Detection of fungal DNA in lysis-centrifugation blood culture for the diagnosis of invasive candidiasis in neonatal patients.

We report data concerning the detection of fungal DNA directly from lysis-centrifugation blood culture to assess its value in the detection of fungaemia in 86 of the 347 patients admitted to the neonatal intensive-care unit between January 2009 and December 2010. The sensitivity and specificity of the PCR were 87.5% and 98.5%, respectively, with a positive predictive value of 93.3% and a negative predictive value of 97.1%. Detection of fungal DNA directly from blood culture Isolator 1.5 microbial tubes, without prior cultivation, is a promising approach for the rapid detection of Candida spp. in neonates with suspected candidaemia.

Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome.

OBJECTIVE: To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by Candida species, of late-onset sepsis and neurological outcome in preterm newborns. STUDY DESIGN: A prospective study was conducted in 249 preterms who were subdivided into three groups: one group (n=83) was supplemented with Lactobacillus (L.) reuteri, one group with L. rhamnosus (n=83) and the other with no supplementation (n=83). The fungal colonization in the gastrointestinal tract, the late onset of sepsis and clinical parameters were recorded. A neurological structured assessment was further performed at 1 year of age. RESULT: Candida stool colonization was significantly higher (P<0.01) in the control group than in the groups treated with probiotics. The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups. Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group. CONCLUSION: The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by Candida, in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms.

Quality of life in parents of children with cerebral palsy: is it influenced by the child's behaviour?

The aims of the present study were: to examine the quality of life (QOL) of parents of children with cerebral palsy (CP) and to establish the possible effect of behaviour problems on their QOL. One-hundred children with CP, aged between 4 and 10 years, and both their parents were included in the study. Both parents completed the WHOQOL-BREF, to assess their QOL. A sample of 60 parents of healthy children was used as control group. The primary caregiver also completed the CHILD BEHAVIOUR CHECKLIST (CBCL). Parents of children with CP showed lower scores on physical and psychological domains than the control group on QOL. In the psychological domain the mothers of children with hemiplegia had the lowest scores. The mothers reported lower scores than the fathers for the physical domain in the group of children with diplegia and quadriplegia and for the psychological domain in the group of children with hemiplegia. Children with hemiplegia showed externalizing scores at CBCL higher than the other groups, that could explain the poorer QOL scores of their mothers. In conclusions our results provide useful information on the QOL in families with different forms of CP, useful in planning interventions for the family of children with CP.

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.

Experience with the Platelia Candida ELISA for the diagnosis of invasive candidosis in neonatal patients.

This preliminary study evaluated the use of the Platelia Candida antigen kit for the diagnosis of invasive candidosis in 70 of 184 pre-term infants admitted to a neonatal intensive care unit between March 2004 and March 2006. The frequency of confirmed candidaemia was 6.5%. The sensitivity and specificity of the assay were 94.4% and 94.2%, respectively, with a positive predictive value of 85% and a negative predictive value of 98%. These results suggest that the inclusion of regular serological surveillance for mannanaemia in some pre-term infants would complement blood cultures for the early detection of candidosis.

Infant neurological examination from 3 to 12 months: predictive value of the single items.

The prognostic value of the single items of a standardised neurological examination, the Hammersmith Infant Neurologic Examination (HINE), was explored longitudinally in 658 infants at 3, 6, 9 and 12 months post-term age. ROC curves were built based on the presence/absence of cerebral palsy at 2 years of age. Global HINE scores showed very high prediction (ROC curve areas above 0.9) at all ages. The items with the highest predictive value were always movement quality and quantity. In the first semester, among the most predictive items were those assessing tone, while beyond that time they were reflexes and reactions. Our results show that the high predictive value of the HINE across the first year of life is granted by the successful combination of different groups of items for each age-period. This should be recognised in clinical practice when assessing the significance of individual neurological profiles.

[Cerebral hemodynamics and major surgery]. / Emodinamica cerebrale e interventi chirurgici maggiori.

AIM: Near infrared spectroscopy (NIRS) is a non invasive optical technique to assess the monitoring of oxygenation and cerebral hemodynamics. Aim of our study was to value cerebral hemodynamics during major surgery to reduce the period of possible modifications of cerebral oxygenation. METHODS: Twenty-five newborns which underwent surgical intervention (8 diaphragmatic hernia, 8 esophageal atresia, 1 neck lymphangioma, 8 intestinal malformation) were studied during surgery by means of NIRS (NIRO 300), using an electrode applied to the scalp in the frontoparietal region. We monitored the Tissue Oxygenation Index (TOI) as well as the changes in concentration of total haemoglobin (tHb), oxygenated haemoglobin (O2Hb) and deoxygenated haemoglobin (HHb). The changes have been expressed as difference from the basal value recorded at the beginning of surgery. RESULTS: During the surgical intervention O2Hb, tHb and TOI decreased (DeltaO2Hb=-11.4+/-6.5 microM; P<0.001; DeltatHb=- 7.54+/-4.3 microM, P<0.05; microTOI=-12.5+/-5.5%, P<0.001), and HHb increased (DeltaHHb=+4.80+/-2.30 microM, P<0.001); the greatest changes occurred when the viscera were positioned into the abdomen (in diaphragmatic hernia and intestinal malformation). CONCLUSION: The present study suggests that NIRS, during major surgery, is able to monitor oxygenation and cerebral hemodynamics thus allowing a real time evaluation of some intraoperative procedure aftereffects that, if timely modified, could reduce cerebral hypoxia risks.

Application of a scorable neurological examination to near-term infants: longitudinal data.

The aim of this study was to follow the evolution of neurological findings in a cohort of near-term infants born between 35 and 37 weeks. A total of 448 infants born between 35 and 36.9 weeks gestational age with normal cranial ultrasonograms or only minor abnormalities, were studied using the Hammersmith Infant Neurological Examination, at 6, 9 and 12 months (corrected for prematurity). Our results showed that while some items such as cranial nerve and movements showed minimal changes over time, other items mainly related to "tone", "posture" and "reflexes" showed progressive maturation. There was no significant difference between the infants born at 35 and 36 weeks gestation. When compared to term infants assessed at the same age intervals, our cohort showed a wider variability of scores. Mean and 10 (th) percentile for global scores were lower than those reported for term infants suggesting that when assessing infants born at 35 and 36 weeks the optimality scores used for infants born full-term should not be used as normative data. Our results, providing longitudinal data in near-term infants without brain lesions, can be used as a reference in both clinical and research setting to monitor early neurological signs in those children.

[Impact of cerebral palsy in patients discharged from neonatal intensive care units]. / Incidenza delle paralisi cerebrali infantili nei dimessi dalle unità di terapia intensiva neonatale.

AIM: The aim of this study was to assess the impact and the peculiarities of cerebral palsy (CP) in children discharged from our neonatal intensive care unit (NICU) from January 1998 to April 2004. METHODS: A total of 2 303 children were discharged from our NICU during this period and 1 912 were followed up for 1 year through neurological examination (traditional, Brazelton, general movements) and cranial ultrasound (US); high-risk newborns were evaluated with brain magnetic resonance imaging (MRI) too. RESULTS: In 65 children (3.4% of the follow-up group) were diagnosed CP, and classified as follows: 21 (32%) diplegia, 19 (29%) quadriplegia, 20 (31%) hemiplegia, 4 (6%) double hemiplegia, 1 (2%) dyskinetic form. In diplegia and quadriplegia prevailed low birth weight infants (less than or equal to 2,500 g) and preterm infants, while in hemiplegia prevailed normal birthweight infants (greater than 2,500 g) and infants at term. The main MRI findings were: in diplegia 82% periventricular white matter lesions; in quadriplegia 94% periventricular and/or subcortical white matter lesions; in hemiplegia 95% bilateral periventricular or subcortical white matter lesions, predominating on contralateral cerebral hemisphere; in double hemiplegia 100% periventricular and/or subcortical white matter lesions, 100% enlargement of subarachnoid spaces; in dyskinetic form 100% basal ganglia lesions. CONCLUSIONS: The impact of CP in children discharged from our NICU, in agreement with the literature, is higher than in the total population of newborns, thus it is very important to evaluate carefully high-risk newborns during hospitalization and follow-up, through neurological examination and radiologic imaging (US, MRI), for an accurate and early treatment.

Troponin I as a biomarker of cardiac injury in neonates with idiopathic respiratory distress.

Troponin I (TnI), an inhibitory protein complex located on the actin filament of cardiac muscle, has become a specific marker of myocardial damage. Troponin has been studied in a wide range of clinical settings. However, many questions are still unanswered, especially in preterm neonates with the most common pathology at birth, such as idiopathic respiratory distress syndrome (IRDS). The aim of this study was to establish a reference range for cardiac TnI for healthy preterm infants and serum levels in sick preterm infants with IRDS. Echocardiography was performed and TnI serum levels were measured at a median age of 62 hours of life in three groups of healthy preterm infants (n = 10), and ventilated infants with moderate (n = 15) and severe IRDS (n = 15). Ventilated infants with idiopathic moderate IRDS had significantly different cardiac parameters (R/L ejection fraction, R/L stroke volume, R/L cardiac output; p < 0.05) and significantly higher cardiac TnI levels than healthy infants (0.037 versus 0.01 microg/mL; p < 0.05). Furthermore, infants with severe IRDS had higher TnI concentrations than infants with moderate IRDS (0.26 versus 0.037 microg/mL; p < 0.05). The results of this study show that increased TnI serum levels in sick preterm infants with IRDS are explained by myocardial injury or dysfunction due to impaired arterial oxygenation or reduction in cardiac output during treatment with mechanical ventilation. These results suggest that cardiac TnI may be a useful, specific marker for myocardial damage in preterm neonates with IRDS.

[Esophageal atresia and malformative association. Clinical contribution]. / Atresia esofagea e patologia malformativa associata. Contributo casistico.

AIM: Esophageal atresia (EA) is a congenital malformation with an incidence of 1/3,000-3,500 live birth, due to anomalies of the foregut. Although an interstitial deletion of chromosome 17 (q22q23.3) has been identified, the etiology seems to be multifactorial and not only genetic. The aim of this retrospective study is to evaluate the association of EA with chromosomal pathologies and/or malformation syndromes. METHODS: The authors report 18 cases of EA admitted to the UTIN of the Pediatric Department, University of Catania, between January 1998 and January 2001, and discuss the phases of preoperative stabilization, the operation, postoperative complications and the follow-up at 12 months. RESULTS: The results obtained concerning the association of EA with chromosomal diseases and malformation syndromes are described in the ''Results'' section of the paper. CONCLUSIONS: The results obtained, notwithstanding the low number of patients, show that the association of EA with chromosomal pathologies and malformation syndromes is relevant both from a numerical and prognostic point of view in comparison to the data published in the literature.

[Transient right ventricular hypertrophy in a newborn infant exposed in utero to nimesulide]. / Ipertrofia ventricolare destra transitoria in un neonato esposto in utero a nimesulide.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy has been sometimes related to harmful cardiac effects secondary to the precocious closure in uterus of ductus arteriosus. This closure is linked to the inhibition of the cyclo-oxygenase (COX) enzyme that plays a key-role in the prostaglandin synthesis. Recently, it has been acquired that, among NSAIDs, nimesulide has a more selective action on the isoform COX-2 that is more strictly related to inflammatory phenomena. The isoform COX-1, instead, steadily expressed in tissues, would be responsible of continuous prostaglandin synthesis maintaining patent the ductus arteriosus in uterus. The case reported in this paper describes a remarkable right ventricle hypertrophy observed in a newborn whose mother, during the whole period of pregnancy, frequently used nimesulide as analgesic. Probably, in spite of its selective action on COX-2, the prolonged use of nimesulide has determined a closure of the ductus, inducing a functional fetal pulmonary hypertension that resolved after birth with the consequent regression of the right ventricular hypertrophy.

[Cerebral venous sinuses thrombosis in an infant with supramitral obstructive membrane associated with partial anomalous pulmonary venous return]. / Trombosi dei seni venosi cerebrali in un lattente con membrana sovramitralica ostruttiva associata a ritorno venoso polmonare anomalo parziale.

Cerebral venous thrombosis is quite rare in newborn infants, but probably its incidence is not well evaluated because clinical signs and cerebral echocardiography are not specific. We report the case of an newborn infant with massive cerebral venous thrombosis associated with heart malformation: supramitral ring and partial anomalous pulmonary venous connection in the superior vena cava.

Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm infants.

AIM: To determine reference values for procalcitonin (PCT) and C-reactive protein (CRP) for gestational age and to use these parameters as diagnostic markers of perinatal bacterial and fungal infection. METHODS: PCT and CRP serum levels were measured in a case-control study in a group of 35 low birthweight infants (< 34 wk of gestation). 27 babies (77%) had clinical signs of infection confirmed by positive blood cultures and were compared to 8 (23%) uninfected matched patients. Seventeen (63%) of them had bacterial infection and 10 (37%) had fungal infection (Candida). Serum PCT (Brahms Diagnostika) and CRP (Immunoassay Vitros 950) were measured serially at 3, 7 and 10d of life. RESULTS: At any time, PCT and CRP levels were significantly higher in neonates with perinatal infection (p < 0.05) (> 0.7 ng ml(-1) and > 1 mg dl(-1) respectively). PCT showed a more rapid response to infection (9.3 +/- 1.5 ng ml(-1)). especially to bacterial infection (10.8 +/- 1.4 ng ml(-1)), than CRP (1.5 +/- 0.5 mg dl(-1)) (sensitivity 99% vs 88%). Lower sensitivity was noted for both parameters. PCT and CRP, to follow babies with fungal infection (6.7 +/- 0.8 ng ml(-1) and 0.9 +/- 0.7 mg dl(-1), respectively) (sensitivity 77% vs 58%). CONCLUSION: This study gives PCT reference values in preterm babies with perinatal infection. In these babies, PCT seems to be more sensitive than CRP as a diagnostic marker of infection. Both parameters can be used alone or in combination for a better identification and follow-up of bacterial and fungal infection during the perinatal period.

Serial protein S-100 serum levels in preterm babies with perinatal asphyxia and periventricular white matter lesions.

In the last years new diagnostic technologies were developed to assess brain development and to identify early brain injury. Some of them are very attractive methods but invasive, expensive, and time-consuming. The availability of clinically useful serum markers of risk for perinatal brain damage will easily permit the development of rational strategies for prevention of cerebral insults in neonates and more accurate prognostic counseling. In this study, protein S-100 (PS-100), a cytosolic constituent of neuroglial cells, was measured serially, during the neonatal period, in a group of preterm infants suffering perinatal asphyxia. Protein S-100 was measured at 1, 7, and 21 days of life by radioimmunoassay. Cerebral ultrasound confirmed cerebral white matter insult. The results of this study show significantly higher protein S-100 serum levels in asphyxiated preterm babies with periventricular white matter lesions, with a peak at 24 hours of life (5.7 +/- 2.9 microg/L) compared with healthy preterm babies (0.6 +/- 0.3 microg/L) ( p <0.05) and progressively lower values at seven (3.3 +/- 2.4 microg/L) and 21 days (2.2 +/- 1.3 microg/L) of life ( p <0.05). These data suggest that elevated protein S-100 serum levels can be considered an indicator of regional brain damage in preterm infants, allowing noninvasive, superior scrutiny of perinatal asphyxia and potential early preventive strategies.

[Neonatal vocal cord palsy. Clinical and therapeutical approaches]. / La paralisi delle corde vocali in età neonatale. Orientamenti clinici, chirurgici e contributo casistico.

Between 1998 and 2000, four newborns have been observed for laryngeal stridor occurred some hours after birth. Otorhinolaryngologic examinations, as well as cardiac, neuroradiologic and serologic investigations have been performed to formulate the diagnosis and verify the etiology. The fiberoptic laryngoscopy showed a bilateral paralysis of the vocal cord in two newborns, a monolateral paralysis of the left vocal cord in another and in the last one, instead, a bilateral cordal hypomobility. The follow-up performed till the age of one year showed a complete remission of the symptomatology in two newborns, respectively in the one with monolateral paralysis and in the other affected by hypomobility of the vocal cords; of the two newborns with bilateral paralysis, instead, one is dead because of Haemophilus Influenzae epiglottitis, three weeks after discharge without physicians' consensus, while in the other patient, affected by lobar holoprosencephaly, it was necessary to perform a tracheotomy because of a severe obstructive apnea. The lobar holoprosencephaly, is a cerebral malformation characterized by the partial separation of the cerebral hemispheres, and it is described for the first time associated with bilateral vocal cords paralysis.

[Neonatal thrombosis of the middle cerebral artery. Three clinical cases with a 24-month follow up]. / Trombosi neonatale dell'arteria cerebrale media. Tre casi clinici con follow-up a 24 mesi.

Three patients with neonatal thrombosis of the middle cerebral artery are described. In two patients the thrombosis was secondary to neonatal asphyxia. The third patient had a porencephalic cyst twenty days after birth suggesting a prenatal origin of the thrombotic event. The follow-up was carried out for two years. In the first year, two patients had infantile spasms and hyparrhythmic pattern of EEG. This type of epilepsy has never been previously reported. Futhermore, all three patients presented hemiplegia and reduction of cranial circumference. The neuroradiologic procedures showed to be very useful for the diagnosis and long term follow-up. These patients must be followed carefully since the development of a subsequent epilepsy is reported to be approx 11%.

Caudal regression syndrome and annular pancreas: a rare association.

A female infant with caudal regression syndrome and annular pancreas is described. This is the first time this association appears to have been described.

Vein of Galen aneurysmal malformation. Different clinical expressiveness. Three case reports.

The vein of Galen aneurysmal malformation (VGAM) is a rare cerebro-vascular disorder in neonates. It is characterized by an abnormal direct communication between one or several cerebral arteries and the vein of Galen. It may appear in the neonatal period or afterwards. Three cases of patients affected by VGAM with different clinical expression are presented. Two of them were treated successfully with endovascular embolization. It was not possible to provide the same treatment to the third patient for an intractable congestive heart failure already existing when VGAM was diagnosed.