Near-infrared spectroscopy measure of limb peripheral perfusion in neonatal arterial thromboembolic disease.

AIM: In critically ill neonates, peripheral perfusion and oxygenation assessment may provide indirect information on circulatory failure in limb arterial thromboembolic emergencies. Aims of our study were: 1) to evaluate the changes on tissue oxygenation index, oxyhemoglobin, deoxyhemoglobin and blood volume obtained by near-infrared spectroscopy (NIRS) on the infants legs; 2) to compare them with ultrasonographic data. METHODS: Tissue oxygenation index (TOI), oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb) and blood volume (BV) differences were assessed by NIRS on the calf of 8 newborn infants (median weight 1995, range 585-3010 g; median gestational age 32.5, range 26-40 wks). An ultrasonographic scan of the arterial system was performed before the NIRS measurements, to validate the site of arterial occlusion. RESULTS: A t-test for independent samples showed lower values in the affected limb for all NIRS measurements. TOI measurements displayed lower values in the thromboembolic limb (mean 44.79±12%) versus unaffected (mean 47.95±17.08%) (P=0.0001). Mean (SD) peak systolic velocity in the patent artery below the occlusion decreased from 108±25 cm/s in the normal limb to 25.6±28 cm/s in the thrombus site (P=0.02). CONCLUSION: In neonatal intensive care units, measurement of limb peripheral perfusion and oxygenation seems to be clinically useful in arterial thromboembolic emergencies.

Fluoxetine may worsen hyperoxia-induced lung damage in neonatal rats.

Fluoxetine shows controversial lung effects as it prevents pulmonary hypertension in adult rats but exposure during gestation causes pulmonary hypertension in neonatal rats. In the present study, we tested the null hypothesis that the antidepressant drug fluoxetine does not modify the development of bronchopulmonary dysplasia (BPD) in neonatal rats. Experimental categories included I: room air (controls) with daily injection of saline; II: room air with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks; III: 60% oxygen with daily injection of saline; and IV: 60% oxygen with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks. Hyperoxia resulted in significant reduction in alveolar density and an increase in pulmonary endocrine cells, as well as increases in muscle layer areas of bronchi and arteries. Fluoxetine treatment generated a further increase in muscularisation and did not significantly modify the hyperoxia-induced reductions in alveolar density and increases in the endocrine cells. In hyperoxia, Real-Time PCR showed a lower pulmonary expression of vascular endothelial growth factor (VEGF) with no significant changes in the expression of matrix metalloproteinases (MMP) 2 and 12. Fluoxetine did not affect VEGF or MMP-2 expression but it significantly increased MMP-12 mRNA in both normoxic and hyperoxic groups. Zymographic analysis of MMP-2 activity in bronchoalveolar fluid showed a significantly reduced MMP-2 activity in hyperoxia, while fluoxetine treatment restored MMP-2 activity to levels comparable with the normoxic group. In conclusion, our data show that fluoxetine may worsen bronchial and arterial muscularisation during development of BPD and may up-regulate MMP expression or activity.

A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block?

While mainly based on the use of fluorinated steroids, there is no standard management of anti-Ro/La-related congenital heart block (CHB). This is a report concerning two consecutive cases of anti-Ro/La-related second-degree block treated with betamethasone (4 mg/day), weekly plasmapheresis, and intravenous immunoglobulins (IVIGs; 1 g/kg) administered every 15 days, a therapy that was begun shortly after CHB was detected and continued until delivery. The newborns were also treated with IVIG (1 g/kg) soon after birth and continued fortnightly until the anti-Ro/La antibody levels became undetectable. In both cases second-degree AV block reverted to a stable sinus rhythm with a first-degree atrioventricular (AV) block. Moreover, there was no recurrence of CHB when therapy was suspended, as confirmed by a 29 month and an eight month follow-up, respectively.

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.

Mixed exhaled nitric oxide and plasma nitrites and nitrates in newborn infants.

Plasma nitrite (NO2-) and nitrate (NO3-) are the stable end-products of endogenous nitric oxide (NO) metabolism. NO is present in the exhaled air of humans, but it is not clear if exhaled NO may be an indicator of the systemic endogenous NO production. The aims of the study were to determine the levels of exhaled NO and plasma NO2-/NO3- in healthy term and preterm newborns, and to assess if exhaled NO correlates with plasma NO2-/NO3- at birth. After the stabilization of the newborn, we measured by chemiluminescence the concentration of NO in the mixed expired breath of 133 healthy newborns. Measurement of exhaled NO was repeated after 24 and 48 hours. Plasma NO2-/NO3- levels at birth were measured by the Griess reaction. NO concentrations were 8.9 (CI 8.1-9.8) parts per billion (ppb), 7.7 (CI 7.2-8.3) ppb and 9.0 (CI 8.4-9.6) ppb at birth, 24 and 48 hours, respectively. At birth, exhaled NO was inversely correlated with gestational age (p=0.008) and birth weight (p<0.001). Plasma NO2-/NO3- level was 27.30 (CI 24.26-30.34) micromol/L. There was no correlation between exhaled NO and plasma NO2-/NO3- levels at birth (p=0.88). We speculate that the inverse correlation between exhaled NO and gestational age and birth weight may reflect a role of NO in the postnatal adaptation of pulmonary circulation. At birth, exhaled NO does not correlate with plasma NO2-/NO3- and does not seem to be an index of the systemic endogenous NO production.

Brain auditory activation measured by near-infrared spectroscopy (NIRS) in neonates.

This study presents a new measure of the hemodynamic changes to an auditory stimulus in newborns. Nineteen newborns born at 28-41 wk and aged 1 to 49 d were studied in waking and/or sleeping state, for a median time of 4 min 40 s before, 2 min 40 s during, and 3 min 5 s after an acustic stimulus (tonal sweep of frequency increasing from 2 to 4 kHz, intensity 90 dB SPL) originating 5 cm from the external auditory meatus. The emitter and detector optodes were placed over the left or right temporal region, corresponding to T3 or T4 EEG electrodes. The concentration changes in cerebral chromophores Delta[HbO2], Delta[Hb] and Deltaoxidized-reduced cytochrome aa(3) were recorded every 5 s. Changes in cerebral blood volume were calculated from the changes in total Hb x 0.89/large vessel Hb concentration. Increased oxyhemoglobin, Delta[HbO2], total Hb, Delta[Hb (sum)], and cerebral blood volume, DeltaCBV, were found in 13/19 neonates, with the exception of a neonate who only had increased in Delta[Hb], Delta[Hb (sum)] and DeltaCBV. During the stimulation phase there was a significant increase in DeltaCBV (t test, p = 0.00006) in the responsive newborns from a mean value of 0.006 (+/-0.02) mL/100 g in the pretest phase to 0.09 (+/-0.06) mL/100 g during the auditory stimulus. After the test DeltaCBV decreased to 0.04 (+/-0.07) mL/100 g (t test, p = 0.01), so did Delta[Hb (sum)] (p = 0.02). Hemodynamic responses of the subjects who showed increases in Delta[Hb (sum)] and Delta[HbO(2)] were analyzed to study the Delta[Hb]. The responder subjects could be classified into two groups according to Delta[Hb] changes: 8/13 (61.5%) showed an increase of Delta[Hb] (pattern A), while 5/13 (38.4%) showed a decrease (pattern B) (t test, p = 0.03). These two patterns did not show differences related to Delta[HbO(2)] and Delta[Hb (sum)]. The DeltaCBV changes in nonresponders presented a decrease during the test phase (t test, p = 0.04). CBV did not return to pretest values, suggesting a fronto-temporal brain pathway for storing unusual sounds. The increase in CBV followed the local increase in oxyhemoglobin and total Hb concentrations due to a greater use of oxygen in the homolateral temporal cortex of the newborns.

Is the CRIB score (clinical risk index for babies) a valid tool in predicting neurodevelopmental outcome inExtremely low birth weight infants?

The study aimed to assess how well the severity of clinical conditions in extremely low birth weight infants in the first 12 h of life, as measured by the CRIB (clinical risk index for babies), relates to hospital outcome and subsequent disability at 18 months of age. The CRIB was confirmed as a valid index of initial neonatal risk, even in extremely low birth weight infants, predicting hospital outcome (death or major brain lesions) more accurately than birth weight or gestational age. However, an adjustment of the CRIB score for gestational age might enhance its positive predictive value in relation to short-term developmental outcome in this particular population.

[The evolution of care for the critical child: pediatric intensive care]. / L'evoluzione dell'assistenza al bambino critico: la terapia intensiva pediatrica.

Pediatric intensive care units (PICUs) have been developed to provide intensive care for children between post-neonatal age and adolescence. These units have largely been developed in North America, mainly in tertiary hospitals. In Italy, critically ill children are still often nursed on adult ICU's, where medical and nursing staff often lack pediatric training. Here we report the first 5-year experience of the multidisciplinary PICU developed at the Department of Pediatrics, University of Padua, focusing on PICU and patients characteristics, as well as on the evaluation of outcome by means of the Pediatric Risk of Mortality (PRISM) score.

[Extracorporeal membrane oxygenation (ECMO) in the newborn infant and the child with intractable respiratory failure]. / Ossigenazione extracorporea a membrana (ECMO) nel neonato e nel bambino con insufficienza respiratoria intrattabile.

Extracorporeal membrane oxygenation (ECMO) has become a nearly standard treatment for neonates with refractory hypoxemic respiratory failure due to various disease. Even though in the non-neonatal age the experience is less extensive, an increased widespread interest on the possible applications in children with severe life-threatening respiratory or cardiovascular insufficiency is well documented in the literature. General contraindications include presence of active bleeding, underlying lethal disease, congenital malformations, or severe brain damage. Whilst in the neonatal population common entry criteria have been widely accepted, the identification of precise parameters capable to predict mortality and thus indicating an ECMO support in older patients are still lacking. At present, nonetheless, more than 10.000 newborns and 1.000 children with severe respiratory insufficiency at high mortality risk have received an ECMO treatment, with a survival rate of more than 80% and 50%, respectively. The initial results of our ECMO program for both neonatal and pediatric patients with refractory respiratory failure are encouraging, both in terms of mortality and morbidity, and they will be briefly discussed.

[Transportation of the critical newborn infant and child]. / II trasporto del neonato e del bambino critico.

Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua.

[Nitric oxide via inhalation in the newborn infant and the child with acute hypoxemic respiratory failure]. / Ossido nitrico per via inalatoria nel neonato e nel bambino con insufficienza respiratoria ipossiemica acuta.

Inhaled nitric oxide (NO) has been recently proposed as a new treatment in newborns and children with severe hypoxemic respiratory failure. Differently from other vasodilators, inhaled nitric oxide selectively lowers pulmonary vascular resistance and pulmonary arterial pressure, and improves the ventilation/perfusion matching by directing pulmonary blood flow toward better ventilated areas, ultimately improving systemic oxygenation. In our experience, we have observed that inhaled NO may acutely ameliorate gas exchange in patients with severe respiratory failure. This may allow a reduction of both ventilatory parameters and fraction of inspired oxygen, thus limiting further damage to the lungs. Nonetheless, the underlying disease and the clinical conditions before NO treatment seem to maintain a crucial role in the ultimate prognosis of these patients. Further studies are needed in order to better define indications, dosages, and safety of nitric oxide treatment, and to verify its authentic prognostic value in neonates and children with acute respiratory failure.

Severity grading of childhood poisoning: the Multicentre Study of Poisoning in Children (MSPC) score.

Scores for severity grading of childhood poisoning may be useful in comparing different causes of poisoning, in order to identify the main risks and their changes over time. The Multicentre Study of Poisoning in Children score is based on four levels of severity (1-mild, 2-moderate, 3-severe, 4-very severe) involving nine target groups: seven relating to organ systems (gastrointestinal, nervous, respiratory, circulatory, renal, hepatic, skin), one to metabolic abnormalities and one to injuries from corrosive substances. Each patient is classified by the highest level attributed to any one of the nine groups. The score has been prospectively tested in 644 symptomatic children, aged 0-13 years, admitted to six pediatric hospitals of Northern Italy from January 1, 1991 to December 31, 1993. Poisoning was categorized as mild (1) in 357 children (53.8%), moderate (2) in 285 (42.9%), severe (3) in 18 (2.7%) and very severe (4) in 4 (0.6%). No deaths occurred. Severity grading according to The Multicentre Study of Poisoning in Children score confirms the prevalence of mild and moderate poisonings in children; the score seems to be an objective method suitable for epidemiological studies in different countries. Its clinical usefulness deserves more investigation.

The molecular basis of hereditary fructose intolerance in Italian children.

We investigated the molecular defects of the aldolase B gene in five unrelated patients affected by hereditary fructose intolerance. The techniques used were DNA amplification, direct sequencing and allele-specific oligonucleotide (ASO) hybridization. The most frequent substitutions found in the hereditary fructose intolerance alleles analysed were the A174D and the A149P mutations, which account for 50% and 30% of the alleles, respectively. In two unrelated families, we found a rare mutation, the MD delta 4 previously described only in one British family, which may be an important cause of the disease in Italy.

Determination of 8-methoxypsoralen in plasma by gas chromatography-mass spectrometry using selected-ion monitoring.

A sensitive and accurate assay was developed for the measurement of 8-methoxypsoralen in plasma using electron-impact positive-ion mass fragmentography. 4,5,8-Trimethylpsoralen was used as an internal standard. Sample preparation consisted of a two-step liquid phase extraction using acetonitrile and methylene chloride. The calibration curve showed a linear relationship between the peak areas of 8-methoxypsoralen and 4,5,8-trimethylpsoralen over a wide range of 8-methoxypsoralen concentrations (1-500 ng/ml). With-in- and between-run precisions, measured at five different drug concentrations, varied from 0.82 to 1.41% and from 0.82 to 1.86%, respectively.

[Computerization of a clinical chart of perinatal data]. / La computerizzazione di una cartella clinica dai dati perinatali.

A computerized protocol, PADOVA-BPD, has been set-up to study prematures affected by RDS, PDA and/or BPD. This protocol consists of a Data Bank, BPDdata, where the information of traditional clinical chart has been stored and of the BPDPadova program, written for this purpose in FORTRAN 77, that allows a wide band of clinical and statistical analysis.

Percutaneous ethyl alcohol intoxication in a one-month-old infant.

A one-month-old child was referred to our hospital for unexplained lethargy. She was found to be intoxicated from ethanol-soaked gauze pads which had been applied to the umbilical stump and contiguous skin for several days for the purpose of promoting umbilical cord detachment. We emphasize the importance of considering the risk of percutaneous alcohol absorption, especially in young infants, and the necessity of toxicology screening in every child with drowsiness of unknown etiology.

[Diagnostic role of echography in acute appendicitis in children]. / Ruolo diagnostico dell'ecografia nell'appendicite acuta del bambino.

Eighty-seven pediatric patients with suspected acute appendicitis underwent high-resolution US with graded abdominal compression. The study was limited to the patients with a questionable clinical diagnosis, accounting for about 40% of the patients examined for acute appendicitis in our Institution. US had 87.3% accuracy, 81.5% sensitivity, and 90% specificity. The main US findings in the positive cases were: visualization of the appendix as a tubular non-compressible structure, with a diameter of 5 mm or more, symmetric/asymmetric wall thickening, possible presence of appendicoliths and variable appearance of the central echogenic layer (preserved, doubled for lumen dilatation, partially/totally lost). The above US findings were grouped in 3 basic patterns: type I (thickened appendix with no structural abnormalities) appeared to be related to non-suppurative and phlegmonous acute appendicitis; type II (detectable appendiceal abnormalities) was observed both in phlegmonous and in suppurative acute appendicitis; type III (pericecal complex mass, frequently with appendicoliths) was found in all cases of periappendiceal abscess. In our experience, the use of US in the diagnosis of acute appendicitis in children allowed a reduction by about 2/3 in the rate of unnecessary laparotomies. Such a finding emerges from the comparison with the results obtained in the 2 years prior to the use of US. The technique also allowed an unquestionable diagnosis of acute appendicitis or periappendiceal abscess to be made in a number of clinically equivocal cases, thus avoiding potentially harmful delays in diagnosis. On the other hand, the incidence of false-negatives on US is not negligible, which calls for a cautious clinical and US evaluation of all equivocal cases following no typical US pattern.