Serum erythroferrone levels during the first month of life in premature infants.

OBJECTIVE: To examine erythroferrone (ERFE)-hepcidin iron regulation in premature infants under intensive care at risk of iron metabolic disorders. STUDY DESIGN: A retrospective cohort recruited 31 infants with a birth weight of <1500 g hospitalized in a tertiary center. Their hematological status was measured at birth and 2 and 4 weeks of life. RESULTS: ERFE was positively correlated with the reticulocyte hemoglobin content at 2 (r2 = 0.2374) and 4 weeks (r2 = 0.6005). An assumed negative correlation between ERFE and hepcidin was not determined during the neonatal period. Hepcidin was positively correlated with the leukocyte count (r2 = 0.3089) and ferritin (r2 = 0.7476) at birth and C-reactive protein (r2 = 0.3591) at 2 weeks and negatively correlated with the reticulocyte count (r2 = 0.2887) at 4 weeks. CONCLUSION: The vulnerability of the ERFE-hepcidin pathway within 4 weeks may contribute to iron imbalance in premature infants.

Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan.

OBJECTIVE: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years. STUDY DESIGN: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy. RESULT: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay. CONCLUSION: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets.

Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants.

OBJECTIVE: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. METHODS: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. RESULTS: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72). CONCLUSIONS: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age.

A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan.

OBJECTIVES: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. METHODS: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. RESULTS: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients. CONCLUSION: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth.

Neurodevelopmental Outcomes in Infants With Birth Weight ≤500 g at 3 Years of Age.

OBJECTIVES: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g. METHODS: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of <70. RESULTS: The overall proportion of NDI was 59.1% (95% confidence interval [CI]: 54.6%-63.5%). The trend revealed no significant change during the study period. In a multivariate modified Poisson regression analysis, NDI was associated with severe intraventricular hemorrhage (adjusted risk ratio [RR]: 1.42; 95% CI: 1.19-1.68; P < .01), cystic periventricular leukomalacia (adjusted RR: 1.40; 95% CI: 1.13-1.73; P < .01), severe necrotizing enterocolitis (adjusted RR: 1.31; 95% CI: 1.07-1.60; P < .01), surgical ligation for patent ductus arteriosus (adjusted RR: 1.29; 95% CI: 1.09-1.54; P < .01), and male sex (adjusted RR: 1.19; 95% CI: 1.01-2.40; P = .04). CONCLUSIONS: This cohort showed that neurodevelopmental outcomes of infants with a BW of ≤500 g have not improved from 2003 to 2012. Multivariate analysis revealed that severe intracranial hemorrhage and cystic periventricular leukomalacia were the strongest risk factors for NDIs. Our data suggested that measures aimed at reducing neurologic morbidities will be important for improving outcomes of infants with a BW of ≤500 g.

Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less in Japan.

OBJECTIVE: To assess the short-term prognosis of Japanese infants with a birth weight (BW) of ≤500 g. STUDY DESIGN: Demographic and clinical data were reviewed for 1473 live born infants with a BW ≤500 g at gestational age ≥22 weeks who were treated in the 204 affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2012. RESULTS: Survival to hospital discharge occurred in 811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW ≤300 g, 301-400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60% (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58-0.81; P < .01), cesarean delivery (0.69; 95% CI 0.56-0.85; P < .01), advanced gestational age per week (0.94; 95% CI 0.89-0.99; P = .02), BW per 100-g increase (0.55; 95% CI 0.49-0.64; P < .01), Apgar score ≥4 at 5 minutes (0.51; 95% CI 0.43-0.61; P < .01), and no major congenital abnormalities (0.38; 95% CI 0.29-0.51; P < .01) were associated with survival to discharge. Despite the improved survival rate over the 10-year study period (from 40% in 2003 [95% CI 30%-51%] to 68% in 2012 [95% CI 61%-75%]), at least 1 severe morbidity was present in 81%-89% of the survivors. CONCLUSIONS: Improvements in perinatal-neonatal medicine have improved the survival, but not the rate of major morbidities, of infants with a BW ≤500 g in Japan.

Successful Liver Transplantation for Transient Abnormal Myelopoiesis-Associated Liver Failure.

Infants with Down syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM occasionally involves liver fibrosis, which can be fatal. The management of liver disease in TAM has not yet been established and is mainly supportive. We report an infant with DS and TAM who developed end-stage liver failure. Liver dysfunction progressed even after blast cells disappeared from the circulation. He underwent a living-donor liver transplantation at 56 days of life without surgical complications. The explanted liver showed atrophy and severe fibrosis without leukemic cell infiltration. The posttransplant course was favorable with no hematological abnormality. He is doing well 8 months after transplantation. To the best of our knowledge, this report is the first showing that liver transplantation might be a treatment option for TAM-related liver failure.