and serum prealbumin concentrations were correlated. When mean intake of calories and protein was lower than 100 kcal/kg/day and less than 2 gm/kg/day, respectively, there was a significant difference in mean prealbumin values, compared with those in infants with a higher intake (P much less than 0.001). For infants with birth weights of 1000 gm or less, prealbumin correlated with protein intake (r = 0.66) and calorie intake (r = 0.64). In these infants, when protein intake exceeded 2 gm/kg/day, prealbumin concentrations increased to values reported for full-term infants in the first months of life. There was no significant correlation between intake of calories or protein and prealbumin values for infants born weighing greater than 1000 gm. Anthropometric measurements did not correlate with protein or calorie intake. We conclude that prealbumin is a sensitive measure of protein and calorie intake in premature infants, and that the definition of adequate nutrition may be different for premature infants of different birth weights and at various postconceptional ages.

Use of high-fat formula for premature infants with bronchopulmonary dysplasia: Metabolic, pulmonary, and nutritional studies

The use of dietary fat in preference to carbohydrate offers the theoretic advantage of diminishing carbon dioxide production and thus the respiratory quotient, which may be beneficial for babies with chronic lung disease. Ten premature infants (birth weight (mean +/- SEM), 1.13 +/- 0.12 kg; postnatal age, 9 +/- 1 weeks) with bronchopulmonary dysplasia were alternately fed a high-fat and a high-carbohydrate formula each for 1 week, in randomized order. Lower rates of carbon dioxide production (6.6 +/- 0.3 versus 7.4 +/- 0.4 ml/kg per minute; p < 0.05), and consequently lower respiratory quotients (0.80 +/- 0.02 versus 0.94 +/- 0.01 ml/kg per minute; p < 0.005), were observed during the administration of the high-fat formula. There were no significant differences in results of pulmonary function tests with the use of either formula. Both formulas were equally well tolerated and able to promote adequate growth and normal biochemical profiles. However, weight gain was significantly greater with the administration of the high-carbohydrate formula, possibly because of an increase in the accretion of body fat. We conclude that the short-term use of high-fat formula for infants with bronchopulmonary dysplasia decreases carbon dioxide production while maintaining adequate growth and nutritional status.

Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions

The effect of heparin dose and infusion rate on plasma lipids, lipases, and unbound bilirubin was investigated in 22 premature infants with physiologic jaundice. Infants were randomly assigned to receive low or high intravenous doses (24 vs 137.3 U/day) of heparin. Each patient then received 2 g/kg/day of 10% Intralipid on 2 successive days: one day during a 15-hour period and the other day over 24 hours, with the order assigned randomly. The results demonstrate a significantly greater change in serum-free fatty acids in infants receiving the high heparin dose during the 15-hour lipid infusion period. Lipoprotein lipase activity rose more with the high heparin dose and equally at either infusion rate. We conclude that lipid infusions of 2 g/kg/day with low heparin dosage infused over 24 hours resulted in less elevation in serum-free fatty acids. There were no adverse effects on unbound bilirubin at either infusion rate or heparin dosage.