Neonatal painful stimuli: skin conductance algesimeter index to measure efficacy 24% of sucrose oral solution.

Pain management is one of the main challenges in addressing the improved care of hospitalized newborns. The administration of oral sucrose with and without non-nutritive suction has been proposed as a nonpharmacological intervention to relieve procedural pain in newborns. The effects have not yet been well characterized. The aim of this study is to investigate, using skin conductance algesimeter (SCA) pain monitor index, the effects of 24% sucrose solution on pain perception during capillary and arterial blood sampling. It is a prospective, randomized controlled study: sucrose versus placebo. Sucrose was given orally to infants who were submitted to arterial or capillary sampling. The SCA was measured during, and for 3 min before and after the intervention. Fifty-six infants were enrolled: 31 in the sucrose group and 25 in the placebo group. SCA showed that the measurement of peaks per second of pain during and 3 min after the procedures was lower in the sucrose group than the placebo group and that this difference was statistically significant (p < .05). In conclusion, 24% sucrose administered orally is effective in reducing pain during and after capillary and arterial sampling in newborns and can be used for the prevention and treatment of pain in the Neonatal Intensive Care Unit.Brief rationaleTo treat neonatal pain, a tiered approach with nonpharmacological and pharmacological method can be used.Among nonpharmacological therapies, sucrose administration is safe and effective in reducing single episodes of minor procedural pain. This study aimed to investigate, the effects of 24% sucrose solution on pain perception during capillary and arterial blood withdrawn by using an objective method: skin conductance algesimeter (SCA) pain monitor index.This randomized controlled trial in which term and/or preterm neonates (postnatal age maximum of 28 days corrected for postmenstrual age) received sucrose for procedural pain. Oral sucrose was administered directly by a disposable plastic vial. SCA was measured by means of a specific device.We demonstrated, using SCA pain monitor index, the efficacy of 24% sucrose solution on pain perception during capillary and arterial blood withdrawn. The results of this study provide an objective evidence of sucrose efficacy for the prevention and treatment of neonatal painful procedures.

Electrocardiographic and echocardiographic changes during therapeutic hypothermia in encephalopathic infants with long-term adverse outcome.

AIM: To assess the electrocardiography and echocardiography changes during therapeutic hypothermia and rewarming period in encephalopathic infants with long-term adverse neurological outcome. METHODS: Prospective multicentre longitudinal study. We included 64 consecutive infants with moderate or severe hypoxic ischaemic encephalopathy undergoing therapeutic hypothermia who had 18-24 month-outcome data. We analysed electrocardiography and heart rate changes before, during and after therapeutic hypothermia. Superior vena cava flow, left ventricular cardiac output and stroke volume were studied using echocardiography during and immediately after therapeutic hypothermia. An abnormal outcome was defined as death or moderate/severe disability at 18-24 months. RESULTS: Neonates with higher superior vena cava flow pre-rewarming had significantly higher odds of documented long-term adverse outcome when compared to newborns with good outcome (OR 1.57; 95%CI, 1.1-1.78; p = 0.01 after adjustment). QTc and RR intervals were significantly longer at 12, 24, 36 and 48 h in infants with good outcome compared with those with adverse outcome (p < 0.001). During therapeutic hypothermia, infants with poor outcome had a higher heart rate at 12, 24, 36, 48, 60 h after birth compared with those with good outcome (p < 0.001). From 36 h on, heart rate gradually increased and RR and QTc intervals progressively shortened with values back to normal after rewarming. CONCLUSIONS: Infants with hypoxic ischaemic encephalopathy who have adverse neurological outcome show a preferential cerebral blood flow redistribution during therapeutic hypothermia. Infants with poor outcome have higher heart rate and shorter RR and QTc intervals during therapeutic hypothermia.

Presepsin for the detection of early-onset sepsis in preterm newborns.

BACKGROUND: Early-onset sepsis (EOS) is responsible for an important fraction of neonatal morbidity and mortality all over the world. The aim of this study was to assess whether presepsin (P-SEP) can be a more accurate biomarker of EOS compared with pro-calcitonin (PCT) and C-reactive protein (CRP). STUDY DESIGN: Consecutive preterm neonates (<34 wk gestational age, admitted to Neonatal Intensive Care Unit by 6 h of age and undergoing sepsis evaluation) were recruited as part of a case-matched control study. We determined CRP, PCT and P-SEP at admission, and then at 12, 24, and 48 h of age. Neonates recruited into the study were divided into the EOS group (n = 32) and the uninfected group (n =38) according to their infection screening. RESULTS: P-SEP values were significantly higher in the EOS group than in the uninfected group at different time intervals. The highest accuracy was achieved by P-SEP at 24 h after birth. The AUC for P-SEP was 0.97. In our sample, P-SEP achieved the best accuracy for prediction of EOS at the cut-off of 788 ng/l with 93% sensitivity and 100% specificity. CONCLUSIONS: This study shows that P-SEP is significantly higher in preterm infants with EOS compared with uninfected infants.

Photoletter to the editor: Lamellar ichthyosis and arthrogryposis in a premature neonate.

Lamellar ichthyosis is a rare congenital disorder characterized by collodion membrane at birth and facial anomalies (eclabium and ectropion). The major underlying genetic defect is in TGM1, with mutations of this gene found in 50% of patients. An early diagnosis is fundamental in view of establishing a specific treatment due to the severity of the disease. We report a case of severe lamellar ichthyosis and arthrogryposis, without the typical facial presentation, negative for TGM1 mutations. The clinical improvement was achieved only after treatment with oral retinoids, highlighting the importance of early diagnosis and prompt administration of a specific therapy.

Cerebral, renal and mesenteric regional oxygen saturation of term infants during transition.

OBJECTIVE: To measure cerebral regional oxygen saturation (CrSO2), renal regional oxygenation saturation (RrSO2) and mesenteric tissue regional oxygen saturation (MrSO2) during immediate transition and continuously for the first 9 hours of age. Fractional tissue oxygen extraction of the brain (CtFOE), kidneys (RtFOE), splanchnic tissue (MtFOE) were also assessed. STUDY DESIGN: Prospective, observational study of 61 term infants, delivered by elective caesarean section. Using near-infrared spectroscopy, changes in CrSO2, RrSO2, MrSO2 and changes in CtFOE, RtFOE and MtFOE were measured all through the first 9 hours of life. All the episodes of feeding during this period were recorded. RESULTS: Mean CrSO2 increased quickly to 7 minutes, with no further changes. On the other hand, mean RrSO2 and mean MrSO2 increased for 10 minutes and thereafter they remained on their newly reached level. RrSO2 and MrSO2 were significantly lower at 3-4-5-6-7 minutes of life compared to the CrSO2 (p<0.05). RtFOE and MtFOE were significantly higher at 3-4-5-6-7 minutes of life compared to the CtFOE (p<0.05). During feeding, CrSO2, RrSO2 and MrSO2 did not significantly change. CONCLUSIONS: During early adaptive period, oxygen delivery is preserved to 'vital' organs, like brain, at the expense of kidneys and splanchnic tissue. Term infants can provide for the increasing metabolic activity of the intestinal tract during feeding periods without compromising oxygenation.

Targeted metabolomics in the expanded newborn screening for inborn errors of metabolism.

Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.

Near infrared spectroscopy in newborns with surgical disease.

NIRS has been used as a key device with the aim to evaluate the impact of surgery and anesthesia on cerebral and splanchnic oxygenation in neonatal population. The main applications has been in cardiac surgery, congenital diaphragmatic hernia and esophageal atresia. In this report we summarized the results published on the application of NIRS in neonatal surgery with particular respect to cerebral and splanchnic oxygenation, presenting also some future prospective.

The scenarios of shock in newborn infants.

Shock defines a complex dysfunction of organ perfusion, that produces a status of cellular energy failure, resulting from an insufficient supply of oxygen and nutrients to tissues. The diagnosis of shock is very difficult because of the lack of sufficiently sensitive and specific clinical criteria, and is substantially based on the demonstration of an arterial hypotension, an indicator unfit to detect the organ hypoperfusion. It determines the necessity of firmly introducing in the diagnostic run the functional echocardiography, the near infrared spectroscopy and the amplitude – integrated electroencephalography, etc., in the monitoring of the critical newborn. In order to simplify the problem, the authors identify the clinical scenarios of the newborn's shock to enhance the different pathogenetic moments and to build up appropriate therapeutic algorithms, without forgetting that at present there is no evidence that treatment of shock improves outcomes, despite the large amount of the studies conducted on this topic.

The physiopathology of the patent ductus arteriosus.

Patent ductus arteriosus (PDA) remains a frequent problem for the very low birth weight infants. Many questions about the role of PDA, the best method of diagnosing it and the appropriate timing of treatment have been, at time, not completely answered. What we now know is that the left to right shunt appears very soon after birth and, if the ductus remains open, results in a progressively lung over circulation and a left ventricular volume overload. Despite the immature myocardium, the heart is able to increase its cardiac output, mainly through an increase in stroke volume, even in extremely preterm newborns. The increment of stroke volume does not increase or maintain an effective systemic perfusion and with the time it will become unproductive. Both animal and human studies showed a compromise of organ blood flow, with the development of systemic hypotension, steal phenomena, organ hypoperfusion, and ultimately congestive heart failure.

Cholestasis in neonatal intensive care unit: incidence, aetiology and management.

AIM: Prevalence, aetiology, management and outcome of cholestasis were evaluated in infants admitted to neonatal intensive care unit (NICU). METHODS: Medical records of all infants admitted to two Italian level III NICUs from January 2005 to August 2007 were retrospectively reviewed. The role of ursodeoxycholic acid (UDCA) therapy was also investigated. RESULTS: Twenty-seven of 1289 enrolled infants developed cholestasis. In 25 infants, cholestasis had a multifactorial basis, while in two, no aetiology was found. UDCA did not significantly affect clinical and biochemical course of cholestasis. During a period of 12 months, eight cholestatic infants died, one underwent liver transplantation and 18 fully recovered. CONCLUSION: Infants admitted in NICU have a rate of cholestasis higher than that reported in the general population of live births; in most cases, cholestasis is associated to multiple risk factors and shows a favourable outcome. UDCA does not seem to affect clinical course of cholestasis in this setting.

Gliadin activates HLA class I-restricted CD8+ T cells in celiac disease intestinal mucosa and induces the enterocyte apoptosis.

BACKGROUND & AIMS: The extensive infiltration of CD8(+) T cells in the intestinal mucosa of celiac disease (CD) patients is a hallmark of the disease. We identified a gliadin peptide (pA2) that is selectively recognized by CD8(+) T cells infiltrating intestinal mucosa of HLA-A2(+) CD patients. Herein, we investigated the phenotype, the tissue localization, and the effector mechanism of cells responsive to pA2 by using the organ culture of CD intestinal mucosa. The target of pA2-mediated cytotoxicity was also investigated by using the intestinal epithelial cell lines Caco2 and HT29, A2(+) and A2(-), respectively, as target cells. METHODS: Jejunal biopsy specimens from CD patients were cultured in vitro with pA2, and cellular activation was evaluated by immunohistochemistry and cytofluorimetric analysis. Cytotoxicity of pA2-specific, intestinal CD8(+) T cells was assayed by granzyme-B and interferon-gamma release and by apoptosis of target cells. RESULTS: pA2 challenge of A2(+) CD mucosa increased the percentage of CD8(+)CD25(+) and of CD80(+) cells in the lamina propria, the former mainly localized beneath the epithelium, as well as the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-positive cells (TUNEL(+)) in the epithelium. Intraepithelial CD3(+) cells and enterocyte expression of Fas were also increased. CD8(+)CD25(+) and CD8(+)FASL(+) T cells were significantly increased in cell preparations from biopsy specimens cultured with pA2. CD8(+) T-cell lines released both granzyme-B and interferon-gamma following recognition of pA2 when presented by Caco2 and not by HT29. CONCLUSIONS: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.

Intravenous magnesium sulphate vs. inhaled nitric oxide for moderate, persistent pulmonary hypertension of the newborn. A Multicentre, retrospective study.

We have compared intravenous magnesium sulphate vs. inhaled nitric oxide in the therapy of moderate persistent pulmonary hypertension of the neonate. A retrospective collection of clinical data from 58 neonates was carried out in six neonatal intensive care units of Southern Italy sharing the same operational protocols. In our setting, both drugs were effective in treating moderate persistent pulmonary hypertension of the neonate but nitric oxide (NO) treatment resulted in much faster amelioration of oxygenation index, taken as a marker of the underlying condition. No significant difference was recorded in immediate or long-term complications. We conclude that, wherever NO facilities are not readily available, magnesium sulphate is a safe and cheaper alternative for first-line treatment of moderate persistent pulmonary hypertension of the neonate.

Patent ductus arteriosus 'stenting' as a life-saving approach in severe neonatal Ebstein's anomaly.

A critical 1-day-old male neonate was referred to cardiac evaluation because of deep cyanosis due to a severe tricuspid valve Ebstein's anomaly with large atrial right-to-left shunt and duct-dependent pulmonary circulation. Ductus arteriosus re-opening by prostaglandin infusion resulted in significant clinical improvement but, after a few hours, it irreversibly closed, and pulmonary vasodilator treatment with inhaled nitric oxide and oral sildenafil did not significantly increase the oxygen saturation. Therefore, it was decided to proceed to ductal recanalization and stenting as an alternative to the surgical shunt. After the procedure, oxygen saturation was raised to over 90%, allowing the baby to be weaned from mechanical ventilation. At 9-month follow-up, he was asymptomatic and showed a systemic saturation over 90% despite complete closure of the stented ductus. In conclusion, ductus arteriosus stenting might be considered to be a reliable and life-saving therapeutic option in severe forms of Ebstein's anomaly as a temporary support to a multidrug vasoactive therapy.