Abstract:
:There is significant uncertainty over the role of assessment of long-term neurodevelopmental outcome (LTO) in neonatal clinical trials. A multidisciplinary working group was established to identify key issues in this area and to make recommendations about optimal approaches to evaluate LTO in therapeutic trials in newborns, which can be developed by sponsors and investigators with other key stakeholders. A key consideration for neonatal trials is the potential for the investigational product to cause widespread effects and drives the need to assess outcome in multiple organs. Thus investigators must assess whether the product has an impact on the brain and the potential for it to cause potential effects on LTO. Critically, is assessment of LTO an important direct therapeutic target or a safety outcome? Such decisions and outcomes need to be specific to the product being studied and use published data, only considering expert opinion when prior evidence does not exist. In designing the trial, the balance of benefits, costs, and burdens of assessments to the researcher and families need to be considered. Families and parent advocates should be involved in design and execution of the study. A framework is presented for use by all key stakeholders to determine the need, nature, and duration of LTO assessments in regulatory trials involving newborn infants.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Marlow N,Doyle LW,Anderson P,Johnson S,Bhatt-Mehta V,Natalucci G,Darlow BA,Davis JM,Turner MA,International Neonatal Consortium (INC).doi
10.1038/s41390-019-0526-1subject
Has Abstractpub_date
2019-11-01 00:00:00pages
567-572issue
5eissn
0031-3998issn
1530-0447pii
10.1038/s41390-019-0526-1journal_volume
86pub_type
杂志文章,评审abstract::Ethylmalonic aciduria is a common biochemical finding in patients with inborn errors of short chain fatty acid beta-oxidation. The urinary excretion of ethylmalonic acid (EMA) may stem from decreased oxidation by short chain acyl-CoA dehydrogenase (SCAD) of butyryl-CoA, which is alternatively metabolized by propionyl-...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199606000-00021
更新日期:1996-06-01 00:00:00
abstract::The lymphocytes of human breast milk have been previously shown to be immunologically competent while the monocytes have been described as actively motile in some reports but not in another. Cells were separated from milk samples collected by lactating women 2 to 9 days postpartum. Milk cell migration and production o...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198510000-00006
更新日期:1985-10-01 00:00:00
abstract::Tracheal epithelial cells obtained from adult and infant ferrets were grown in primary culture in vitro. Cells from adult animals grew readily, and many ciliated cells were observed in the cultures. Successful cultures were derived from infant animals, but cell number in infant and adult cultures began to decrease aft...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199107000-00016
更新日期:1991-07-01 00:00:00
abstract::Phagocytosis of apoptotic cells, e.g., neutrophils, by monocytes is essential for resolution of inflammation. Delayed removal leads to secondary necrosis, perpetuating inflammation, and tissue destruction. Common histologic features in neonatal chronic inflammatory disorders are an accumulation of apoptotic cells in i...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181b9b470
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. MET...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2016.267
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:The pathogenesis of neonatal group B Streptococcus (GBS) lung infection may be associated with surfactant dysfunction or deficiency. This study aimed to investigate the efficacy of surfactants on early postnatal GBS infection in ventilated newborn rabbit lungs. METHODS:A near-term newborn rabbit model was e...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-019-0421-9
更新日期:2019-08-01 00:00:00
abstract::Hereditary surfactant protein B (SP-B) deficiency has been lethal in the first year of life without lung transplantation. We tested the hypothesis that SP-B gene mutations may result in milder phenotypes by investigating the mechanisms for lung disease in two children with less severe symptoms than have been previousl...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200009000-00003
更新日期:2000-09-01 00:00:00
abstract::Low IGF-I levels are found in patients with chronic liver disease, but it is not known whether these reductions in IGF-I are secondary to hepatic dysfunction or to malnutrition. To determine whether malnutrition associated with hepatic dysfunction causes the decrease in these levels, serum and liver IGF-I concentratio...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198911000-00009
更新日期:1989-11-01 00:00:00
abstract::Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are mitogenic to the intestinal epithelium. To further clarify their role in the developing human fetal gut, their expression was studied in fetuses at 15 to 20 wk of gestation. TGF-alpha mRNA was present throughout the gastrointestinal tra...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199305000-00012
更新日期:1993-05-01 00:00:00
abstract::Intratracheal lipopolysaccharide (LPS) causes acute inflammation and injurious mechanical ventilation results in pulmonary and systemic inflammation. We aimed to determine in preterm lungs if continuous positive airway pressure (CPAP) protects against pulmonary and systemic inflammation, compared with conventional mec...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318189487e
更新日期:2009-01-01 00:00:00
abstract::Early detection of developmental delay and childhood disorders are important for early intervention. This study aimed to describe the distribution of responses in a large population-based survey, identify cutoff points for the parent concern checklist (PCC) suitable for the Chinese language and culture, and explore ho...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181c8ed3d
更新日期:2010-02-01 00:00:00
abstract::One of two slightly different influenza A/ts-1[E] recombinant candidate live vaccines was given intranasally to each of 23 young children. Twelve of 15 children who had no serum HI antibody but who did have serum ANAB at the time of administration became infected and 1 had mild rhinitis. All eight who lacked both type...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197604000-00008
更新日期:1976-04-01 00:00:00
abstract::Twelve critically ill neonates mechanically ventilated for respiratory failure (mean weight 1.33 kg, mean gestation 31 wk) were studied to quantitate the effects of radiant power from a radiant warming device, body weight, and body surface area on insensible water loss. Radiant power density (Mw/cm2) was measured usin...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198112000-00008
更新日期:1981-12-01 00:00:00
abstract::To investigate the role of nutrition in the regulation of IGFs during the perinatal period, 10-d-old rats were infused intravenously with various concentrations of nutrients for 24 h. Breast-fed litter mates served as controls. The effect of caloric intake on concentrations of IGF-I and IGF-II as well as IGF-binding p...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198908000-00012
更新日期:1989-08-01 00:00:00
abstract::Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000075084.56255.E0
更新日期:2003-08-01 00:00:00
abstract::The purpose of this study was to investigate the effect of blue light phototherapy on the expression of circadian genes in peripheral blood mononuclear cells (PBMC) and plasma melatonin levels in neonates. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was used to determine the expression of Bmal1 ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000183663.98446.05
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:No study has examined the association between prenatal phthalate exposure and intrauterine growth retardation (IUGR). This study aimed to investigate whether prenatal exposure to phthalates was associated with increased risk of IUGR. METHODS:A total of 126 mother-newborn pairs, including 42 IUGR cases and 8...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2014.103
更新日期:2014-10-01 00:00:00
abstract::In the small bowel of patients with cystic fibrosis, primary defects involving both chloride transport and mucus secretion have been demonstrated, but there is no general consensus about the morphologic counterpart of functional and biochemical abnormalities. We have studied the intestinal mucosa in a group of patient...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199802000-00013
更新日期:1998-02-01 00:00:00
abstract::Deficient quantity of amniotic fluid causes fetal guinea pig lung hypoplasia. Oligohydramnios that lasts only 5 days in early gestation is sufficient to reduce fetal lung growth significantly. We quantitated lung structural alterations at 50 days gestation (term is 67 days) of fetal guinea pigs whose amniotic fluid wa...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198610000-00013
更新日期:1986-10-01 00:00:00
abstract::Human autoimmune lymphoproliferative syndrome (ALPS) is caused by defective CD95-mediated apoptosis of lymphocytes. In most patients, heterozygous mutations within the CD95 gene are found. Mutated proteins interfere with CD95-signaling in a dominant-negative way. However, the penetrance of clinical disease is variable...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318191f7e4
更新日期:2009-02-01 00:00:00
abstract::The microchemical study of growth cartilage biopsies may improve the classification and the genetic advice of some types of growth disturbances and contribute to the understanding of biochemical defects. Small tibial growth cartilage biopsies were performed during orthopedic surgery in cases with achondroplasia, pseud...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197510000-00006
更新日期:1975-10-01 00:00:00
abstract::This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arteria...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198412000-00026
更新日期:1984-12-01 00:00:00
abstract::Tyrosine (Tyr) phosphorylation is implicated in the modification of several erythrocyte functions, such as metabolic pathways and membrane transport, as well as in signal transduction systems. Here we describe the map of Tyr-phosphorylated soluble proteins of newborn red blood cells (RBC) using an in vitro model simul...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000180545.24457.AC
更新日期:2005-10-01 00:00:00
abstract::Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of rat milk (RM)-versus...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000050657.56817.E0
更新日期:2003-03-01 00:00:00
abstract::Iron is essential for fetal organ development, but the effect of isolated iron deficiency on nephrogenesis is unknown. Human premature infants are at risk for disrupted nephrogenesis because glomerular development is incomplete until 36-wk gestation. We modeled the effects of iron on postnatal glomerulogenesis in four...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181be79c2
更新日期:2009-12-01 00:00:00
abstract::Alveolar hypoxia increases pulmonary artery pressure in lambs and sheep but increases lung lymph flow only in lambs; the reasons for this are unknown. To test the hypothesis that hypoxia-induced pulmonary venous constriction could in part explain the fluid filtration response in young lambs, eight young lambs (13 +/- ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198712000-00013
更新日期:1987-12-01 00:00:00
abstract::Treatment with phototherapy or with the lipase inhibitor orlistat decreases plasma unconjugated bilirubin (UCB) concentrations in hyperbilirubinemic Gunn rats. We investigated the mechanism(s) underlying the effects of orlistat, phototherapy, and combined treatment, using steady-state 3H-UCB kinetics. After three week...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000203180.79636.98
更新日期:2006-04-01 00:00:00
abstract::Quantitation of the body's fat and learn masses is an important component of nutritional assessment. Such measurements, however, are difficult to conduct routinely in infants due to the numerous limitations of traditional methods. The application of total body electrical conductivity measurements for quantitating fat-...
journal_title:Pediatric research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::To assess the National Institutes of Health extramural activity in the area of pediatric nephrology research, the rate of submission of grant applications to the National Institutes of Health and available indicators of the quality of these applications were analyzed. This was accomplished by utilizing the grant appli...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198511000-00001
更新日期:1985-11-01 00:00:00
abstract::In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supp...
journal_title:Pediatric research
pub_type: 临床试验,杂志文章
doi:10.1203/00006450-200208000-00025
更新日期:2002-08-01 00:00:00