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Delayed Cord Clamping T. Flint Porter, MD, MPH. Background Placental transfusion: blood volume transfused to baby after delivery Umbilical Cord Blood.

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Presentation on theme: "Delayed Cord Clamping T. Flint Porter, MD, MPH. Background Placental transfusion: blood volume transfused to baby after delivery Umbilical Cord Blood."— Presentation transcript:

1 Delayed Cord Clamping T. Flint Porter, MD, MPH

2 Background Placental transfusion: blood volume transfused to baby after delivery Umbilical Cord Blood Flow (UCBF) Factors that influence transfusion −Delayed cord clamping (DCC) −Cord milking (MUC) −Gravity −Uterotonics

3 Purported Advantages Decreased RDS in preterm neonates Decrease need for transfusion −(60-80% of < 32 weeks get transfusion) Less IVH in preterm neonates Less iron deficiency

4 Mechanisms of DCC and Improved Outcome Increased neonatal blood volume −Improved perfusion −Reduction in organ injury Allow spontaneous breathing to begin −Smoother transition of cardiopulmonary and cerebral circulation −Reduce need for resuscitation Increase iron stores, reduce anemia Transfusion of blood enriched with stem cells and immunoglobulin

5 Potential Drawbacks Delayed resuscitation Increase risk for neonatal hypothermia, polycythemia, hyperbilirubinemia Increase risk for maternal hemorrhage Interfere with cord blood collection

6 How long does umbilical cord blood flow continue? Prospective observational trial of UCBF after delivery in 30 term infants Protocol −Placed skin-to-skin by CNM −Doppler of straight portion until clamping −Cord clamped at CNM discretion (pulsation) −Pulse cessation determined by researcher −Measurements after 1 st breath (30/30) and oxytocin (28/30) Boere et al, Arch Dis Child Fet Neo Ed, 2014

7 UCBF After Delivery Venous Flow No venous flow at initial exam 3/30 (10%) Flow stopped 04:36 (03:03–08:22) Cord clamped 06:02 (04:47–09:35) 17/30 (57%) Flow still present when cord clamped 05:13 (02:56–09:15) 10/30 (33%) Boere et al, Arch Dis Child Fet Neo Ed, 2014

8 UCBF After Delivery Venous Flow Flow stopped during deep breaths Breathing Flow stopped Flow reversed flow with “hard” crying Crying

9 UCBF After Delivery Arterial Flow No flow at initial exam 5/30 (17%) Flow stopped 04:22 (02:29–07:17) Cord clamped 06:15 (05:02–09:30) 12/30 (40%) Flow still present when cord clamped 05:16 (03:32–10:10) 13/30 (43%) Most flow was toward the placenta

10 UCBF After Delivery Time Differences In 15 infants arterial and venous flow stopped simultaneously Flow to baby 7 infants Arterial stopped first 01:08 (00:51–03:03) Net flow from baby! 8 infants Venous stopped first 01:43 (00:51–02:45)

11 UCBF After Delivery Conclusions UCBF longer than previously described Complex process affected by −Breathing and crying −Differing arteriovenous flow cessation −Arterial flow toward the placenta UCBF unrelated to pulsations… reconsider as a time point for cord clamping

12 Term Infants Cochrane RCTs of 3911 women > 37 weeks Clamping Groups 1.< 60 seconds after delivery 2.> 60 seconds after delivery or pulse cessation Primary outcomes −PP hemorrhage −maternal and neonatal mortality Secondary outcomes −Maternal blood loss and related morbidity −Neonatal morbidity

13 Term Infants Cochrane 2013 Severe PPH or mortality Maternal blood loss Apgar scores NICU admission RDS Polycythemia

14 Term Infants Cochrane 2013 Hemoglobin (g/dL) Newborn-2.17 g/dL (-4.06 to -0.28) 24 – 48 hours-1.49 g/dL (-1.78 to -1.21) 3 – 6 monthsNo difference Jaundice Phototherapy0.62 (0.41 to 0.96) Clinical jaundice0.84 (0.66 to 1.07) ND

15 Term Infants Cochrane 2013 Authors’ Conclusion “Delayed cord clamping is likely to be beneficial as long as access to treatment for jaundice requiring phototherapy is available.”

16 Gravity Vain et al, Lancet, 2014 RCT in Argentina −All had DCC for 2 mins after NSVD −Introitus vs. Abdomen Primary outcome was weight −Proxy for volume of placental transfusion ProcedureDCC −Weighed < 15 secs of delivery −Weighed again at 2 mins after

17 Gravity Vain et al, Lancet, 2014 Introitus (197)Abdomen (194) Mean Weight Change Difference P (– ) NS It doesn’t matter where you hold the baby.

18 Iron and Neuro. Status at 1 Year Andersson, JAMA Ped 2014 Randomized controlled trial of DCC in full term infants Groups −Delayed: >180 secs after delivery −Early: < 10 secs after delivery Outcomes −Ferritin levels at 12 months −Neurodevelopment at 12 months assessed by ASQ (Ages and Stages Questionnaire)

19 Iron and Neuro. Status at 1 Year Andersson, JAMA Ped 2014 Cord Clamping MeasureDCC (174)ECC (163)P Hb NS Hematocrit35 NS Ferritin NS Proportion with Iron Status Outside Norm (%) Anemia NS Iron deficiency3.45.4NS

20 Iron and Neuro. Status at 1 Year Andersson, JAMA Ped 2014 Proportion of infants with low ASQ Scores (%) Cord Clamping ASQ MeasureDCC (174)ECC (163)P Communication3.53.6NS Gross Motor5.94.8NS Fine Motor6.54.2NS Problem Solving4.12.4NS Personal-Social5.94.2NS

21 DCC in Term Infants Conclusions Probably not going to hurt… No apparent effect long term Doesn’t matter if you keep the baby below the placenta… Waiting for cord to stop pulsing is as useful as ….

22 Preterm Infants Cochrane studies, 738 infants, < 37 weeks Study Groups −Immediate −Placental transfusion strategies: Delayed (≥ seconds) Cord milking Outcomes −Death, severe IVH, PVL, neurodevelopment

23 Preterm Infants Cochrane 2012 Neonatal death Severe IVH PVL Neurodevelopmental outcome

24 Preterm Infants Cochrane 2012 Secondary OutcomesRR (95% CI) Inotropic support0.42, (0.23 to 0.77) NEC0.62, (0.43 to 0.90) Transfusion0.61 (0.46 to 0.81) Phototherapy1.21 (0.94 to 1.55) Secondary OutcomesRR (95% CI) Inotropic support0.42, (0.23 to 0.77) NEC0.62, (0.43 to 0.90) Transfusion0.61 (0.46 to 0.81) Phototherapy1.21 (0.94 to 1.55)

25 Preterm Infants Cochrane 2012 Authors’ Conclusion Less need for transfusion Better circulatory stability Less IVH (all grades) Lower NEC Insufficient data for reliable conclusions about any of the primary outcomes

26 Placental Transfusion in VPN Backes et al, OG 2014 Systematic review and meta-analysis of DCC and MUC < 32 week neonates (28 wks) RCTs with the following interventions −Early clamping: < 15 seconds −DCC: at least 20 seconds −MUC: milking at least 3 times Outcomes −Maternal and obstetric −Safety −Hematological status −Neonatal Outcomes

27 Placental Transfusion in VPN Backes et al, OG 2014 Safety VariablesRCT #MD (95% CI)P BP (4 hours)43.24 (1.76, 4.72)<.01 Apgar (-.48, 0.33)NS Temp30.02 (-.18, 0.22)NS

28 Placental Transfusion in VPN Backes et al, OG 2014 Hematologic Outcomes RCT # RR (95% CI)P Transfusion60.75 (0.63, 0.90)<.01 MD (95% CI) Transfusion (#) (-2.01, 0.27)<.01 Hematocrit (1 st ) (2.48, 6.5)<.01 Bilirubin80.53 (-0.01, 1.07)0.05 Hematologic Outcomes RCT # RR (95% CI)P Transfusion60.75 (0.63, 0.90)<.01 MD (95% CI) Transfusion (#) (-2.01, 0.27)<.01 Hematocrit (1 st ) (2.48, 6.5)<.01 Bilirubin80.53 (-0.01, 1.07)0.05

29 Placental Transfusion in VPN Backes et al, OG 2014 Neonatal OutcomesRCT #Risk Ratio (95% CI)P Total IVH90.62 (0.43,0.91)<.01 Severe IVH60.64 (0.34, 1.21)NS NEC40.55 (0.23, 1.31)NS Sepsis50.73 (0.44, 1.20)NS Mortality80.42 (0.19, 0.95).04 Neonatal OutcomesRCT #Risk Ratio (95% CI)P Total IVH90.62 (0.43,0.91)<.01 Severe IVH60.64 (0.34, 1.21)NS NEC40.55 (0.23, 1.31)NS Sepsis50.73 (0.44, 1.20)NS Mortality80.42 (0.19, 0.95).04

30 DCC in Preterm Neonate Elimian et al, OG 2014 RCT of DCC for neonates weeks Groups −< 5 seconds −> 30 seconds (3-4 passes of milking allowed) Intention to treat Primary outcome −Need for transfusion (hb < 10 or symptomatic) Secondary outcomes −Hematocrit and IVH

31 DCC in Preterm Neonate Elimian et al, OG 2014 Clamping Outcome Delayed (99)Immediate (101)P Transfusion25 (25.3)24 (23.7).80 Anemia36 (36.4)48 (47.5).11 Phototherapy55 (55.6)55 (54.5).89 IVH (grade III)3 (3.0) 1.0

32 Cord Milking in ELGANs Patel et al, AJOG 2014 MUC provides benefits of placental transfusion but avoids delay in resuscitation Cohort study of outcomes < 30 weeks −MUC from 9/2011 – 8/2013 −Historical EGLANs from 1/2010-8/2011 Composite outcome −IVH, NEC, death before discharge Improvement in markers of hemodynamic stability

33 MUC in ELGANs Patel et al, AJOG 2014 MUC Procedure Neonate held 10 cm below level of the placenta Twisting and nuchal cords released Milking technique −Pinched close to the placenta −Milked over 2-3 seconds X 3 −Pause for 2-3 seconds between milking −Total procedure < 30 seconds

34 MUC in ELGANs Patel et al, AJOG 2014 Resuscitation Characteristics VariableHistorical (160)MUC (158)P Gestation Birthweight Temp on admit NS Max resuscitation*20 (13%)34 (22%)NS Chest compress.8 (5%)10 (6%)NS Intubation (mins)56NS Surfactant (mins)2938NS *blow by oxygen, positive airway pressure, positive pressure

35 MUC in ELGANs Patel et al, AJOG 2014 Variable Control (160) MUC (158)P Hematocrit 45.1 ± ± 5.5<.01 PRBC 127 (79) 90 (57)<.01 Dopamine <72 51 (32) 28 (18)<.01 NEC* 32 (20) 18 (11<.05 Severe IVH 27 (17) 15 (10)<.05 Death or IVH 40 (25) 22 (14)<.05 Composite 63 (39) 34 (22)<.01 Neonatal Outcomes < 30 Weeks

36 MUC in ELGANs Patel et al, AJOG 2014 Effect of MUC on Mean BP First Day of Life P < 0.01

37 DCC with and without MUC Krueger, AJOG 2015 RCT −DCC: 30 second delay in cord clamping −DCC + MUC (4 times, 4-5 sec. between) 24 – 31 6/7 weeks −Stratified results by gestational age Primary outcome: hematocrit Secondary outcomes −Mortality, days on ventilator, LOS, peak bilirubin, days of phototherapy, “neonatal complications

38 DCC with and without MUC Krueger, AJOG 2015 No difference in primary outcome −Hematocrit No difference in secondary outcomes −Bilirubin −Phototherapy −Days on ventilator −Length of stay −Other neonatal morbidities MUC added nothing to DCC

39 Placental Transfusion Strategies Conclusions for Preterm Babies Seems to improve short term outcomes −Longer term? Better for < 30 weeks Inconsistent findings among latest round of trials −Different protocols MUC as good as DCC?

40 “Perinatal medicine is replete with examples of promising interventions the short-term benefits of which did not translate into long-term benefits, including some that caused harm.” Tarnow-Mordi et al, AJOG 2014


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