Precursors of adrenomedullin, endothelin and atrial natriuretic peptide as diagnostic markers of neonatal infection

Aim: To evaluate the serum levels of three precursors of vasoactive peptide as diagnostic markers for neonatal infections. Methods: Overall, 356 neonates (160 without infection, 114 with mild infections and 82 with severe infections) were enrolled in this study. Their serum levels of mid‐regional pro‐adrenomedullin (MR‐pro‐ADM), C‐terminal pro‐endothelin‐1 (CT‐pro‐ET‐1) and mid‐regional pro‐atrial natriuretic peptide (MR‐pro‐ANP) were measured by immunoassay, and receiver operating curve analysis was performed for each biomarker to evaluate their diagnostic values for neonatal infection. Results: The serum levels of MR‐pro‐ADM (2.079 ± 1.195 nm ), CT‐pro‐ET‐1 (109.4 ± 62.9 pm ) and MR‐pro‐ANP (1221.4 ± 725.0 pm ) in the severe infection group were significantly higher than those in the mild infection group (1.025 ± 0.421 nm , 86.7 ± 51.8 pm , and 687.6 ± 575.7 pm , respectively) and in the non‐infection group (0.853 ± 0.488 nm , 51.3 ± 40.6 pm , and 943.3 ± 847.3 pm , respectively) (p < 0.01–0.001). Their areas under the curve were 0.72, 0.76 and 0.61, respectively. Among them, CT‐pro‐ET‐1 had the highest sensitivity (82.65%), whereas MR‐pro‐ADM had the highest specificity (86.25%). Conclusions: MR‐pro‐ADM, CT‐pro‐ET‐1 and MR‐pro‐ANP may serve as useful laboratory markers to indicate bacterial infection in neonates.     

The successful use of alemtuzumab for treatment of steroid‐refractory acute graft‐versus‐host disease in pediatric patients

SR‐aGVHD remains a significant cause of morbidity and mortality in allogeneic HCT recipients. Alemtuzumab has been used with success in adult patients but has not been studied in the pediatric setting. To estimate the effectiveness of alemtuzumab for the treatment of SR‐aGVHD in pediatric patients, we retrospectively reviewed the charts of 19 patients (median age 4 yr, range 0.5–28 years) with grades II (n = 3), III (n = 10), or IV (n = 6) SR‐aGVHD who received alemtuzumab treatment. Patients received a median dose of 0.9 mg/kg alemtuzumab (range 0.3–2 mg/kg) divided over 2–6 days. Eighty‐nine percent of patients received additional courses. A complete response, defined as GVHD of grade 0 at four wk following the first alemtuzumab course, was observed in nine patients (47%). A partial response, defined as an improvement in grade after four wk, was observed in five patients (26%). There was no response in five patients (26%). The overall response rate at four wk was 73%. Infectious complications included bacteremia (47%), presumed or documented fungal infections (21%), adenovirus viremia (52%), EBV viremia (36%), and CMV viremia (36%). We conclude that alemtuzumab is effective for SR‐aGVHD in pediatric patients with a tolerable spectrum of complications.     

The reliability of weight‐for‐length/height Z scores in children

The World Health Organisation (WHO) recommends weight‐for‐length/height (WFL/H), represented as a Z score for diagnosing acute malnutrition among children aged 0 to 60 months. Under controlled conditions, weight, height and length measurements have high degree of reliability. However, the reliability when combined into a WFL/H Z score, in all settings is unclear. We conducted a systematic review of published studies assessing the reliability of WFL/Hz on PubMed and Google scholar. Studies were included if they presented reliability scores for the derived index of WFL/Hz, for children under 5 years. Meta‐analysis was conducted for a pooled estimate of reliability overall, and for children above and below 24 months old. Twenty six studies on reliability of anthropometry were identified but only three, all community‐based studies, reported reliability scores for WFL/Hz. The overall pooled intra‐class correlation coefficient (ICC) estimate for WFL/Hz among children aged 0 to 60 months was 0.81 (95% CI 0.64 to 0.99). Among children aged less than 24 months the pooled ICC estimate from two studies was 0.72 (95% CI 0.67 to 0.77) while the estimate reported for children above 24 months from one study was 0.97 (95% CI 0.97 to 0.99). Although WFL/Hz is recommended for diagnosis of acute under nutrition among children below 5 years, information on its reliability in all settings is sparse. In community settings, reliability of WFL/Hz is considerably lower than for absolute measures of weight and length/height, especially in younger children. The reliability of WFL/Hz needs further evaluation.     

Prompt administration of antibiotics is associated with improved outcomes in febrile neutropenia in children with cancer

Background

Time‐to‐antibiotic (TTA) administration is a widely used quality‐of‐care measure for children with cancer and febrile neutropenia (FN). We sought to determine whether TTA is associated with outcomes of FN.

Procedure

A single‐center, retrospective cohort study was conducted of 1,628 FN admissions from 653 patients from 2001 to 2009. Outcome variables included (1) an adverse event (AE) composite of in‐hospital mortality, pediatric intensive care unit (PICU) admission within 24 hours of presentation, and/or fluid resuscitation ≥40 ml/kg within 24 hours of presentation and (2) length of stay (LOS). TTA was measured as a continuous variable and in 60‐minute intervals. Mixed regression models were constructed to evaluate associations of TTA with the outcome variables after adjusting for relevant covariates including cancer diagnosis, degree of myelosuppression, and presence of bacteremia.

Results

The composite AE outcome occurred in 11.1% of admissions including 0.7% in‐hospital mortality, 4.7% PICU admission, and 10.1% fluid resuscitation. In univariate analysis, TTA was associated with the composite AE outcome (Odds Ratio [OR] 1.29, 95% CI 1.02–1.64) but not LOS. In multivariate analysis, after adjustment for relevant covariates, 60‐minute TTA intervals were associated with the composite AE outcome (61–120 minutes vs. ≤60 minutes, OR 1.81, 95% CI 1.01–3.26). Unexpectedly, admission from the emergency department (ED) was also independently associated with the composite AE outcome (ED vs. clinic, OR 3.15, 95% CI 1.95–5.09).

Conclusions

TTA and presentation to the ED are independently associated with poor outcomes of FN. Pediatr Blood Cancer 2013;60:1299–1306. © 2013 Wiley Periodicals, Inc.     

Prospects of vaccination as a means of preventing mother-to-child transmission of HIV-I

Although short-course antiretroviral therapy is efficient in reducing mother-to-child transmission (MTCT) of HIV-1, it does not prevent transmission during the breastfeeding period. There is therefore an urgent need to test various approaches, including HIV-1 vaccination, to try to prevent postnatal transmission of HIV-1 in breastfeeding populations in developing countries.     

A 5‐HT2A/2C receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane,mitigates developmental neurotoxicity of ethanol to serotonergic neurons

Prenatal ethanol exposure causes the reduction of serotonergic (5‐HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5‐HT_2A and 5‐HT_2C receptors during the fetal period is able to prevent the reduction of 5‐HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague–Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair‐fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), an agonist for 5‐HT_2A/2C receptors, during GDs 13 to 19 (Et‐DOI or Pf‐DOI), and another was injected with saline vehicle only (Et‐Sal or Pf‐Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5‐HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5‐HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et‐Sal fetuses compared to that of the Pf‐Sal and Pf‐DOI fetuses, whereas there were no significant differences between Et‐DOI and each Pf control. Thus, we concluded that the reduction of 5‐HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5‐HT_2A/2C receptors during the fetal period.     

Simultaneous occurrence of foetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies: a case study and review of the literature

Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia caused by maternal autoantibodies against HNA-1b. This appears to be the first case of simultaneous occurrence of these two conditions. CONCLUSION: This case report and review of the literature demonstrate that anti-HPA-3a antibodies can be overlooked by standard assays.     

Cholestasis as the leading sign of a transmesenteric hernia in a split-liver transplanted child - a case report and review of literature

Internal hernias are an extremely rare complication after pediatric liver transplantation, and its presentation with cholestasis has not been described to date. We report the case of a 12-yr-old boy who presented with moderate abdominal pain 11 yr after split liver transplantation and biliary-enteric anastomosis. He developed severe jaundice within 24 h of initial presentation. Imaging studies revealed ascites, dilation of the intrahepatic bile ducts, a dilated Roux-en-Y-loop, with the loop truncated at the level of the mesenteric artery, which performed a narrow right-to-left loop. At laparotomy, a transmesenteric internal hernia at the root of the jejunal mesentery was identified, originating from the creation of the Y-loop; the Roux-en-Y-loop and its adjacent intestinal loops had slipped through the opening. The Roux-en-Y loop was ischemic from strangulation, and the rest of the intestine well perfused. No surgical resection was necessary following reduction. The patient recovered completely. We discuss diagnosis and management of internal hernias, and review radiological signs. Internal transmesenteric hernias can occur at any time after liver transplantation and prompt diagnosis and surgical treatment are vital.     

Epstein-Barr virus related opsoclonus-myoclonus-ataxia does not rule out the presence of occult neuroblastic tumors

Opsoclonus-myoclonus-ataxia (OMA) secondary to Epstein-Barr virus (EBV) infection has only been described in three pediatric patients. Previous reports suggested that evidence for a recent EBV infection in the absence of an occult neoplasm would predict a favorable prognosis for OMA as well as no tumor development. We present the case of a 20-month-old child with OMA associated with a microbiologically documented acute EBV infection and an occult thoracic ganglioneuroblastoma diagnosed 5 months later.     

The reliability of the disabled children's quality-of-life questionnaire in Swedish children with diabetes

Aim: To determine the reliability of the disabled children’s quality‐of‐life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health‐related quality‐of‐life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use. Methods: Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split‐half reliability correlation and intraclass correlation (ICC) coefficients were calculated. Bland & Altman plots were calculated on the generic HRQoL domain. Results: Both child and parent versions showed good internal consistency. Test–retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split‐half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents. Conclusion: The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes.     

Optimal birth weight percentile cut‐offs in defining small‐ or large‐for‐gestational‐age

Aims: It remains questionable what birth weight for gestational age percentile cut‐offs should be used in defining clinically important poor or excessive foetal growth. We aimed to evaluate the optimal birth weight percentile cut‐offs for defining small‐ or large‐for‐gestational‐age (SGA or LGA). Methods: In a birth cohort‐based analysis of 17 979 120 non‐malformation singleton live births, U.S. 1995–2001, we assessed the optimal birth weight percentile cut‐offs for defining SGA and LGA. The 25th–75th percentile group served as the reference. Primary outcomes are the risk ratios (RR) of neonatal death and low 5‐min Apgar score (<4) comparing SGA or LGA versus the reference group. More than 2‐fold risk elevations were considered clinically significant. Results: The 15th birth weight cut‐off already identified SGA infants at more than 2‐fold risk of neonatal death at pre‐term, term or post‐term, except for extremely pre‐term births <28 weeks (continuous risk reductions over increasing birth weight percentiles). LGA was associated with a reduced risk of low 5‐min Apgar score at pre‐term, but an elevated risk at term and post‐term. The 97th cut‐off identified LGA infants at 2‐fold risk of low 5‐min Apgar at term. Conclusion: The commonly used 10th and 90th birth weight percentile cut‐offs for defining SGA and LGA respectively seem largely arbitrary. The 15th and 97th percentiles may be the optimal cut‐offs to define SGA and LGA respectively.     

Successful treatment of a child with late-onset T-cell post-transplant lymphoproliferative disorder/lymphoma

We report a novel regimen for refractory post-transplant T-cell lymphoma (PTL). Our patient presented with non-Epstein-Barr virus (EBV) related, T-cell post-transplant lymphoproliferative disease (PTLD) 3.5 years after liver transplantation. Initially diagnosed as polyclonal PTLD, the disease progressed to a monoclonal, T-cell PTL that was refractory to several chemotherapy regimens but responded to a regimen consisting of fludarabine, cyclophosphamide, cytarabine, and alemtuzumab. Consolidation therapy included high-dose chemotherapy, autologous hematopoietic stem cell rescue, and radiation therapy. She remains in remission 2.5 years later. T-cell PTL is a rare disease with a poor prognosis; this regimen provides a novel, potentially curative approach for its treatment.     

Incidence of necrotizing enterocolitis in very‐low‐birth‐weight infants related to the use of Lactobacillus GG

Background: One of the five level III neonatal intensive care units (NICU) in Finland has used prophylactic Lactobacillus GG (LGG) for very‐low‐birth‐weight (VLBW) infants since 1997. Aim: To examine retrospectively the incidence of necrotizing enterocolitis (NEC) in all five university hospital NICUs in Finland in relation to the use of LGG during the years each unit has belonged to the Vermont Oxford Network (VON). Methods: The incidence of NEC was analysed from the national database and from the VON databases separately in all five level III NICUs and additionally in three groups according to the probiotic practice in the hospitals: prophylactic LGG group, probiotics ‘on demand’ group and no probiotics group. Results: The incidence of NEC was 4.6% vs. 3.3% vs. 1.8% in the prophylactic LGG group, the probiotics ‘on demand’ group and the no probiotics group, respectively; p = 0.0090, chi‐square. LGG had no influence on the clinical course of NEC. Conclusions: The results of this retrospective report failed to show that LGG prophylaxis protects VLBW infants from the occurrence of NEC, in contrast to previously published results. Our results call for more research regarding effective ways to administer probiotics, including data on appropriate bacteria, strain, dose and timing of administration to achieve clinically robust effects.