Masanori Fujimura

Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial

AIM To investigate the colonisation withBifidobacterium breve of the bowels of very low birthweight (VLBW) infants. METHODS The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody. RESULTS In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B brevesignificantly decreased aspirated air volume from the stomach and improved weight gain. CONCLUSIONS B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules.

Morbidity and Mortality of Infants With Very Low Birth Weight in Japan: Center Variation

OBJECTIVES. The objectives of this study were to describe the characteristics and morbidity of very low birth weight infants, to identify the medical intervention for these infants, and to evaluate the factors affecting the mortality of these infants among the participating hospitals. METHODS. A large multicenter neonatal research network that included level III NICUs from throughout Japan was established. A standardized mortality rate was formulated by giving a ratio of the observed deaths and the predicted deaths based on a 100-g birth weight interval mortality. A regression model was used to predict the factors that affect neonatal mortality. RESULTS. The network included 37 centers and 2145 infants weighing ≤1500 g, born or admitted to the centers in 2003. Gestational age and birth weight of studied infants were 28.6 ± 3.6 gestational weeks (mean ± SD) and 1025 ± 302 g, respectively. Overall, 11% of the infants died before being discharged from hospitals (range: 0%–21%). The standardized mortality rate varied among the facilities (range: 0%–30%). No association between the annual number of patients admitted and standardized mortality rate was found. Among all of the very low birth weight infants, 14% were outborn infants, 72% were delivered by cesarean sections, 27% had patent ductus arteriosus, 3% had gastrointestinal perforation, 8% had bacterial sepsis, and 13% had intraventricular hemorrhage. Medical interventions involved were: 41% antenatal corticosteroids, 54% surfactant therapy, 18% postnatal steroids for chronic lung disease, and 29% high-frequency oscillatory ventilation. We found variations in the medical interventions and the clinical outcomes among the centers. CONCLUSIONS. The overall survival rate for very low birth weight infants among neonatal centers in Japan was ∼90%. However, differences in the morbidity and mortality were observed among these centers.

Mortality rates for extremely low birth weight infants born in Japan in 2005.

OBJECTIVE. Our goal was to investigate the neonatal mortality rate and the mortality rate during the NICU stay for extremely low birth weight infants born in Japan in 2005. METHODS. The Committee of Neonatal Medicine of the Japan Pediatric Society retrospectively surveyed the deaths of extremely low birth weight infants born and hospitalized between January 1 and December 31, 2005. From 297 institutions in Japan, data on 3065 extremely low birth weight infants, which represented 98.4% of those reported in the maternal and health statistics of Japan in 2005, were collected. RESULTS. The neonatal mortality rate and the mortality rate during the NICU stay were 13.0% and 17.0%, respectively, which were lower than 17.7% and 21.5% in the survey in 2000. The neonatal mortality rates and the mortality rates during the NICU stay were 53.3% and 67.7% in the <400-g birth weight group (n = 62), 42.1% and 53.5% in the 400- to 499-g birth weight group (n = 159), 22.2% and 27.7% in the 500- to 599-g birth weight group (n = 387), 16.8% and 22.2% in the 600- to 699-g birth weight group (n = 537), 9.4% and 12.7% in the 700- to 799-g birth weight group (n = 574), 6.3% and 9.1% in the 800- to 899-g birth weight group (n = 649), and 3.9% and 5.3% in the 900- to 999-g birth weight group (n = 697), respectively. The factors involved in the deaths of extremely low birth weight infants included lower gestational age, lower birth weight, male gender, multiple birth, institutions in which <10 extremely low birth weight infants were admitted per year, and no prenatal maternal transfer. CONCLUSION. The mortality rates of extremely low birth weight infants who were born in 2005 demonstrated definite improvement.

Outcomes of Infants Born at 22 and 23 Weeks’ Gestation

OBJECTIVE: To provide instructive information on death and neurodevelopmental outcomes of infants born at 22 and 23 weeks’ gestational age. METHODS: The study cohort consisted of 1057 infants born at 22 to 25 weeks in the Neonatal Research Network, Japan. Neurodevelopmental impairment (NDI) at 36 to 42 months’ chronological age was defined as any of the following: cerebral palsy, hearing impairment, visual impairment, and a developmental quotient <70. A systematic review was performed by using databases of publications of cohort studies with neonatal and neurodevelopmental outcomes at 22 and 23 weeks. RESULTS: Numbers and incidences (%) of infants with death or NDI were 60 (80%) at 22 weeks and 156 (64%) at 23 weeks. In logistic regression analysis, gestational ages of 22 weeks (odds ratio [OR]: 5.40; 95% confidence interval [CI]: 2.48–11.76) and 23 weeks (OR: 2.14; 95% CI: 1.38–3.32) were associated with increased risk of death or NDI compared with 24 weeks, but a gestational age of 25 weeks (OR: 0.65; 95% CI: 0.45–0.95) was associated with decreased risk of death or NDI. In the systematic review, the medians (range) of the incidence of death or NDI in 8 cohorts were 99% (90%–100%) at 22 weeks and 98% (67%–100%) at 23 weeks. CONCLUSIONS: Infants born at 22 and 23 weeks’ gestation were at higher risk of death or NDI than infants at born at 24 weeks. However, outcomes were improved compared with those in previous studies. There is a need for additional discussions on interventions for infants born at 22 or 23 weeks’ gestation.

Trends in morbidity and mortality among very-low-birth-weight infants from 2003 to 2008 in Japan

Background:Although medical care for very-low-birth-weight (VLBW) infants has improved over time, it is unclear how this has affected mortality and morbidity. To characterize these trends, a network database was analyzed.Methods:This is a cohort study of VLBW infants born from 2003 through 2008.Results:Over the 6-y period, 19,344 infants were registered and analyzed. Crude mortality rates among the infants at discharge decreased significantly (from 10.8 to 8.7%) during the study period. The greatest improvement in mortality was observed among infants with birth weights between 501 and 750 g (25.6–17.7 %). The odds ratio (OR) of mortality over year adjusted for potential confounders by a logistic regression model was 0.94 (95% confidence interval 0.92–0.97). Significant increases were observed in some morbidities, including symptomatic patent ductus arteriosus with an OR of 1.11 (1.09–1.13); late-onset adrenal insufficiency, 1.21 (1.17–1.26); and necrotizing enterocolitis/intestinal perforation, 1.10 (1.01–1.12). However, the severe form of intraventricular hemorrhage, with an OR of 0.98 (0.92–0.99), decreased significantly. Risk-adjusted trends in other morbidities showed no significant change.Conclusion:Mortality of VLBW infants decreased significantly over the 6-y study period. Decreasing morbidity is essential for further improvement in the outcomes in VLBW infants.

The progression of retinopathy of prematurity and fluctuation in blood gas tension

In this study, the relationship between the fluctuation in blood oxygen and carbon dioxide tension and the progression of acute retinopathy of prematurity (ROP) was evaluated. Eighteen extremely premature infants were selected on the basis of the following criteria: gestational age less than 26 weeks, oxygen supply or mechanical ventilation for more than 50 days, transcutaneous oxygen pressure (TcPO2) recorded almost once per hour, and arterial oxygen pressure (PaO2) and arterial carbon dioxide pressure (PaCO2) measured intermittently, for over 8 weeks after birth. All of these infants developed ROP, which ceased progressing in 7 infants (group 1, stage 1 or 2 ROP, international classification), but advanced in 11 (group 11, stage 3 or 3+). The fluctuations in TcPO2, PaO2, and PaCO2 are represented as coefficients of both variation (CV) and mean difference (D) in these two groups.The results demonstrate that both the CV and D values of TcPO2 are significantly elevated in group II infants compared with group I infants, in the first and second 3-weeks periods, and over the entire 9-week period after birth. The incidences of extreme hyperoxemia (TcPO2 ≧ 100 mm Hg) and hypoxemia (TcPO2 < 30 mm Hg) in recorded TCPO2 time series show no significant differences between these two groups. We conclude that extremely premature infants with widely fluctuating arterial oxygen tension may have a greater chance of developing progressive ROP.

Antenatal Corticosteroids Promote Survival of Extremely Preterm Infants Born at 22 to 23 Weeks of Gestation

OBJECTIVE To evaluate the effectiveness of antenatal corticosteroid (ACS) to improve neonatal outcomes for infants born at <24 weeks of gestation. STUDY DESIGN We performed a retrospective analysis of 11,607 infants born at 22 to 33 weeks of gestation between 2003 and 2007 from the Neonatal Research Network of Japan. We evaluated the gestational age effects of ACS administered to mothers with threatened preterm birth on several factors related to neonatal morbidity and mortality. RESULTS By logistic regression analysis, ACS exposure decreased respiratory distress syndrome and severe intraventricular hemorrhage in infants born between 24 and 29 weeks of gestation. Cox regression analysis revealed that ACS exposure was associated with a significant decrease in mortality of preterm infants born at 22 or 23 weeks of gestation (adjusted hazard ratio, 0.72; 95% CI, 0.53 to 0.97; P=.03). This effect was also observed at 24 to 25 and 26 to 27 weeks of gestation and in the overall study population. CONCLUSIONS ACS exposure improved survival of extremely preterm infants. ACS treatment should be considered for threatened preterm birth at 22 to 23 weeks of gestation.

Comparison of Mortality and Morbidity of Very Low Birth Weight Infants Between Canada and Japan

OBJECTIVE: To compare neonatal outcomes of very low birth weight (VLBW) infants admitted to NICUs participating in the Canadian Neonatal Network and the Neonatal Research Network of Japan. METHODS: Secondary analyses of VLBW infants in both national databases between 2006 and 2008 were conducted. The primary outcome was a composite of mortality or any major morbidity defined as severe neurologic injury, bronchopulmonary dysplasia, necrotizing enterocolitis, or severe retinopathy of prematurity at discharge. Secondary outcomes included individual components of primary outcome and late-onset sepsis. Logistic regression adjusting for confounders was performed. RESULTS: A total of 5341 infants from the Canadian Neonatal Network and 9812 infants from the Neonatal Research Network of Japan were compared. There were higher rates of maternal hypertension, diabetes mellitus, outborn, prenatal steroid use, and multiples in Canada, whereas cesarean deliveries were higher in Japan. Composite primary outcome was better in Japan in comparison with Canada (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.79–0.96). The odds of mortality (AOR 0.40, 95% CI 0.34–0.47), severe neurologic injury (AOR 0.57, 95% CI 0.49–0.66), necrotizing enterocolitis (AOR 0.23, 95% CI 0.19–0.29), and late-onset sepsis (AOR 0.22, 95% CI 0.19–0.25) were lower in Japan; however, the odds of bronchopulmonary dysplasia (AOR 1.24, 95% CI 1.10–1.42) and severe retinopathy of prematurity (AOR 1.98, 95%CI 1.69–2.33) were higher in Japan. CONCLUSIONS: Composite outcome of mortality or major morbidity was significantly lower in Japan than Canada for VLBW infants. However, there were significant differences in various individual outcomes identifying areas for improvement for both networks.

Epidemiology of neonatal chronic lung disease in Japan.

A nationwide survey on the epidemiology of chronic lung disease (CLD) of the newborn was conducted. Questionnaires were sent to 391 level II and III neonatal centers in Japan and the registration of infants born in 1990 with chronic lung disease was requested. CLD was defined as an oxygen requirement greater than that obtainable in room air at 28 days after birth, with symptoms of persistent respiratory distress and a hazy or emphysematous and fibrous appearance on chest X‐ray. A total of 301 neonatal centers (77.0%) responded and 50,290 infants at these centers were registered. Of these, 97% survived the first month and 1,135 of 48,762 neonatal survivors developed CLD. The mortality of infants with CLD was 6.2%. Survival rates at 28 days of age increased consistently with birthweight. Survival at 28 days of age in infants below 1,000 g at birth was 73.7%, but the rate was 93.9% in infants weighing 1,000–1,499 g. The incidence of CLD was inversely proportional to birthweight. Approximately one quarter of neonatal survivors with a birthweight below 1,500 g and approximately half of extremely small infants (<1,000 g) developed CLD. The analysis of CLD infants showed that 28.2% of them had a history of respiratory distress syndrome (RDS) and a typical fibrous appearance on chest X‐ray (Type I), while 29.3% also had a history of RDS but had an atypical X‐ray appearance (Type II). Approximately 13% of CLD infants showed evidence of intra‐uterine infection and typical X‐ray findings (Type III), 11.8% showed a typical X‐ray appearance but no preceding diseases (Type IV), and another 11.5% showed atypical chest X‐ray appearance and no preceding diseases (Type V). Only 5.8% of CLD infants could not be classified into any of these five types, and were grouped as Type VI. Ninety‐two per cent of CLD infants were discharged, 6.2% died in hospital and 1.8% were still in hospital at the time of the survey.

Case‐control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight

Abstract Background: There is a significant association between hepatoblastoma and low birthweight. A case‐control study was conducted to reveal risk factors for hepatoblastoma in children of extremely low birthweight (<1000 g).