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.

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.

[Organisational aspects of a donated breast milk bank: experience of the Treviso hospital]. / Aspetti organizzativi di una banca di latte umano donato: l'esperienza dell'Ospedale di Treviso.

AIM: This study analyses the organisational aspects and the volume of milk managed by the donated breast milk bank (banca del latte umano donato, BLUD) in Treviso. METHODS: The data gathered refer to the years 2003, 2004 and 2005. In particular the hygiene methodology is described in order to obtain a high-quality product from a clinical point of view which is in line with the recent norms regarding the management of food products. RESULTS: During the three-year study 5,647 L of milk were collected (on average: 155 L/month; 5 L/day). Seventy-two percent of breast milk collected was from mothers for their own children; the remaining 28% of milk was from ''donors for the pool''. In the same period 5,053 L of milk was pasteurised and distributed (pool=31%; frozen breast milk=61%; chilled unpasteurized breast milk =8%). Microbiological data show total effectiveness of the methods of pasteurisation used (Holder method). The tracking of the product is possible through the BLUD organisation. CONCLUSION: We propose: 1) that scientific organisations and legislators try to optimise the control of this important product by providing guidelines, indications, microbiological parameters and legal obligations for the correct continuation of the work carried out by BLUDs; 2) that BLUDs create a network for rapid communication, integration and possible collaboration; 3) that a study be carried out regarding BLUDs and population density in order to balance costs and benefits.

Retrospective analysis of post-hemorrhagic ventricular dilatation in very low birth weight infants, short and long-term outcome.

AIM: The aim of this paper was to study the evolution of ventriculomegaly, the treatment and the developmental problems of a group of very low birth weight infants (VLBWI) born between 1985 and 1999 who met Levene's percentiles for post-hemorrhagic ventricular dilatation (PHVD). METHODS: A retrospective hospital-based study of a cohort of 66 VLBWI who fulfilled the diagnostic criteria for PHVD was performed. Measures of neurodevelopmental outcome were evaluated by analyzing neurosensorial patterns as well as mental and behavioral adjustment up to pre-school age in 35 survivors. RESULTS: The PHVDs initially (1985-1989) were due to a grade 4 intraventricular hemorrhage (IVH) (71.4%), and in the latter period (1995-1999) to IVH grade 2 (36.4%), grade 3 (31.8%) and grade 4 (31.8%). Acetazolamide has been used since the 90's in neonates with progressive PHVD. The 90s were characterized by an increasing incidence of tiny babies and rapidly-progressive PHVD. Taps were more frequent in the arrested dilatation group. Similarly, taps and acetazolamide were administered to newborns with persistent, slowly-progressive ventricular dilatation (PHVD > 4 weeks). The highest correlation was found for gestational age with the mental and psychomotor developmental indexes. Delayed performance and/or mental retardation were diagnosed in 71.4% of the survivors. CONCLUSION: Acetazolamide and lumbar puncture, associated with other risk variables (severity of IVH, PHVD evolution and associated parenchymal lesions) are harmful in terms of development, but they have a role in the short-term arrested and slowly progressive PHVD of the surviving babies, and not in the mortality incidence. Our retrospective data demonstrated that lower gestational age at birth increased the risk of lower mental and psychomotor developmental indexes.

[Permanent neurological damage]. / Il danno neurologico permanente.

Permanent neonatal neurologic injury is often a result of intraventricular and intraparenchymal hemorrhage, hydrocephalus or porencephaly, cerebral congenital malformation, congenital infections, or hypoxic-ischemic encephalopathy syndrome. The damage must be communicated to the newborn's parents, who will obviously ask about their child's future. The news given to both parents must be truthful, showing a sense of empathy, with some degree of the problem's severity withnel however, so as to allow the time necessary for them to adjust to the blow slowly. It is also useful to emphasize that the individual medical facility is capable of timely diagnoses, correct therapy, and long-term follow-up. In short, of truth and human kindness.

Neonatal tuberous sclerosis presenting with intractable seizures.

A 2-day old girl with status epilepticus, unresponsive to maximum pharmacological intervention, is reported. Findings of brain and cardiac lesions pointed to the diagnosis of tuberous sclerosis. One of the brain lesions was unusually large, occupying most of the right temporo-parietal lobe.

Rapid improvement of static compliance after surfactant treatment in preterm infants with respiratory distress syndrome.

Respiratory mechanics were measured in 20 preterm infants before and in the 24-hr period after treatment with surfactant. All infants were enrolled in the rescue clinical trial with Curosurf carried out in the Neonatal Intensive Care Unit. They received a dose of 200 mg/kg lipid surfactant intratracheally after birth. Static compliance of the respiratory system (Crs) was measured by the single breath occlusion technique during both spontaneous and mechanical ventilation. Resistance of the respiratory system (Rrs) and expiratory time constant (Trs) were also measured. As early as 3 hr after surfactant administration a significant improvement of 45% in Crs measured during mechanical ventilation (CrsV) was noted (0.40 +/- 0.14 vs 0.58 +/- 0.17 mL/cm H2O/kg, P < 0.001), together with a significant improvement of the arterial/alveolar O2 tension ratio (Pa/AO2) (0.12 +/- 0.03 vs 0.30 +/- 0.16, P < 0.01). The improvement of CrsV and Pa/AO2 was confirmed 24 hr later (0.55 +/- 0.15 mL/cm H2O/kg and 0.33 +/- 0.18, respectively). A significant correlation was found between Crs and Pa/AO2 ratio (r = 0.56, P < 0.001). Time constant values were significantly higher after surfactant treatment (0.15 +/- 0.07 vs 0.09 +/- 0.03 sec; P < 0.01). Rrs remained unchanged. These data indicate that Curosurf given intratracheally after birth determines a rapid improvement of respiratory mechanics as soon as 3 hr after dosing, together with the improvement of oxygenation. From the findings obtained with the present study we show evidence that respiratory system mechanics may be a useful physiological measure to guide ventilatory strategy following surfactant therapy.

Congestive heart failure secondary to cerebral arterio-venous fistula.

Arteriovenous fistula is a relatively rare cause of severe congestive heart failure in the newborn. An intracranial arteriovenous malformation associated with an aneurysm of the great vein of Galen is the most frequent of such malformations and, although well known, it remains a difficult diagnosis in the neonate because the clinical picture first presents with findings suggesting cardiac disease. The newborn with a vein of Galen aneurysm has volume and pressure overload on his myocardium; cyanosis is often present due to persistent fetal circulation; peripheral pulses are generally decreased in amplitude except in those arteries near the fistula where they are bounding, as an expression of a hyperdynamic status. A continuous murmur may be heard over the scalp, but this highly suggestive sign is often not present. The majority of newborns with intracranial arteriovenous fistula die very soon. Unfortunately, most of these infants are at first considered to have congenital heart disease and are, therefore, subjected to cardiac catheterization and angiography, with their well-known risks, before a correct diagnosis is made. Cross-sectional echocardiography, by demonstrating normal intracardiac anatomy, eliminates the need for an invasive investigation in a very sick neonate. Ultrasonography of the head will then provide a rapid and accurate demonstration of the aneurysm of vein of Galen. Cerebral angiography will complete the diagnosis in those cases in which a neurosurgical intervention is contemplated.

Popliteal pterygium syndrome presenting with orofacial abnormalities. Report of a family.

A family with popliteal pterygium syndrome is reported: two children presented a mild form of the syndrome, while their mother exhibited full expression of the gene. Only 11 families with 29 affected members and 25 sporadic cases have been published. This malformation syndrome is inherited in an autosomal dominant pattern, but environmental factors or genetic heterogeneity cannot be excluded in sporadic occurrences. The variability of expression is discussed and a comparison with previously published familial cases is made: minor anomalies, if present in relatives of patients with full gene expressions, are as helpful in making the diagnosis as are major abnormalities. Careful evaluation of the proband's family is essential for diagnosis and subsequent genetic counselling.

Congenital choanal atresia: the postoperative care.

A case of congenital bilateral bony choanal atresia treated by surgery is reported. A new method of insertion and retention of the modelling tubes to prevent stenosis is described. This method has the following advantages: 1. it provides a good insertion and retention of the modelling tubes; 2. it doesn't provoke any trauma of the nasal septum, soft palate and nostril; 3. the insertion of the tubes doesn't require general anesthesia; 4. it's well tolerated.

Simple estimate of creatinine clearance from plasma creatinine in neonates.

Thirteen newborn infants, 8 preterm and 5 term, with either mild or serious neonatal asphyxia were studied. From the first 24 hours of life to day 13, glomerular filtration rate (GFR) estimated by creatinine clearance was compared with the values obtained using Schwartz's formula: GFR (ml/min per 1.73 m2) = 0.55 x length (cm)/plasma creatinine (mg/100 ml). Both in term and preterm infants, values of formula-calculated creatinine clearance were slightly higher than values obtained by the classical method; nevertheless the data show significant correlations, respectively r = 0.867 and r = 0.795 (P less than 0.001). This formula provides an adequate estimation of neonatal creatinine clearance (a marker for GFR) directly from plasma creatinine provided that body length is taken into consideration. The necessity for urine collection and the associated problems are thus obviated. The simplicity of Schwartz's formula permits easy monitoring of renal function, especially in neonatal asphyxia in which the risk of developing renal failure is great.

Clinical and aortographic assessment of the complications of arterial catheterization.

Catheterization of the umbilical artery for the treatment of critically ill neonates provides a convenient method for monitoring blood gas tension and chemistry. The most important complications are thrombotic. Thirty eight aortographs were carried out in infants who underwent umbilical artery catheterization. 17/38 of the aortographs were pathological. Bacterial cultures were positive in 11/17, but only 4 coincided with pathological aortographs. Clinical signs indicating complications due to the presence of the catheter wwere observed in 10 cases. Post-mortem examination of eight subjects--three of whom had pathological aortographs--during the course of the investigation revealed only one case of thrombosis. This baby was considered to have died as a direct result of a thrombotic complication. In our experience the clinical signs of vascular complications and evaluation of the peripheral circulation in the ipsilateral leg remain the most important ways of assessing the indication for catheter-withdrawal.

Postnatal changes in blood S-adenosylmethionine concentration. Some observations in hyaline membrane disease.

The blood concentration of S-adenosylmethionine in 18 premature neonates affected by hyaline membrane disease did not differ from that found in a control group of healthy premature newborns. However, these values are higher than those found in full-term infants: this fact suggests that the methionine cycle is active in both the fetus and premature neonate with consequent conservation of homocysteine sulfur. These data provide ancillary evidence in support of the hypothesis that in premature babies cyst(e)ine is an essential amino acid. The concentration of S-adenosylmethionine reaches its lowest level 30 days after birth and then stabilizes at the age of 2--5 months with blood levels similar to those of the normal adult.

Umbilical vessel catheterization; the immediate risks with the venous route.

Seven cases of heart arrest or pronounced bradycardia during 308 correct catheterizations of the umbilical vein in the first hours of life are reported. The indications for the catheterization were: 1. unsuccessful catheterization of the umbilical arteries in newborns with respiratory distress or post-asphyxia syndrome; 2. exchange transfusions for severe neonatal hyperbilirubinemia or sepsis; 3. monitoring the central vein pressure in severely compromised shocky newborns. Cardiac massage was always effective, at least temporarily, in restoring the heart activity. However, only three infants survived. Two of them had normal follow-up reported at 6 and 12 months respectively. The immediate risks and the necessary precautions for carrying out umbilical vein catheterization in severely ill newborns in the first hours of life are stressed.

Amniotic fluid surface tension during pregnancy.

A good correlation between the amniotic fluid surface tension and gestational age was found in 51 amniotic fluid samples from normal pregnancies. The samples were obtained between the 20th and 43rd week of gestation. A good relation also exists between amniotic fluid lecithin concentration and fluid surface tension, and between said surface tension and the foam test carried out according to Clements et al. (4).