How To Know The Effects Of Cord Clamping

Transcription

1 Delayed Cord Clamping: Worth the Wait? Ryan M. McAdams MD Disclosure Neither I nor any member of my immediate family has a financial relationship or interest with any proprietary entity producing health care goods or services related to the content of this CME activity. My content will not include discussion/ reference of any commercial products or services. I do not intend to discuss an unapproved/ investigative use of commercial products/ devices. Objectives Discuss risks and benefits of delayed cord clamping in term and preterm infants Understand the effects of cord clamping at different times on maternal and neonatal outcomes Apply this information to improve patient outcomes Assumption of evidence Immediate umbilical cord clamping (CC) after delivery is the current practice in U.S. CDC estimates 3,952,937 births in 2012 Early CC practiced on millions of babies What is the evidence for this practice? Live births and fertility rates: United States,

2 Etiology of current practice Not totally clear Early 1900 s, pregnant mothers routinely given general anesthesia before delivery Newborns had severe respiratory depression Doctors quickly clamped and cut the umbilical cord to prevent babies from receiving further chloroform or ether being given to their unconscious mothers 2

3 Umbilical Cord Clamping (CC) 3 rd stage of labor Active management to reduce postpartum hemorrhage: Prophylactic uterotonic drug Immediate umbilical CC Controlled cord traction Prophylactic uterotonic drugs clearly reduce risk of major hemorrhage Umbilical CC timing does not appear to have a major impact on the risk of hemorrhage Cochrane review of 15 trials, 3911 women and infant pairs No significant difference in postpartum hemorrhage rates when early & late CC compared (RR 1.04, 95% CI 0.65 to 1.65) Timing of Umbilical CC Deferring CC will allow a larger placental transfusion that may affect the newborn A neglected topic for decades, there is now growing interest in assessing the effects of placental transfusion for both term and preterm infants McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev The umbilical cord (UC) In a full term neonate ~50 cm (20 in) in length 2 cm (0.75 in) in diameter Umbilical artery: 3 mm intravital diameter Umbilical vein: 6 mm intravital diameter Blood flow 115 ml / min / kg at 20 weeks 64 ml / min / kg at 40 weeks In absence of external interventions The UC occludes shortly after birth Explained both by a swelling and collapse of Wharton's jelly in response to a reduction in temperature Vasoconstriction of the blood vessels by smooth muscle contraction In air at 18 C, this physiological clamping will take three minutes or less 3

4 Umbilical vessel closure after birth Umbilical artery closure begins after 15 sec Functional closure by 45 se Umbilical vein closure begins after 15 sec Diameter decreases significantly by 1-2 min Term baby and placenta blood volumes Term fetus blood volume is ~70 ml/kg Placenta contains 45 ml/kg of blood Total fetoplacental volume 115 ml/kg Preterm baby and placenta blood volumes Premature infants have larger placenta compared to term neonates Preterm fetus blood volume is ~90 ml/kg Fetoplacental volume is 150 ml at 26 weeks gestation Up to 2/3 of the preterm infant s blood amount can be distributed in the placenta at the time of delivery Placental transfusion after birth One quarter (40 ml) of blood enters the term infant within 15 sec One half (80 ml) within 60 sec The corresponding volume for a 70 kg adult would be 1600 ml in a minute Factors influencing placental transfusion Timing to clamp the umbilical cord Position at which the delivered infant is held relative to the placenta in utero Timing of onset of breathing by the infant Strength of uterine contractions with or without use of oxytocin 4

5 Uterine Contraction and Maternal Hypotension Oxytocin given at the onset of 3rd stage of labor augments placental transfusion In the absence of uterine contraction, placental transfusion occurs if the infant is in the dependent position Residual placental blood volume shown to correlate inversely with maternal blood pressure during the first 20 to 40 sec Ogata ES, et al. The effect of time of cord clamping and maternal blood pressure on placental transfusion with cesarean section. Am J Obstet Gynecol 1977;128: Yao AC, et al. Placental transfusion rate and uterine contraction. Lancet 1968;1: Delayed cord clamping (DCC) Allows extra transfer of fetal blood from the placenta to the infant Results in ~10-15 ml/kg of additional whole cord blood for a VLBW infant 8% - 24% increase in blood volume with DCC of sec in preterm infants Aladangady N, et al. Infants blood volume in a controlled trial of placental transfusion at preterm delivery. Pediatrics 2006; 117(1): Aladangady N, et al. Is it possible to promote placental transfusion at preterm delivery? Pediatr Res. 1998;44:454. Premature Infants Preterm birth: Affects 11.99% of US pregnancies (2010 data) Global Statistics (2005 data) 9.6% of all births preterm (12.9 million births) 10.9 million (~85%) in Africa and Asia ~0.5 million in Europe ~0.5 million in North America 0.9 million in Latin America and Caribbean Beck, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization. Vol 88 (1), Jan 2010,

6 Preterm births in the US ~10,000 infants born prematurely per wk 600 (6%) of these are ELBW ~90% of ELBW neonates will receive at least one RBC transfusion Martin JA, et al. Births: final data for 2008 national Vital Statistics Reports. Centers Disease Control Prevent 2009;57:7. Maier RJ, et al. Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g. J Pediatr 2000;136: Sacher RA, et al. Blood component therapy during the neonatal period: a national survey of red cell transfusion practices, Transfusion 1990;30: Premature infants at risk for: Respiratory problems Blood pressure instability Intraventricular hemorrhage (IVH) Neurodevelopmental delays Cerebral palsy Reported CP prevalence rates vary from 19 to 152 per 1,000 live births for very premature and very low-birth-weight infants Premature infants at risk for: Anemia of prematurity (AOP) Hyperbilirubinemia Necrotizing Enterocolitis Longer hospital stays Anemia Neonatal anemia and low iron stores not immediately seen as serious or lifethreatening If more serious consequences of CC considered, the need for timing and documentation of the intervention would be obvious 6

7 Anemia of prematurity (AOP) Typically occurs at 4 to 6 weeks after birth in infants < 32 weeks gestation. Onset inversely proportional to GA at birth Causes: Reduced RBC life span 60 to 80 days: Term infants 45 to 50 days: Extremely low birth weight infants Blood loss from phlebotomy 2 to 4 ml/kg per week Iron depletion May impair recovery from AOP Lin, JC et al. Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics. 2000;106(2):E19. AOP Many infants asymptomatic despite having Hgb values < 7 g/dl Other infants symptomatic at similar or even higher Hgb levels Tachycardia, poor weight gain, requirement of supplemental oxygen, or episodes of apnea or bradycardia The Anemia Argument Blood is a scarce and costly resource Risk of multiple donor exposures Iron stores at birth show large individual variations, but correlate with later iron status in infancy Iron deficiency & anemia in infancy may be associated with later cognitive deficits Michaelsen KJ, et al. A longitudinal study of iron status in healthy Danish infants: effects of early iron status, growth velocity and dietary factors. Acta Paediatr 1995;84: Grantham-Mcgregor S, et al. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649 66S. Lozoff B, et al. Iron deficiency and iron therapy effects on infant developmental test performance. Paediatrics 1987;79: Algarín C, et al. Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. Dev Med Child Neurol

8 Placental transfusion Immediately after birth placental blood continues to flow in the direction of the baby For a term infant, placental transfusion increases total volume of blood by ~ 30% Within a few hours, additional plasma is lost to the circulation, leaving a high red cell mass Red cell mass broken down in 1 st 2 mo of age and iron is re-used or stored Differences in clinical trial designs Summary of literature on CC Associated with imprecision in quantitating the increase in RBC volume/mass achieved by DCC Placental blood volume transfused into the neonate varied depending on clamp time No consensus about definition of ECC or DCC regarding time intervals How early is early? Term infants Most trials: <15 s Immediately following birth Preterm infants Immediately Up to 10 s Up to 20 s Hutton E. Late versus early clamping of the umbilical cord in full-term neonates, systematic review and meta-analysis of controlled trials. JAMA 2007;297: Mercer J. Current best evidence: a review of the literature on umbilical cord clamping. Journal of Midwifery and Women s Health 2001;46(6):

9 How delayed is delayed? Term Infants 30-45s 3 min (most common) Up to 10 min Until cessation of cord pulsations Preterm Infants s or 45 s Hutton E. Late versus early clamping of the umbilical cord in full-term neonates, systematic review and meta-analysis of controlled trials. JAMA 2007;297: Mercer J. Current best evidence: a review of the literature on umbilical cord clamping. Journal of Midwifery and Women s Health 2001;46(6): Early Cord Clamping (ECC): Studies from the 1960 s Infants with decreased Blood volume, red cell volume and hematocrits Central venous and atrial pressures Pulmonary and aortic pressures Differences well compensated for and tolerated in full-term newborn infants Theoretical risk in premature infants, in cesarean section babies and following complicated deliveries Polycythemia and CC Concerns about polycythemia raised repeatedly DCC so frequently identified as a cause of polycythemia that it has become accepted as an unsubstantiated fact in the literature Symptomatic polycythemia not seen in any RCTs Polycythemia and CC Blood volume being denied to baby unknown and unpredictable What is higher risk? ECC: A baby with decreased blood viscosity and low blood pressure due to hypovolemia DCC: A baby with increased blood viscosity and a normal blood pressure Clinical trials DCC versus ECC Preterm neonates, several clinical trials with mixed results Favorable (pro-dcc): Improved circulatory hemodynamics Better cardiopulmonary adaptation to extrauterine life Diminished need for RBC transfusions Decreased IVH after DCC Term infants Concerns*: (anti-dcc) Results in hypervolemia with respiratory distress, Erythrocytosis with plethora and hyperviscosity Hyperbilirubinemia *Theoretical DCC vs ECC in preterm infants: Major benefits based on RCTs DCC Raju TN. Timing of umbilical cord clamping after birth for optimizing placental transfusion. Curr Opin Pediatr

10 DCC: Benefits in term infants Increased Hgb and Hct in early neonatal period Total body iron stores, 2 4 mo of age Circulating ferritin level, 2 4 mo of age Decreased Incidence of iron-deficiency anemia, around 4 mo of age DCC: Benefits in preterm infants Increased Hgb and Hct during the early neonatal period Systemic blood pressure between 4 and 24 h of age Blood volume Urine output during the first 48 h Cerebral oxygenation Transfer of autologous stem cells Myocardial function (systolic time intervals and cardiac output) DCC: Benefits in preterm infants Decreased Need for inotropic medications Need for blood transfusions for anemia Incidence of intraventricular hemorrhage (all grades) DCC: Adverse outcomes Increased Peak bilirubin values during the first week in preterm infants Need for phototherapy in both preterm and term infants Maternal and neonatal outcomes unchanged by DCC vs. ECC Maternal Any or severe postpartum hemorrhage Incidence of retained placenta Need for maternal blood transfusions, operative delivery, episiotomy Newborn Apgar scores, need for resuscitation, or umbilical cord ph values Frequency of respiratory distress Severe intraventricular hemorrhage or periventricular leukomalacia Incidence of polycythemia Requirement of exchange transfusions Bayley II Scale of Development at 7 months of age What has prevented DCC from becoming routine practice? Cord blood gases Resuscitation Concern regarding nuchal cord Cord blood banking Need for neonatal blood group in rhesus negative mothers Pediatricians waiting to get the baby 10

11 Not All or None Likely situations where ECC is indicated Ruptured vasa previa results in fetal blood loss & need for urgent delivery Baby likely hypovolemic Waiting for a placental transfusion may be fruitless due to continued loss of blood from the cord vein May create a placental transfusion by cord milking and lowering the baby below the placenta RCTs unlikely to study these situations Assuming that ECC will always be the best management not evidence based Unresolved issues What is the optimal position to hold the infant in relation to the placenta, especially after cesarean birth? What is the optimal time to CC in high-risk mothers? HIV, hepatitis A, B, C positive Placental abruption or previa Unresolved issues What is the optimal time to CC for highrisk infants? Multiple gestations At risk fetal polycythemia IUGR, LGA, IDM What will the effect of DCC be on umbilical cord blood gases? Should NRP be started before CC? Delay is preferable to error. Thomas Jefferson Conclusions: Changing Times One of the problems of evidence-based medicine is how to handle interventions that entered medical practice without proper evidence To avoid negating clinical experience (>100 yrs with ECC) evidence is needed to remove these interventions from clinical practice Changing Times DCC since the 1 st human birth ECC is the newer intervention Introducing a new intervention requires evidence beyond a reasonable doubt that it will produce a benefit Removing an intervention does not require the same level of proof if harm is being caused 11

12 Conclusions Clamping of the umbilical cord soon after birth has no physiological rationale and may cause harm (regarding iron status) The terms early and delayed cord clamping should be abandoned since they are misleading, suggest unsafe practice, and are inconsistent Describe the procedure: e.g., CC at <15 s, CC at 45 s Documenting timing of CC Record CC time in the medical records of the mother and her infant Alert pediatric/nicu team to monitor infants bilirubin status and to implement appropriate follow-up plans Possible increased need for phototherapy, in settings where early discharge of term and late preterm infants is a common practice Wait a Minute Incorporate the practice of cord clamping after at least 30 s, whenever feasible, especially for preterm infants Benefits outweigh risks Motto should be to, Just wait a minute, and not, Just wait a second. The Iron Minute should precede the Golden Minute References McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev Jul 11;7:CD Mercer JS et al. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006; 117(4): Mercer JS, et al. Seven-month developmental outcomes of very low birth weight infants enrolled in a randomized controlled trial of delayed versus immediate cord clamping. Journal of Perinatology 2010;30 (1):11 6. Philip AGS, Teng SS. Role of respiration in effecting transfusion at cesarean section. Biol Neonate 1977;31: Philip AGS, Saigal S. When should we clamp the umbilical cord? NeoReviews 2004;5:e Rabe H, Wacker A, Hu lskamp G, et al. A randomized controlled trial of delayed cord clamping in very low birth weight preterm infants. Eur J Pediatr 2000;159: Rabe H. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev Sisson TRC, Knutson S, Kendall N. The blood volume of infants: IV. Infants born by cesarean section. Am J Obstet Gyenecol. 1973;117: Sommers R, et al. Hemodynamic effects of delayed cord clamping in premature infants. Pediatrics. 2012;129(3):e Yao AC, Lind J. Effect of gravity on placental transfusion. Lancet. 1969;2: Yao AC, Moinian M, Lind J. Distribution of blood between the infant and the placenta after birth. Lancet 1969;7626(2): Yao AC, Hirvensalo M, Lind J. Placental transfusion rate and uterine contraction. Lancet 1968;1: Yao AC, Lind J. Blood volume in the asphyxiated term neonate. Biol Neonate 1972;21: Yao AC, Wist A, Lind T. The blood volume of the newborn infant delivered by caesarean section. Acta Paediatr Scand 1967;56: