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      Ventilation before Umbilical Cord Clamping Improves the Physiological Transition at Birth

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          Abstract

          The transition from a fetus to a neonate at birth represents a critical phase in our life. Most infants make this transition without complications, but preterm infants usually require some form of assistance due to immature cardiopulmonary systems that predispose them to lifelong sequelae. As the incidence of preterm birth is increasing, there is now an urgent need for the development of management strategies that facilitate this transition, which will likely include improved strategies for the management of the maternal third stage of labor. For instance, recent studies on the physiological transition at birth have led to the discovery that establishing ventilation in the infant before the umbilical cord is clamped greatly stabilizes the cardiovascular transition at birth. While most benefits of delayed clamping previously have been attributed to an increase in placenta to infant blood transfusion, clearly there are other significant benefits for the infant, which are not well understood. Nevertheless, if ventilation can be established before cord clamping in a preterm infant, the large adverse changes in cardiac function that normally accompanies umbilical cord clamping can be avoided. As preterm infants have an immature cerebral vascular bed, large swings in cardiovascular function places them at high risk of cerebral vascular rupture and the associated increased risk of mortality and morbidity. In view of the impact that cord clamping has on the cardiovascular transition at birth, it is also time to re-examine some of the strategies used in the management of the third stage of labor. These include the appropriate timing of uterotonic administration in relation to delivery of the infant and placenta. As there is a lack of evidence on the effects these individual practices have on the infant, there is a necessity to improve our understanding of their impact in order to develop strategies that facilitate the transition to newborn life.

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          Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes.

          Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord more than one minute after the birth or when cord pulsation has ceased. The benefits and potential harms of each policy are debated. To determine the effects of early cord clamping compared with late cord clamping after birth on maternal and neonatal outcomes We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 February 2013). Randomised controlled trials comparing early and late cord clamping. Two review authors independently assessed trial eligibility and quality and extracted data. We included 15 trials involving a total of 3911 women and infant pairs. We judged the trials to have an overall moderate risk of bias. Maternal outcomes: No studies in this review reported on maternal death or on severe maternal morbidity. There were no significant differences between early versus late cord clamping groups for the primary outcome of severe postpartum haemorrhage (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.65 to 1.65; five trials with data for 2066 women with a late clamping event rate (LCER) of ~3.5%, I(2) 0%) or for postpartum haemorrhage of 500 mL or more (RR 1.17 95% CI 0.94 to 1.44; five trials, 2260 women with a LCER of ~12%, I(2) 0%). There were no significant differences between subgroups depending on the use of uterotonic drugs. Mean blood loss was reported in only two trials with data for 1345 women, with no significant differences seen between groups; or for maternal haemoglobin values (mean difference (MD) -0.12 g/dL; 95% CI -0.30 to 0.06, I(2) 0%) at 24 to 72 hours after the birth in three trials. Neonatal outcomes: There were no significant differences between early and late clamping for the primary outcome of neonatal mortality (RR 0.37, 95% CI 0.04 to 3.41, two trials, 381 infants with a LCER of ~1%), or for most other neonatal morbidity outcomes, such as Apgar score less than seven at five minutes or admission to the special care nursery or neonatal intensive care unit. Mean birthweight was significantly higher in the late, compared with early, cord clamping (101 g increase 95% CI 45 to 157, random-effects model, 12 trials, 3139 infants, I(2) 62%). Fewer infants in the early cord clamping group required phototherapy for jaundice than in the late cord clamping group (RR 0.62, 95% CI 0.41 to 0.96, data from seven trials, 2324 infants with a LCER of 4.36%, I(2) 0%). Haemoglobin concentration in infants at 24 to 48 hours was significantly lower in the early cord clamping group (MD -1.49 g/dL, 95% CI -1.78 to -1.21; 884 infants, I(2) 59%). This difference in haemoglobin concentration was not seen at subsequent assessments. However, improvement in iron stores appeared to persist, with infants in the early cord clamping over twice as likely to be iron deficient at three to six months compared with infants whose cord clamping was delayed (RR 2.65 95% CI 1.04 to 6.73, five trials, 1152 infants, I(2) 82%). In the only trial to report longer-term neurodevelopmental outcomes so far, no overall differences between early and late clamping were seen for Ages and Stages Questionnaire scores. A more liberal approach to delaying clamping of the umbilical cord in healthy term infants appears to be warranted, particularly in light of growing evidence that delayed cord clamping increases early haemoglobin concentrations and iron stores in infants. Delayed cord clamping is likely to be beneficial as long as access to treatment for jaundice requiring phototherapy is available.
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            Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes.

            Optimal timing for clamping the umbilical cord at preterm birth is unclear. Early clamping allows for immediate transfer of the infant to the neonatologist. Delaying clamping allows blood flow between the placenta, the umbilical cord and the baby to continue. The blood which transfers to the baby between birth and cord clamping is called placental transfusion. Placental transfusion may improve circulating volume at birth, which may in turn improve outcome for preterm infants. To assess the short- and long-term effects of early rather than delaying clamping or milking of the umbilical cord for infants born at less than 37 completed weeks' gestation, and their mothers. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 May 2011). We updated this search on 26 June 2012 and added the results to the awaiting classification section. Randomised controlled trials comparing early with delayed clamping of the umbilical cord and other strategies to influence placental transfusion for births before 37 completed weeks' gestation. Three review authors assessed eligibility and trial quality. Fifteen studies (738 infants) were eligible for inclusion. Participants were between 24 and 36 weeks' gestation at birth. The maximum delay in cord clamping was 180 seconds. Delaying cord clamping was associated with fewer infants requiring transfusions for anaemia (seven trials, 392 infants; risk ratio (RR) 0.61, 95% confidence interval (CI) 0.46 to 0.81), less intraventricular haemorrhage (ultrasound diagnosis all grades) 10 trials, 539 infants (RR 0.59, 95% CI 0.41 to 0.85) and lower risk for necrotising enterocolitis (five trials, 241 infants, RR 0.62, 95% CI 0.43 to 0.90) compared with immediate clamping. However, the peak bilirubin concentration was higher for infants allocated to delayed cord clamping compared with immediate clamping (seven trials, 320 infants, mean difference 15.01 mmol/L, 95% CI 5.62 to 24.40). For most other outcomes (including the primary outcomes infant death, severe (grade three to four) intraventricular haemorrhage and periventricular leukomalacia) there were no clear differences identified between groups; but for many there was incomplete reporting and wide CIs. Outcome after discharge from hospital was reported for one small study; there were no significant differences between the groups in mean Bayley II scores at age seven months (corrected for gestation at birth (58 children)).No studies reported outcomes for the women. Providing additional placental blood to the preterm baby by either delaying cord clamping for 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion, better circulatory stability, less intraventricular haemorrhage (all grades) and lower risk for necrotising enterocolitis. However, there were insufficient data for reliable conclusions about the comparative effects on any of the primary outcomes for this review.
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              Distribution of blood between infant and placenta after birth.

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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                20 October 2014
                2014
                : 2
                : 113
                Affiliations
                [1] 1The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University , Melbourne, VIC, Australia
                [2] 2Department of Obstetrics and Gynaecology, Monash University , Melbourne, VIC, Australia
                [3] 3Department of Pediatrics, Leiden University Medical Centre , Leiden, Netherlands
                Author notes

                Edited by: Heber C. Nielsen, Tufts School of Medicine, USA

                Reviewed by: Drucilla Jane Roberts, Massachusetts General Hospital, USA; Jonathan Michael Klein, University of Iowa, USA

                *Correspondence: Stuart B. Hooper, The Ritchie Centre, Monash Institute of Medical Research, 27-31 Wright Street, Clayton, VIC 3168, Australia e-mail: stuart.hooper@ 123456monash.edu

                This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics.

                Article
                10.3389/fped.2014.00113
                4203108
                25368858
                22885902-2758-4c9d-bd71-2e20d1b93091
                Copyright © 2014 Bhatt, Polglase, Wallace, te Pas and Hooper.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 July 2014
                : 03 October 2014
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 64, Pages: 8, Words: 7385
                Categories
                Pediatrics
                Review Article

                neonatal,preterm birth,transition,umbilical cord clamping,delayed cord clamping

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