The incidence of osteopenia of prematurity in preterm infants without phosphate supplementation: A prospective, observational study.

ABSTRACT: To meet their requirements for bone mineralization, it is recommended that preterm infants receive nutritional support containing calcium and phosphate. There are no clear data on the incidence of osteopenia of prematurity (OFP) in preterm infants without phosphate supplementation.This study aimed to investigate the incidence of OFP in preterm infants without phosphate supplementation and its relationship with the duration of parenteral nutrition (PN).This was a prospective and observational study.This study included 30 infants aged <32 gestational weeks and weighed <1500 g at birth. All infants received PN according to a standard protocol, beginning on day 1 with calcium, without phosphate. Starting from the first day of life, all infants received human milk without fortifiers. Oral vitamin D (400 IU/d) was administered when enteral nutrition reached 100 mL/kg/d.The diagnosis of OFP was based on radiographs that were taken of both wrists. Serum alkaline phosphatase (ALP) was measured 3 times: at the start of PN (ALP 1), at the end of PN (ALP 2), and at discharge or the expected due date (ALP 3). Radiographs were obtained on the same day as ALP 3. The duration of PN was analyzed in the presence of OFP using receiver operating characteristic curve analysis.Among the 30 infants, 13 (43%) were diagnosed with OFP. The duration of PN was significantly longer in the OFP group than in the group without OFP (16 vs 12 days; P < .05). The provision of PN for >15 days significantly increased the risk of OFP (odds ratio, 5.40; 95% confidence interval, 1.12-26.04; P = .035).We found a high incidence of OFP in preterm infants without phosphate supplementation. An association was found between the duration of PN and the incidence of OFP. Further research is needed to prevent the development of osteopenia in preterm infants.

Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle.

Cardiorespiratory function is not only the foremost determinant of life after premature birth, but also a major factor of long-term outcomes. However, the path from placental disconnection to nutritional autonomy is enduring and challenging for the preterm infant and, at each step, will have profound influences on respiratory physiology and disease. Fluid and energy intake, specific nutrients such as amino-acids, lipids and vitamins, and their ways of administration -parenteral or enteral-have direct implications on lung tissue composition and cellular functions, thus affect lung development and homeostasis and contributing to acute and chronic respiratory disorders. In addition, metabolomic signatures have recently emerged as biomarkers of bronchopulmonary dysplasia and other neonatal diseases, suggesting a profound implication of specific metabolites such as amino-acids, acylcarnitine and fatty acids in lung injury and repair, inflammation and immune modulation. Recent advances have highlighted the profound influence of the microbiome on many short- and long-term outcomes in the preterm infant. Lung and intestinal microbiomes are deeply intricated, and nutrition plays a prominent role in their establishment and regulation. There is an emerging evidence that human milk prevents bronchopulmonary dysplasia in premature infants, potentially through microbiome composition and/or inflammation modulation. Restoring antibiotic therapy-mediated microbiome disruption is another potentially beneficial action of human milk, which can be in part emulated by pre- and probiotics and supplements. This review will explore the many facets of the gut-lung axis and its pathophysiology in acute and chronic respiratory disorders of the prematurely born infant, and explore established and innovative nutritional approaches for prevention and treatment.

A Review of Bioactive Factors in Human Breastmilk: A Focus on Prematurity.

Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.

Accuracy of transcutaneous bilirubinometry in the preterm infants: a comprehensive meta-analysis.

BACKGROUND: Transcutaneous bilirubin (TcB) measurement is widely used in term babies. But its effectiveness till debated in preterm infants. So, our objective was to pool data to see the accuracy of transcutaneous bilirubinometry in preterm infants. METHOD: MEDLINE, Embase, Cochrane Library database were searched from 2000 to July 2017. The included studies had compared TcB with total serum bilirubin (TSB) in preterm infants before phototherapy and data were presented as correlation coefficients. Data were extracted by two reviewers and checked for accuracy by the third reviewer. The risk bias assessments were done by an assessment quality assessment of diagnostic accuracy studies tool. Pooled correlation coefficient assed after Fisher's z transformation and then converted to r. RESULTS: We included 28 studies; all those studies reported results as correlation coefficients. In combination of both sternal and forehead site measurement, our pooled estimates of r = 0.82 (95% CI: 0.78-0.85) in random effect and r = 0.803 (95% CI: 0.78-0.81) in fixed effect model. For separate sites of measurement of TcB pooled r for forehead and sternum were comparable, r = 0.82 (95% CI: 0.78-0.85), and pooled correlation coefficient for the two devices JM103 and Bilicheck the estimated pooled r were also comparable (Pooled r = 0.83). CONCLUSION: Our study found that TcB measurement is well related with TSB values and can represent a reliable method for evaluating preterm infants with possible hyperbilirubinemia. Our findings support the use of investigated devices at both forehead and sternum sites in preterm infants.

[Hypophosphatemia in preterm infants: a bimodal disorder]. / Hipofosfemia en recién nacidos prematuros: un trastorno bimodal.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure.

The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency and aberration in sex hormone levels. As a neurotrophic hormone that is intimately involved in the cardiovascular regulation and whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus a therapeutic agent. As a product of maternal and late fetal adipocytes and the placenta, circulating leptin typically surges late in gestation and declines after delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish the circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation.

Mineral status of premature infants in early life and linear growth at age 3.

BACKGROUND: Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease (metabolic bone disease of prematurity, MBDP). MBDP is frequently found in very low-birthweight (VLBW) infants, but long-term height prognosis is not well known. METHODS: VLBW infants from two major neonatal intensive care units were studied. Medical records were reviewed. A total of 143 subjects were analyzed after excluding subjects who died, or who had severe complications that could affect linear growth, Silver-Russell syndrome, severe cholestasis, and/or chromosomal abnormality. The relationship between MBDP and height at age 3 was investigated. RESULTS: Height standard deviation score (SDS) at age 3 negatively correlated with peak serum alkaline phosphatase (ALP) activity in early life (r = -0.30, P = 0.0003) and positively correlated with serum phosphorus (P) at peak ALP (r = 0.33, P = 0.0002). In addition, serum P independently affected height SDS at 3 years of age (ß = 0.19, P = 0.018), and was significantly different between infants with and without catch-up growth in height (difference: 0.23 mmol/L, 95%CI: 0.09-0.36, P = 0.0010). CONCLUSIONS: MBDP, particularly hypophosphatemia in the early period of life, is associated with linear growth until 3 years of age in VLBW infants.

Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease.

Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.

Biomarkers of brain damage in preterm infants.

OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.

Skin bilirubin measurement during phototherapy in preterm and term newborn infants.

BACKGROUND: The few existing studies evaluating the reliability of transcutaneous bilirubin monitoring during phototherapy gave controversial results. AIMS: To evaluate the accuracy of transcutaneous bilirubin measurement in a large population of newborn infants, during phototherapy. STUDY DESIGN AND METHODS: Total serum bilirubin and transcutaneous bilirubin on patched and unpatched skin areas were simultaneously measured in newborn infants undergoing phototherapy. Transcutaneous measurements were performed with a multiwavelength transcutaneous bilirubinometer (Respironics BiliCheck). The Passing-Bablok regression and the Bland-Altman plot were used to estimate the relationship between serum and transcutaneous bilirubin. RESULTS: We studied 364 newborn infants with a mean (SD) gestational age of 34.6 (3) weeks and a mean birth weight of 2371 (805) grams. Total serum bilirubin, patched transcutaneous bilirubin and unpatched transcutaneous bilirubin were similar before phototherapy. After 52 (33) hours of phototherapy, the difference between serum bilirubin and patched transcutaneous bilirubin was 0.2 (3.1) mg/dL (not significant) while the difference between serum bilirubin and unpatched transcutaneous bilirubin was 3.2 (3.0) mg/dL (p<0.001). Statistical analysis showed a good agreement between serum bilirubin and patched transcutaneous bilirubin, while unpatched transcutaneous bilirubin underestimates serum levels. The difference between patched and unpatched values was significantly lower in preterm than in term infants (2.8 mg/dL vs. 3.6 mg/dL; p<0.001). CONCLUSION: BiliCheck can be safely used for the evaluation of bilirubin levels in newborn infants under phototherapy. Its reliability on patched skin of the forehead is high enough to consistently reduce blood draws and to ascertain when to discontinue phototherapy. Because of the individual variance, any clinical decision has to be taken on the basis of the transcutaneous bilirubin trend more than on a single value.

Metabolic responses to early and high protein supplementation in a randomized trial evaluating the prevention of hyperkalemia in extremely low birth weight infants.

OBJECTIVE: To determine whether early and higher intravenous amino acid (EHAA) supplementation decreases hyperkalemia in extremely low birth weight (ELBW) infants (<1000 g). STUDY DESIGN: Infants were enrolled at birth in a randomized, double-masked, prospective fashion and treated for 7 days. The standard group (SAA) infants received intravenous amino acid (AA) starting at 0.5 g x kg(-1) x d(-1) and increased by 0.5 g x kg(-1) every day to a maximum of 3 g x kg(-1) x d(-1). EHAA group infants received 2 g x kg(-1) x d(-1) of AA soon after birth and advanced by 1 g x kg(-1) every day to 4 g x kg(-1) x d(-1). Data analysis was by SPSS 11.5, with statistical significance at alpha = 0.05 and 90% power to determine a difference in mean K(+) level of 2. RESULTS: Sixty-two patients, mean gestational age of 26.0 +/- 2.0 weeks and birth weight of 775 +/- 136 g, were enrolled. Hyperkalemia (K(+) > or =6.5 mEq/L) occurred in 13% of the studied population; no difference in incidence of hyperkalemia was found between the SAA and EHAA groups (16% vs 10%, respectively, P = .70). Serum blood urea nitrogen was higher in the EHAA group. AA infusion was stopped early in 6 patients for high blood urea nitrogen or elevated ammonia level. CONCLUSIONS: During the study period, hyperkalemia decreased significantly and was not affected by EHAA supplementation in the first week of life.

Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants.

BACKGROUND: Metabolic bone disease of prematurity is a common problem in preterm infants. The aim of the present paper was to measure the effect of vitamin D, in order to see the relation between vitamin D and urinary excretion of deoxypyridinoline (DPD), serum osteocalcin (OC), calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (ALP). METHODS: Three different doses of vitamin D, 200 IU/kg (group 1, 11 infants), 400 IU/kg (group 2, 15 infants) and 800 IU/kg bodyweight/day (group 3, 11 infants), were administered to a total of 37 preterm infants between 15th day of birth until the 30th day of birth. RESULTS: There were no significant differences in levels of serum Ca and P before and after vitamin D supplementation in all groups. Serum ALP levels were increased in all but significantly only in groups 1 and 3. Serum OC levels were also increased in each group by the treatment. Urinary DPD excretion was increased gradually by the increase in vitamin D intake, but it was significant only in group 3. CONCLUSION: High dose of vitamin D supplementation might accelerate bone turnover and increased urinary DPD levels might reflect increased bone resorption. To the best of the authors' knowledge this is the first study comparing the effects of different vitamin D dose, by the means of urinary collagen cross-links, on bone turnover in preterm infants.

The neonatal energy triangle. Part2: Thermoregulatory and respiratory adaption.

In the second part of this two part article the neonatal energy triangle elements of hypoxia and hypothermia are explored and the physiology of the first few hours of neonatal life drawn together into an integrated whole. This framework can assist in understanding the three most common difficulties encountered by the preterm baby and directing integrated and holistic care.

Vitamin A and preterm infants: what we know, what we don't know, and what we need to know.

Vitamin A is essential for optimal growth and development. In the developing world, vitamin A supplementation of the newborn infant reduces mortality. In the developed world, extremely preterm infants are born with low body stores of vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A supplementation for this population is not clearly defined, however, and, despite evidence of benefit, early vitamin A supplementation of extremely preterm infants is not uniformly practised in the United Kingdom. There is an urgent need for studies in preterm infants that include quantification of hepatic stores and functional assessment of vitamin A status as well as long term outcome.

Pulmonary antioxidant concentrations and oxidative damage in ventilated premature babies.

OBJECTIVE: To determine the relation between lipid peroxidation and the antioxidants ascorbate, urate, and glutathione in epithelial lining fluid in ventilated premature babies, and to relate the biochemical findings to clinical outcome. DESIGN: A cohort study conducted between January 1999 and June 2001. SETTING: A NHS neonatal intensive care unit. PATIENTS: An opportunity sample of 43 ventilated babies of less than 32 weeks gestation. MAIN OUTCOME MEASURES: The duration of supplementary oxygen according to the definition of bronchopulmonary dysplasia (BPD; oxygen dependency at 36 weeks gestational age). METHODS: Epithelial lining fluid was sampled by bronchoalveolar lavage. Ascorbate, urate, glutathione, and malondialdehyde (a marker of lipid peroxidation) were measured. RESULTS: Babies who developed BPD had significantly lower initial glutathione concentrations (mean (SEM) 1.89 (0.62) v 10.76 (2.79) microM; p = 0.043) and higher malondialdehyde concentrations (mean (SEM) 1.3 (0.31) v 0.345 (0.09) microM; p < 0.05) in the epithelial lining fluid than those who were not oxygen dependent. These variables were poor predictors of the development of BPD. Gestational age, endotracheal infection, and septicaemia had good predictive power. The level of oxidative damage was associated with the presence of endotracheal infection/septicaemia rather than inspired oxygen concentration. CONCLUSIONS: Endotracheal infection, septicaemia, and gestational age, rather than antioxidant concentrations, are the most powerful predictors of the development of BPD.

Jaundice in low birthweight infants: pathobiology and outcome.

Jaundice in preterm, as well as full term, infants results from (a) an increased bilirubin load in the hepatocyte, (b) decreased hepatic uptake of bilirubin from the plasma, and/or (c) defective bilirubin conjugation. Hyperbilirubinaemia in preterm infants is more prevalent, more severe, and its course more protracted than in term neonates.

Iron status and the treatment of the anemia of prematurity.

Many unanswered issues regarding rhEPO therapy in prematurity remain, including which premature infants best respond to rhEPO, what the long-term effect of decreased erythrocyte transfusions is, how nutritional supplementation optimizes the effect of rhEPO, whether or not rhEpo therapy causes iron deficiency later in life, and whether or not it is safe to supplement with parenteral iron. Further study of rhEPO therapy and iron status in prematurity is necessary.

Bilirubin and jaundice in the micropremie.

Although it has been customary to treat neonatal jaundice at lower serum bilirubin levels in low-birth weight infants than in term infants, the threshold bilirubin levels and long-term benefits for early treatment of preterm infants have not been validated. This article summarizes and evaluates existing evidence and strategies for early treatment of bilirubin in micropremies and recommends a conservative but flexible approach to early monitoring and phototherapy for jaundice in extremely low-birth weight infants.

Assessing the effect of disease on nutrition of the preterm infant.

OBJECTIVE: To review existing data on nutritional requirements of extremely low birth weight (ELBW) and very low birth weight (VLBW) preterm infants (those who weigh < 1000 g and 1000-1500 g at birth, respectively), and the effects of diseases on these nutritional requirements. DATA SOURCES: A literature search was conducted on applicable articles related to nutritional requirements of preterm ELBW and VLBW infants and the effects of diseases in these infants on their nutritional and metabolic requirements. DATA SYNTHESIS: The literature was analyzed to determine nutritional requirements of preterm ELBW and VLBW infants, to select the most common diseases that have significant and important effects on nutrition and metabolism in these infants, and to make recommendations about diagnostic and therapeutic approaches to nutritional problems as affected by diseases in ELBW and VLBW infants. CONCLUSIONS: Many diseases unique to preterm infants, either directly or by enhancing the effects of stress on the metabolism of such infants, provide important changes in the nutrient requirements. The overriding observation from all studies, however, is that ELBW and VLBW preterm infants are underfed during the early postnatal period and that this condition, combined with additional stresses from various diseases, increases the risk of long-term neurological sequelae. The value of achieving a specific body composition and growth weight is less certain. There remains a critical need for determining the right quality as well as quantity of nutrients for these infants.