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1.
Pediatr Res ; 95(1): 233-240, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37626120

RESUMO

BACKGROUND: Advanced perinatal medicine has decreased the mortality rate of preterm infants. Long-term neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs) remain to be investigated. METHODS: Participants were 124 VLBWIs who had in-hospital birth from 2007 to 2015. Perinatal information, developmental or intelligence quotient (DQ/IQ), and neurological comorbidities at ages 3 and 6 years were analyzed. RESULTS: Fifty-eight (47%) VLBWIs received neurodevelopmental assessments at ages 3 and 6 years. Among them, 15 (26%) showed DQ/IQ <75 at age 6 years. From age 3 to 6 years, 21 (36%) patients showed a decrease (≤-10), while 5 (9%) showed an increase (≥+10) in DQ/IQ scores. Eight (17%) with autism spectrum disorder or attention-deficit hyperactivity disorder (ASD/ADHD) showed split courses of DQ/IQ, including two with ≤-10 and one with +31 to their scores. On the other hand, all 7 VLBWIs with cerebral palsy showed DQ ≤35 at these ages. Magnetic resonance imaging detected severe brain lesions in 7 (47%) of those with DQ <75 and 1 (18%) with ASD/ADHD. CONCLUSIONS: VLBWIs show a broad spectrum of neurodevelopmental outcomes after 6 years. These divergent profiles also indicate that different risks contribute to the development of ASD/ADHD from those of cerebral palsy and epilepsy in VLBWIs. IMPACT: Very-low-birth-weight infants (VLBWIs) show divergent neurodevelopmental outcomes from age 3 to 6 years. A deep longitudinal study depicts the dynamic change in neurodevelopmental profiles of VLBWIs from age 3 to 6 years. Perinatal brain injury is associated with developmental delay, cerebral palsy and epilepsy, but not with ASD or ADHD at age 6 years.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Paralisia Cerebral , Epilepsia , Lactente , Feminino , Gravidez , Humanos , Recém-Nascido , Criança , Pré-Escolar , Estudos Longitudinais , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso
2.
Pediatr Blood Cancer ; 71(3): e30809, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38078568

RESUMO

OBJECTIVE: CHARGE syndrome is a congenital malformation syndrome caused by heterozygous mutations in the CHD7 gene. Severe combined immunodeficiency (SCID) arises from congenital athymia called CHARGE/complete DiGeorge syndrome. While cultured thymus tissue implantation (CTTI) provides an immunological cure, hematopoietic cell transplantation (HCT) is an alternative option for immuno-reconstitution of affected infants. We aimed to clarify the clinical outcomes of patients with athymic CHARGE syndrome after HCT. METHODS: We studied the immunological reconstitution and outcomes of four patients who received non-conditioned unrelated donor cord blood transplantation (CBT) at Kyushu University Hospital from 2007 to 2022. The posttransplant outcomes were compared with the outcomes of eight reported patients. RESULTS: Four index cases received CBT 70-144 days after birth and had no higher than grade II acute graft-versus-host disease. One infant was the first newborn-screened athymic case in Japan. They achieved more than 500/µL naïve T cells with balanced repertoire 1 month post transplant, and survived more than 12 months with home care. Twelve patients including the index cases received HCT at a median 106 days after birth (range: 70-195 days). One-year overall survival rate was significantly higher in patients who underwent non-conditioned HCT than in those who received conditioned HCT (100% vs. 37.5%, p = .02). Nine patients died, and the major cause of death was cardiopulmonary failure. CONCLUSIONS: Athymic infants achieved a prompt reconstitution of non-skewing naïve T cells after non-conditioned CBT that led to home care in infancy without significant infections. Non-conditioned CBT is a useful bridging therapy for newborn-screened cases toward an immunological cure by CTTI.


Assuntos
Síndrome CHARGE , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Timo/anormalidades , Lactente , Recém-Nascido , Humanos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Síndrome CHARGE/complicações , Doença Enxerto-Hospedeiro/etiologia , Controle de Infecções , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
3.
Pediatr Blood Cancer ; 71(3): e30824, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38155150

RESUMO

OBJECTIVES: To determine the optimal management for early-onset thrombophilia (EOT), the genetic and clinical features of protein C (PC)-, protein S (PS)-, or antithrombin (AT)-deficient patients of ≤20 years of age were studied in Japan. METHODS/RESULTS: Clinical and genetic information of all genetically diagnosed cases was collected through the prospective, retrospective study, and literature review. One-hundred-one patients had PC (n = 55), PS (n = 29), or AT deficiency (n = 18). One overlapping case had PC- and PS-monoallelic variant. Fifty-five PC-deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS-deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT-biallelic variants. The frequent low-risk allele p.K193del (PC-Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low-risk allele p.K196E (PS-Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother-newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients: three deaths with PC deficiency and 20 complication-free survivors. Neurological complications were more frequently found in patients with PC-biallelic variants than those with PC-, PS-, or AT-monoallelic variants (73% vs. 24%, p = .019). CONCLUSIONS: We demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother-infant pairs may prevent perinatal thrombosis in them.


Assuntos
Deficiência de Antitrombina III , Deficiência de Proteína C , Deficiência de Proteína S , Trombofilia , Trombose , Recém-Nascido , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Japão/epidemiologia , Deficiência de Proteína S/complicações , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/genética , Trombofilia/complicações , Trombose/etiologia , Trombose/genética , Deficiência de Proteína C/genética , Deficiência de Proteína C/complicações , Proteína C/genética , Anticoagulantes , Antitrombina III , Antitrombinas
4.
Ther Drug Monit ; 44(3): 404-413, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629445

RESUMO

BACKGROUND: Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring-informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics. METHODS: Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15-30 mg/L quicker than the current standard regimen. RESULTS: Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: (1) decreased dose for premature babies (PMA ≤28 weeks), (2) decreased dose for children with renal dysfunction, and (3) increased dose for children (0.5-11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2. CONCLUSIONS: This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Teicoplanina , Antibacterianos/farmacocinética , Criança , Monitoramento de Medicamentos , Humanos , Recém-Nascido , Método de Monte Carlo , Teicoplanina/farmacocinética
5.
J Pediatr ; 230: 119-125.e7, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33246013

RESUMO

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 Tempo
6.
J Pediatr ; 238: 259-267.e2, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34245770

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/genética
7.
Am J Med Genet A ; 185(11): 3459-3465, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34415101

RESUMO

Trisomy 18 (T18) is one of the most commonly diagnosed aneuploidies leading to poor survival outcome. However, little is known about the dual risk of T18 and very low birth weight (VLBW, weighing <1500 g at birth). We aimed to investigate the survival and clinical features of VLBW infants with T18. In this observational cohort study, infants with T18 admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2019 were eligible. Among 30 infants with T18 who were enrolled as study participants, 11 (37%) were born with VLBW. VLBW infants had lower gestational age (34.4 vs. 39.4 weeks, p < 0.01) and a higher incidence of esophageal atresia (64% vs. 11%, p < 0.01) than non-VLBW infants. The proportions of patients who underwent any surgery (55% vs. 5%, p < 0.01) and positive pressure ventilation (82% vs. 32%, p = 0.02) were higher in VLBW than non-VLBW infants. One-year overall survival rate (45% vs. 26%, p = 0.32 by log-rank test) did not differ between the two groups. In conclusion, being born at VLBW may not be fatal for infants with T18 undergoing active interventions.


Assuntos
Peso ao Nascer/genética , Mortalidade Infantil , Recém-Nascido de muito Baixo Peso , Síndrome da Trissomía do Cromossomo 18/genética , Aneuploidia , Idade Gestacional , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Taxa de Sobrevida , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/epidemiologia , Síndrome da Trissomía do Cromossomo 18/patologia
8.
BMC Pediatr ; 21(1): 360, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433439

RESUMO

BACKGROUND: The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. METHODS: Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children's Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. RESULTS: A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87-0.96 and 0.88-0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82-0.88 and 0.83-0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87-0.98 and 0.84-0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84-0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83-0.96). CONCLUSIONS: These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.


Assuntos
Desenvolvimento Infantil , Peso ao Nascer , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Estudos Prospectivos
9.
Dev Med Child Neurol ; 62(7): 874-878, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31763690

RESUMO

This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0-47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. WHAT THIS PAPER ADDS: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea.


Assuntos
Apneia , Epilepsia , Unidades de Terapia Intensiva Neonatal , Avaliação de Resultados em Cuidados de Saúde , Respiração com Pressão Positiva , Síndrome da Trissomía do Cromossomo 18 , Apneia/diagnóstico , Apneia/etiologia , Apneia/mortalidade , Apneia/terapia , Epilepsia/diagnóstico , Epilepsia/mortalidade , Epilepsia/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Síndrome da Trissomía do Cromossomo 18/complicações , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/mortalidade , Síndrome da Trissomía do Cromossomo 18/terapia
10.
Pediatr Int ; 62(2): 169-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845473

RESUMO

BACKGROUND: This study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO2 ) and carbon dioxide (tcPCO2 ) monitoring in neonatal intensive care units (NICUs) in Japan. METHODS: At the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring. RESULTS: The questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO2 and tcPO2 , and 42 (60.9%) measured tcPCO2 alone. Transcutaneous PCO2 or tcPO2 monitoring was applied for "pre-viable" infants born at 22-23 weeks' gestational age (18.6% vs 23.5%), and infants of <500 g birthweight (30.5% vs 17.6%). The tcPCO2 and tcPO2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at <38°C for tcPCO2 in 54.3% and >42°C for tcPO2 in 58.9% of NICUs. The accuracy for tcPO2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO2 as 1.7% or 93.2%of institutions , respectively. CONCLUSION: Transcutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan.


Assuntos
Monitorização Transcutânea dos Gases Sanguíneos/métodos , Dióxido de Carbono/sangue , Oxigênio/sangue , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/sangue , Unidades de Terapia Intensiva Neonatal , Japão , Inquéritos e Questionários
11.
J Pediatr ; 212: 117-123.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31229321

RESUMO

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 Risco
15.
J Immunol ; 196(6): 2779-87, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26880761

RESUMO

Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.


Assuntos
Morte Fetal/prevenção & controle , Retardo do Crescimento Fetal/imunologia , Proteína Adaptadora de Sinalização NOD1/metabolismo , Oligopeptídeos/administração & dosagem , Vasculite/imunologia , Animais , Quimiocina CCL2/metabolismo , Feminino , Morte Fetal/etiologia , Retardo do Crescimento Fetal/induzido quimicamente , Humanos , Interleucina-6/metabolismo , Ligantes , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Adaptadora de Sinalização NOD1/agonistas , Proteína Adaptadora de Sinalização NOD1/genética , Gravidez , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Vasculite/induzido quimicamente
16.
J Pediatr ; 190: 112-117.e3, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28746032

RESUMO

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 Sobrevida
17.
Pediatr Res ; 79(1-1): 81-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26372516

RESUMO

BACKGROUND: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation. METHODS: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis. RESULTS: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism. CONCLUSION: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.


Assuntos
Resistência à Proteína C Ativada/epidemiologia , Deficiência de Antitrombina III/epidemiologia , Deficiência de Proteína C/epidemiologia , Deficiência de Proteína S/epidemiologia , Tromboembolia/etiologia , Trombofilia/genética , Resistência à Proteína C Ativada/sangue , Resistência à Proteína C Ativada/diagnóstico , Resistência à Proteína C Ativada/genética , Adolescente , Idade de Início , Antitrombina III/análise , Antitrombina III/genética , Deficiência de Antitrombina III/sangue , Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/genética , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Fator V/genética , Feminino , Genótipo , Humanos , Lactente , Japão/epidemiologia , Masculino , Regiões Promotoras Genéticas/genética , Proteína C/análise , Proteína C/genética , Deficiência de Proteína C/sangue , Deficiência de Proteína C/diagnóstico , Deficiência de Proteína C/genética , Proteína S/análise , Proteína S/genética , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/genética , Protrombina/genética , Tromboembolia/epidemiologia , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/epidemiologia
18.
Pediatr Nephrol ; 31(6): 983-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26809806

RESUMO

BACKGROUND: Cystatin C (Cys-C) is a more sensitive marker of renal function than creatinine (Cre) in pediatric and adult populations. However, the reference values of serum Cys-C for estimating glomerular filtration rates (eGFRs) in premature infants during the first year of life have not been sufficiently studied. METHODS: In this prospective study, 481 blood samples were collected from 261 preterm infants with uncomplicated clinical courses during their first year of life. Infants were divided into three groups according to gestational age at birth: 27-30 weeks, 31-33 weeks, and 34-36 weeks. Serum Cys-C and Cre levels were measured at 6-30 days, 3-5 months, 7-9 months, and 12-14 months after birth and the eGFR was calculated using two previously published equations. RESULTS: The median serum Cys-C levels were 1.776, 1.248, 1.037, and 0.960 mg/L at the first, second, third, and fourth measurement time-point, respectively, with the value significantly decreasing with age up to 12-14 months. Cys-C levels were independent of gestational age and gender. In contrast to Cys-C, serum Cre values declined rapidly up to 3-5 months, then remained constant up to 12-14 months. Using the Cys-C-based equation, the eGFR significantly increased with increasing age until approximately 1 year after birth; however, no such trend was noted using the equation based on Cys-C + Cre. CONCLUSIONS: Reference ranges for Cys-C in premature infants decline gradually over the first year after birth. Cys-C appears to be a more reliable marker than Cre for estimating GFR in preterm infants.


Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Recém-Nascido Prematuro/fisiologia , Testes de Função Renal/métodos , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/sangue , Estudos Longitudinais , Masculino , Estudos Prospectivos , Valores de Referência
19.
J Perinat Med ; 42(4): 499-505, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24413214

RESUMO

AIM: To determine the factors affecting neonatal prognosis in preterm premature rupture of membranes (PPROM). METHOD: We conducted a case-control study involving 92 women between the years 2000 and 2010 diagnosed with PPROM between 25 and 31 weeks' gestation, who received antenatal steroids, and delivered between 26 and 31 weeks' gestation; a retrospective cohort study was conducted based on the results. We used data from four tertiary centers and compared the frequencies of neonatal neurologic deficits and neonatal deaths. RESULTS: There was a difference between the two groups; specifically, the ND group (n=18) consisted of patients whose infants had neurologic deficits and/or neonatal deaths and the neurologically normal (NN) group (n=74) included NN neonates amongst the patients who had expectant management (94% vs. 73%, respectively). Multivariable analysis revealed that expectant management was independently associated with an increased risk for neonatal neurologic deficits and neonatal deaths (odds ratio, 16.14). All neonates with poor prognosis in the expectant-management group delivered within 14 days after PPROM. CONCLUSIONS: Expectant management within 14 days after PPROM is associated with poor neonatal outcomes. Decisions regarding an expectant strategy should be made carefully. An immediate, planned delivery after steroid administration should be considered to improve neonatal prognosis in patients who have PPROM after 26 weeks' gestation.


Assuntos
Ruptura Prematura de Membranas Fetais/terapia , Glucocorticoides/administração & dosagem , Nascimento Prematuro , Adulto , Betametasona/administração & dosagem , Estudos de Casos e Controles , Estudos de Coortes , Parto Obstétrico , Dexametasona/administração & dosagem , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Gravidez , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
20.
Infect Control Hosp Epidemiol ; 44(6): 988-990, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35770388

RESUMO

To compare the culture sensitivities of MRSA detection, we collected 988 paired umbilical and nasal cultures from screened neonates. MRSA positivity rates were 79.1% from umbilicus and 41.9% from nares (P = .01). The umbilicus was a more useful culture site than the nares for surveillance of MRSA among neonates upon admission.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Recém-Nascido , Humanos , Unidades de Terapia Intensiva Neonatal , Umbigo , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Nariz , Unidades de Terapia Intensiva
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