Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study.

OBJECTIVE: To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. DESIGN: A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at

Nutritional follow-up of the breastfeeding premature infant after hospital discharge.

In summary, fortification of human milk may be beneficial in preterm infants, particularly those born at less than 34 weeks' gestation or less than 1800 g birth weight, during and after initial hospitalization. This fortification after hospital discharge is more crucial for infants who cannot consume ad libitum quantities of breast milk, have poor growth, or have abnormalities in the biochemical screen of nutritional status. Although data indicate that in-hospital, short-term gains in growth and mineral status are achieved, information is fragmentary regarding the influence on long-term growth and neurodevelopmental outcomes of feeding supplemented human milk. Also, no data are available on outcomes when providing these mixtures to premature infants after hospital discharge. It is recommended that a nutritional survey be accomplished before and approximately 1 month after discharge and that fortification or supplementation be initiated if an infant is failing to achieve normal growth and biochemical measures of nutrition.

Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.

OBJECTIVE: At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA). METHODS: Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling. RESULTS: One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different. CONCLUSIONS: Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.

Readmission of breastfed infants in the first 2 weeks of life.

OBJECTIVE: Readmission of breastfeeding infants for hyperbilirubinemia and/or dehydration has been increasing in recent years. The purpose of the current study was to characterize the indications for the condition of these infants at readmission, and to determine factors present prior to initial hospital discharge which might have identified them to be at risk. STUDY DESIGN: The records of 125 breastfeeding infants who were admitted to Children's Mercy Hospital from 1995 to 1997 in the first 2 weeks of life with diagnoses of hyperbilirubinemia, dehydration, or feeding problems were reviewed. Infants with hemolytic disease, infection, or other underlying causes were excluded. At readmission, 80 infants had total bilirubin levels > 342 mumol/l (20 mg/dl) and gestational age > or = 38 weeks or total bilirubin levels > 308 mumol/l (18 mg/dl) and gestational age < 38 weeks. Forty-nine infants had a weight loss > or = 12% from birth weight or a serum sodium concentration > or = 145 mmol/l. Twenty-six infants had both hyperbilirubinemia and excessive weight loss or hypernatremia. RESULTS: The mean gestational age of all infants was 38.6 weeks, 95% CI, 38.3 to 38.9 weeks. Mean length of initial hospital stay was 1.8 days (SD 1.03) for vaginally delivered infants compared with 3.4 days (SD 2.1) for those delivered by C-section (p = 0.003). The Cesarean birth rate (9%) was disproportionally low in infants readmitted compared with overall C-section rate in Kansas City, MO (17%) (p = 0.03). There was a significantly lower rate of readmission for infants whose initial hospital stay was > or = 3 days (p = < 0.002), but not for infants whose initial stay was > or = 2 days (p = 0.1). Infants admitted for hyperbilirubinemia only were at 38.3 +/- 1.6 weeks gestation compared with infants admitted for excessive weight loss or hypernatremia, 39.2 +/- 1.3 (p = 0.06), and 1 days older, 5.4 +/- 1.9 days vs. 4.4 +/- 2.5 days (p = 0.05). CONCLUSIONS: This study confirms that prematurity and short hospital stays are risk factors for readmission of breastfeeding infants with hyperbilirubinemia and/or excessive weight loss and hypernatremia. An initial hospital stay > or = 3 days was associated with a reduced risk for readmission of these infants.

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial.

OBJECTIVE: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the growth and nutritional status of preterm infants receiving preterm human milk supplemented with a newly formulated powdered human milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF). METHODS: Infants (n = 144) with a birth weight

Prevention of premature birth: do pediatricians have a role?

The rate of prematurity in the United States has increased over the past 15 years despite a reduction in overall infant mortality and birth weight-specific mortality. The major factors contributing to premature birth exist before pregnancy and therefore will require intervention strategies in the pediatric patient. The high-risk factors include young age at conception (16 years), use of illicit drugs and smoking, poor nutritional status, and certain vaginal infections. Pediatric intervention strategies should include sociologic as well as health education stressing heightened self-esteem and communication skills, avoidance of pregnancy and unprotected sexual activity, avoidance of smoking and drug use, and promotion of a good nutritional status.

Double-blind, randomized study of the effects of influenza vaccination on the specific antibody response and clinical course of patients with chronic fatigue syndrome.

OBJECTIVE: To determine whether influenza immunization is associated with early side effects, a deleterious impact on the illness course and depressed antibody response in patients with chronic fatigue syndrome (CFS). DESIGN: Prospective, randomized, double-blind, placebo controlled trial. CFS patients and healthy volunteers filled out a questionnaire on immunization side effects and had hemagglutination-inhibiting (HI) antibody titres measured pre- and three weeks after immunization. CFS patients completed symptom and function questionnaires before and during the six-week, postimmunization period. SETTING: Ambulatory care. POPULATION STUDIED: Convenience sample of 40 CFS patients fulfilling the Centers for Disease Control and Prevention criteria and 21 demographically matched healthy volunteers. INTERVENTIONS: CFS patients were randomly selected to receive commercially available whole virus influenza vaccine (n=19) or an injection of saline placebo (n=21). Healthy volunteers received vaccine only. MAIN RESULTS: As a group, immunized CFS patients had lower geometric mean HI antibody rises than healthy volunteers (P<0.001). However, there was no difference in the rates of fourfold titre rises, and immunization did achieve a probably protective titre (1:32 or greater) in most CFS patients. No difference could be detected between immunized and placebo CFS patients in immunization side effects, although CFS patients as a group reported four times as many side effects as healthy volunteers. Further, in the six weeks following immunization, placebo and immunized CFS patients did not demonstrate any differences in terms of functioning, symptom severity and sleep disturbance. CONCLUSIONS: In patients with CFS, influenza immunization is safe, not associated with any excess early reactions, and stimulates an immunizing response comparable with that of healthy volunteers.

Indications for surfactant therapy--the aAPO2 coming of age.

Indications for administration of surfactant to infants with established respiratory distress syndrome (RDS; rescue therapy) remains an area of continued investigation. Current recommendations vary from use in infants who are intubated and have an aAPO2 <0.22 to use in infants receiving >/=40% oxygen administered in a hood when the PaO2 is <80 TORR (aAPO2 approximately <0.36). This commentary is written in response to the article by Verder et al, in this issue of Pediatrics, who evaluated early versus late treatment of RDS in 60 preterm infants <30 weeks' gestation receiving nasal continuous positive airway pressure (CPAP). Early-treated infants (aAPO2, 0.22 to 0.35; mean, 0.26) had a lower incidence of mechanical ventilation or death (21%) than did late-treated infants (63%), who did not receive surfactant treatment until the aAPO2 was <0.22 (0.15 to 0.21; mean, 0.16). The authors conclude that although approximately half of infants <30 weeks' gestation with RDS can be treated with nasal CPAP alone, early treatment with surfactant when the aAPO2 is 0.22 to 0.36 reduced significantly the need for mechanical ventilation. Limitations of applicability of the study to widespread use include determination of PO2 values from transcutaneous measurements, which may vary from those obtained from arterial samples and affect significantly aAPO2 ratios. Likewise, use of nasal CPAP significantly affects oxygenation, and interpretation of results cannot be extrapolated to intubated infants or those receiving oxygen delivered under a hood. Nonetheless, the use of the aAPO2 ratio and early administration of surfactant are supported by this study.

Increased survival in low birth weight neonates given prophylactic surfactant.

OBJECTIVE: To compare the effectiveness of a prophylactic surfactant treatment strategy (PRO) to the effectiveness of a rescue (RESC) surfactant treatment strategy in patients at high risk for developing hyaline membrane disease (HMD). STUDY DESIGN: We analyzed data from a retrospective cohort consisting of all patients admitted to the neonatal intensive care units at the centers participating in the recently completed Infasurf-Survanta Comparative Trial. To be in the cohort, a patient had to be admitted during the trial, be <48 hours of age on admission, have a gestational age of <30 weeks, have a birth weight of 501 to 1250 gm, and be free of congenital anomalies. Twelve centers participated in this study. They contributed 1097 patients of whom 381 were treated with a PRO strategy. RESULTS: Survival was significantly higher in the PRO-strategy patients (84% vs 72%, p < 0.05) as was survival without oxygen requirement at a postconceptional age of 36 weeks (60% vs 46%, p < 0.05). In addition, the patients with PRO had a lower prevalence of grade III and IV intraventricular hemorrhage (IVH, 9% vs 14%, p < 0.05). All analyses were controlled for birth weight and type of study center. CONCLUSION: These data support the conclusion that using a PRO treatment strategy results in improved survival in patients at risk for developing HMD. A PRO treatment strategy may also decrease the likelihood of developing a severe IVH.

High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: a randomized, prospective study with three-year follow-up.

OBJECTIVE: To determine whether 40 mg/kg phenobarbital given to term infants with severe asphyxia would result in a lower incidence of seizures in the newborn period and an improved neurologic outcome. METHODS: We conducted a randomized, controlled, prospective study. Entry criteria included (1) an initial arterial pH less than or equal to 7.0 with a base deficit 15 mEq/L or more, (2) Apgar score less than or equal to 3 at 5 minutes of age, or (3) failure to initiate spontaneous respiration by 10 minutes of age. Sample size was calculated to detect a 50% reduction in the incidence of neonatal seizures. RESULTS: No differences were present between treatment and control groups with respect to severity of asphyxia assessed by initial arterial pH, base excess, cerebrospinal fluid lactate dehydrogenase concentration or detection of CSF creatine kinase of its BB isoenzyme. Seizures occurred in 9 of 15 infants in the treatment group and 14 of 16 infants in the control group (p = 0.11). No adverse effects were observed from phenobarbital on heart rate, respiratory rate, blood pressure, or arterial blood gas values. Three-year follow-up revealed normal outcome in 11 of 15 infants in the treatment group and 3 of 16 in the control group (p = 0.003). CONCLUSION: Phenobarbital, when administered in a dose of 40 mg/kg intravenously over 1 hour in term, severely asphyxiated newborn infants appeared to be safe and was associated with a 27% reduction in the incidence of seizures and a significant improvement in neurologic outcome at 3 years of age.

Comparison of Infasurf (calf lung surfactant extract) to Survanta (Beractant) in the treatment and prevention of respiratory distress syndrome.

OBJECTIVE: To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. PATIENTS: The treatment arm enrolled infants of

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Salt supplementation, growth, and nephrocalcinosis in the furosemide-treated weanling rat.

OBJECTIVE: Furosemide treatment in the human neonate is associated with sodium depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary sodium intake is known to directly influence urinary calcium excretion. The objectives of this study were to create a rat model of furosemide-induced nephrocalcinosis and to test the effects of dietary sodium supplementation on growth, electrolyte balance, calciuria, and renal calcifications. METHODS: Initially, 18 weanling Sprague-Dawley rats were randomly divided into three groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium-enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally daily for 28 days. At the end of the study, serum, urine, and kidney samples were obtained for biochemical and histologic analyses. The three groups were then compared for differences in growth, electrolyte homeostasis, calcium excretion and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm our findings regarding urinary calcium excretion and kidney calcifications. RESULTS: Treatment with furosemide without sodium supplementation (group B) resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0 +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05), and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney; p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected electrolyte abnormalities without increasing calciuria or nephrocalcinosis. CONCLUSIONS: We conclude that in this animal model, chronic furosemide treatment results in growth failure and development of nephrocalcinosis. Sodium supplementation protects against the deleterious effects of furosemide on weight gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.

Evaluation of neonatal whole blood versus plasma glucose concentration by ion-selective electrode technology and comparison with two whole blood chromogen test strip methods.

OBJECTIVE: Determination of glucose concentration from whole blood samples in neonates is confounded by variable hematocrit values, sample source, user technique, and test method, which results in poor correlation with glucose values measured from plasma or serum. Recently developed ion-selective electrodes (ISE) allow measurement of glucose in the water phase of both red blood cells and plasma with a small sample size (200 microliters). STUDY DESIGN: The purpose of this study was to compare (1) whole blood and plasma glucose measurements by the ISE method and (2) ISE glucose values with those determined by two chromogen reagent test strip colorimetric methods. Values were determined in 180 different samples obtained from 145 infants. RESULTS: Correlation of whole blood and plasma glucose concentrations determined by the ISE method was excellent (y = 0.99x, R2 = 0.99) and no effect was seen from hematocrit values. The two chromogen test strip methods also revealed good linearity with ISE whole blood and plasma glucose values but had large confidence intervals for individual values. Sensitivity for detecting blood glucose levels < 40 mg/dl by the two test strip methods was 9 of 11 and 9 of 10 with four and one false-positive results, respectively. CONCLUSION: These data indicate that the ISE method provides an excellent correlation of whole blood and plasma glucose measurement results, overcoming technical problems of differing hematocrit values and serum or plasma sample acquisition in neonates. Chromogen test strip methods have limited value in estimating specific glucose values, but can be useful in screening infants for hypoglycemia.

Feeding of premature infant formula after hospital discharge of infants weighing less than 1800 grams at birth.

A randomized, double-blind study was conducted to determine whether continued feeding of premature infant formula after hospital discharge improve biochemical measures of bone mineral or protein status and anthropometrics during the first 8 and 12 weeks, respectively, after initial hospital discharge. Forty-three subjects were randomized to receive either a 20 kcal/ounce standard cow's milk-based formula with iron or a 20 kcal/ounce premature infant formula with iron for 8 weeks after hospital discharge. Sixteen exclusively breast-fed infants (mother's own milk) who received a multivitamin supplement with iron were compared with infants in both formula groups. There were no differences among the three groups in gender, birth weight, gestational age, or weight and age at the time of study entry. Alkaline phosphatase values were lower in infants receiving premature infant formula than in those receiving standard formula 8 weeks after discharge. Phosphorus values were lower and alkaline phosphatase values higher in the human milk-fed group than in both formula groups 8 weeks after discharge despite supplementation with calcium, phosphorus, and vitamin D before and during the study. At 8 weeks after discharge, human milk-fed infants also had lower transferrin levels than infants fed formulas. Infants in both formula groups grew similarly in weight, whereas the infants fed human milk weighed less throughout the study. The group fed premature infant formula had greater mean length and head circumference than the standard formula or human milk-fed groups. These data indicate that premature infants weighing < 1800 gm at birth may benefit from the continuation of premature infant formula during the first 8 weeks after initial hospital discharge.

Value of negative nose and ear cultures in identifying high-risk infants without early-onset group B streptococcal sepsis.

Initiation of antibiotic therapy shortly after birth in infants at high risk for early-onset group B streptococcal sepsis is a common practice. The purpose of the current study was to evaluate whether the absence of group B streptococcal isolation from nose or ear cultures in such infants would have a high negative predictive value and low false-negative rate in predicting infants without sepsis and therefore whether such cultures would be of value in determining in which infants antibiotics could be safely discontinued. Infants admitted to the neonatal intensive care unit during 1989 and 1990 had a nasal culture obtained at admission and during 1991 and 1992 had an ear canal culture. Infants in whom sepsis was suspected had a blood culture in addition to a complete blood cell count, urine latex agglutination study for group B streptococci antigen, chest roentgenography and frequent monitoring of physiologic variables. The negative predictive value of nose and ear was 99% (2144 of 2149) and the false-negative rate was 7% (five negative surface cultures from 72 infants with sepsis in whom surface cultures were obtained). All five false-negative cultures were obtained from the ear canal. The false-negative rate of nose cultures was 0% (0 of 35). The high negative predictive value and low false-negative rate of nose cultures in identifying infants without sepsis suggest that nose cultures may provide additional valuable information in identifying the infant in whom antibiotics may be safely discontinued in the absence of other factors suggestive of systemic infection.

Mixed venous oxygenation in critically ill neonates.

OBJECTIVE: To describe the typical ranges for central venous oxygen saturation and PO2 in a group of critically ill neonates and the relationship of these measurements to measurements of arterial oxygenation and indicators of oxygen supply and demand. DESIGN: Survey. SETTING: Newborn intensive care unit (ICU) in a children's hospital. PATIENTS: Eighteen newborn infants (1 to 3 days old) who required mechanical ventilation for respiratory diseases, but who were hemodynamically stable and in acid-base balance. INTERVENTIONS: Umbilical artery and right atrial catheterization were performed, allowing simultaneous blood gas sampling. MEASUREMENTS AND MAIN RESULTS: Simultaneous umbilical arterial and right atrial blood gas measurements were analyzed (n = 100). Mean mixed venous oxygen saturation was 83.3% and mixed venous oxygen tension 37.8 torr (5.1 kPa). The mixed venous oxygen saturation correlated well with the arterial-venous oxygen content difference (C[a-v]O2) and fractional oxygen extraction, r = -.77 (r2 = .59) and -.85 (r2 = .72), respectively (p < .0005). Poor correlation was found between the mixed venous oxygen saturation and arterial oxygen saturation values. Two cases are presented in which measurements of mixed venous oxygenation led to recognition of apparent tissue hypoxia earlier than did measurements of arterial oxygenation. CONCLUSIONS: We conclude that measurement of central venous oxygenation in ill neonates may reflect more accurately the oxygen supply and demand status of the neonate than measurement of arterial oxygenation alone.