Hidehiko Nakanishi

Effect of Bifidobacterium administration on very-low-birthweight infants.

Background:  The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very‐low‐birthweight (VLBW) infants.

Clinical characterization and long-term prognosis of neurological development in preterm infants with late-onset circulatory collapse

Objective:To characterize the risk factors for late-onset circulatory collapse (LCC) in preterm infants responsive to corticosteroid therapy and evaluate the long-term neurological prognosis.Study Design:A retrospective case–control study for preterm infants (⩽32 weeks’ gestation) admitted to our neonatal intensive care unit from 1994 through 2002.Result:Sixty-five infants (11%) were diagnosed with LCC. Infants with a shorter gestation and lower birth weight had a higher incidence of LCC. LCC infants had a significantly lower 1-min Apgar score, significantly higher incidence of severe intraventricular hemorrhage, chronic lung disease, and postnatal periventricular leukomalacia, and significantly longer duration of ventilation use, oxygen use, and hospital stay. Somatic growth at 36 weeks’ postmenstrual age was poorer in infants with LCC than without LCC (controls). LCC infants were significantly more likely than controls to have cerebral palsy at 3 years.Conclusion:LCC is associated with poor neurodevelopmental outcomes. Prevention of LCC can lead to improved neurological prognoses.

Impact of pulmonary hypertension on neurodevelopmental outcome in preterm infants with bronchopulmonary dysplasia: a cohort study.

Objectives:To evaluate the impact of pulmonary hypertension (PH) on long-term growth and neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD).Study Design:A single-center retrospective cohort of preterm infants born at <28 weeks gestational age from 2000 to 2011 was evaluated at 3 years of age. Growth and neurodevelopmental outcomes were compared among 3 groups: non-BPD, BPD without PH and BPD with PH. BPD was defined according to oxygen demand at 36 weeks postmenstrual age. PH was diagnosed by echocardiography during the neonatal intensive care unit stay.Results:Sixty-two infants without BPD, 60 with BPD without PH and 20 with BPD with PH were analyzed. Regardless of PH status, somatic growth was smaller in both BPD groups of infants than in non-BPD infants, with further reduction in the group having BPD with PH. Furthermore, a developmental quotient of <70 was more prevalent in the BPD infants with PH than in the BPD infants without PH (odds ratio (OR): 4.37; 95% confidence interval, CI: 1.16 to 16.5). Multivariate analysis demonstrated that BPD with PH was one of the independent perinatal risk factors for developmental quotient <70 at 3 years of age (OR: 4.94, 95% confidence interval: 1.06 to 24.1).Conclusion:PH had an additional negative effect on long-term growth and neurodevelopmental outcomes of extremely preterm infants with BPD.

Biopterin in the acute phase of hypoxia-ischemia in a neonatal pig model

To clarify the participation of inducible NOS (iNOS) in the hypoxia-ischemia, we examined iNOS and its tetrahydrobiopterin co-factor in the cerebral cortex and plasma in a newborn-piglet model. We also investigated the role of hypothermia in iNOS expression and biopterin production. Male newborn piglets were ventilated 6% oxygen for 45 min. Their common carotid arteries were clamped during hypoxia. Then they were resuscitated with 30% oxygen (HI group). Piglets of the hypothermia group were treated as the HI group and their body was cooled to 35.5 degrees C after hypoxic-ischemic insults. Sham-treated piglets were also reserved. In the HI group, iNOS was present in neurons and macrophages of the cerebral cortex 12h after the insult. The concentrations of nitrite and nitrate were elevated in the cerebral cortex 12h after hypoxic-ischemic insults but the biopterin level was unchanged. The plasma biopterin concentration after the insult (377.9+/-78.7 nM) was five times higher than before the insult (80.1+/-4.3 nM); this level peaked 4h after the insult (604.8+/-200.9 nM) and only slightly decreased after 12h (445.9+/-57.8 nM). In the hypothermia group, no iNOS expression was observed 12h after the insult. The plasma biopterin concentration after the insult (464.2+/-92.3 nM) was similar to that in the HI group, but was suppressed by 4h of hypothermia (229.3+/-106.8 nM). In this study, neuronal iNOS expression and increase of NO production were found in the acute phase of hypoxia-ischemia. Brain biopterin did not increase in hypoxia-ischemia although plasma biopterin was five-fold elevated. The discrepancy may also affect hypoxic-ischemic organ damage.

Hemodynamic analysis in infants with late-onset circulatory collapse

Late‐onset circulatory collapse (LCC) is a disorder in which blood pressure decreases and oliguria suddenly occurs in preterm infants who have survived the acute stage, leading to shock, without contributing underlying factors. In order to evaluate hemodynamic changes during LCC, the correlation between myocardial functions and organ blood flow was investigated with echography.

Differences in mortality and morbidity according to gestational ages and birth weights in infants with trisomy 18.

The aim of this study was to clarify the effects of gestational age and birth weight on outcomes of the infants. Medical records of 36 infants with trisomy 18 admitted to Tokyo Womens Medical University Hospital from 1991 to 2012 were reviewed retrospectively. We compared clinical characteristics between term infants (n = 15) and preterm infants (n = 21). There were one very‐low‐birth‐weight (VLBW) term infant (5%) and 12 VLBW preterm infants (80%). Although there were no significant differences in clinical characteristics and provided management between the two groups, none of the preterm infants achieved survival to discharge. On the other hand, 6 of 21 term infants (29%) achieved survival to discharge (P < 0.05). Similar results were obtained for comparisons between the VLBW infants and non‐VLBW infants. Multiple logistic regression analysis revealed that shorter gestational age had a more negative impact than lower birth weight to survival to discharge in infants with trisomy 18. In both preterm and term groups, the infants who died before 30 days commonly died of respiratory failure or apnea. Whereas, the infants who survived more than 30 days mostly died of heart failure.

Hydrocortisone and long-term outcomes in very-low-birthweight infants

Background:  The long‐term effects of hydrocortisone (HDC) used for very‐low‐birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short‐term clinical effects and long‐term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants.

Persistent pulmonary hypertension of the newborn in extremely preterm infants: a Japanese cohort study

Objective To investigate the characteristics of persistent pulmonary hypertension of the newborn (PPHN) in extremely preterm infants and its impact on neurodevelopmental outcomes at 3 years of age. Design A retrospective multicentre cohort study. Settings 202 tertiary perinatal centres registered in the Neonatal Research Network of Japan (NRNJ). Patients Infants born at <28 weeks of gestational age (GA), between 2003 and 2012, were extracted from tertiary perinatal centres participating in NRNJ. Main outcome measures Demographic characteristics, morbidity, interventions and mortality were compared for infants with and without PPHN. Multivariable logistic analysis was performed to evaluate the impact of PPHN on long-term neurodevelopmental outcomes (the prevalence rate of cerebral palsy, need for home oxygen therapy, and visual, hearing and cognitive impairment) at 3 years of age. Results The prevalence of PPHN among the 12 954 extremely preterm infants enrolled was 8.1% (95% CI 7.7% to 8.6%), with the trend increasing annually, and a higher proportion as GA decreased: 18.5% (range, 15.2% to 22.4%) for infants born at 22 weeks compared with 4.4% (range, 3.8% to 5.2%) for those born at 27 weeks. Clinical chorioamnionitis and premature rupture of membranes were associated with PPHN. On multivariate analysis of the data from 5923 infants followed up for 3 years, PPHN was a significant independent risk factor for visual impairment (adjusted OR, 1.42, 95% CI 1.03 to 1.97). Conclusions The prevalence of PPHN in extremely preterm infants has been increasing over the past decade in Japan. Clinicians should be aware of visual impairments as a neurodevelopmental abnormality among infants with PPHN.

Identification of practices and morbidities affecting the mortality of very low birth weight infants using a multilevel logistic analysis: clinical trial or standardisation?

Objectives To determine the feasibility of clinical trials of newly developed treatments or standardisation of existing practices to further improve outcomes among very low birth weight (VLBW) infants, a nationwide database was analysed with a two-dimensional approach using two multivariate logistic models. Design Retrospective observational analysis. Setting Level III perinatal centres in Japan. Participants 15 920 VLBW infants admitted at 38 participating centres from 2003 through 2010. Outcome measures Clinical information for the infants was collected until discharge from the centres. A multivariate logistic model identified practices and morbidities associated with mortality. Then, those which were significantly associated with mortality were analysed using a multilevel logistic model. The residues calculated by the multilevel analysis were used as an indicator of centre variation. Results Among practices, antenatal steroids and intubation at birth showed relatively high centre variations (0.9 and 0.8) and favourable ORs (0.7 and 0.5) for mortality, while caesarean section showed a low centre variation (0.4) and a favourable OR (0.8). Sepsis and air leak showed high centre variations (0.4 and 0.4) and high ORs (3.8 and 3.4) among morbidities. Pulmonary haemorrhage, persistent pulmonary hypertension of the newborn, and intraventricular haemorrhage showed moderate variations (0.2, 0.3 and 0.2, respectively) and high ORs (5.6, 4.1 and 2.9, respectively). In contrast, necrotising enterocolitis showed the lowest variation (0.1) and a high OR (4.9). Conclusions The two-dimensional approach has clearly demonstrated the importance of clinical trial or standardisation. The practices and morbidities with low centre variations and high ORs for mortality must be improved through clinical trials of newly introduced techniques, while standardisation must be considered for practices and morbidities with a high centre variation. Trial registration The database was registered as UMIN000006961.

Trends in the neurodevelopmental outcomes among preterm infants from 2003–2012: a retrospective cohort study in Japan

ObjectivesTo determine the trends in mortality and the prevalence of abnormal neurodevelopmental outcomes among preterm Japanese infants.Study designA retrospective multicenter cohort of 30,793 preterm infants born at a gestational age ≤32 weeks, between 2003 and 2012, in the Neonatal Research Network, Japan, was evaluated in the primary analysis. Finally, 13,661 infants were followed-up until 3 years of age and evaluated for neurodevelopmental outcomes, including cerebral palsy (CP), home oxygen therapy (HOT) use, and visual, hearing, and cognitive impairments. Multivariable logistic regression analysis was performed to determine the risk-adjusted trends in mortality and long-term neurodevelopmental outcomes.ResultsThe trends in overall mortality (adjusted odds ratio, (AOR): 0.92; 95% confidence interval, (CI): 0.89–0.94), the prevalence of CP (AOR: 0.95, 95% CI: 0.92–0.98), HOT use (AOR: 0.84, 95% CI: 0.75–0.93), and visual (AOR: 0.84, 95% CI: 0.81–0.87) and hearing impairments (AOR: 0.78, 95% CI: 0.63–0.97) showed a significant downward trend, while cognitive impairment showed no significant changes (AOR: 1.02, 95% CI: 0.99–1.05). Intravenous hyperalimentation was significantly correlated with visual impairment (AOR 0.74, 95% CI 0.59–0.91). Early establishment of enteral feeding was associated with improved long-term outcomes.ConclusionsMortality was improved, and this did not lead to increased risks for abnormal neurodevelopmental outcomes. Nutritional support might improve long-term neurodevelopmental outcomes.