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      Association of Deferred vs Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates

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      , MD, DM, MSc 1 , 2 , 3 , , , MD, MSc 4 , 5 , , DM, MSc 2 , 3 , , MD 2 , 3 , , MD, MSc 2 , 3 , , MD 2 , 3
      JAMA Network Open
      American Medical Association

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          Abstract

          This cohort study compares neonatal outcomes after deferred cord clamping vs immediate cord clamping in extremely low-gestational-age neonates.

          Key Points

          Question

          Is deferred cord clamping associated with reduced odds of severe neurological injury or mortality in extremely low-gestational-age neonates?

          Findings

          In this cohort study of 4680 extremely preterm neonates (22-28 weeks of gestation), 1852 received deferred cord clamping and 2828 received immediate cord clamping. Neonates who received deferred cord clamping had lower odds of severe neurological injury or mortality than neonates who received immediate cord clamping.

          Meaning

          In extremely low-gestational-age neonates, deferred cord clamping is associated with reduced risk for severe neurological injury or mortality.

          Abstract

          Importance

          Deferred cord clamping (DCC) is recommended for term and preterm neonates to reduce neonatal complications. Information on the association of DCC with outcomes for extremely low-gestational-age neonates is limited.

          Objective

          To compare neonatal outcomes after DCC and immediate cord clamping (ICC) in extremely low-gestational-age neonates.

          Design, Setting, and Participants

          In this retrospective cohort study, eligible neonates born between January 1, 2011, and December 31, 2015, were divided into 2 groups: DCC and ICC. Neonates were recruited from tertiary neonatal intensive care units participating in the Canadian Neonatal Network, and analysis began in January 2018. Neonates were eligible if they were born at 22 to 28 weeks’ gestational age and admitted to a participating Canadian Neonatal Network neonatal intensive care unit during the study period. Neonates who were born outside a tertiary-level neonatal intensive care unit, were moribund at birth, needed palliative care before delivery, had major congenital anomalies, or lacked cord clamping information were excluded.

          Main Outcomes and Measures

          Composite of severe neurological injury (intraventricular hemorrhage grade ≥3 with or without persistent periventricular echogenicity) or mortality before discharge.

          Results

          Of 8221 admitted neonates, 4680 were included in the study, of whom 1852 (39.6%) received DCC and 2828 (60.4%) received ICC. There were 974 (52.7%) male neonates in the DCC group and 1540 (54.5%) male neonates in the ICC group. Median (interquartile range) gestational age was 27 (25-28) weeks for the DCC group and 26 (25-27) weeks for the ICC group. Median (interquartile range) birth weight was 930 (760-1120) g and 870 (700-1060) g for DCC and ICC groups, respectively. Neonates who received DCC had significantly reduced odds of the composite outcome of severe neurological injury or mortality (adjusted odds ratio [AOR], 0.80; 95% CI, 0.67-0.96), mortality (AOR, 0.74; 95% CI, 0.59-0.93), and severe neurological injury (AOR, 0.80; 95% CI, 0.64-0.99). The odds of bronchopulmonary dysplasia (AOR, 1.00; 95% CI, 0.84-1.19), retinopathy of prematurity stage 3 or higher (AOR, 0.94; 95% CI, 0.71-1.25), necrotizing enterocolitis stage 2 or higher (AOR, 0.86; 95% CI, 0.66-1.12), late-onset sepsis (AOR, 1.02; 95% CI, 0.85-1.22), and receipt of 2 or more blood transfusions (AOR, 0.93; 95% CI, 0.79-1.10) did not differ between the groups. Propensity score–matched analyses revealed lower odds of mortality (AOR, 0.79; 95% CI, 0.65-0.95), late-onset sepsis (AOR, 0.81; 95% CI, 0.69-0.95), and treatment for hypotension (AOR, 0.75; 95% CI, 0.60-0.95) in the DCC group.

          Conclusions and Relevance

          In this study of extremely low-gestational-age neonates who received DCC or ICC, DCC was associated with reduced risk for the composite outcome of severe neurological injury or mortality.

          Related collections

          Most cited references40

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          Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.

          Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated web site (http://www.strobe-statement.org) should be helpful resources to improve reporting of observational research.
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            • Article: not found

            The International Classification of Retinopathy of Prematurity revisited.

            (2005)
            The International Classification of Retinopathy of Prematurity (ICROP) was published in 2 parts, the first in 1984 and later expanded in 1987. It was a consensus statement of an international group of retinopathy of prematurity experts. The original classification has facilitated the development of large multicenter clinical treatment trials and furthered our understanding of this potentially blinding disorder. With improved imaging techniques in the nursery, we are able to offer a more quantitative approach to some of the characteristics described in the ICROP. An international group of pediatric ophthalmologists and retinal specialists has developed a consensus document that revises some aspects of ICROP. Few modifications were felt to be needed. The aspects that differ from the original classification include introduction of (1) the concept of a more virulent form of retinopathy observed in the tiniest babies (aggressive, posterior ROP), (2) a description of an intermediate level of plus disease (pre-plus) between normal posterior pole vessels and frank plus disease, and (3) a practical clinical tool for estimating the extent of zone I.
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              Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period.

              The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs or symptoms. A total of 119 infants were identified and the neonatal oxygen requirements of these infants were compared with those of 486 infants who had normal pulmonary function. A requirement for oxygen at 28 days of life had a positive predictive value for abnormal pulmonary findings at the time of follow-up of only 38%, whereas 31% of those with normal pulmonary findings at the time of follow-up were still receiving oxygen at this age. The need for oxygen at 28 days was a good predictor of abnormal findings in infants of greater than or equal to 30 weeks' gestational age at birth but became increasingly less useful as gestational age decreased. It was found that, irrespective of gestational age at birth, the requirement for additional oxygen at 36 weeks' corrected postnatal gestational age was a better predictor of abnormal outcome, increasing the positive predictive value to 63%. The prediction of a normal outcome remained 90% for infants not receiving oxygen at this corrected gestational age.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                29 March 2019
                March 2019
                29 March 2019
                : 2
                : 3
                : e191286
                Affiliations
                [1 ]Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
                [2 ]Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
                [3 ]Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
                [4 ]Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
                [5 ]Department of Pediatrics, Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
                Author notes
                Article Information
                Accepted for Publication: February 6, 2019.
                Published: March 29, 2019. doi:10.1001/jamanetworkopen.2019.1286
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Lodha A et al. JAMA Network Open.
                Corresponding Author: Abhay Lodha, MD, DM, MSc, Department of Pediatrics, University of Calgary, Foothills Medical Centre, C211, 1403 29 St NW, Calgary, AB T2N 2T9, Canada ( aklodha@ 123456ucalgary.ca ).
                Author Contributions: Drs Lodha and Shah had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: All authors.
                Acquisition, analysis, or interpretation of data: Lodha, Shah, Rabi.
                Drafting of the manuscript: Lodha, Rabi.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Lodha, Rabi.
                Administrative, technical, or material support: Shah, Rabi, Abou Mehrem, Singhal.
                Supervision: Rabi, Singhal.
                Conflict of Interest Disclosures: None reported.
                Group Information: The Canadian Neonatal Network Investigators are Prakesh S. Shah, MD, MSc, and Shoo K. Lee, MBBS, PhD (Mount Sinai Hospital, Toronto, Ontario, Canada); Jaideep Kanungo, MD (Victoria General Hospital, Victoria, British Columbia, Canada); Joseph Ting, MD (B.C. Women’s Hospital and Health Centre, Vancouver, British Columbia, Canada); Zenon Cieslak, MD (Royal Columbian Hospital, New Westminster, British Columbia, Canada); Rebecca Sherlock, MD (Surrey Memorial Hospital, Surrey, British Columbia, Canada); Wendy Yee, MD (Foothills Medical Centre, Calgary, Alberta, Canada); Jennifer Toye, MD (Royal Alexandra Hospital, Edmonton, Alberta, Canada); Zarin Kalapesi, MD (Regina General Hospital, Regina, Saskatchewan, Canada); Koravangattu Sankaran, MD, MBBS, and Sibasis Daspal, MD (Royal University Hospital, Saskatoon, Saskatchewan, Canada); Mary Seshia, MBChB (Winnipeg Health Sciences Centre, Winnipeg, Manitoba, Canada); Ruben Alvaro, MD (St. Boniface General Hospital, Winnipeg, Manitoba); Amit Mukerji, MD (Hamilton Health Sciences Centre, Hamilton, Ontario, Canada); Orlando Da Silva, MD, MSc (London Health Sciences Centre, London, Ontario, Canada); Chuks Nwaesei, MD (Windsor Regional Hospital, Windsor, Ontario, Canada); Michael Dunn, MD (Sunnybrook Health Sciences Centre, Toronto, Ontario); Brigitte Lemyre, MD (Children’s Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario, Canada); Kimberly Dow, MD (Kingston General Hospital, Kingston, Ontario, Canada); Ermelinda Pelausa, MD (Jewish General Hospital, Montréal, Québec, Canada); Anie Lapoint, MD (Hôpital Sainte-Justine, Montréal, Québec); Christine Drolet, MD, and Bruno Piedboeuf, MD (Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec, Canada); Martine Claveau, MSc, LLM, NNP, and Marc Beltempo, MD (Montreal Children’s Hospital at McGill University Health Centre, Montréal, Québec); Valerie Bertelle, MD, and Edith Masse, MD (Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada); Roderick Canning, MD (Moncton Hospital, Moncton, New Brunswick, Canada); Hala Makary, MD (Dr. Everett Chalmers Hospital, Fredericton, New Brunswick, Canada); Cecil Ojah, MBBS, and Luis Monterrosa, MD (Saint John Regional Hospital, Saint John, New Brunswick, Canada); Julie Emberley, MD (Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland, Canada); and Jehier Afifi, MB BCh, MSc (IWK Health Centre, Halifax, Nova Scotia, Canada).
                Additional Contributions: We thank the data abstractors from the Canadian Neonatal Network and all of the staff at the Canadian Neonatal Network coordinating center for providing organizational support. Sarah Hutchinson, PhD, and Junmin Yang, MSc (biostatistician), from the Maternal-Infant Care Research Center provided editorial and statistical support in the preparation of the manuscript. These individuals did not receive compensation outside of their typical salary. The Maternal-Infant Care Research Center is supported by grant funding from the Canadian Institutes of Health Research (grant CTP 87518), the Ontario Ministry of Health, and support from Mount Sinai Hospital.
                Article
                zoi190070
                10.1001/jamanetworkopen.2019.1286
                6450317
                30924898
                8f2f3e00-a248-40f6-8bc6-58502c387f5e
                Copyright 2019 Lodha A et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 13 October 2018
                : 6 February 2019
                : 6 February 2019
                Categories
                Research
                Original Investigation
                Online Only
                Pediatrics

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