Randomized trial of early erythropoietin supplementation after preterm birth: Iron metabolism and outcome.

BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30.0weeks). OUTCOME MEASURES: The iron status, postnatal morbidities and follow-up at the age of two years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants were recruited. A requirement of red blood cell transfusions during first 28days was similar between the study groups. EPO treatment decreased total serum iron concentration (p=0.035). EPO supplementation had no significant effect on serum transferrin receptors or reactive non-protein-bound iron. There were no differences in neonatal morbidity or in survival without major neurological abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the iron load in preterm infants. There was no change in reactive, non-protein bound iron plasma levels and no influence on the outcomes during early childhood. Whether the neurocognitive effects of early EPO treatment can be detectable later in childhood remained to be verified.

Lipid and protein oxidation in newborn infants after lutein administration.

OBJECTIVES: To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period. METHODS: A randomized controlled, double-blinded clinical trial was conducted among 150 newborns divided into control group, not supplemented (n = 47), and test group, supplemented with lutein on the first day postpartum (n = 103). Blood Samples were collected at birth from cord and at 48 hrs postpartum while routine neonatal metabolic screenings were taking place. Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and biological antioxidant potential (BAP) were measured by spectrophotometry and data were analyzed by Wilcoxon rank sum test and by multivariate logistic regression analysis. RESULTS: Before lutein supplementation, the mean blood concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and 2361.04 umol/L in the test group. After lutein supplementation, significantly higher BAP increment (0.17 ± 0.22 versus 0.06 versus ± 0.46) and lower TH increment (0.46 ± 0.54 versus 0.34 ± 0.52) were observed in the test group compared to controls. CONCLUSION: Neonatal supplementation with lutein in the first hours of life increases BAP and reduces TH in supplemented babies compared to those untreated. The generation of free radical-induced damage at birth is reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

The use of melatonin in hypoxic-ischemic brain damage: an experimental study.

OBJECTIVE: Oxidative stress (OS) plays a key role in perinatal brain damage. The aim of this study is to evaluate the effectiveness of melatonin as a neuroprotective drug by investigating the influence of melatonin on OS and inflammation biomarkers in an animal model of cerebral hypoxia-ischemia. METHODS: Five minutes after hypoxic-ischemic (HI) injury melatonin was administered to 28 rats (HI-Mel group). At the same time, 28 hypoxic-ischemic rats were vehicle-treated (V-HI group). Five rats were used as sham operated controls (CTL). OS biomarkers: isoprostanes (IsoPs), neuroprostanes (NPs) and neurofurans (NFs), and microglial activation markers (glial fibrillary acidic protein [GFAP] and monoclonal antirat CD68 [ED1]) were measured in the cerebral cortex of the two lobes. RESULTS: A significant increase of IsoPs on the left lobe was observed in V-HI after 1 hour (h) from HI injury (p < 0.001); a significant increase of NPs on both side (p < 0.05) and a significant increase of NFs on the left (p < 0.05) were also observed in V-HI after 24 h. A significant increase of IsoPs on the left (p < 0.05) and of NPs on both lobes (p < 0.05) were observed in HI-Mel after 48 h. The ED1 and GFAP expression was lower in the HI-Mel brain tissue. CONCLUSIONS: Melatonin reduces OS and inflammatory cells recruitment and glial cells activation in cerebral cortex after neonatal HI damage. These results lay the groundwork for future clinical studies in infants.

PIVKA-II plasma levels as markers of subclinical vitamin K deficiency in term infants.

BACKGROUND: As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD). OBJECTIVES: To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns. METHODS: A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 µg/die of vitamin K (G I), 12 µg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life. RESULTS: G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 (p = 0.001) and from 2.3 to 3.5 (p < 0.001). No significant changes were found in GI. PT showed no significant changes among groups. CONCLUSIONS: PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 µg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk.

A case of transient zinc deficiency in a breast-fed preterm infant successfully treated with oral zinc supplementation: review of zinc metabolism and related diseases.

A 15-week-old baby girl, born at the 29 week of gestation, presented with a four-week history of demarcated, erythematous, erosive and exudative patches on the perianal, perioral and acral areas. A clinical diagnosis of zinc deficiency was considered. Serum zinc level was decreased (0.5 mg/L; normal 0.70-1.50 mg/L), the mother's serum and milk had normal zinc values. The baby was started an empiric trial of oral zinc supplementation (3 mg zinc gluconate/kg body weight/ day) with complete healing of lesions after two weeks. Treatment was gradually withdrawn at six months of age with no relapse. Transient zinc deficiency due to increased zinc requirements in breast-fed mainly preterm infants is a condition similar to acrodermatitis enteropathica, an autosomal recessive disorder of enteric zinc absorption affecting almost exclusively not breast-fed infants. Early recognition of the disorder and introduction of zinc supplementation rapidly reverses transient zinc deficiency, that probably will become more and more frequent, because of the rising rate of premature infants with breast-feeding only.

Calcium homeostasis in the first days of life in relation to feeding.

Determinations of serum calcium (Ca), phosphorus (P), magnesium (Mg), calcitonin (CT) and parathyroid hormone (PTH) were carried out in full term newborn infants during the first 168 h of life. The infants were randomly assigned to two different diets: glucose and breast feeding (BF) only or early formula feeding (F). The Ca serum levels decreased from birth to the 24th h; after that time they increased until the 72nd h. The values of serum Ca at the 48th and 72nd h were significantly lower in the F than in the BF group. In contrast, the P serum levels increased from birth to the 48th h and then they decreased; the values of serum P at the 48th h were significantly higher in F than in the BF group. The CT serum levels increased from birth to the 24th h and then they decreased. No difference between the F and BF groups was found during the first 48 h, while at the 72nd h the F group demonstrated significantly higher values of serum CT. PTH serum levels also increased from birth to the 24th h with significantly higher values at the 72nd h in the F group. The results of this investigation demonstrate that the difference in feeding in the first hours of life affects the calcium homeostasis and the secretion of hormones involved in the regulation of serum Ca levels.

Calcitonin and parathyroid hormone in newborn infants with fracture of the clavicle.

Determinations of serum calcium (Ca), phosphorus (P), calcitonin (CT), and parathyroid hormone (PTH) were carried out in 36 full-term newborn infants with fracture of the clavicle (CF) and in 46 normal neonates (N). At the 6th hour of life the CF neonates demonstrated lower serum Ca and higher serum CT in comparison with normal infants. In the hours following, no significant differences between the two groups for the Ca levels were found, whereas serum CT remained significantly higher in the CF newborns at the 24th, 48th, and 72nd hour of life. Significant differences between normal and CF infants in the PTH serum levels were detected only at the 48th hour, when PTH was lower in the CF newborns. The results of this investigation indicate that the fracture of the clavicle is a significant and peculiar factor in stimulating CT secretion. Serum Ca level appeared to be controlled by CT rather than auto-regulating the secretion of the hormone.

[Serum levels of parathormone, calcium, magnesium and phosphorus in the perinatal period]. / Livelli serici di paratormone, calcio, magnesio e fosforo nel periodo perinatale.

Two groups of newborns on different diets were studied: group A was given artificial milk, while group B was breast fed. Blood samples from the cord artery and vein were taken at birth and further blood samples after 1, 6, 12, 24, 48, 72, 96 and 168 hours. No baby underwent more than three blood samples. Calcium (Ca), magnesium (Mg), phosphorus (P) and parathormone (PTH) were measured in all samples. There was a rapid increase in PTH levels in all subjects in the first hours after birth. At 48th the babies in group A had significantly higher serum levels of P than the group B subjects, and their serum Ca and Mg levels were significantly lower. At 72th PTH serum levels were significantly higher in group A, while Ca and Mg levels were significantly higher in group B. In conclusion, the subjects demonstrated a normal secretion of PTH at birth, and the type of diet notably influenced the homeostasis of calcium in the perinatal period.

[The effects of diet on the secretion of calcitonin in the newborn infant]. / Effetti della dieta sulla secrezione di calcitonina nel neonato.

Determinations of serum calcium (Ca), phosphorus (P) and calcitonin (CT) were carried out in two groups of full term newborn infants: 80 on bottle feeding (group A) and 80 breast feeding (group B). Samples of blood were drawn at 1, 6, 12, 24, 48, 72, 96 and 168 hours of life. Each newborn was tested no more than twice. No differences between the two groups could be detected before the 72th hour. At that time, the Ca of group A was significantly lower than Ca of group B while the CT and P were significantly higher in the same group A. So that, the P serum level appears to be one of the most important factor regulating the homeostasis of Ca after the first 72 hours of life.