2 BackgroundPlacental transfusion: blood volume transfused to baby after deliveryUmbilical Cord Blood Flow (UCBF)Factors that influence transfusionDelayed cord clamping (DCC)Cord milking (MUC)GravityUterotonicsBlood in umbilical arteries thought to stop flowing within 25 – 45 s after delivery.
3 Purported Advantages Decreased RDS in preterm neonates Decrease need for transfusion(60-80% of < 32 weeks get transfusion)Less IVH in preterm neonatesLess iron deficiency
4 Mechanisms of DCC and Improved Outcome Increased neonatal blood volumeImproved perfusionReduction in organ injuryAllow spontaneous breathing to beginSmoother transition of cardiopulmonary and cerebral circulationReduce need for resuscitationIncrease iron stores, reduce anemiaTransfusion of blood enriched with stem cells and immunoglobulin
5 Potential Drawbacks Delayed resuscitation Increase risk for neonatal hypothermia, polycythemia, hyperbilirubinemiaIncrease risk for maternal hemorrhageInterfere with cord blood collection
6 How long does umbilical cord blood flow continue? Prospective observational trial of UCBF after delivery in 30 term infantsProtocolPlaced skin-to-skin by CNMDoppler of straight portion until clampingCord clamped at CNM discretion (pulsation)Pulse cessation determined by researcherMeasurements after 1st 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 exam3/30 (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 breathsBreathingFlow stoppedFlow reversed flow with “hard” cryingCrying
9 UCBF After Delivery Arterial Flow No flow at initial exam5/30 (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 simultaneouslyFlow to baby7 infantsArterial stopped first 01:08 (00:51–03:03)Net flow from baby!8 infantsVenous stopped first 01:43 (00:51–02:45)
11 UCBF After Delivery Conclusions UCBF longer than previously describedComplex process affected byBreathing and cryingDiffering arteriovenous flow cessationArterial flow toward the placentaUCBF unrelated to pulsations… reconsider as a time point for cord clamping
12 Term Infants Cochrane 2013 15 RCTs of 3911 women > 37 weeks Clamping Groups< 60 seconds after delivery> 60 seconds after delivery or pulse cessationPrimary outcomesPP hemorrhagematernal and neonatal mortalitySecondary outcomesMaternal blood loss and related morbidityNeonatal morbidity
13 Term Infants Cochrane 2013 Severe PPH or mortality Maternal blood loss Apgar scoresNICU admissionRDSPolycythemia
14 Term Infants Cochrane 2013 Hemoglobin (g/dL) Jaundice 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 differenceJaundicePhototherapy0.62 (0.41 to 0.96)Clinical jaundice0.84 (0.66 to 1.07) ND
15 Term Infants Cochrane 2013Authors’ 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 ArgentinaAll had DCC for 2 mins after NSVDIntroitus vs. AbdomenPrimary outcome was weightProxy for volume of placental transfusionProcedureDCCWeighed < 15 secs of deliveryWeighed again at 2 mins after
17 Gravity Vain et al, Lancet, 2014 Introitus (197)Abdomen (194)Mean Weight ChangeDifferenceP56533 (– )NSIt 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 infantsGroupsDelayed: >180 secs after deliveryEarly: < 10 secs after deliveryOutcomesFerritin levels at 12 monthsNeurodevelopment at 12 months assessed by ASQ (Ages and Stages Questionnaire)
19 Iron and Neuro. Status at 1 Year Andersson, JAMA Ped 2014 Cord ClampingMeasureDCC (174)ECC (163)PHb11.812.0NSHematocrit35Ferritin35.433.6Proportion with Iron Status Outside Norm (%)Anemia16.111.6Iron deficiency3.45.4
20 Iron and Neuro. Status at 1 Year Andersson, JAMA Ped 2014 Proportion of infants with low ASQ Scores (%)Cord ClampingASQ MeasureDCC (174)ECC (163)PCommunication3.53.6NSGross Motor5.94.8Fine Motor6.54.2Problem Solving4.12.4Personal-Social
21 DCC in Term Infants Conclusions Probably not going to hurt… No apparent effect long termDoesn’t matter if you keep the baby below the placenta…Waiting for cord to stop pulsing is as useful as ….
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’ ConclusionLess need for transfusionBetter circulatory stabilityLess IVH (all grades)Lower NECInsufficient 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 interventionsEarly clamping: < 15 secondsDCC: at least 20 secondsMUC: milking at least 3 timesOutcomesMaternal and obstetricSafetyHematological statusNeonatal Outcomes
27 Placental Transfusion in VPN Backes et al, OG 2014 Safety VariablesRCT #MD (95% CI)PBP (4 hours)43.24 (1.76, 4.72)<.01Apgar5-0.07 (-.48, 0.33)NSTemp30.02 (-.18, 0.22)
29 Placental Transfusion in VPN Backes et al, OG 2014 Neonatal OutcomesRCT #Risk Ratio (95% CI)PTotal IVH90.62 (0.43,0.91)<.01Severe IVH60.64 (0.34, 1.21)NSNEC40.55 (0.23, 1.31)Sepsis50.73 (0.44, 1.20)Mortality80.42 (0.19, 0.95).04Neonatal OutcomesRCT #Risk Ratio (95% CI)PTotal IVH90.62 (0.43,0.91)<.01Severe IVH60.64 (0.34, 1.21)NSNEC40.55 (0.23, 1.31)Sepsis50.73 (0.44, 1.20)Mortality80.42 (0.19, 0.95).04
30 DCC in Preterm Neonate Elimian et al, OG 2014 RCT of DCC for neonates weeksGroups< 5 seconds> 30 seconds (3-4 passes of milking allowed)Intention to treatPrimary outcomeNeed for transfusion (hb < 10 or symptomatic)Secondary outcomesHematocrit and IVH
31 DCC in Preterm Neonate Elimian et al, OG 2014 ClampingOutcomeDelayed (99)Immediate (101)PTransfusion25 (25.3)24 (23.7).80Anemia36 (36.4)48 (47.5).11Phototherapy55 (55.6)55 (54.5).89IVH (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 resuscitationCohort study of outcomes < 30 weeksMUC from 9/2011 – 8/2013Historical EGLANs from 1/2010-8/2011Composite outcomeIVH, NEC, death before dischargeImprovement in markers of hemodynamic stability
33 MUC in ELGANs Patel et al, AJOG 2014 MUC ProcedureNeonate held 10 cm below level of the placentaTwisting and nuchal cords releasedMilking techniquePinched close to the placentaMilked over 2-3 seconds X 3Pause for 2-3 seconds between milkingTotal procedure < 30 seconds
34 MUC in ELGANs Patel et al, AJOG 2014 Resuscitation CharacteristicsVariableHistorical (160)MUC (158)PGestation220.127.116.11Birthweight8809600.009Temp on admit36.336.5NSMax resuscitation*20 (13%)34 (22%)Chest compress.8 (5%)10 (6%)Intubation (mins)56Surfactant (mins)2938*blow by oxygen, positive airway pressure, positive pressure
36 MUC in ELGANs Patel et al, AJOG 2014 Effect of MUC on Mean BP First Day of LifeP < 0.01P < 0.01P < 0.01
37 DCC with and without MUC Krueger, AJOG 2015 RCTDCC: 30 second delay in cord clampingDCC + MUC (4 times, 4-5 sec. between)24 – 31 6/7 weeksStratified results by gestational agePrimary outcome: hematocritSecondary outcomesMortality, days on ventilator, LOS, peak bilirubin, days of phototherapy, “neonatal complications
38 DCC with and without MUC Krueger, AJOG 2015 No difference in primary outcomeHematocritNo difference in secondary outcomesBilirubinPhototherapyDays on ventilatorLength of stayOther neonatal morbiditiesMUC added nothing to DCC
39 Placental Transfusion Strategies Conclusions for Preterm Babies Seems to improve short term outcomesLonger term?Better for < 30 weeksInconsistent findings among latest round of trialsDifferent protocolsMUC 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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