Ventilator-induced diaphragmatic dysfunction in extremely preterm infants: a pilot ultrasound study.

To investigate the development of diaphragmatic dysfunction in ventilated extremely preterm infants (EPI) using diaphragm ultrasound (DU). EPI of less than 28 weeks' gestational age who required mechanical ventilation within six hours of birth were included in this prospective, observational study. DU was performed once a day until four days of life. End-inspiratory and end-expiratory thicknesses of the diaphragm were measured, and the diaphragm thickening fraction was calculated. A total of 20 EPI were enrolled. After intubation, there was a progressive reduction in end-inspiratory thickness of the diaphragm from baseline to day 1 (P < 0.001), but not from day 1 to day 2 (P = 0.092), day 2 to day 3 (P = 1.0), or day 3 to day 4 (P = 1.0). There was also a significant reduction in the diaphragm thickening fraction from baseline to day 1 (P < 0.001), but not from day 1 to day 2 (P = 1.0), day 2 to day 3 (P = 1.0), or day 3 to day 4 (P = 1.0).    Conclusions: This study provides the first evidence of diaphragmatic dysfunction in ventilated EPI. We demonstrated a rapid progression of ventilator-induced diaphragmatic dysfunction, with a significant reduction in diaphragm thickness and thickening fraction within 24 h of ventilation. What is Known: • Over-assistance of the ventilator suppresses respiratory effort and induces diaphragm unloading, resulting in diaphragm atrophy or dysfunction. • Diaphragmatic dysfunction contributes to prolonged ventilator dependence and poor clinical outcomes. What is New: • Most extremely preterm infants develop diaphragmatic dysfunction after intubation within 24 hours. • Diaphragm thickness and contraction ability measured by ultrasound would be important indicators of worsening breathing or respiratory outcomes.

Diagnosis and management of neonatal respiratory distress syndrome in Japan: A national survey.

BACKGROUND: Respiratory distress syndrome (RDS) is characterized by a lack of lung surfactant; therefore, biochemical evidence of surfactant deficiency is needed to diagnose RDS. European guidelines recommend surfactant administration when patients need fraction of inspired oxygen exceeding 0.3 on continuous positive airway pressure or intubation. We hypothesized that the European guidelines for surfactant administration were not adopted in Japan because of the lack of RDS diagnosis. This study aimed to investigate neonatologists' attitudes and practices regarding the diagnosis and management of RDS in Japan. METHODS: A mail-based survey regarding the diagnosis and management of RDS was conducted at 111 level III or ΙV neonatal intensive care units in Japan. The questionnaire was completed by the person in charge of each unit. RESULTS: The overall response rate for the questionnaire was 91% (101/111 centers). All respondents referred to chest radiography, and the majority (83%) of respondents referred to stable microbubble rating (SMR) for establishing the diagnosis of RDS. Surfactant administration was chiefly based on clinical conditions, chest radiography, and/or SMR. Most units in Japan do not adopt the European criteria for surfactant administration. CONCLUSION: In Japan, chest radiography and/or SMR are commonly used for the diagnosis of RDS and as the rationale for surfactant administration. Further studies from other countries are required to establish the ideal criteria for surfactant administration.

Gravity-induced loss of aeration and atelectasis development in the preterm lung: a serial sonographic assessment.

OBJECTIVE: To assess the impact of gravity and time on the changes in the distribution patterns of loss of aeration and atelectasis development in very preterm infants. STUDY DESIGN: Preterm infants less than 32 weeks gestation were included in this prospective, observational study. Infants were assessed via serial lung ultrasound (LUS) score in four lung zones, performed on days 7, 14, 21, and 28 after birth. RESULT: Eighty-eight patients were enrolled. There was a significant main effect of gravity (P < 0.001) and time (P = 0.01) on the LUS score between gravity-dependent lungs and non-dependent lungs. Moreover, there was a significant main effect of gravity (P = 0.003) on atelectasis development between the lungs. CONCLUSION: Gravity and time have an impact on the changes in the distribution patterns of gravity-induced lung injuries in preterm infants.

Lung Ultrasound for Predicting the Respiratory Outcome in Patients with Bronchopulmonary Dysplasia.

OBJECTIVE: This study aimed to investigate the utility of lung ultrasound (LUS) with whole chest scanning for predicting respiratory outcomes in patients with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We performed a prospective observational study. Preterm infants of less than 32 weeks' gestational age requiring oxygen therapy at 28 days of life were included. LUS was performed on day 28, at 36 weeks' postmenstrual age, and at the time of discharge. Each lung was divided into three regions by the anterior and posterior axillary lines and received an LUS score of 0 to 3 points; the total score was obtained by adding the six regional scores. The classification of BPD was determined based on the National Institute of Child and Human Development. The outcomes of this study were the development of moderate-to-severe BPD and the need for home oxygen therapy (HOT). RESULTS: We enrolled 87 patients; 39, 33, and 15 infants had mild, moderate, and severe BPD, respectively. The LUS score correlated with BPD severity and exhibited an improvement trend with time toward the point of discharge. LUS at 28 days of life predicted moderate-to-severe BPD with an area under the curve of 0.95 (95% confidence interval: 0.91-0.99) and HOT with an area under the curve of 0.95 (95% confidence interval: 0.81-1.0). CONCLUSION: LUS with whole chest scanning is useful for predicting respiratory outcomes in patients with BPD, as well as for understanding BPD severity or clinical improvement trends. KEY POINTS: · LUS predicts respiratory outcomes in patients with BPD.. · LUS indicates BPD severity.. · LUS can show clinical improvement with time..

Ideal endotracheal tube insertion depth in neonates with a birthweight less than 750 g.

BACKGROUND: Appropriate management of the endotracheal tube (ETT) insertion depth is important. The depth calculated using Tochen's formula is overestimated in extremely-low- birthweight infants, particularly those with a birthweight <750 g. Gestational age has been shown to be particularly useful in the Neonatal Resuscitation Program, 7th edition.5 However, a randomized trial for estimating the ETT insertion depth failed to show the advantage of using gestational age over birthweight.6 Therefore, we aimed to estimate the appropriate ETT insertion depth in neonates weighing <750 g. METHODS: This was a single-center, retrospective observational study including neonates weighing <750 g who required intubation. The appropriate depth was determined by adjusting the distance between the actual ETT position and the area from the first to the second thoracic vertebra on the radiograph. Correlations between gestational age and physique were investigated using Pearson's correlation coefficient. We examined small-for- gestational-age (SGA) infants and non-SGA infants separately. RESULTS: Forty neonates were enrolled in this study. The mean gestational age and birthweight were 26.3 weeks and 620 g respectively. Twenty infants were SGA. The ETT position was deep in 35 of 40 cases, with the strongest correlation between weight and ETT insertion depth. The correlation with gestational age was not observed in this study. CONCLUSIONS: Our study showed that the ideal ETT insertion depth at birth correlates with birthweight in neonates weighing <750 g. Therefore, determination by gestational age may not be feasible in populations with a high proportion of SGA infants.

Ultrasonographic confirmation of endotracheal intubation in extremely low birthweigh infants - secondary publication.

BACKGROUND: The purpose of this study was to investigate the usefulness of ultrasonography (US) for confirmation of endotracheal tube (ETT) placement during resuscitation in extremely low birthweight (ELBW) infants. METHODS: We conducted a retrospective review of the medical records of ELBW infants in whom ETT position was verified using US between June 2016 and September 2017. We investigated the backgrounds of the patients and US investigators, and the time required for the detection of exhaled carbon dioxide using the colorimetric method and US. RESULTS: Eleven ELBW infants were evaluated using US by four neonatologists. The median duration required to determine the ETT position by the colorimetric method and US were 11 s and 3 s, respectively. In six ELBW infants, we were able to verify the ETT position more rapidly using US than using the colorimetric method, and were able to perform prompt resuscitation. Unnecessary reintubations were avoided in three ELBW infants. CONCLUSION: Ultrasonography allowed the swift confirmation of the tracheal intubations. The colorimetric method yielded false negative results; in such cases, unnecessary reintubation could have been avoided if US was used. We assessed the mechanism of false negative results and performed appropriate resuscitation.

Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement.

Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and muscle biopsy) and genetic features of nine Japanese patients with VICIS. Genetic dissection of these nine patients from seven families identified 14 causative mutations in EPG5. These included five nonsense, two frameshift, three splicing, one missense, and one multi-exon deletion mutations, and two initiation codon variants. Furthermore, cultured skin fibroblasts (SFs) from two affected patients demonstrated partial autophagic dysfunction. To investigate the function of EPG5, siRNA based EPG5 knock-down, and CRISPR/Cas9 mediated EPG5 knock-out HeLa cells were generated. EPG5-depleted cells exhibited a complete block of autophagic flux caused by defective autophagosome-lysosome fusion. Unexpectedly, endocytic degradation was normal in both VICIS SFs and EPG5 depleted cells, suggesting that EPG5 function is limited to the regulation of autophagosome-lysosome fusion.

Group B streptococcal disease in infants in the first year of life: a nationwide surveillance study in Japan, 2011-2015.

PURPOSE: This study aimed to describe the epidemiology of childhood group B streptococcus (GBS) disease including late late-onset disease (LLOD) and to clinically characterize recurrent cases and twin-sibling cases in Japan. METHODS: We collected information on infants (<1 year of age) with invasive GBS disease and institutional information about births and transfers through a nationwide questionnaire between 2011 and 2015. RESULTS: We identified 133 infants with early-onset disease (EOD), 274 late-onset disease (LOD), and 38 LLOD from 149 institutes. The case fatality rate (CFR) of EOD, LOD, and LLOD was 4.5, 4.4, and 0%, respectively. CFR in EOD was significantly (P < 0.001) associated with preterm birth, but not that in LOD and LLOD. Twenty-nine percent of infants with meningitis (49/169) had neurologic sequelae. We showed clinical details of 12 recurrent cases that accounted for 2.8% of the total patients, and 4 sets of both twins affected; 4 of 12 recurrent cases and 3 of 4 twin-sibling sets were also associated with preterm birth. Based on the livebirth number of 581,488, the instituted-based incidence of EOD, LOD, and LLOD was estimated as 0.09 (95% CI 0.06-0.11), 0.12 (95% CI 0.11-0.14), and 0.01 (95% CI 0.01-0.02) per 1000 livebirths, respectively. CONCLUSIONS: CFR of EOD and LOD in Japan is comparable with that in high-income European countries or the United States, and their incidence is much lower. Our findings also describe the clinical details of LLOD, recurrent infections, and infections in twin siblings. This study is the largest among Asian childhood GBS studies ever reported.