American Academy of Pediatrics 2013 Annual Conference and Exhibition Orlando, FL

Transcription

1 Optimal Timing for Clamping of the Umbilical Cord after Birth American Academy of Pediatrics 2013 Annual Conference and Exhibition Orlando, FL Tonse N. K. Raju, MD, DCH Chief, Pregnancy and Perinatology Branch Eunice Kennedy Shriver National Institute of Child Health & Human Development National Institutes of Health Bethesda, MD

2 Greetings from the NIH National Library of Medicine Home of the PubMed NIH-Building 1 Director s Office Eunice Kennedy Shriver National Institute of Child Health and Human Development

3 An Icelandic Mare Giving Birth Umbilical cord clamping in horses Alexander, J. BMJ, Volume 306, 6 th February, 1993 Just delivered a colt 72 seconds after birth 79 seconds after birth In equine practice, it is mandatory... to wait until the umbilical cord has stopped pulsating before clamping it; this takes seconds...

4 Erasmus Darwin ( ) l Another thing very injurious to the child, is the tying and cutting of the navel string too soon; which should always be left till the child has not only repeatedly breathed but till all pulsation in the cord ceases. As otherwise the child is much weaker than it ought to be, a portion of the blood being left in the placenta, which ought to have been in the child... Zoonomia: Or the Laws of Organic Life 1794

5 How Many Papers on Cord Clamping? Since 2000: 291 publications Clinical trials (59) Physiological studies Cochrane & other systematic reviews (28) Editorials/opinions National and international professional group recommendations & guidelines

6 European Consensus Guidelines ILCOR All these bodies recommend delay in cord clamping for at least 30 seconds (and up to 2 minutes) in: WHO: All births SOGC and ECG: Preterm ILCOR and ACOG: Preterm when possible

7 ~10 ml/kg ~25 ml/kg Yao AC, Hirvensalo M, Lind J. Placental transfusion-rate and uterine contraction. Lancet Feb 24;1(7539):380-3.

8 Weigh the baby with cord intact ~120 grams

9 Blood Volume and Iron 1 minute delay ~70-80 ml extra blood 3 minute delay to ~ 100 ml extra blood. Added with plasma leads to ~ mg/kg of body weight of extra iron. Additional iron from may help prevent iron deficiency during the first year of life (Hutton EK, JAMA 2007)

10 Iron Deficiency Anemia ~ 3.6 billion are iron deficient, and ~ 2 billion are overtly iron deficiency anemic. In low and middle income countries, iron deficiency anemia is highly prevalent in women and in children <5 years( ~30%) Adequate iron is crucial for cognitive development In industrialized nations, iron supplements have reduced the prevalence of iron deficiency anemia

11 Meta Analysis: Term Infants 15 trials, 3011 women The Cochrane Library, Issue 7, 2013

12 Cochrane Systematic Review Term Infants: Conclusions Delaying clamping of the cord for at least 2-3 minutes. Higher mean birth weight, ~100 grams (95% CI: g) Higher hemoglobin (~2 g/dl CI: ) at birth Lower frequency of anemia 2-4 months Higher ferritin levels up to 4 months Fewer in early clamping required phototherapy RR 0.62 (CI: 041, 0.96) Indications for phototherapy varied; mean peak bilirubin values were similar No difference in postpartum hemorrhage in any of the five trials which measured this outcome No clinical polycythemia McDonald SJ and Middleton P Cochrane Library, Issue 7, 2013

13 Rabe H, et al. Cochrane Database of Systematic Reviews, 2012 Issue 8, August 15, 2012

14 2012 Cochrane Systematic Review Preterm Infants 15 trials, 738 infants weeks gestation Maximum delay: 180 seconds

15 2012 Cochrane Systematic Review Preterm Infants Main Results: Higher BP at 1 and 4 hours Transfusions for anemia: 7 trials, 392 infants, RR: 0.61 (95% CI 0.46 to 0.81) All grades of IVH 10 trials, 539 infants, RR 0.59 (95% CI, 0.41 to 0.85) NEC 5 trials, 241 infants, RR 0.62, (95% CI, 0.43 to 0.90)

16 2012 Cochrane Systematic Review Preterm Infants Higher peak bilirubin concentrations 7 trials, 320 infants, mean difference mmol/l (95% CI, 5.62 to 24.4) Polycythemia: no difference No clear difference in other outcomes Infant death Severe, grade 3 or 4 IVH PVL, RDS etc.

17 Other Physiological Studies in Preterm Infants

18 SVC-Normal and Low Flow Stable preterm infant: SVC flow 90 ml/kg/min; SVC velocity: 0.53 meters/s Preterm infant with low SVC flow, 20 ml/kg/min; SVC velocity: 0.2 meters/s Kluckow, M. Early Human Development, 2005, 81, 429

19 Regional Cerebral Blood Flow 39 infants, 24 to 32 weeks 24 cord clamped within 20 seconds 15 cord clamped seconds Cerebral oxygenation measured at 4, 24, 72 hours, and at 32 weeks of PMA (NIRS) In the experimental group-- 5%--6% higher hematocrit up to 72 hours Higher mean cerebral tissue oxygenation at 4 hours 69.9% versus hours: 71.3% versus 68.1% Baenziger O, et al, Pediatrics, 2007

20 Milking Versus Immediate Cord Clamping Probability of NOT needing a transfusion Hosono S, et al Arch Dis Fetal, 2008

21 BP and Urine Output Higher BP during the first 24 hours More urine output up through 72 hrs. Hosono S, et al Arch Dis Fetal, 2006

22 If delayed cord clamping is so good, why are we not doing it!!

23 Why are we Worried about Delaying Cord Clamping? Delay in initiation of resuscitation of asphyxia (term: nuchal cord variable deceleration) and respiratory support Problem in collecting cord blood for banking Hypothermia (especially in preterm infants) Polycythemia and jaundice/phototherapy

24 Counterpoints? It is precisely those that require resuscitation may benefit from delayed cord clamping The baby may be out, but the placenta keeps working Intrauterine asphyxia (nuchal cord) occludes umbilical vein, but fetal heart keeps pumping blood through umbilical arteries Asphyxiated fetuses are hypovolemic & anemic. Placental transfusion after birth is the first step of resuscitation (Huchon, DJR; BMJ, 2006) Warm blood from the placenta keeps the baby warmer Based on ~150 infants: Rabe et al, 2012 Cochrane Review

25 What Dr. George Gregory might say... It is physiology, stupid

26 Special Features of Fetal Circulation Placenta is the fetal lungs Umbilical vein carries oxygenated blood from the placenta Descending aorta (via umbilical arteries perfuses the low resistance placenta Brain gets the most oxygenated blood!

27 Fetal Circulation The oxygenated blood flows in from the placenta Enters the RA through ductus venosus Passes via the foramen ovale to LA and LV. LV output-->oxygenated blood to the brain Venous return to right flows via PA, and bypasses via PDA to the descending aorta Very little blood goes to and returns from the lungs

28 At Birth When all goes well Infant cries on obstetrician s hands Someone shouts time of birth, please Cord tied and the baby handed to the pediatric team Basic resuscitation done under the warmer, Apgar scores given Nurse shows off the baby Dad takes pictures 1

29 1 Meanwhile, behind the scene Physiological changes Infant cries FRC PVR RV output to the lungs Oxygenated blood returns to the LA, LA pressure, foramen ovale closes Increasing LV filling increases LV output Lung perfusion continues to increase & the PDA closes Cord is tied 2 Everything looks nice and quiet from the outside

30 When an infant does not cry and the cord is clamped Infant is handed to the resuscitation team; NRP steps started Bag and mask ventilation not effective: infant blue Intubated: stomach distends Infant is pale and gray ET in the stomach Senior takes over, re-inserts ETT Pulse <50; infant pale/gray/blue Someone says, she is hypovolemic, give 10 ml normal saline

31 Meanwhile, behind scene Immediate cord clamping simultaneous decrease in preload and increase in afterload Right ventricle (RV) filling volume drops due to the cessation of umbilical venous blood flow (of relatively oxygenated blood) from the placenta 40%-50% drop in RV output to LA No lung expansion---no pulmonary perfusion ---and no pulmonary venous return to the left atrium, and to LV. Increase in LV after-load (clamped UA) All these are risk factors for a drop in LV output All due to clamping of cord before establishing ventilation!

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33 Results: Clamp 1 st group Cardiovascular changes Heart rate Cord clamped Vent began Heart rate and RVO drop soon after cord clamping and recover slowly after vent onset RV Output Bhatt et al. J Physiol 2013; 591: Figure courtesy: Dr. Stuart Hooper

34 Both Groups: HR & RVO In the Vent 1 st group, HR and RVO remain stable throughout HR and RVO drop precipitously soon after cord clamping Gr 2 Vent began Gr 1: Cord clamped Gr 2 Vent began Gr 2 Cord clamped Gr 1: Vent began Gr 2 Cord clamped They rebound only after ventilation is started in the Clamp 1 st group Bhatt et al. J Physiol 2013; 591: ; Figure courtesy: Dr. Stuart Hooper Gr 1: Cord clamped Gr 1: Vent began

35 Results: Clamp-1 st group Carotid artery flow & pressure There is a transient increase in CA pressure and flow soon after cord clamping Carotid artery pressure Cord clamped Vent began But, by 1 minute both CA pressure and flow begin to drop profoundly to <50% baseline Carotid artery flow They recover slowly after ventilation onset Bhatt et al. J Physiol 2013; 591: Figure courtesy: Dr. Stuart Hooper

36 Term Preterm Median heart rate among infants NOT requiring resuscitation was below 100 at 1 minute of age in both term and preterm Arch Dis Child Fetal Neonatal Ed 2010;95:F177 F181. doi: /adc

37 Does it work in ELGANs?

38 Umbilical Cord Milking Four RCTs have been published (n=75 milking & 87 comparison groups) 1. Two Japanese trials in preterm: milking versus immediate clamping (Hosono, 2008; and Takami 2012) 2. One UK study in preterm, milking compared to delayed clamping by obstetricians (Rabe 2011) 3. One US study in term, C-Section births, milking compared to immediate clamping (Erickson-Owens, 2012)

39 Summary of Cord Milking Studies Compared to immediate clamping: Higher hematocrit, and higher blood volume Improved SVC flow, LV end-diastolic volume, and LV output Improved combined ventricular function index Improved cerebral blood flow, and higher cerebralfraction of O2 extraction Stabilizes CBS swings Takami et al, J Pediatr 2012

40 Summary of Cord Milking Studies (2) Compared to delayed cord clamping Similar effects on hematocrit, blood pressure, cardiac and cerebral functions. Can be carried out in term infants after elective c/sections No differences in any maternal complications Takami et al, J Pediatr 2012

41 Why not resuscitate with the cord connected to the placenta? Cheetah chasing a baby gazelle Massi Mara, Kenya EMBO Cover, 23 January 2008

42 BASICS Resuscitation Trolley Courtesy, Dr. David Hutchon

43 Take Home Points White Rhinoceros, Botswana EMBO Cover, 16 November, 2006 Clinical data and physiological rationale are compelling: Cord clamping at least after 30s is beneficial in all births Milking appears to be equally beneficial Although many issues remain to be solved, several organizations and societies are recommending it It is likely to become the standard of care in the US, too.

44 Worst Scenario The infant does NOT breathe immediately after birth and the umbilical cord is occluded soon after birth 50% drop in RV output, and flow through foramen ovale. Assisted ventilation is not well established & pulmonary vascular resistance remains high, preventing the normal increase of pulmonary blood flow and return of the oxygenated blood via the pulmonary veins into the left atrium. Plus, an increased afterload - drop in LV output If we give fluid boluses in rapid sequence, a stage is set to for IVH, especially in very preterm infants, with an already maximally vasodilated cerebral vascular bed, superimposed upon an immature cerebral autoregulatory systems. (Hooper SB, Personal communications, 2012).

45 Unresolved Issues Clamping versus Milking What is the length and speed of the cord to be milked? Who should do the milking OB? Peds? Direct placental transfusion is pulsatile does it matter that milking may not be exactly physiological?

46 Unresolved Issues The best time: 30 seconds? 60 seconds? In cases of maternal hemorrhage? Should the cord-clamping time be different in women positive for HIV? IUGR, LGA, Infants born at high altitudes Infant s position in relation to placenta in cesarean deliveries? Recording the Apgar scores and resuscitation? Effect of clamping time on cord blood gases? What about babies with asystole?

47 Cord clamping is an intervention... no evidence that amputation of the functioning placenta soon after birth is beneficial either to the baby or to the mother...don t rush to clamp the cord David J. R. Hutchon, BMJ 2010

48 Long Umbilical Cords in Primates Homosepians newborns have the longest Cords Long cords help the mother to pick up her newborn...carry it away from danger, without exerting traction on the placenta, and put the infant to the breast This facilitates placental delivery... Walker CW, Pye BG. The length of the human umbilical cord BMJ, Feb 20, 1960,

49 Thank You