RESUMO
OBJECTIVE: To clarify the incidence and genetic risk of neonatal-thromboembolism, we conducted a nationwide study exploring the impact of thrombophilia on neonatal-thromboembolism in Japan. STUDY DESIGN: A questionnaire survey was conducted for perinatal centers in Japan, focusing on the clinical expression, genotype, treatment, and outcome of patients who developed thromboembolism within 28 days of birth from 2014 to 2018. RESULTS: The estimated incidence of neonatal-thromboembolism was 0.39 cases per 10 000 live births. Intracranial lesions and purpura fulminans occurred in 66 and 5 of 77 patients, respectively. Fifty-eight (75.3%) infants presented within 3 days after birth. Four (5.2%) died, and 14 (18.2%) survived with disability. At the diagnosis, <20% plasma activity of protein C was noted in 16 infants, protein S (in 2), and antithrombin (in 1). Thirteen genetic tests identified 4 biallelic and 5 monoallelic protein C-variants but no protein S- or antithrombin-variants. Protein C-variants had purpura fulminans (P < .01), ocular bleeding (P < .01), positive-family history (P = .01), and death or disability (P = .03) more frequently than others. Protein C-variants were independently associated with disability (OR 5.74, 95% CI 1.16-28.4, P = .03) but not death. Four biallelic variants had serious thrombotic complications of neurologic disability, blindness, and/or amputation. Three monoallelic variants survived without complications. The only protein C-variant death was an extremely preterm heterozygote infant. CONCLUSIONS: Monoallelic protein C-variants had a higher incidence of neonatal-thromboembolism than biallelic variants. Thrombophilia genetic testing should be performed in the setting of neonatal-thromboembolism and low protein C to identify the underlying genetic defect.
Assuntos
Deficiência de Proteína C/complicações , Tromboembolia/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Japão , Masculino , Deficiência de Proteína C/genética , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Tromboembolia/genéticaRESUMO
OBJECTIVE: To investigate recent trends in bronchopulmonary dysplasia (BPD) and its risk factors among extremely preterm infants. STUDY DESIGN: Demographic and clinical data were reviewed for 19 370 infants born at 22-27 weeks of gestation registered in the affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2016. We investigated the overall survival and prevalence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age and risk factors for developing BPD among the survivors. RESULTS: Among 19 370 infants, 2244 (11.6%) died by 36 weeks' postmenstrual age. The mortality rate decreased from 19.0% (99% CI, 15.7%-22.8%) in 2003 to 8.0% (99% CI, 6.2%-10.3%) in 2016. Among 17 126 survivors, BPD developed in 7792 (45.5%) infants, and its proportion significantly increased from 41.4% (99% CI, 36.5%-46.4%) in 2003 to 52.0% (99% CI, 48.2%-55.9%) in 2016. A multivariable analysis of the survivors showed a positive association of BPD with ≥4 weeks' supplemental oxygen or invasive ventilation, birth weight <750 g, small for gestational age, ≥4 weeks' noninvasive positive pressure ventilation, chorioamnionitis, <26 weeks' gestational age, <20 cases per year of center patient volume, or treated patent ductus arteriosus. Although the median duration of invasive ventilation was shortened, the proportions of factors associated adversely with BPD generally showed increasing trends over time. CONCLUSIONS: The mortality rate of extremely preterm infants has decreased, but the rate of BPD has increased in survivors between 2003 and 2016. Despite the decreasing duration of invasive ventilation over time, increasing rates of BPD suggest that differences in the patient population or other management strategies influence the development of BPD.
Assuntos
Displasia Broncopulmonar/epidemiologia , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Japão/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: To clarify the frequency and characteristics of discrepant outcomes of intravenous immunoglobulin (IVIG) between fever and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: This study included 325 patients who responded to oral aspirin and IVIG alone. The main outcome was CAA 4 weeks after disease onset. CAA was defined as ≥2.5 of maximum z score (Zmax) representing the highest value of 4 coronary artery branches. Immunoglobulin dosage and sequential changes in Zmax were reviewed to investigate the effects on fever and timing of CAA development. Logistic regression analyses with receiver operating characteristic curves using clinical and laboratory variables including the initial Zmax were performed to identify predictors of CAA at 4 weeks. RESULTS: CAAs were either persistent or appeared de novo 4 weeks after diagnosis in 13 of 325 patients who responded to a single or repeated IVIG. Four single-dose IVIG-responders developed CAA although they had pretreatment Zmax of <2.0. The 2 single-dose IVIG responders with the greatest pretreatment Zmax (>4.5) developed persistent CAA. Receiver operating characteristic analysis demonstrated Zmax of 2.57 as the cut-off for predicting CAA. Multivariable analyses identified >2.5 Zmax (OR 9.08, 95% CI 1.26-65.3, P = .028, 50% sensitivity, 91% specificity) as the sole risk factor for CAA at 4 weeks in single-dose IVIG responders. CONCLUSIONS: Delayed development and persistence of CAA in single-dose IVIG responders indicate that some factors other than those responsible for systemic inflammation may contribute to vasculitis in CAA. Baseline Zmax 2.5 aids in predicting CAAs.
Assuntos
Aneurisma Coronário/etiologia , Aneurisma Coronário/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.
Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , DNA/genética , Diarreia/congênito , Previsões , Erros Inatos do Metabolismo/genética , Mutação , Vigilância da População , Transportadores de Sulfato/genética , Antiportadores de Cloreto-Bicarbonato/metabolismo , Análise Mutacional de DNA , Diarreia/epidemiologia , Diarreia/genética , Diarreia/metabolismo , Feminino , Seguimentos , Testes Genéticos , Humanos , Incidência , Recém-Nascido , Japão/epidemiologia , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/metabolismo , Estudos Retrospectivos , Transportadores de Sulfato/metabolismo , Taxa de Sobrevida/tendências , Fatores de TranscriçãoRESUMO
Compared with a 5% intravenous immunoglobulin, a 10% intravenous immunoglobulin as the first-line treatment of Kawasaki disease significantly reduced the fever duration (10 vs 13 hours, P = .022) among the responders, and the interval to adjunctive therapy for nonresponders (47 vs 49 hours, P = .035). There were no severe adverse events.
Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Infusões Intravenosas/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
Assuntos
Paralisia Cerebral/epidemiologia , Doenças do Prematuro/epidemiologia , Choque/epidemiologia , Estudos de Casos e Controles , Paralisia Cerebral/etiologia , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Japão , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
Assuntos
Mortalidade Infantil , Recém-Nascido de muito Baixo Peso , Bases de Dados Factuais , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Morbidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: To assess the etiology, prognosis, and appropriate treatment of hemophagocytic lymphohistiocytosis (HLH) in neonates. STUDY DESIGN: We collected information on neonates in whom HLH was diagnosed between 1997 and 2007 from participating members of the Japanese Society of Pediatric Hematology. RESULTS: HLH was diagnosed in 20 patients within 4 weeks after birth. Of the diagnostic criteria for HLH-2004, the incidence of fever was quite low in preterm infants, and hypertriglyceridemia and neutropenia were uncommon. Familial HLH (n = 6) or severe combined immunodeficiency-associated HLH (n = 1) was diagnosed in 7 patients, and 2 of them have survived. Herpes simplex virus-associated HLH was diagnosed in 6 patients, and 2 of them have survived. The overall survival rate for the 20 patients was 40%. CONCLUSIONS: HLH is rare in neonates and has a poor prognosis. Early diagnosis and immediate treatment are required when considering the possibility of herpes simplex virus-associated or familial HLH.
Assuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/mortalidade , Aciclovir/uso terapêutico , Corticosteroides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Antivirais/uso terapêutico , Transtornos da Consciência/epidemiologia , Ciclosporina/uso terapêutico , Eritema/epidemiologia , Etoposídeo/uso terapêutico , Exantema/epidemiologia , Feminino , Sofrimento Fetal/epidemiologia , Febre/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpes Simples/epidemiologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Recém-Nascido , Recém-Nascido Prematuro , Japão , L-Lactato Desidrogenase/sangue , Leucocitose/epidemiologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Transtornos da Motilidade Ocular/epidemiologia , Troca Plasmática , Prognóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Convulsões/epidemiologia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/epidemiologia , Microglobulina beta-2/urina , gama-Globulinas/uso terapêuticoRESUMO
In this report, we describe a boy who showed mild symptoms of neonatal-onset multisystem inflammatory disease. Although his symptoms and laboratory findings were similar to those of systemic juvenile idiopathic arthritis, further examinations revealed papilledema, meningitis, and a NLRP3 mutation. His peripheral blood monocytes died within 24 hours after lipopolysaccharide stimulation, a test that may be useful for diagnosis even in mild cases.
Assuntos
Inflamação/diagnóstico , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Morte Celular , Criança , Humanos , Inflamação/sangue , Masculino , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To develop a new scoring system for computed tomography (CT) of the chest for assessing the clinical status of patients with bronchopulmonary dysplasia (BPD) in comparison with a modified Edwards roentgenographic scoring system. STUDY DESIGN: Preterm infants diagnosed with BPD (n = 42) were assessed prospectively by chest CT scan at the time of discharge. Three radiologists classified the CT findings into 1 of 3 categories--hyperexpansion, emphysema, or fibrous/interstitial abnormalities--and developed a new scoring system. We assessed interobserver reproducibility and investigated whether this classification system reflected the severity of BPD in these patients. RESULTS: The CT scores had acceptable reproducibility (coefficient of correlation [cc] = 0.721 to 0.839). The subgroup with a more severe form of BPD had a higher CT score. The CT score correlated with the clinical score at 36 weeks of postmenstrual age (cc = 0.367) and the duration of oxygen therapy (cc = 0.537). Patients who were discharged home on oxygen had higher CT scores than patients who were not. CONCLUSIONS: The new chest CT scoring system may have higher objectivity and accuracy in terms of predischarge assessment of clinical status as well as prediction of the prognosis of patients with BPD.