OBJECTIVE:In the process of sampling blood through an umbilical arterial catheter (UAC), infant blood comes into stagnant contact with infusion solution in the "waste syringe" before being reinfused. We have previously demonstrated in vitro that this process is associated with less hemolysis of red blood cells (RBCs) with use of an isotonic solution compared with a hypotonic 0.25 normal saline (NS) solution. The objective of this study was to compare the in vivo effect on hemolysis of 2 UAC infusion/flush regimens (an isotonic regimen vs a hypotonic regimen) and to assess the early nutritional benefit of an amino acid solution as the isotonic UAC infusion solution. METHODS:Infants who had a birth weight of < or =1.5 kg and were expected to have a UAC for > or =3 days were enrolled within 24 hours of life into this prospective, double-blind, randomized, clinical trial of 2 UAC infusion solution/flush regimens. Power analysis demonstrated that 40 infants were needed to determine differences in hemolysis quantified by plasma-free hemoglobin (PFH) level. Nutrition from glucose was evaluated by measurement of daily dextrose calories. C-peptide was measured to evaluate endogenous insulin production. Adverse events and protein tolerance were tracked. RESULTS:Twenty-two infants (mean gestational age: 27 weeks; 945 g birth weight) were enrolled in each group, for an average of 4.2 days (range: 2.5-8 days). There were no group differences in demographics. PFH levels were lower for infants who received isotonic amino acid (IAA) in comparison with 0.25 NS (33 +/- 14 mg/dL vs 62 +/- 27 mg/dL, respectively). C-peptide was higher in those who received IAA, as were nonprotein calories received on days 4 to 6 of the study (51 +/- 11 kcal/kg/day vs 44 +/- 12 kcal/kg/day, IAA vs 0.25 NS, respectively). CONCLUSIONS:Lower PFH levels in IAA versus 0.25 NS group were consistent with our hypothesis of decreased hemolysis with an isotonic infusion/flush regimen. IAA use may also allow greater early glucose nutrition, as indicated by the higher level of endogenous insulin production and improved glucose tolerance. IAA seems to be a superior UAC solution to 0.25 NS in that it is associated with less hemolysis and improved nutrition.

OBJECTIVE:Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are long-chain polyunsaturated fatty acids found in breast milk and recently added to infant formulas. Their importance in infant nutrition was recognized by the rapid accretion of these fatty acids in the brain during the first postnatal year, reports of enhanced intellectual development in breastfed children, and recognition of the physiologic importance of DHA in visual and neural systems from studies in animal models. These considerations led to clinical trials to evaluate whether infant formulas that are supplemented with DHA or both DHA and ARA would enhance visual and cognitive development or whether conversion of linoleic acid and alpha-linolenic acid, the essential fatty acid precursors of ARA and DHA, respectively, at the levels found in infant formulas is sufficient to support adequately visual and cognitive development. Visual and cognitive development were not different with supplementation in some studies, whereas other studies reported benefits of adding DHA or both DHA and ARA to formula. One of the first trials with term infants that were fed formula supplemented with DHA or both DHA and ARA evaluated growth, visual acuity (Visual Evoked Potential; Acuity Card Procedure), mental and motor development (Bayley Scales of Infant Development), and early language development (MacArthur Communicative Developmental Inventories). Growth, visual acuity, and mental and motor development were not different among the 3 formula groups or between the breastfed and formula-fed infants in the first year of life. At 14 months of age, infants who were fed the formula with DHA but no ARA had lower vocabulary production and comprehension scores than infants who were fed the unsupplemented control formula or who were breastfed, respectively. The present follow-up study evaluated IQ, receptive and expressive vocabulary, visual-motor function, and visual acuity of children from the original trial when they reached 39 months of age.METHODS:Infants were randomized within 1 week after birth and fed a control formula (n = 65), one containing DHA (n = 65), or one containing both ARA and DHA (n = 66) to 1 year of age. A comparison group (n = 80) was exclusively breastfed for at least 3 months after which the infants continued to be exclusively breastfed or were supplemented with and/or weaned to infant formula. At 39 months, standard tests of IQ (Stanford Binet IQ), receptive vocabulary (Peabody Picture Vocabulary Test-Revised), expressive vocabulary (mean length of utterance), visual-motor function (Beery Visual-Motor Index), and visual acuity (Acuity Card Procedure) were administered. Growth, red blood cell fatty acid levels, and morbidity also were evaluated.RESULTS:Results were analyzed using analysis of variance or linear regression models. The regression model for IQ, receptive and expressive language, and the visual-motor index controlled for site, birth weight, sex, maternal education, maternal age, and the child's age at testing. The regression model for visual acuity controlled for site only. A variable selection model also identified which of 22 potentially prognostic variables among different categories (feeding groups, the child and family demographics, indicators of illness since birth, and environment) were most influential for IQ and expressive vocabulary. A total of 157 (80%) of the 197 infants studied at 12 months participated in this follow-up study. Characteristics of the families were representative of US families with children up to 5 years of age, and there were no differences in the demographic or family characteristics among the randomized formula groups. As expected, the formula and breastfed groups differed in ethnicity, marital status, parental education, and the prevalence of smoking. Sex, ethnicity, gestational age at birth, and birth weight for those who participated at 39 months did not differ from those who did not. The 12-month Bayley mental and motor scores and 14-month vocabulary scores of the children who participated also were were not different from those who did not. At 39 months, IQ, receptive and expressive language, visual-motor function, and visual acuity were not different among the 3 randomized formula groups or between the breastfed and formula groups. The adjusted means for the control, ARA+DHA, DHA, and breastfed groups were as follows: IQ scores, 104, 101, 100, 106; Peabody Picture Vocabulary Test, 99.2, 97.2, 95.1, 97.4; mean length of utterance, 3.64, 3.75, 3.93, 4.08; the visual-motor index, 2.26, 2.24, 2.05, 2.40; and visual acuity (cycles/degree), 30.4, 27.9, 27.5, 28.6, respectively. IQ was positively associated with female sex and maternal education and negatively associated with the number of siblings and exposure to cigarette smoking in utero and/or postnatally. Expressive language also was positively associated with maternal education and negatively associated with the average hours in child care per week and hospitalizations since birth but only when the breastfed group was included in the analysis. The associations between maternal education and child IQ scores are consistent with previous reports as are the associations between prenatal exposure to cigarette smoke and IQ and early language development. Approximately one third of the variance for IQ was explained by sex, maternal education, the number of siblings, and exposure to cigarette smoke. Growth achievement, red blood cell fatty acid levels, and morbidity did not differ among groups.CONCLUSIONS:We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development, but those who were fed DHA without ARA had lower vocabulary scores on a standardized, parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed. When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ, visual-motor function and visual acuity, no differences among the formula groups or between the formula and breastfed groups were found. The 14-month observation thus may have been a transient effect of DHA (without ARA) supplementation on early vocabulary development or may have occurred by chance. The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants. In conclusion, adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months.

OBJECTIVESTo develop a succinct and comprehensive breast-feeding assessment score (BAS) to accurately identify infants at risk for early cessation of breast-feeding before initial hospital discharge.STUDY DESIGNMothers who intended to breast-feed their infants were solicited from 9 suburban hospitals. Two detailed data forms covering 107 items were completed before hospital discharge. A third form was completed at 7 to 10 days of age after telephone contact with the mother.RESULTSCessation of breast-feeding occurred in 113 of 1075 infants (10.5%). A multiple logistic regression analysis revealed 8 variables that were significant (P <.05) in predicting breast feeding cessation. A BAS was developed based on the odds ratios and relative risks of breast-feeding cessation for these 8 variables.CONCLUSIONSThe BAS was easily and quickly performed before hospital discharge for near term and term infants, which accurately predicted the risk of breast-feeding cessation within 7 to 10 days of age in the population studied.

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 </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament.RESULTS:AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated.CONCLUSIONS:These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.

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.

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.

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 ≤1600 g and gestational age at birth of ≤33 weeks were enrolled and randomized before 21 days of life. Study day (SDAY) 1 was defined as the day full-strength fortification (4 packets/100 mL) began and the infant reached an intake of at least 100 mL/kg/day. Growth, biochemical indices of nutritional status, enteral intake, feeding tolerance, clinical histories, and morbidity were assessed serially. The primary outcome variable was weight gain (g/kg/day) from SDAYs 1 to 29 or hospital discharge, whichever came first. Results. Infants fed human milk supplemented with SF consistently grew more rapidly from SDAYs 1 to 29 (or hospital discharge), regardless of whether the statistical analyses were performed on all subjects who were randomized into the study and reached SDAY 1 (intent-to-treat) or were limited to those able to adhere strictly to the feeding protocol of the study (subgroup). Using mean values adjusted for study site (least square [LS] means), the weight gain differences were 2.6 and 3.8 g/kg/day for the intent-to-treat and subgroup analyses, respectively. Likewise, the length-gain differences were .14 and .18 cm/week for the intent-to-treat and subgroup analyses, respectively. Infants in the SF group reached a weight of 1800 g at SDAY 18, and those in the CF group at SDAY 25. Mean alkaline phosphatase values among infants in the SF group were higher than for the CF infants (eg, LS means: 327 U/L vs 272 U/L, intent-to-treat analysis), likely reflecting the more rapid linear growth of the SF infants. Mean serum calcium values tended to be lower in the SF group in the intent-to-treat analysis and were significantly lower in the subgroup analysis (LS means: 10.3 mg/dL vs 11.2 mg/dL). Both fortifiers were generally well-tolerated, although an increased number of infants in the CF group exited the feeding protocol because of gastric residuals and abdominal distention. Conclusion. A new powdered HMF was shown to enhance the growth of preterm infants, compared with a commercially available powdered HMF in the United States.

Growth, Tolerance, and Morbidity of Preterm Infants Fed Exclusively Human Milk, Exclusively Preterm Infant Formula, or a Combination of Human Milk and a Preterm Infant Formula until Term Corrected Age (CA)

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.

Randomized Trial of Premature Infants Fed Human Milk and/or a Nutrient Enriched Formula with and without a Source of Arachidonic Acid (AA) and DocosahexaenoicAcid (DHA)

The article of Hall et al (J Pediatr 1998;132:345-8) is intriguing and exciting, but concerns should be raised over the study design and method. The entry criteria were soft; no information is provided as to when the ìinitialî arterial blood gas was obtained or whether resuscitative intervention had been started before measurement; depressed Apgar scores and delayed spontaneous respirations can be seen from a host of causes other than intrapartum asphyxia. More than half of the infants qualified on the basis of the latter 2 criteria only. Additional evidence of acute asphyxial injury and other features of the neonatal neurologic syndrome were not provided. Because all subjects in this study were outborn, care practices, experience, and expertise in referring hospitals may have varied considerably. The study was not blinded, and this is particularly concerning, because seizures were diagnosed clinically and without electroencephalographic confirmation. Moreover, there is no description as to what events were classified as seizures. Determination of the sample size was based on a 67% incidence of postasphyxial seizures, which is considerably higher than the range of 30% to 69% previously cited in the review by Brann,1Brann Jr, AW Factors during neonatal life that influence brain disorders.in: Prenatal and perinatal factors associated with brain disorders. National Institutes of Health Publication No. 85-1149, Bethesda (MD)1985: 263-358Google Scholar suggesting that a much larger sample size might have been required. Further demographic, obstetric, and intrapartum information regarding the nature of the ìperinatal asphyxiaî would have been helpful in determining whether the event (or events) was prenatal in origin or at what point in labor it occurred. The difference in the age at first seizure in the 2 groups could be related to the phenobarbital intervention, but it might also be related to an earlier time of injury in the control group, perhaps after the ìwindowî of therapeutic intervention had closed. The dose of phenobarbital chosen (40 mg/kg) is only slightly higher than that which many use as a standard loading dose2Donn SM Grasela TH Goldstein GW Safety of a higher loading dose of phenobarbital in the term infant.Pediatrics. 1985; 75: 1061-1064PubMed Google Scholar and is less than is often required to control postasphyxial seizures in this population. At this level it is not likely to have exerted much of an effect on cerebral metabolism and oxygen consumption. Adult literature addressing barbiturate-induced neuroprotection suggests the need to achieve close to an isoelectric state. Intrapartum asphyxia is still a considerable problem throughout the world, and I certainly applaud the efforts of these investigators to explore a solution. However, the problems they encountered in the performance of this study indicate that what is necessary is a very large, multicenter, randomizedóand blindedócontrolled, clinical trial.

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. (J Pediatr 1998;132:345-8)

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.

Objective: To describe the typical ranges for central venous oxygen saturation and Po-2 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) over bar]o(2)) and fractional oxygen extraction, r = -.77 (r(2) = .59) and -.85 (r(2) = .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.