Temporary Renal Enlargement in Children with a First Episode of Febrile Urinary Tract Infection is a Significant Risk of Recurrent Infection.

PURPOSE: Although morphological renal abnormalities in children with febrile urinary tract infection (fUTI) have been showed a predictive factor for recurrent infection, there are no available data on recurrence regarding sonographic renal enlargement at first fUTI episode, especially focusing on whether renal enlargement is temporary or not. MATERIALS AND METHODS: This cohort study reviewed the medical records of children who underwent renal ultrasound during their first fUTI during 2005-2013 and who were aged <15 years at diagnosis. We defined a kidney as temporary enlarged when the kidney length was ≥2 standard deviation above normal renal length for that age on sonography or a difference of ≥1 cm in sonographic length between the right and left kidneys, following normal renal length after antibiotic treatment. RESULTS: A total of 132 children were enrolled, of whom 11 had sonographic temporary temporal renal enlargement during their first fUTI. After completing antibiotic therapy for a first fUTI episode, 20 (15%) children had fUTI recurrence. The clinical characteristics at first episode of fUTI were not significantly different between renal enlargement and nonrenal enlargement groups. Children with temporary renal enlargement at a first fUTI episode had significantly lower fUTI recurrence-free survival proportion than those with nonrenal enlargement according to the Kaplan-Meier method (p = 0.003) Conclusion: Identification of temporary temporal renal enlargement as a predictor of recurrent fUTI may help identify children with a first episode of fUTI who will be warned of close monitoring.

Predictive factors of continuous negative extrathoracic pressure management failure in children with moderate to severe respiratory syncytial virus infection.

Continuous negative extrathoracic pressure (CNEP) might be beneficial for children with severe respiratory tract infections. However, there are no available data on the predictors of its failure among individuals with respiratory syncytial virus (RSV) infections. Here, we conducted a retrospective cohort study between October 1, 2015 and October 31, 2018 in hospitalized children with moderate to severe symptoms of respiratory syncytial virus (RSV) infections. We divided 45 children requiring CNEP ventilation with a non-fluctuating negative pressure of - 12 cm H2O into two groups. They were classified based on improvement or deterioration of their respiratory disorder under CNEP ventilation (responder group: n = 27, failure group: n = 18). Based on the univariate analysis, the responder and failure groups significantly differed in terms of median age, days elapsed from RSV onset to the initiation of CNEP, white blood cell count (WBC), titer of venous pCO2, body temperature at admission, and modified Wood-Downes Score (mWDS) 6 h after initiating CNEP. Based on a logistic regression analysis adjusted for age < 1 year upon admission, less than 5 days elapsed from RSV onset to the initiation of CNEP, not high value of WBC and body temperature at admission, and high values of mWDS 6 h after initiating CNEP were found to be significant independent risk factors for CNEP ventilation failure. The former two variables were associated with less failure (odds ratio was approximately 5), and the latter two variables are associated with more failure (odds ratio was approximately 8-9). Thus, CNEP could be a valid option for children with moderate to severe RSV infections, especially in those who were aged > 1 year, and specific clinical and laboratory findings.

Management of bronchopulmonary dysplasia in Japan: A 10-year nationwide survey.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication in very preterm infants. Despite advances in perinatal medicine, the number of BPD patients is increasing in Japan. The aim of this study was to conduct a nationwide survey of the strategies used for the prevention or treatment of BPD. METHODS: Questionnaires assessing the current strategies used to prevent or treat BPD, including neonatal resuscitation, drug therapy, and respiratory supportive care, were sent to secondary or tertiary perinatal units in 2015; responses were compared with those obtained from similar surveys in 2005 and 2010. The annual trend in incidence of BPD among the very low birth weight infants (VLBWIs) was determined using the Neonatal Research Network of Japan database. RESULTS: The response rates in 2005, 2010, and 2015 were 86.8% (230/265), 64.5% (185/287), and 82.8% (236/285) of units, respectively. The use of patient-triggered ventilation for initial management significantly increased from 50% of units in 2005 to 91% in 2015. By contrast, decreased use of high-frequency oscillatory ventilation (HFOV) from 72% to 65% and that of nasal continuous positive airway pressure from 79% to 68% were reported. The proportion of units where the upper limit of targeted blood oxygen saturation before a diagnosis of BPD was set to ≥95% decreased substantially from 92% to 56% over the 10-year period. Despite these changes in management of BPD, the incidence of BPD among VLBWIs in Japan was increasing over a decade. CONCLUSION: This survey demonstrated that there were various changes in practice regarding the prevention or treatment of BPD in Japan. Continuous surveys are required to understand the current clinical situation, and research is needed to develop and evaluate a novel treatment for BPD in premature infants.

Dual Factors May Be Necessary for Development of Atopic March in Early Infancy.

The incidence of atopic diseases, including atopic dermatitis (AD), food allergies, allergic rhinitis, and asthma, has increased in recent decades, and currently affects approximately 20% of the population. Atopic march is the development of AD in infancy and subsequent food allergies, allergic rhinitis, and asthma in later childhood. Patients with infantile eczema may develop typical symptoms of AD, allergic rhinitis, and asthma at certain ages. Some patients' symptoms persist for several years, whereas others may have resolution with aging. Development of these diseases is strongly influenced by the following two factors: skin dysfunction caused by filaggrin mutations and development of colonization of microflora in early infancy. Filaggrin mutations predisposing to asthma, allergic rhinitis, and allergic sensitization, only in the presence of AD, strongly support the role of filaggrin in the pathogenesis of AD and in subsequent progression of the atopic march. Several studies have shown that development of colonization of microflora in early infancy might affect development of allergic disease or food desensitization. Therefore, massive allergen exposure to genetic skin dysfunction in early infancy and an imbalance of microflora might be necessary for development of atopic march.

Immunotherapy for cow's milk allergy.

Oral immunotherapy (OIT) is used regularly for young children with cow's milk (CM) allergy and has been shown to be effective in several studies. However, adverse events occur frequently during OIT. Furthermore, there are only 5 randomized controlled trial studies of CM-OIT and these are low-powered single center trials. Therefore, evidence levels are also low and sometimes frequent and severe allergic events occur during the OIT. Furthermore, there are no standardized protocols in pediatric allergy guidelines from several countries and studies with long-term follow-up observations and clinical tolerance defined as sustained unresponsiveness are rare. Additionally, clinical tolerance by OIT is generally not well defined and obscure. Thus, several problems remain to be resolved, however we hope OIT in combination with omalizumab and less allergenic heated CM products will resolve these problems in the future.

Transcutaneous bilirubin measurement during phototherapy in term neonates.

BACKGROUND: We tested whether direct transcutaneous bilirubin (TcB) measurement from an area unexposed to phototherapy is reliable for estimation of total serum bilirubin (TSB) in neonates during phototherapy and whether it contributes to reduction in TSB blood sampling in phototherapy decision making. METHODS: This was a retrospective observational study of term neonates who received phototherapy in the mother's room. TSB and TcB from the neonate's sternum were measured before and during phototherapy and compared using linear regression analysis and Bland-Altman plot, respectively. Various cut-offs of TcB for estimating TSB during phototherapy at >72 h after birth were analyzed. RESULTS: There were moderate correlations between TSB and TcB before (r = 0.56) and during (r = 0.47) phototherapy in 125 neonates. The mean difference (TSB-TcB) before and during phototherapy was 1.2 ± 1.7 mg/dL and 1.0 ± 1.7 mg/dL, respectively. The 95% limits of agreement for the difference before and during phototherapy ranged from -2.1 to 4.5 and from -2.3 to 4.3 mg/dL, respectively. For TSB ≤18 mg/dL during phototherapy, a TcB cut-off of 14 mg/dL had a specificity of 1.0; with this method, 43% of the TSB measurements could have been avoided. CONCLUSIONS: Direct measurement of TcB during phototherapy using a bed-type device is a reliable method to estimate TSB in term neonates and would contribute to a reduction in blood sampling. It cannot, however, be used as a substitute for TSB measurement.

Effect of Volume Guarantee in Preterm Infants on High-Frequency Oscillatory Ventilation: A Pilot Study.

Objectives Although adding volume guarantee (VG) to conventional ventilation has been a well-established respiratory management for preterm infants, the evidence of VG combined with high-frequency oscillatory ventilation (HFOV) has not been studied well. The aim of this study was to investigate the effect of VG added to HFOV on respiratory and other physiological parameters. Methods We conducted a pilot study in extremely low-birth-weight infants ventilated with HFOV + VG with stable pulmonary status after 28 days of age. VG was applied for 6 hours and removed for the following 6 hours, and data were collected during these 12 hours. Results Six neonates were included in this study (gestational age: 22w5d-23w6d, birthweight: 424-584 g). High-frequency expired tidal volume per weight and amplitude were similar between periods with and without VG. Fluctuation of SpO2, but not heart rate, was significantly smaller when babies were ventilated with VG than without VG. Fluctuation of minute volume and carbon dioxide diffusion coefficient significantly increased after VG removal. The proportion of time with SpO2 < 80% was decreased by VG overall, especially in three cases. Conclusion This pilot study suggests VG combined with HFOV attenuates fluctuation of SpO2 and CO2 clearance, which may prevent hypoxemia and hypocapnia.

Acquired palatal groove and delayed oral feeding in preterm infants.

BACKGROUND: Acquired palatal groove has been reported in the 1970s and 1980s, but its current incidence in Japanese newborns is unclear. The aims of this study were to determine the incidence of palatal groove in preterm infants and to evaluate whether this condition affects oral feeding ability. METHODS: We conducted a prospective observational study among very low-birthweight infants born at Takatsuki General Hospital, Osaka, between March and October in 2010. The shape of the hard palate was classified into three types: normal, narrow high-arched palate, and palatal groove. RESULTS: Among the 37 enrolled infants, 14 (38%) had palatal groove. In particular, among the 29 infants with birthweight <1000 g, palatal groove was observed in 48% of these patients, and only 10% were normal. Infants with palatal groove were ventilated for considerably more days with oral endotracheal tube than those without palate groove, even after adjustment for gestational age, birthweight, and duration of oral duodenal tube placement (OR, 1.11). Establishment of oral feeding and disappearance of choking on milk were considerably delayed in infants with palatal groove. Transient oral feeding difficulty requiring thickened-feed intervention was observed only in infants with palatal groove; on multi-regression analysis this difficulty seemed to be induced by the palatal groove. CONCLUSIONS: Palatal groove formation induced by oral endotracheal intubation occurs with a high frequency in preterm infants, and this is likely to affect oral feeding ability.

Reliability of Total Bilirubin Measurements in Whole Blood from Preterm Neonates Using a Blood Gas Analyzer.

BACKGROUND: Blood gas analyses are usually required more frequently in preterm neonates than in term neonates. If total bilirubin (TB) levels in whole blood measured using a blood gas analyzer are reliable, blood sampling for total serum bilirubin (TSB) levels alone can be reduced in preterm neonates. We investigated the reliability of measuring TB levels in whole blood from preterm neonates using the latest generation blood gas analyzer. METHODS: TB measured on an ABL90 FLEX blood gas analyzer and TSB analyzed in the hospital laboratory were simultaneously analyzed. TB and TSB levels (300 data sets in 85 preterm neonates) were compared using linear regression and Bland-Altman difference plots. RESULTS: Concordance correlation coefficient analysis showed a strong relationship between TB and TSB levels (a CCC value of 0.94) with a Pearson's coefficient of 0.97 and a bias correction of 0.97. Bland-Altman difference p lots demonstrated that, on average, TB tended to underestimate the TSB, with a mean (95% confidence interval) bias of -0.7 (-0.6 to -0.8) mg/dL. CONCLUSIONS: Whole blood TB levels measured using an ABL90 FLEX are reliable and can lead to a reduction in blood sampling for TSB in preterm neonates.

Hydralazine in infants with persistent hypoxemic respiratory failure.

BACKGROUND: Most deaths of infants with chronic lung disease (CLD) are caused by respiratory failure, unremitting pulmonary artery hypertension (PAH) with cor pulmonale, or infection. Although the exact prevalence of PAH in infants with CLD is unknown, infants with CLD and severe PAH have a high mortality rate. Except for oxygen supplementation, no specific interventions have been established as effective in the treatment for PAH in premature infants with CLD. Little has been proven regarding the clinical efficacy of vasodilators and concerns remain regarding adverse effects. OBJECTIVES: To review current evidence for the benefits and harms of hydralazine therapy to infants with persistent hypoxemic respiratory failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE via PubMed and EMBASE, and other clinical trials registries through November 2011 using the standard search strategy of the Cochrane Neonatal Review Group. We searched these databases using a strategy combining a variation of the Cochrane highly sensitive search strategy for identifying randomised trials in MEDLINE; sensitivity-maximising version with selected MeSH and free-text terms: hydralazine, vasodilator agent, antihypertensive agent, heart diseases, lung diseases, respiratory tract diseases, infant, and randomised controlled trial. SELECTION CRITERIA: We considered only randomised controlled trials and quasi-randomised trials for inclusion. We included low birth weight (LBW) infants with persistent hypoxemic respiratory failure who were treated with any type of hydralazine therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality according to pre-specified criteria. MAIN RESULTS: We found no studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: There was insufficient evidence to determine the safety and efficacy of hydralazine in LBW infants with persistent hypoxemic respiratory failure. Since hydralazine is inexpensive and potentially beneficial, randomised controlled trials are recommended. Such trials are particularly needed in settings where other medications such as sildenafil, inhaled nitric oxide (iNO), or extracorporeal membrane oxygenation (ECMO) are not available.

High-dose calcium reduces early-onset hyperkalemia in extremely preterm neonates.

BACKGROUND: Early-onset hyperkalemia often occurs in extremely preterm infants during a few days after birth. While there are several treatments for hyperkalemia, calcium infusion to reduce plasma potassium concentrations remains controversial. The purpose of this study is to investigate whether a high dosage of calcium reduces early-onset hyperkalemia. METHODS: Extremely low-birthweight neonates born at 22-25 weeks' gestation were enrolled. We analyzed data using multivariate regression analysis and performed a retrospective cohort study with patients divided into two groups according to the dosage of calcium in their initial infusion. RESULTS: A total of 103 patients were eligible. Early-onset hyperkalemia was observed in 27 patients. The dosage of calcium gluconate during 24 h after birth was the only independent factor affecting early-onset hyperkalemia. The maximum plasma potassium concentration during 72 h after birth was negatively correlated with the dosage of calcium. High-dose calcium reduced occurrences of hyperkalemia and hypoglycemia caused by insulin infusion given for treatment of hyperkalemia, without increasing the risk of any other complications. CONCLUSIONS: Infusion of calcium gluconate may reduce early-onset hyperkalemia in a dose-dependent manner.

Culture-proven neonatal sepsis in Japanese neonatal care units in 2006-2008.

BACKGROUND: Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. OBJECTIVES: To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. METHODS: We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. RESULTS: Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants <1,000 g of birth weight was significantly higher than that in infants who weighed >1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant Staphylococcus aureus was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. CONCLUSIONS: The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh <1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.

The significance of measurement of serum unbound bilirubin concentrations in high-risk infants.

BACKGROUND: In the management of neonatal hyperbilirubinemia, total bilirubin (TB) concentration is not specific enough to predict the brain damage caused by bilirubin toxicity. Unbound bilirubin (UB) easily passes the blood-brain barrier and causes neurotoxicity. We aimed to evaluate whether serum UB concentration would be a useful predictor of bilirubin encephalopathy in high-risk infants. METHODS: We measured the serum TB and UB concentrations of 388 newborn infants treated with phototherapy or exchange transfusion for their hyperbilirubinemia at Takatsuki General Hospital between January 2002 and October 2003. Peak serum TB and UB levels and UB/TB ratios were studied on each birthweight group: below 1500 g (very low birthweight), 1500 g-2499 g (low birthweight), above 2500 g (normal birthweight); and several clinical factors influencing hyperbilirubinemia were also studied. RESULTS: Peak serum TB and UB levels increased with increasing birthweight, while UB/TB ratios decreased. The very low birthweight group showed higher UB levels and UB/TB ratios despite lower TB levels in intraventricular hemorrhage or severe infection compared to those in the others. The low birthweight and normal birthweight groups showed higher TB and UB levels in cases of hemolytic disease of the newborn compared to non-hemolytic disease of the newborn cases. Eight of 44 cases showed high UB levels accompanied by abnormal auditory brainstem responses, one of whom subsequently developed ataxic cerebral palsy with hearing loss, whereas the other seven showed transient abnormalities of auditory brainstem responses by the treatment of exchange transfusion or phototherapy. CONCLUSION: The UB measurement was considered to be significant for the assessment of the risk of bilirubin neurotoxicity and the appropriate intervention for hyperbilirubinemia in high-risk infants.

Randomized controlled trial of magnesium sulfate infusion for severe birth asphyxia.

OBJECTIVE: To determine whether postnatal MgSO(4) infusion (250 mg/kg per day) for 3 days is both safe and able to improve outcome in infants with severe birth asphyxia, as had been suggested by a small pilot study. METHODS: A multicenter randomized controlled trial was conducted. Entry criteria included 5-min Apgar score of seven or less and either failure to initiate spontaneous respiration at 10 min after birth because of asphyxia, or occurrence of clinically apparent seizures within 24 h after birth. Number of subjects was calculated to detect a 50% reduction in incidence of adverse outcomes. RESULTS: Distributions of perinatal factors, neonatal baseline characteristics and severity of hypoxic-ischemic encephalopathy were similar in treated and control groups. No significant differences were observed in duration of clinical seizures, or need for assisted ventilation. Survival with normal results of cranial computed tomography, electroencephalography and establishment of oral feeding by 14 days of age, was significantly more frequent in the treated group than in the control group (12/17 vs 5/16, P = 0.04). No significant differences in blood pressure, heart rate or respiratory rate were observed between groups. CONCLUSION: Postnatal MgSO(4) infusion as above is safe and can improve short-term outcome in infants with severe birth asphyxia.