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      Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study

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          Abstract

          Objective To determine whether exposure to any antenatal corticosteroids is associated with a lower rate of death at each gestational age at which administration is currently recommended.

          Design Prospective cohort study.

          Settings 300 participating neonatal intensive care units of the Pediatrix Medical Group in the United States.

          Participants 117 941 infants 23 0/7 to 34 6/7 weeks’ gestational age born between 1 January 2009 and 31 December 2013.

          Exposure Any antenatal corticosteroids.

          Main outcomes measures Death or major hospital morbidities analyzed by gestational age and exposure to antenatal corticosteroids with models adjusted for birth weight, sex, mode of delivery, and multiple births.

          Results Infants exposed to antenatal corticosteroids (n=81 832) had a significantly lower rate of death before discharge at each gestation 29 weeks or less, 31 weeks, and 33-34 weeks compared with infants without exposure (range of adjusted odds ratios 0.32 to 0.55). The number needed to treat with antenatal corticosteroids to prevent one death before discharge increased from six at 23 and 24 weeks’ gestation to 798 at 34 weeks’ gestation. The rate of survival without major hospital morbidity was higher among infants exposed to antenatal corticosteroids at the lowest gestations. Infants exposed to antenatal corticosteroids had lower rates of severe intracranial hemorrhage or death, necrotizing enterocolitis stage 2 or above or death, and severe retinopathy of prematurity or death compared with infants without exposure at all gestations less than 30 weeks and most gestations for infants born at 30 weeks’ gestation or later.

          Conclusion Among infants born from 23 to 34 weeks’ gestation, antenatal exposure to corticosteroids compared with no exposure was associated with lower mortality and morbidity at most gestations. The effect size of exposure to antenatal corticosteroids on mortality seems to be larger in infants born at the lowest gestations.

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          Most cited references19

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          Early CPAP versus surfactant in extremely preterm infants.

          There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants. We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen). A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups. The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.) 2010 Massachusetts Medical Society
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            Intensive care for extreme prematurity--moving beyond gestational age.

            Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients. We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone. The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 [ClinicalTrials.gov] and NCT00009633 [ClinicalTrials.gov].). Copyright 2008 Massachusetts Medical Society.
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              Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia.

              Bronchopulmonary dysplasia (BPD) is the focus of many intervention trials, yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians. Thus, we wished to define BPD by a standardized oxygen saturation monitoring at 36 weeks corrected age, and compare this physiologic definition with the standard clinical definition of BPD based solely on oxygen administration. A total of 199 consecutive very low birthweight infants (VLBW, 501 to 1500 g birthweight) were assessed prospectively at 36+/-1 weeks corrected age. Neonates on positive pressure support or receiving >30% supplemental oxygen were assigned the outcome BPD. Those receiving or =88% for 60 minutes) or "BPD" (saturation < 88%). At the conclusion of the test, all infants were returned to their baseline oxygen. Safety (apnea, bradycardia, increased oxygen use), inter-rater reliability, test-retest reliability, and validity of the physiologic definition vs the clinical definition were assessed. A total of 199 VLBW were assessed, of whom 45 (36%) were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks corrected age. The physiologic definition identified 15 infants treated with oxygen who successfully passed the saturation monitoring test in room air. The physiologic definition diagnosed BPD in 30 (24%) of the cohort. All infants were safely studied. The test was highly reliable (inter-rater reliability, kappa=1.0; test-retest reliability, kappa=0.83) and highly correlated with discharge home in oxygen, length of hospital stay, and hospital readmissions in the first year of life. The physiologic definition of BPD is safe, feasible, reliable, and valid and improves the precision of the diagnosis of BPD. This may be of benefit in future multicenter clinical trials.
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                Author and article information

                Contributors
                Role: clinical fellow
                Role: vice president and co-director
                Role: senior vice president and director
                Role: senior research statistician
                Role: professor
                Role: professor
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2017
                29 March 2017
                : 356
                : j1039
                Affiliations
                [1 ]Division of Neonatology, University of Alabama at Birmingham, AL 35233, USA
                [2 ]Center for Research, Education, and Quality, Pediatrix Medical Group and MEDNAX, Sunrise, FL, USA
                [3 ]Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, NC, USA
                [4 ]Department of Obstetrics and Gynecology, University of California, Irvine, CA, USA
                Author notes
                Correspondence to: W A Carlo wcarlo@ 123456peds.uab.edu
                Article
                trac035191
                10.1136/bmj.j1039
                5373674
                28351838
                a7b73ea0-a674-473f-828e-9b9522dd11bf
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 February 2017
                Categories
                Research
                1779

                Medicine
                Medicine

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