Effect of Fentanyl for Preterm Infants on Mechanical Ventilation: A Systematic Review and Meta-Analysis.

INTRODUCTION: Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. METHODS: A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. RESULTS: Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36-1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: -0.63-0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: -7.12-15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. CONCLUSION: The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children.

The Japanese experience and pharmacokinetics of antenatal maternal high-dose immunoglobulin treatment as a prophylaxis for neonatal hemochromatosis in siblings.

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.

Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis.

Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use.

Umbilical catheterization training: Tissue hybrid versus synthetic trainer.

BACKGROUND: This study of umbilical catheterization deliberate practice training compared skill and knowledge outcomes of umbilical catheterization using a tissue-hybrid simulator (REAL) versus a synthetic simulated umbilical cord task trainer (ART). METHODS: This was a prospective randomized control study. Pediatric residents were randomized to REAL or ART umbilical catheterization deliberate practice training. Pre-post-training changes in skill performance and knowledge scores for REAL and ART groups were compared. Fidelity of REAL and ART were compared by neonatologists. RESULTS: Twenty-seven pediatric residents completed training. Post-training mean skill scores were improved compared to pre-test scores (REAL, P < 0.001; ART, P < 0.0001). Post-training skill, knowledge, and self-efficacy scores were not different between the REAL and ART groups. Fidelity of REAL was higher than ART for neonatologists (P < 0.01). CONCLUSIONS: The face validity of REAL was superior to ART, but resident umbilical cord deliberate practice training demonstrated no difference in skill, knowledge, and self-efficacy improvements between REAL and ART. Further studies on real patients are needed to evaluate the impact of using real or simulated umbilical cords for umbilical venous catheter/umbilical arterial catheter training.

Bone fracture in severe small-for-gestational-age, extremely low birth weight infants: A single-center analysis.

INTRODUCTION: Bone fracture is a complication of extremely low birth weight infants (ELBWIs). This study aimed to analyze risk factors for bone fracture in a population of severe small-for-gestational-age (SGA) ELBWIs. METHODS: We retrospectively studied data from ELBWIs with a birth weight <1000g and <-2 standard deviations (SDs) born at the National Center for Child Health and Development, Japan, from 2013 to 2015. Infants were divided into fracture and control groups. Serum calcium (Ca) and phosphorus (P) levels, perinatal factors, and previously reported risk factors were analyzed. RESULTS: Of 25 cases of severe SGA ELBWIs, 5 cases of bone fracture were identified. Gestational age was 27.7±2.2, 29.1±2.6weeks (mean difference [MD] -1.4, 95% confidence interval [CI]: -4.0, -1.2, p=0.280), birth weight (BW) 448±105, 673±216g (MD -225, 95% CI: -433, -17, p=0.036) and BW-SD -4.1±0.1, -3.4±0.8 (MD -0.8, 95% CI: -1.5, -0.02, p=0.045) in the fracture and control groups, respectively. Minimums of serum Ca and P were 6.6±1.4, 8.1±0.8mg/dl (MD -1.5, 95% CI: -2.5, -0.6), p=0.003) and 2.3±0.6, 3.5±1.1mg/dl (MD -1.2, 95% CI: -2.2, -0.1, p=0.027) in the fracture and control groups, respectively. CONCLUSION: Lower BW and BW-SD were possible risk factors for bone fracture. Hypocalcemia and hypophosphatemia may also contribute to the condition.

A Case of Fatal Pulmonary Hypoplasia with Congenital Diaphragmatic Hernia, Thoracic Myelomeningocele, and Thoracic Dysplasia.

Background Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported. Case Report A male infant with a prenatal diagnosis of thoracic MMC with severe hydrocephalus and scoliosis was born at 36 weeks of gestation. CDH was found after birth and the patient died of respiratory failure due to pulmonary hypoplasia and persistent pulmonary hypertension of the newborn at 30 hours of age despite neonatal intensive care. An autopsy revealed a left CDH without herniation of the liver or stomach into the thoracic cavity, severe hydrocephalus, Chiari malformation type II, MMC with spina bifida from Th4 to Th12, hemivertebrae, fused ribs, deformities of the thoracic cage and legs, short trunk, and agenesis of the left kidney. Conclusion We speculate that two factors may be associated with the severe pulmonary hypoplasia: decreased thoracic space due to the herniation of visceral organs caused by CDH and thoracic dysplasia due to skeletal deformity and severe scoliosis.