Protein/amino acid metabolism and nutrition in very low birth weight infants.

A large number of studies in recent years have described protein and nitrogen metabolism in the neonate. However, the majority of these data are difficult to interpret because of a number of confounding variables, particularly in very low birth weight (VLBW) infants. In contrast, application of state-of-the-art tracer isotopic and molecular biology methods in isolated cell system and whole animals has resulted in major advances in our understanding of the regulation of protein breakdown, synthesis, and protein accretion. The following workshop summary reviews the recent developments in basic physiology of protein metabolism in cellular and animal models in relation to human preterm infants, and identifies the important areas toward which future basic and clinical research should be directed to provide for optimal nitrogen accretion and growth of the VLBW infant.

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS: Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS: Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Malnutrition and drug metabolism in fetal and neonatal animals.

Protein-calorie malnutrition in experimental animals resulted in a complex picture of changes in various drug-metabolic pathways. The need for these studies is discussed in the context that undernutrition is prevalent in many countries and coincides with many intercurrent illnesses in the affected populations. The need of these affected populations for appropriate therapies is recognized, and these therapies should be based on scientific principles rather than on empiricism.

Environmental hazards in milk and infant nutrition.

Epidemiologic studies have provided much of the knowledge concerning adverse side effects of exposure to drugs and other xenobiotics transmitted via breast milk. Adverse effects can be immediate and usually recognizable or long-term and difficult to define. Acute effects may be due to individual idiosyncrasy, allergic reaction, or manifestation of acute toxicity. We need further human clinical investigations to determine actual dosing to nursing infants and to ascertain the existence of subtle and presently unrecognized long-term effects.

Effect of protein depletion and intrauterine growth retardation on rat hepatic drug metabolism.

The effect of intrauterine malnutrition in rats on in vivo and in vitro drug metabolism at weaning was investigated. We have employed two experimental designs to produce intrauterine malnutrition, maternal dietary protein depletion starting at day 7 of gestation and unilateral ligation of the uterine artery on day 17 of gestation. At birth cross-fostering of newborns was done, experimental and control group of litters raised separately until weaning (21 days of age). Both methods produced offspring with lower body and liver weights and these changes were present at weaning. However, only in the protein-restricted group were significant differences for liver:body weight ratio and hepatic microsomal protein content observed. Liver microsomal cytochrome P-450 and b5 contents were significantly decreased in small animals from mothers with intrauterine vessels ligated but not in the prenatal protein-restricted group. A significant increase in aminopyrine N-demethylase and a decrease in aniline hydroxylase enzyme activities was observed in both experimental groups. No significant differences were found in reductive or conjugative pathways of drug metabolism. Hexobarbital sleeping time was significantly increased in weanling animals from the prenatal protein-restricted mothers but not in the uterine-vessels-ligated group. These results suggest that maternal malnutrition may play an important role in modulation of postnatal drug metabolism pattern of progeny.

Alpha fetoprotein screening and diagnosis of fetal open neural tube defects: the need for quality control.

A workshop, held in May, 1978, at the National Institute of Child Health and Human Development, considered the quality control of reagents and assays for measuring alpha fetoprotein (AFP) in maternal serum and amniotic fluid for the antenatal screening and diagnosis of open neural tube defects. The recommendations, published in detail elsewhere and summarized in this article, were based on what was known to be readily achievable and on estimates of the effect of assay performance on screening and diagnostic sensitivity and specificity. Main points considered included: (1) choice of units for AFP measurement and interpretation, (2) need for National AFP Reference Preparations and the need for a scientific panel to assess the adequacy of these reference materials, (3) information needed from reagent manufacturers, (4) criteria for assay performance, (5) biological sources of reagents, (6) need for laboratory and epidemiologic monitoring, and (7) need for a minimum assay workload.