Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection.

This study was performed to assess oral valganciclovir V-GCV (GCV pro-drug), 15 mg/kg bid for 6 weeks to 13 neonates with symptomatic congenital cytomegalovirus (CMV). We monitored plasma levels of GCV within 30 days of therapy: C(trough), and C(2h) (before and the 2 hours after administration), we performed viral assessment in plasma and urine and tolerability at baseline, and every fortnight. Pharmacokinetics showed GCV stable and effective plasma concentrations: mean C(trough) = 0.51 +/- 0.3 and C(2h) : 3.81 +/- 1.37 microg/ml. No significant variability was seen neither intra-patient nor inter-patients. One newborn discontinued therapy because of thrombocytopenia, another finished with a neutrophils count of 1,000/microl. At the end of therapy 6 out of 12 and 8 out of 12 newborns were negative for CMV in urine and plasma. The 4 newborns positive for CMV DNA showed a 90% reduction of pre-therapy values. Clinically, the 4 patients reporting hepatic disease and the 3 with thrombocytopenia recovered after 6 weeks of therapy. Eight newborns suffered from SNHL; at the 6-month follow-up no patients had worsened, 2 had improved, and no deterioration was reported in 3 newborns with chorioretinitis scarring. The paucity of adverse events, and the effectiveness and stability of drug plasma concentrations are the important findings of our study.

Effectiveness of pamidronate in severe neonatal hypercalcemia caused by subcutaneous fat necrosis: a case report.

Subcutaneous fat necrosis of the newborn (SCFN) is a panniculitis that develops in fatty areas during the first weeks of life after foetal distress or perinatal complications. Prognosis is generally good with complete regression, but it can be complicated by metabolic abnormalities like hypoglycemia, hypertriglyceridemia, thrombocytopenia, and also potentially life-threatening hypercalcemia. We report a case of severe hypercalcemia complicating SCFN in a newborn who was treated with hyperhydration, furosemide, prednisone, and pamidronate.

Depressive symptoms and maternal psychological distress during early infancy: A pilot study in preterm as compared with term mother-infant dyads.

BACKGROUND: Preterm birth does not only affect infants but also represents an unexpected and traumatic event for parents. There are few reports on parenting stress during early infancy comparing preterm and term mothers, with the results being somewhat inconsistent. METHODS: As part of a longitudinal study, preterm mother-infant and term mother-infant dyads were enrolled. Dyads were assessed twice: during hospitalisation in the neonatal intensive care unit (NICU) and at 3 months of infant age (corrected age for preterm). Each mother completed a self-report set of psychological questionnaire in both time points. All the children underwent a neurological examination at 40 weeks post conceptional age and at 3 months (corrected age for preterm). RESULTS: 20 preterm and 20 term dyads were included. NICU mothers reported elevated postnatal depressive symptoms and high stress level, even if the preterm infants were with low perinatal risk and normal neurological examination. Comparing preterm infant with low perinatal risk and normal neurological examination with term-born children at 3 months, we found higher parental stress in term mothers than in preterm mothers. LIMITATIONS: This study was limited by a relatively small sample size; findings are preliminary and warrant further investigation in larger-scale study. CONCLUSIONS: Findings confirm that becoming a mother of a preterm infant is an event associated with emotional distress. These symptoms may resolve with time, and sometimes are independent of the infant's clinical severity. Assessing parental sources of stress and subsequent follow-up is essential to promote parental support, both for preterm and term mothers.

Cord and blood levels of newborn IgE: Correlation, role and influence of maternal IgE.

The role of cord blood immunoglobulin E (IgE) levels in predicting the development of atopy has been widely investigated. The aim of the study was to evaluate the correlation between serum and cord blood total IgE in newborns and the possible influence of the atopic status of the mother on them. It was also investigated the possible role of gestational age on neonatal total IgE levels. We considered 763 deliveries, 724≥37 weeks of gestation and 39<37 weeks of gestation. 14% of mothers (13.7% at term, 15.4% preterm) showed high total IgE levels. The results showed a significant correlation between serum and cord IgE levels both in preterm and term newborns. The data revealed also that mother's total IgE levels affect both neonatal serum and cord total IgE levels. For the latters we also found child gender as an additional independent predictor. On the contrary total IgE levels are not affected by gestational age. Clinical limitations of total IgE is known but their determination can be useful to define atopy and to suggest follow-up of the children.

Response to pain in a group of healthy term newborns: behavioral and physiological aspects.

Various reports have documented the difficulty in assessing neonatal response to painful stimuli. The aim of our study was to evaluate previously described scales for assessing pain in a group of 18 healthy term newborns selected according to Prechtl's optimality criteria and subjected to a routine metabolic screening blood test performed on the 5th day of life. Both a modified CHEOPS scale and Grunau-Craig Scale, to assess pain behavior response before, during and after a painful stimulus, revealed definite modifications in scores. Response to pain was also evaluated by measuring variations in decreases in transcutaneous oxygen pressure in all newborns during application of the stimulus and in returns to baseline or higher values upon removal of the stimulus. Our study confirms that healthy term newborns feel pain when subjected to limited painful stimuli such as the routine blood test and suggests useful and easy methodological tools to evaluate pain in the newborn.

[Neonatal sepsis: new preventive strategies]. / Sepsi neonatali: nuove strategie preventive.

More than one million neonatal deaths every year in the world are attributable to infection. In nurseries, infections occur with a reported incidence of 0.3-3%; in Neonatal Intensive Care Units (NICUs) the reported incidence is 7-24.5%, and up to 40% in newborns with birth weight less than 1000 g or gestational age at birth <28 weeks. Sepsis is the most severe and frequent infection, accounting for 45-55% of all infections. Several practices have been demonstrated to be effective in reducing the incidence of infection in NICUs, including hand hygiene practices, correct management of central venous catheters (CVC), accurate diagnostic strategies and correct use of antimicrobial drugs. Despite the reduction in the incidence of infection after implementation of these practices, nosocomial infections are still a relevant problem, with high mortality and morbidity rates in hospitalized newborns, especially preterm newborns. Searching for new strategies to further reduce the incidence of nosocomial sepsis in NICUs is a priority of clinical research. New and promising strategies for the prevention of nosocomial infection in NICU include: lactoferrin administration, early identification of infants at risk of infection by means of specific markers (e.g. mannose binding lectin), heparin use for the prevention of CVC-related infections, judicious use of antibiotics, and prevention of fungal sepsis with antifungal agents. On the contrary, recent studies demonstrated that the use of specific immunoglobulins directed against different staphylococcal antigens is not effective in preventing neonatal sepsis.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Circulating endothelial progenitor cells and diseases of the preterm infant.

During the last decade, multiple techniques have been developed to isolate and quantify human endothelial progenitor cells (EPCs). In parallel, a number of studies have applied these methodologies to investigate the number and function of circulating EPCs in adult diseases characterized by vascular dysfunction. However, very little is known about different subtypes of EPCs during gestation, during the neonatal age or in neonatal diseases. Initial evidence supports the hypothesis that circulating angiogenic cells may play an important role during development, and attention has particularly focused in clarifying the function of EPCs in lung vascular development, and the role of the impairment of EPC mobilization and homing in hyperoxia-induced lung injury characteristic of bronchopulmonary dysplasia. Among different subtypes of EPCs, both the role of angiogenic mononuclear cells (triple-positive CD34+CD133+VEGFR-2+ cells and colony forming unit-Hill cells) and endothelial colony forming cells (ECFCs) in physiological vascular development and during neonatal diseases need to be elucidated. A better understanding of EPC biology during gestation, during the neonatal age and in preterm infants will unravel the pathologic basis of bronchopulmonary dysplasia and other preterm and term neonatal diseases characterized by a prominent defect in vascular growth, including retinopathy of prematurity and persistent pulmonary hypertension of the newborn.

Lactoferrin and prevention of late-onset sepsis in the pre-term neonates.

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Spiramycin treatment of Toxoplasma gondii infection in pregnant women impairs the production and the avidity maturation of T. gondii-specific immunoglobulin G antibodies.

The aim of the study was to evaluate the influence of treatment with spiramycin on the increase of immunoglobulin G (IgG) titers and IgG avidity indexes (AI) in pregnant women with seroconversion from the beginning of therapy until delivery and after delivery. This group was compared with adult patients with recently acquired untreated toxoplasmosis. One hundred four samples from 32 pregnant women with seroconversion for toxoplasmosis and/or very low IgG AI were followed from the beginning of therapy with spiramycin until delivery. Twenty-nine women were further followed some months after delivery and interruption of therapy. Thirty-eight samples from 16 untreated, nonpregnant patients were evaluated as the control group. The Toxoplasma gondii-specific IgG antibody and the T. gondii-specific IgG AI were significantly delayed in pregnant women receiving therapy compared to nonpregnant, untreated controls, and the findings were consistent with the results of assays from two different manufacturers. The T. gondii-specific IgG AI increased in pregnant women after they gave birth. Avidity maturation is delayed during pregnancy and treatment, and low-avidity antibodies in pregnant women within 3 to 4 months cannot be taken as a sign of infection.

Antibiotics in neonatal intensive care units (NICUs).

Antibiotics, the most effective tools against pathogens, are overused in neonatal intensive care units (NICUs). Prolonged and unnecessary empirical use of broad-spectrum antibiotics selects resistant bacteria and increases the risk of sever fungal infections. Judicious use of antibiotics and development of appropriate intervention strategies and policies in order to reduce antibiotic use should be a primary objective in all NICUs. The choice of the best empirical antibiotic regiment should be base on the age of the infant, on the clinical signs and on the pharmacokinetics of the drug, but the narrowest spectrum antibiotics should be used.

The early maturation of the circadian system in newborns.

The time of maturation of the circadian periodicity in humans has been differently considered. The present study aimed to investigate the existence of rhythmic variations in the body temperature of healthy full-term infants just after birth. We studied 19 healthy term newborns, nursed in their cribs at environment temperature of 25 degrees C and moderately dimmed artificial lighting during the night. Continuous recording of body temperature was performed with a solid memory recorder (Fiamarker) connected to a disposable rectal probe, during the first three days of life. Data were analyzed by means of single and mean cosinor methods and spectral analysis. All the newborns, except two, demonstrated a statistically significant circadian periodicity of temperature (p < .001). Acrophases were distributed along the 24h since the synchronization to environment was not yet completed. A clear ultradian fluctuation of body temperature was observed in all 19 newborns with an unexpected fall of temperature every three-four hours. Our data show that the maturation of the circadian system is probably almost complete in newborns, but the adjustment to the new environment can be expected in the subsequent weeks of life.

[Risk factors in maternal-fetal infections. Research conducted in 93 cases]. / Fattori di rischio nell'ambito dell'infezione materno fetale (IMF). Indagine condotta su 93 casi.

The results of microbiologic cultures from 186 vaginal samples obtained from 93 labouring women have been compared with the results of the microbiologic cultures from meconium of their newborns, to test possible risk-factors for IMF. The high frequency of positive cultures from vaginal samples (83.3%), constantly with strong bacterial charge, and the proved direct mother to foetus transmission for many potential pathogens (23.6%), cause various interpretative problems and require further studies.

Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women with primary infection and of congenitally infected newborns.

Human cytomegalovirus (HCMV) immediate-early messenger RNA (IEmRNA) in sequential blood samples from 32 pregnant women with primary infection and from 14 congenitally infected newborns was qualitatively investigated by nucleic acid sequence-based amplification. IEmRNA was detected in 100%, 75%, 36.3%, 22.2%, and 0% of samples collected 1, 2, 3, 4-6, and >6 months after onset of primary HCMV infection, respectively, showing 83.7% sensitivity and 92.2% specificity, compared with results of quantitative DNAemia (detection of viral DNA in blood). In infected newborns, IEmRNA was positive in 100% of samples collected 1-7 days (median, 1.5 days) and in 46.4% of samples collected 27-260 days (median, 88 days) after birth, showing 75.7% sensitivity and 100% specificity, compared with DNAemia results. IEmRNA was not detected in HCMV-immune individuals with remote or recurrent HCMV infection or in uninfected newborns. IEmRNA determination appears to be a valuable tool for early diagnosis of both primary and congenital HCMV infection.