Biology of the neonate最新文献

{"title":"Can cerebrospinal fluid uric acid levels differentiate intraventricular hemorrhage from traumatic tap?","authors":"Didem Aliefendioğlu,&nbsp;Tuğba Gürsoy,&nbsp;K Mutlu Hayran,&nbsp;Ayşe Tana Aslan","doi":"10.1159/000094319","DOIUrl":"https://doi.org/10.1159/000094319","url":null,"abstract":"<p><strong>Objective: </strong>To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH.</p><p><strong>Material and methods: </strong>The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to normal CSF samples. The IVH group (n = 21, group III) consisted of neonates who had been diagnosed by cranial ultrasonography or computed tomography scans. Data are presented as median (range).</p><p><strong>Results: </strong>There was no significant difference between groups with respect to serum UA levels. While no significant difference was observed between CSF UA levels of the control [0.6 (0.1-1.8) mg/dl] and traumatic tap group [0.5 (0.3-1.1) mg/dl], the IVH group [1.6 (0.7-6.9) mg/dl] was found to have significantly higher CSF UA levels than groups I and II. Furthermore, although there were significant correlations between serum and CSF UA levels in the control and traumatic tap groups, no correlation was observed in the IVH group.</p><p><strong>Conclusion: </strong>CSF UA levels are increased in neonates with IVH and they may be used to differentiate a real hemorrhage from a traumatic tap.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 4","pages":"268-72"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000094319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26119476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerning the article by s. Belda et Al.: screening for retinopathy of prematurity: is it painful?","authors":"José Figueras-Aloy,&nbsp;J Manuel Rodríguez-Miguélez,&nbsp;M Dolors Salvia-Roiges,&nbsp;Francesc Botet-Mussons","doi":"10.1159/000089754","DOIUrl":"https://doi.org/10.1159/000089754","url":null,"abstract":"Therefore, we consider that it is as important to relieve the pain as to prevent systemic effects of mydriatics in low-weight infants [3] . The main prophylactic measures are [4] : (1) To use in neonates only the minimum effective concentration of drugs: 2% ophthalmic phenylephrine solution and 0.5% ophthalmic cyclopentolate solution. (2) To reduce systemic absorption of drugs by applying pressure to the lacrimal sac during and for 2 min after instillation. Without lacrimal sac occlusion, approximately 80% of each drop may pass through the nasolacrimal system and be available for rapid systemic absorption by the nasal mucosa. To perform this correctly, two persons are needed: one for applying pressure to the lacrimal sac and the other for instilling the drops. (3) Not to repeat the doses. Usually it is enough to instill one drop of each drug in the eye at least 10 min prior funduscopic procedures, especially if lacrimal sac occlusion is complete. This procedure can be exceptionally repeated 15 min later, but a third dose should never be given. Dear Sir, We read with interest the article by Belda et al. ‘Screening for retinopathy of prematurity: Is it painful?’ [Biol Neonate 2004; 86: 195–200]. We agree with its content but we have a few concerns about some of the information presented in the above referenced article [1] and about practical recommendations that have not been included for neonatologists and nurses taking care of the preterm infants. The objective of the study was to evaluate the ophthalmologic examination side effects in preterm neonates with specially focusing on the occurrence of pain. Gastrointestinal side effects (vomiting and gastric aspirates), minimum oxygen saturation, apneas, and the need for respiratory assistance or intensive care unit admission within 24 h after the examination were assessed. These late clinical side effects are probably not due to pain but to the instillation of mydriatics, as the same authors refer to in the Discussion. These changes on physiologic variables may be life-threatening and can produce, although rarely, a cardiorespiratory arrest [2] . Published online: November 15, 2005","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"89 3","pages":"197; author reply 198"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000089754","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25711495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical excitatory amino acid release and cell function during hypotension in near-term born lambs.","authors":"Sandra van Os,&nbsp;Wim Ruitenbeek,&nbsp;Jeroen Hopman,&nbsp;John Klaessens,&nbsp;Margot van de Bor","doi":"10.1159/000092450","DOIUrl":"https://doi.org/10.1159/000092450","url":null,"abstract":"<p><strong>Background: </strong>Energy failure due to insufficient cerebral O2-supply leads to excess accumulation of calcium ions in presynaptic neurons, followed by excess release of excitatory amino acids, which are potent neurotoxins, into the synaptic cleft.</p><p><strong>Aim: </strong>To investigate whether electrocortical brain activity (ECBA) can provide an adequate measure for excitatory amino acid release due to hemorrhagic hypotension.</p><p><strong>Methods: </strong>Ten near-term lambs were delivered at 127 days of gestation (term: 147 days). After a stabilization period, hypotension was induced by stepwise withdrawal of blood. Cerebral microdialysis was used to measure the concentrations of glutamate and aspartate.</p><p><strong>Results: </strong>During hypotension, mean arterial blood pressure, cerebral O2-supply and ECBA decreased and the extracellular concentration of glutamate increased significantly. ECBA was significantly related to glutamate (R2: 0.67, p < 0.001) and aspartate (R2: 0.57, p < 0.001) concentrations.</p><p><strong>Conclusion: </strong>The extracellular release of glutamate and aspartate in the cerebral cortex increases after hemorrhagic hypotension in near-term born lambs. The extracellular overflow of glutamate and aspartate were significantly inversely related to ECBA.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 2","pages":"128-34"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25944620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normal serum alanine concentration differentiates transient neonatal lactic acidemia from an inborn error of energy metabolism.","authors":"Eva Morava,&nbsp;Marije Hogeveen,&nbsp;Maaike De Vries,&nbsp;Wim Ruitenbeek,&nbsp;Willem-Pieter de Boode,&nbsp;Jan Smeitink","doi":"10.1159/000093590","DOIUrl":"https://doi.org/10.1159/000093590","url":null,"abstract":"<p><strong>Background: </strong>Elevated blood lactate levels are common in the critically ill neonate; however, sometimes they are difficult to interpret. Persistent or recurrent lactic acidemia might point to an inborn error of metabolism, like disturbances of the oxidative phosphorylation. Chronic lactic acidemia results in increased serum alanine levels. Serum alanine levels in newborns with transient lactic acidemia have not yet been studied.</p><p><strong>Objective: </strong>We designed a pilot study to evaluate the use of serum alanine levels as an additional metabolic marker to differentiate the transient effect of circulatory failure from a possible mitochondrial dysfunction.</p><p><strong>Methods: </strong>We prospectively evaluated 10 newborns with transient lactic acidemia after mild dysoxia, and 10 newborns with recurrent lactic acidemia consecutively diagnosed with a disorder in oxidative phosphorylation.</p><p><strong>Results: </strong>No significant serum alanine level elevation was found in transient lactic acidemia. Increased serum alanine was a sensitive marker in mitochondrial dysfunction.</p><p><strong>Conclusions: </strong>We propose to measure the serum alanine level in hypotonic newborns with lactic acidemia to facilitate the decision making in further diagnostics and management.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 3","pages":"207-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000093590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26053662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary repair of esophageal atresia in extremely low birth weight infants: a single-center experience and review of the literature.","authors":"Guido Seitz,&nbsp;Steven W Warmann,&nbsp;Juergen Schaefer,&nbsp;Christian F Poets,&nbsp;Joerg Fuchs","doi":"10.1159/000094037","DOIUrl":"https://doi.org/10.1159/000094037","url":null,"abstract":"<p><strong>Background: </strong>Advances in neonatal intensive care have led to an increased survival of very low birth weight (VLBW, <1,500 g) and extremely low birth weight infants (ELBW, <1,000 g). Several abnormalities may occur in these children, e.g. esophageal atresia (EA), imperforate anus or abdominal wall defects. Correction of EA is often performed as a staged procedure in this group of patients.</p><p><strong>Objectives: </strong>To evaluate the feasibility of a primary correction of EA in 4 ELBW and VLBW infants.</p><p><strong>Methods: </strong>Between 2002 and 2004, 4 infants below 1,200 g were operated on in our institution with a diagnosis of EA with lower tracheoesophageal fistula. Birth weight ranged from 780 to 1,120 g (median: 920 g), gestational age from 28 to 30 weeks. Treatment included closure of the tracheoesophageal fistula and primary anastomosis of the esophagus in a one-step procedure.</p><p><strong>Results: </strong>Primary correction of EA and fistula repair was feasible in all children. Initially, all children had a normal passage of the esophagus as observed in barium swallowing. One child suffering from a leakage of the anastomosis was managed conservatively. Another infant suffered from spontaneous small bowel perforation 6 days after surgery, which was treated by laparotomy. One child developed stenosis of the esophagus and required a single dilatation 14 months after initial treatment. In the 4th child, a type II cleft syndrome was subsequently diagnosed, requiring secondary cleft repair together with semifundoplication. This child eventually died from cytomegalovirus pneumonia.</p><p><strong>Conclusions: </strong>Primary repair of EA and closure of a tracheoesophageal fistula is technically feasible and offers a good treatment option for ELBW and VLBW infants. Staged repair can be avoided. Infants with cleft syndrome are still a diagnostic and therapeutic challenge.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 4","pages":"247-51"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000094037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26096868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection.","authors":"Pak Cheung Ng,&nbsp;Geng Li,&nbsp;Kit Man Chui,&nbsp;Winnie Chiu Wing Chu,&nbsp;Karen Li,&nbsp;Raymond Pui On Wong,&nbsp;Tai Fai Fok","doi":"10.1159/000088288","DOIUrl":"https://doi.org/10.1159/000088288","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the diagnostic utilities of monocyte HLA-DR as an infection marker in the identification of early-onset clinical infection and pneumonia in newborn infants.</p><p><strong>Methods: </strong>Term newborns in whom infection was suspected when they were <72 h of age were eligible for enrollment in the study. C-reactive protein (CRP), monocyte HLA-DR and neutrophil CD64 expressions were quantitatively measured at the time of sepsis evaluation (0 h) and 24 h afterwards by flow cytometry and standard laboratory method.</p><p><strong>Results: </strong>A total of 288 infants with suspected sepsis were investigated, and 93 were found to be clinically infected. There were no significant differences in monocyte HLA-DR expression between the infected, non-infected and control groups at 0 h (median (interquartile range): 13,986 (10,994-18,544), 14,234 (12,045-17,474) and 18,441 (14,250-21,537) antibody phycoerythrin (PE) molecules bound/cell), and between infected and non-infected infants at 24 h (median (interquartile range): 17,772 (12,933-25,167) and 19,406 (14,885-24,225) antibody PE molecules bound/cell). The areas under the receiver operating characteristics (ROC) curves for HLA-DR, CD64 and CRP were 0.52-0.54, 0.88-0.94 and 0.75-0.77, respectively. We were unable to determine an optimal cutoff value for HLA-DR, as the diagnostic utilities of any cutoff point on the ROC curves were unable to satisfy the criteria (i.e. sensitivity and specificity >or=80%) for consideration as an useful diagnostic marker of infection.</p><p><strong>Conclusions: </strong>Our findings did not support the use of monocyte HLA-DR alone or in combination with other infection markers in the diagnosis of early-onset clinical infection and pneumonia in term newborns.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"89 2","pages":"75-81"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000088288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25005544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of tenascin-C and matrix metalloproteinases in vascular abnormalities in murine hypoplastic lungs.","authors":"Mala R Chinoy, Shane A Miller","doi":"10.1159/000093308","DOIUrl":"10.1159/000093308","url":null,"abstract":"<p><strong>Background: </strong>Tenascin-C (TN-C), an extracellular matrix glycoprotein, is crucial to cell-migration, proliferation, apoptosis and remodeling of tissues, with a potential role in pathobiology of pulmonary hypertension. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial to the integrity of the extracellular matrix. TN-C and MMPs are counter-regulatory molecules, which influence the vascular integrity through modulations of elastin. We have a murine model of pulmonary hypoplasia with coexistent diaphragmatic hernia, vascular abnormalities and excessive arterial smooth muscle cell (SMC) proliferation.</p><p><strong>Objectives: </strong>Our objective was to investigate modulations of TN-C and MMPs in hypoplastic lungs and their possible contribution to the observed pulmonary vascular abnormalities.</p><p><strong>Methods: </strong>We addressed our objectives by pursing immunoblotting and immunohistochemistry and zymography/reverse zymography to assess the alterations in activities of MMPs and their inhibitors.</p><p><strong>Results: </strong>We observed significant down-regulation of MMP-9 activity in hypoplastic lungs at the later fetal developmental stages, whereas MMP-2 activity assessed by gelatin zymography remained unaltered. Reverse zymography revealed up-regulation of activities of TIMP-1, -2, -3 and -4 in hypoplastic lungs during later fetal development, with pronounced increases in TIMP-3 and -4 activities. Furthermore, immunoblot analyses and immunohistochemistry revealed that TN-C protein was down-regulated in developing hypoplastic lungs, compared to normal lungs.</p><p><strong>Conclusions: </strong>(1)TN-C is known to inhibit vascular SMC proliferation. But, decrease in TN-C in hypoplastic lungs may support the observed arterial SMC proliferation. (2) Our studies showed that in hypoplastic lungs the SMC apoptosis is not affected, thus suggesting that SMC proliferation and apoptosis may be two separate processes in pulmonary hypoplasia with coexistent diaphragmatic hernia. Together, our data showed an imbalance in the extracellular matrix proteins, which may contribute to the pulmonary vascular abnormalities.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 3","pages":"185-96"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000093308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26022760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partial liquid ventilation with low-dose perfluorochemical and high-frequency oscillation improves oxygenation and lung compliance in a rabbit model of surfactant depletion.","authors":"Takashi Wakabayashi,&nbsp;Masanori Tamura,&nbsp;Tomohiko Nakamura","doi":"10.1159/000088874","DOIUrl":"https://doi.org/10.1159/000088874","url":null,"abstract":"<p><strong>Background: </strong>Partial liquid ventilation (PLV) with perfluorochemical (PFC) has been advocated as a new therapy for acute respiratory distress syndrome in both clinical and animal studies, meconium aspiration syndrome, and RDS. PFC is referred to as liquid PEEP because it gets distributed to the most gravity-dependent regions of the lung due to its density. High-frequency oscillation (HFO) has been shown to prevent both acute and chronic lung injury in the management of very low birth weight infants with RDS, with gentle ventilation approach. Specifically, HFO with aggressive and adequate lung volume recruitment has been shown to reduce the incidence of chronic lung disease in very low birth weight infants. We hypothesized that PLV along with HFO might be effective in ARDS in an adult rabbit model.</p><p><strong>Objectives: </strong>To examine the efficiency of low-dose PLV with with HFO on pulmonary gas exchange and lung compliance in a surfactant-depleted rabbit model.</p><p><strong>Methods: </strong>After induction of severe lung injury by repeated saline lung lavage, 19 adult white Japanese rabbits were randomized into two groups that received PLV with HFO (n=9) or HFO gas ventilation (n=10). Physiological and blood gas data were compared between the two groups by analysis of variance.</p><p><strong>Results: </strong>The HFO-PLV group showed improved total lung compliance with maintenance of significantly lower mean airway pressure as compared with the HFO-GAS group so as to keep SpO2>90%.</p><p><strong>Conclusions: </strong>The addition of a low dose of PFC with HFO was effective in achieving adequate oxygenation, with a reduction in further lung injury in neonates.</p>","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"89 3","pages":"177-82"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000088874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25631005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surfactant therapy: present and future perspectives. Proceedings of the 21st International Workshop on Surfactant Replacement. June 1-4, 2006. Oslo, Norway.","authors":"","doi":"10.1159/000090115","DOIUrl":"https://doi.org/10.1159/000090115","url":null,"abstract":"Biol Neonate 2006;89:257–259 258 10 Revak S, Merritt TA, Cochrane CG: Effi cacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys. Pediatr Res 1996; 39: 715–724. 11 Walther FJ, Gordon LM, Zassadzinski JA, Sherman MA, Waring AJ: Surfactant protein B and C analogues. Mol Genet Metab 2000; 71: 342–351. 12 Manalo E, Merritt TA, Kheiter A, Amirkhanian J, Cochrane C: Comparative effects of some serum components and proteolytic products of fi brinogen on surface tension-lowering abilities of beractant and a synthetic containing surfactant KL 4 . Pediatr Res 1996; 39: 540– 545. 13 Nutt M, Patel N, Rairkart M, Niven R: Comparison of the novel lung surfactant Surfaxin (lucinactant) with currently available commercial products. Pediatr Res 2004; 50: 466A. 14 Christofi dou-Solomidou M, Argyris E, Bohen A, Stephens S, Niven R, Segal R: Novel lung surfactant (KL 4 -surfactant) prevents hyperoxic lung injury in mice and decreases neutrophil transmigration in vitro. PAS 2005: 57: 2497. 15 Cochrane CG, Revak SD, Merritt TA, et al: The effi cacy and safety of KL 4 -surfactant in preterm infants with respiratory distress syndrome. Am J Respir Crit Care Med 1996; 153: 404–410. 16 Moya FR, Gadzinowski J, Bancalari E, et al: A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants. Pediatrics 2005; 115: 1018–1029. 17 Sinha SK, Lacaze-Masmonteil T, Soler AV, et al: A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome. Pediatrics 2005; 115: 1030–1038.","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"89 4","pages":"282-351"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000090115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25733847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stopping a randomized trial early: from protocol to publication. Commentary to Thome at al.: outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life (Biol Neonate 2006;90:218-225).","authors":"Pollyanna Hardy,&nbsp;Felicity Clemens","doi":"10.1159/000092724","DOIUrl":"https://doi.org/10.1159/000092724","url":null,"abstract":"even reverse itself, and so fi xed stopping rules dictated by predetermined signifi cance levels for differences in outcome are increasingly discouraged [3] . Additional information such as the medical plausibility of the difference, ethical considerations both for the trial participants and for the wider target population, evidence from other relevant trials and the nature of the disease under consideration may also be important [2, 4–6] . The decision to stop a trial for harm can also be based on adverse events, although attribution of the cause of an adverse event may be diffi cult [3] . There is less guidance available on when and how trials should be stopped for futility. The 2005 DAMOCLES study [3] highlights a recognition in the literature that termination of a trial may be recommended where it is considered that there is no longer a reasonable chance of accumulating suffi cient evidence against the null hypothesis (usually due to poor recruitment or to external information becoming available [7] ). However, it is unclear whether trials should be stopped on these grounds [3, 4] . Another reason for stopping for futility is that the trial is unlikely to come to a sound conclusion [3] . This is illustrated in the trial by Thome et al. The diffi culty with this trial was that, at the time of the interim analysis, the majority of the patients randomized to the active arm (minimal ventilation to achieve higher PaCO 2 ) had not An important, often neglected element to planning a clinical trial is to consider the possibility of stopping the trial early, before either recruitment or follow-up is completed. A trial may be stopped for futility, harm or benefi t. A trial that is stopped on the grounds of benefi t is one that early on identifi es important treatment effects unlikely to be due to chance. A trial stopped for harm provides evidence that the treatment under investigation is unsafe for trial subjects. A trial stopped for futility requires a decision that the trial would not provide suffi ciently useful information to warrant continuation. Stopping a trial early is always a diffi cult decision to make and consideration must be given to who will be making these decisions and on what grounds they will be made. This issue of Biology in the Neonate publishes a trial by Thome et al. investigating the use of increased PaCO 2 targets on outcomes in extremely preterm neonates. It appears that this trial was stopped for futility on the grounds that the increased target levels of PaCO 2 were not being reached in the active arm of the trial. Guidance for stopping a trial for benefi t or harm is well documented [1] although approaches remain controversial. Statistical methods exist and may contribute to deciding whether the observed data imply that benefi t is very likely or, in the case of stopping for harm, very unlikely, or that the new treatment is harmful [2] . An early trend in the data under consideration may fl uctuate and Published online: Apr","PeriodicalId":9091,"journal":{"name":"Biology of the neonate","volume":"90 4","pages":"226-8"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25991838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}