Higher C-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment.

The aim of the study was to characterize factors that may serve as clinical tools to identify neonates with transient neonatal hyperinsulinism hypoglycemia (HH) who may benefit from diazoxide treatment. This retrospective study included 141 neonates with transient HH (93 males) of whom 34 (24%) were treated with diazoxide. Diazoxide treatment was started at median age of 13 days (range 5-35) and discontinued at median age of 42 days (range 14-224). The maximal dose was 7.1 ± 2.3 mg/kg/day. Diazoxide-treated neonates required a higher glucose infusion rate (GIR) compared with non-treated neonates (16.6 ± 3.4 vs. 10.4 ± 4.0 mg/kg/min, respectively, P < .01), had a longer duration of intravenous fluids (15.9 ± 9.3 vs. 7.8 ± 6.5 days, P < .01), a longer hospitalization (32.8 ± 22.7 vs. 20.4 ± 13.4 days, P < .01), a longer duration of carbohydrate supplementation (38.9 ± 40.4 vs. 17.8 ± 21.4 days, P < .01), and higher mean C-peptide levels on "critical sample" (1.4 ± 0.9 vs. 0.8 ± 0.5 ng/ml, P < .01). Their insulin levels also tended to be higher (3.5 ± 2.9 vs. 2.2 ± 3.8 µU/ml, P = .07). A stepwise logistic regression model revealed that significant predictors of prolonged HH were maximal GIRs (odds ratio (OR) 1.56, 95%; confidence interval (CI) 1.3-1.88, P < .001) and C-peptide levels (OR 3.57, 95%; CI 1.3-12.1, P = .005).Conclusion: Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.What is Known:• Neonates with transient hyperinsulinism usually do not require treatment beyond glucose supplementation due to its self-limited clinical course, but some may benefit from diazoxide treatment.What is New:• Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.• The incidence of prolonged neonatal HH is higher than the currently accepted figures.

[THE EFFECT OF MUSIC IN PRETERM ON RESTING ENERGY EXPENDITURE - A PROSPECTOVE RANDOMIZED CLINICAL TRIAL].

BACKGROUND: We have recently showed that Wolfgang Amadeus Mozart's music significantly lowers resting energy expenditure (REE) in preterm infants. Whether or not this effect is specific to Mozart is unknown. OBJECTIVES: To study whether familiar ("ethnic") music has the same effect on REE in preterm infants as music by Mozart. METHODS: A prospective, randomized clinical trial with cross-over was conducted in 9 healthy, appropriate weights for gestational age, gavage fed, preterm infants. Infants were randomized to be exposed to a 30-minute period of Mozart music or "ethnic" music or no music over 3 consecutive days. Metabolic measurements were performed by indirect calorimetry. RESULTS: A total of 27 REE measurements were performed. On average REE was lower in preterm infants who were exposed to "ethnic" music compared to preterm infants who were exposed to music by Mozart (p=0.388). REE was lower in preterm infants who didn't listen to music at all compared to Mozart (p=0.014) or to "ethnic" (p=0.134). CONCLUSIONS: Exposure to music by Mozart significantly elevated REE in healthy preterm infants compared to preterm infants who didn't listen to music at all. Nevertheless a trend of lower REE was demonstrated when preterm infants listened to "ethnic" music compared to Mozart. DISCUSSION: We were unable to demonstrate a significant decrease in REE by exposure of preterm infants to Mozart- or "familiar" music. At this time point we cannot recommend music therapy for preterm infants in order to lower the REE. We speculate that a larger study sample might show a definite effect.

Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.

Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations. All affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle. Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of the seven subjects, and the other three case subjects harbored the same c.703C>G (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of AAC1 protein levels and loss of respiratory chain complexes containing mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant proteins are severely impaired in ADP/ATP transport, affecting most likely the substrate binding and mechanics of the carrier, respectively. This highly reduced capacity for transport probably affects mitochondrial DNA maintenance and in turn respiration, causing a severe energy crisis. The confirmation of the pathogenicity of these de novo SLC25A4 mutations highlights a third distinct clinical phenotype associated with mutation of this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo mutations, which has significant implications for the application and analysis of whole-exome sequencing data in mitochondrial disease.

Twin pregnancy in women above the age of 45 years: maternal and neonatal outcomes.

Childbearing age continues to rise and, with the increasing implementation of assisted reproductive technology (ART), the number of multiple pregnancies has also risen. This is a retrospective cohort study on maternal and neonatal outcomes of the twin pregnancies of 57 women aged ≥45 years compared to 114 younger women who gave birth in our institution between January 2011 and August 2015. Data were extracted from the real-time computerized database. The rates of hypertensive complications and pre-eclampsia (PE) were much higher in the study group compared to the controls (24/57 vs. 19/114, P=0.000 and 15/57 vs. 13/114, P=0.013, respectively). The respective incidence of very low birth weight (VLBW) was also significantly higher (14/114 vs. 12/228, P=0.021). Infants in the study group required four times more intubation and had a higher admission rate to the neonatal intensive care unit (NICU) compared to control infants (14/114 vs. 6/228 P=0.000 and 42/114 vs. 57/228, P=0.023, respectively). We conclude that women older than 45 years with twin pregnancies have higher maternal and perinatal complications with worse outcomes in comparison with younger women. When pregnancy is attempted via ART, embryo transfer of only one embryo should be considered in this age group.

Electroencephalographic characteristics in preterm infants born with intrauterine growth restriction.

OBJECTIVE: To determine the impact of fetal growth on postnatal amplitude-integrated electroencephalography (aEEG) and power spectrum electroencephalography (EEG) data in preterm infants born with intrauterine growth restriction (IUGR). STUDY DESIGN: We defined IUGR as birth weight <10th percentile, and control as birth weight appropriate for gestational age (GA). We performed single-channel (C3-C4) EEG during the first 48 hours of life and measured the upper and lower margins of the aEEG trace width. EEG readings were analyzed by spectral analysis, and the relative power of the frequency bands was calculated. The Lacey Assessment of the Preterm Infant was administered before discharge. RESULTS: We enrolled 14 infants with IUGR (mean GA, 34.3 ± 1.8 weeks; mean birth weight 1486 ± 304 g) and 16 appropriate for GA controls (mean GA, 33.7 ± 2 weeks; mean birth weight, 1978 ± 488 g). There were no significant between-group differences in perinatal complications. The mean aEEG trace width was 20.8 ± 1.4 µv in the infants with IUGR versus 17.3 ± 1.6 µv in controls (P < .001). The infants with IUGR also had significantly greater delta frequency activity and decreased theta, alpha, and beta frequency activities compared with controls. Delta frequency activity decreased with increasing GA (r = -0.8; P = .001 for infants with IUGR and r = -0.9; P < .001 for controls). The Lacey Assessment of the Preterm Infant developmental score was significantly lower in the infants with IUGR (P < .02) and was correlated with aEEG trace width (r = -0.6; P = .002) and with delta activity (r = -0.5; P = .02). CONCLUSION: Preterm infants with IUGR have delayed EEG maturation associated with delayed neuromotor development. The predictive value of these alterations regarding developmental deficits associated with IUGR remains undetermined, however.

Late presentation of massive pleural effusion from intrathoracic migration of a ventriculoperitoneal shunt catheter: case report and review of the literature.

We report an unusual case of ventriculoperitoneal (VP) shunt intrathoracic migration, associated with massive symptomatic hydrothorax. The VP shunt was inserted 10 years before presentation, after hemorrhagic hydrocephalus caused by prenatal intraventricular hemorrhage. The pleural fluid was drained via tube thoracostomy and the shunt was externalized, with full resolution of symptoms and signs. The patient was subsequently managed with shunt revision with drainage into the abdominal cavity. We review the 10 pediatric cases of cerebrospinal fluid hydrothorax reported in the literature and discuss the mechanism of shunt tip migration. Pleural effusion secondary to VP shunt insertion is a rare and potentially life-threatening occurrence, and it should be suspected in any patient with a VP shunt and respiratory distress.

A silent outbreak of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit.

OBJECTIVE: To describe the containment of a widespread silent outbreak of vancomycin-resistant Enterococcus faecium (VRE-fm) in the Tel-Aviv Medical Center (TASMC) neonatal intensive care unit (NICU). METHODS: Setting - an NICU, participants - 49 cases of VRE-fm-colonized neonatal inpatients. RESULTS: A newborn was transferred from the TASMC NICU to another hospital and screened positive for VRE-fm upon arrival. All TASMC NICU patients were then immediately screened for VRE and 21/38 newborns were identified as VRE carriers. Interventional measures were strictly enforced. By the end of the outbreak, 49 cases of VRE carriage had been identified. There were no VRE clinical infections. The source of the outbreak was not identified. CONCLUSION: Our study highlights the importance of screening implementation in a NICU setting since this outbreak could have been prevented by active screening of all out-born transfer patients and by having adopted mandatory screening into the NICU's routine procedures. Screening for multi-drug resistant organisms upon admission of all transferred patients to the NICU has been implemented.

Neonatal acute kidney injury: recording rate, course, and outcome: one center experience.

Background: Neonates, and particularly preterm newborns, are at increased risk for acute kidney injury (AKI) due to immature kidney function. While specific criteria have been defined for AKI in this particular population, this diagnosis is frequently overlooked, and consequently, is often not recorded in patients' medical files. AKI-associated short- and long-term morbidity and mortality underline the importance of this diagnosis Objective: To assess the recording rate of AKI in the neonatal intensive care unit (NICU), and to identify clinical features that may promote awareness to this condition. Study design: The database of one medical center was searched for serum creatinine values above 1 mg% among all the newborns (more than 48 hours old) who were hospitalized in the neonatal intensive care unit (NICU) during the years 2010-2015, and who underwent at least two blood tests during their hospitalization. The files of patients who met acute kidney injury (AKI) diagnostic criteria were searched for AKI diagnosis, maternal, fetal, and postnatal course and outcome. Results: Of 59 newborns who met AKI criteria, 51 (86%) were preterm and 8 term newborns. The respective mean gestational weeks at birth were: 28 ± 3 and 38.5 ± 1, and mean birth weights: 1002 ± 57 and 3157 ± 375 grams. Mortality rates were 14/51 (27%) versus 1/8 (12.5%). Of the 44 survivors, AKI was recorded in the medical files of 9/37 (24%) preterm versus 5/7 (71%) term-newborns. AKI associated with twin pregnancy in preterm neonates: 22 (43%) versus 1 (12.5%) in term-newborn. Unexpected high frequencies of maternal obstetrical problems and cesarean section delivery: 62.5 and 78%, respectively, along with persistently depressed 5-min Apgar 6.6 ± 3.5 were found in term newborns with AKI. Congenital anomalies of the urinary tract (CAKUT) were suspected prenatally on fetal ultrasound in 3 (6%) and 1 (12.5%) of the respective groups, a 10-fold higher rate than that observed in the general population. AKI recurred in 18 (35%) of the preterm and none of the term neonates. Mild AKI episodes (Stage 1-2) occurred in 30/37 (81%) by contrast to severe events (Stage 3) in 4/7 (57%) preterm and term survivors, respectively. Ventilation duration associated significantly with AKI recurrence, and sepsis with mortality: OR 1.25 (95%CI = 1.09-1.43) (p < .001) and OR = 4.65 (95%CI = 1.26-17.2) (p = .014), respectively. Conclusions: We demonstrated underreporting of AKI, particularly among preterm newborns, a population at high risk of developing recurrent episodes. Our data suggest different clinical profiles of AKI among preterm and term neonates: with later onset, milder but recurrent episodes in the former. Increased alertness for AKI diagnosis is needed for neonates with prolonged respiratory support, treated with diuretics and after sepsis. Newborns suspected of CAKUT (Congenital Anomalies of Kidneys and Urinary Tract) as per fetal ultrasound might need closer observation for AKI occurrence.

Pulmonary hemorrhage due to Coxsackievirus B infection-A call to raise suspicion of this important complication as an end-stage of enterovirus sepsis in preterm twin neonates.

BACKGROUND: Prematurity is an important risk factor for the fulminate form of neonatal enteroviral infection. Pulmonary hemorrhage is a morbid complication that should be anticipated and managed aggressively due to its fatal outcome. OBJECTIVE: To emphasize the significance of pulmonary hemorrhage as a complication of severe enterovirus infection in preterm neonates. STUDY DESIGN: This report is a description of the clinical history, medical management and clinical outcomes of two pairs of preterm twin newborns (30 weeks and 36 weeks) with fulminant infection due to Coxsackievirus B (CBV) infection. RESULTS: Maternal fever was reported in both deliveries and it was a factor in the decision for urgent cesarean section of the 30-week twins. Three of the four infants failed to survive. Their clinical course involved multiple organ system failure complicated with profound disseminated intravascular coagulopathy and pulmonary hemorrhage. Pulmonary bleeding leading to hypovolemic shock and respiratory failure was the direct cause of death in two cases. CONCLUSIONS: This small series of preterm neonates with the diagnosis of CBV sepsis highlights the importance of correct diagnosis of maternal enterovirus infection in order to extend pregnancy and allow the fetus time to passively acquire protective antibodies. This report emphasizes the morbid complication of pulmonary hemorrhage as a result of enterovirus infection that should be anticipated and managed aggressively due to its potentially fatal outcome. Moreover, evaluation and observation of the asymptomatic twin is recommended in order to detect early signs of infection and deterioration in that sibling as well.

Prevalence of breastfeeding difficulties in newborns with a lingual frenulum: a prospective cohort series.

OBJECTIVE: The prevalence of a lingual frenulum in newborn infants is reportedly 0.3-12%. The purpose of this study was to describe the prevalence of a lingual frenulum based on the Coryllos classification in nonselected newborn infants after delivery, hypothesizing that it is higher than the values reported in the literature. STUDY DESIGN: The lingual frenula of 200 healthy infants were evaluated by visual examination and palpation within the first 3 days after delivery. The frenulum was categorized according to the four Coryllos classifications. Each infant's mother responded, immediately after the examination, to a structured questionnaire on the quality and type of feeding. An additional structured telephone interview with the 179 breastfeeding mothers was conducted 2 weeks later. RESULTS: All but one infant (n=199) had an observable or palpable lingual frenulum that was Coryllos type 1 (n=5), type 2 or 3 (n=147), or type 4 (n=47). Although our study was not powered enough to test for any correlation between the cessation of breastfeeding and the type of frenulum, we found no statistical correlation between the Coryllos type of lingual frenulum and the presence of breastfeeding difficulties. CONCLUSIONS: A lingual frenulum is a normal anatomical finding whose insertion point and Coryllos classification are not correlated with breastfeeding difficulties. We suggest that the term "lingual frenulum" should be used for anatomical description and that the term "tongue-tie" be reserved for a lingual frenulum associated with breastfeeding difficulties in newborns.