2/4/2016 DELAYED CORD CLAMPING An old idea revisited 211 YEARS AGO……………… Another thing very injurious to the child is the tying and cutting of the naval 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 part of the blood being left in the placenta which ought to have been in the child and at the same time the placenta does not so naturally collapse and withdraw itself from the sides of the uterus, and is not therefore removed with so much safety and certainty. 1
2/4/2016 137 YEARS AGO………………… During my time at the Maternité in Paris, my chief…..recommended me not to tie and not to cut the umbilical cord as soon as the child was born. When one hurries too much in performing this operation…one finds the placenta full of blood, and one risks…. depriving the child of a certain quantity of blood, which….would have returned to his circulatory system. Pierre Budin 1875 “A Quel Moment Doit-On Pratiquer La Ligature du Cordon Ombilical ” EARLY 1900 S • “Early” clamping was about 1 minute after birth • “Late” clamping was after 5 minutes 2
2/4/2016 BARKER FOAL SYNDROME Two veterinarians at a race track in England in 1959 • Foals delivered in captivity had immediate cord clamping and often developed cough and fatal respiratory distress after birth with pulmonary hyaline membranes noted on autopsy — similar to RDS. • These foals had high amounts of residual blood volume in placenta. • Wild-born foals had no cord clamping and low residual placental blood and did not develop fatal respiratory distress with hyaline membranes. • Bound et al (1962), Usher et al (1975) linked placental transfusion to incidence and severity of RDS, Linderkamp (1978) RBC mass lower in those w/RDS • Considerable research in 1960s and 70s into delayed cord clamping showed increased blood volume by about 10 to 15%, lower residual placenta blood volumes, and higher RBC masses by 20 to 60%. PLACENTAL TRANSFUSION • The flow of blood from the placenta to the baby after birth • Influenced by Intrauterine asphyxia (causes antenatal placental transfusion) Onset of respirations prior to clamping umbilical cord Boston City Hospital Study (1965, Lancet) Diabetic mothers (1965, Lancet), Edinburgh (1973) and for C-sections in Honolulu (1977) Timing of clamping of cord — 50 to 60% of transfusion in 1 st min Gravity/Position of baby — lower increases amount of transfusion but infants held above mother can still receive positive flow Uterine contractions — increase venous pressure in placental circuit 3
2/4/2016 MATERNAL EFFECTS OF TIMING OF CORD CLAMING Post Partum Hemorrhage Botha (1968) found that unclamped cord allowed placenta to drain Decreased duration of 3 rd stage of labor from 10.5 ± 4 min in ECC to 3.5 ± 2 min when cord is left unclamped Decreased maternal blood loss from 236 ± 135 ml to 100 ± 83 ml Magnitude of post-delivery placenta-maternal hemorrhage decreased by leaving cord unclamped but not by delaying clamping (Dunn, 1966). Nevertheless, “active management” of third stage of labor necessitates early cord clamping and is used to decrease post partum hemorrhage. CURRENT PRACTICE E arly cord clamping soon after delivery due to …… • Fear of polycythemia and significant hyperbilirubinemia • Presence of resuscitation team awaiting infant • Need to obtain cord blood gases • Desire for Skin-to-skin contact and early breast feeding • Promote active management of 3 rd stage of labor to decrease post partum hemorrhages 4
2/4/2016 LATE VS EARLY CLAMPING OF THE UMBILICAL CORD FOR TERM INFANTS • Hutton and Hassan (2007) JAMA Meta-analysis of 15 controlled trials totalling 1912 term newborns (ICC v DCC at 2 min) • Signficant differences in: HCT at 24 to 48 hr and at 5 days (Figure 1) Blood viscosity (figure 2) and polycythemia (Fig 7) Improved mean ferritin concentrations at 2 to 3 mo (Fig 4) Less Anemia at 2 to 3 mo (Fig 5) • No differences in mean Hgb at 2-3mo (Fig 1 bottom), mean bilirubin (Fig 3), clinical jaundice or need for phototherapy (Fig 6), or resp distress (Fig 8) BMJ 2011: EFFECT OF DELAYED VS EARLY UMBILICAL CORD CLAMPING ON NEONATAL OUTCOMES AND IRON STATUS AT 4 MONTHS: A RANDOMIZED CONTROLLED TRIAL • 400 Term infants born after low risk pregnancy (no cigs, no DM, no drugs, etc) • Randomized to DCC at 180 sec or ICC at < 10 sec • At 4 mo post partum: No difference is Hgb concentrations 45% higher ferritin in DCC group ( P < 0.001) ECC had significantly more iron deficiency (5.7% v 0.6%, P 0.01) ECC had significantly lower total body iron (P < 0.001) Iron indices significantly better in DCC group (iron concentration, transferrin levels, transferrin receptors, transferrin saturation) • No difference in mean bilirubin levels, bilirubin > 15 mg/dL, or phototherapy 5
2/4/2016 DELAYED CORD CLAMPING IN PREMATURE INFANTS After initial interest in 1960s to 1970s as a way to ameliorate RDS research tapered off for about 15 to 20 years 1990s to early 2000s — multiple small studies examining DCC Led to Cochrane review in 2004 7 studies included (297 infants < 37 wk) and 9 studies excluded Actual gestational ages 24 to 33 wk Inconsistent interventions, controls, variation in outcomes measured Cord clamp time 30 to 120 seconds 2004 COCHRANE REVIEW RESULTS • Transfusions for anemia : Higher among infants with ICC 29/55 in ICC vs 14/55 in DCC RR 2.01 95% CI 1.24 to 3.27 • Transfusions for low BP : Fewer in infants with DCC 2 trials with 58 total infants, RR 2.58 95% CI 1.17 to 5.67 • IVH : DCC had a protective effect for overall risk for IVH 5 trials with 225 infants, RR 1.74 95% CI 1.08 to 2.81 Caveat to this is that S African studies had high rates of IVH • Severe IVH : too little data • Peak Bili : higher in DCC infants (WMD 1.26 mg/dL) 95% CI 2.22-0.29) • Treatment for jaundice : too little data for conclusions • Exchange transfusions : not reported • Hematocrit at 1 and 4 hours : no differences. 6
2/4/2016 2006 MERCER, OH, ET AL PEDIATRICS • DCC in Very Preterm Infants Reduces the Incidence of IVH and Late Onset Sepsis: A Randomized, Controlled Trial at Univ. Rhode Island • Goal was to examine DCC with primary outcomes of BPD and NEC • Secondary outcomes: LOS, IVH, ROP < 32 wk • Method: RCC, unmasked, < 32 wk, DCC at 30 to 45 sec vs ICC • 72 Babies MERCER, OH, ET AL 2006 RESULTS ICC (n=36) DCC (n=36) P value OR 95%CI All IVH 13 (36%) 5 (14%) 0.03 3.5 1.1-11 Grade I 4 (11%) 3 (8%) Grade II 8 (22%) 2 (6%) Grade III 0 0 Grade IV 1(3%) 0 LOS 8 (22%) 1 (3%) 0.03 Mean time to clamping was shorter in those with IVH (13 v 22 sec, p = 0.03) 7
2/4/2016 PROTECTIVE EFFECT WAS IN BOYS ICC ICC DCC DCC Boys (n=19) Girls (n=18) Boys(n=23) Girls (n=13) All IVH 8 (42%) 5 (29%) 2 (9%) 3 (23%) Sepsis 6 (32%) 2 (12%) 0 1 (8%) NEC 3 (16%) 1 (6%) 0 2 (15) Differences for boys between DCC and ICC were significant (p<0.05) by Fisher’s Exact test IVH prophylaxis, gest age distribuion was similar between DCC and ICC Analysis based on Intent to Treat and one boy in DCC w/IVH actually had ICC PREMIE BLOOD VOLUME WITH DCC V ICC (ALADANGADY, ET AL 2006) • Obj: compare infant blood volume after ICC v DCC of 30 to 90 sec • Hold infant as low as possible and administer oxytocin • Resuscitation commenced with infant attached to cord • 46 infants 24 to 32 6/7 wk 23 in DCC, 23 ICC Delivered by CS: 11/23 in DCC, 9/23 in ICC • Measure blood volume In those needing transfusion, measure dilution of fetal by adult Hgb Those not needing transfusion, infuse biotin labeled autologous RBC 8
2/4/2016 ALADANGADY RESULTS 2006 Mean BV for DCC deliveries: 74.4 ml/kg (range 45 to 103 ml/kg) Mean BV for ICC deliveries: 62.7 ml/kg (range 47 to 77 ml/kg) p < 0.001 Vaginal DCC delivery estimated BV: 80.5 ml/kg Vaginal ICC delivery estimated BV: 61.3 ml/kg p < 0.001 C Section DCC estimated BV: mean 70.4 ml/kg (range 45 to 83 ml/kg) C Section ICC esteimated BV: mean 64 ml/kg (range 48 to 77ml/kg) p =0.1 *but 3 infants in the C-section DCC group actually underwent ICC due to short cords. Excluding them produced statistical significance (DCC 72.8 ml/kg, ICC 63.6 ml/kg p = 0.01 95% CI 2 to 16.4) Mean HCt for DCC = 0.53, Mean for ICC = 0.49 p = 0.1. Clinical Outcomes were not recorded other than “no complications” BLOOD VOLUME AS A FUNCTION OF TIME TO CORD CLAMPING 9
2/4/2016 BLOOD VOLUME DISCUSSION Authors report that their findings were similar to those of others: Yao 1969----Term infants using I125- labeled serum albumin DCC at ≥1 min 83.7 ± 2.7 versus ICC 70.3 ± 2.3 ml/kg Saigal (1972) preterm infants 28 to 36 wk ICC 79.7 ml/kg v 89.6 ml/kg with 1 min DCC Albumin method can overestimate due to leakage of albumin from vessels in sick patients. CEREBRAL OXYGENATION AND DCC • 2007 Baenziger et al. The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized Controlled Trial • 39 infants mean GA of 30.4 wk. 15 underwent DCC, 24 ICC. Subset of patients from larger RCT on DCC so uneven randomization • ICC v DCC at 60 to 90 sec with infant 15 cm below placenta, oxytocin infusion. • At 4 and 24 hr, use NIRS to measure cerebral Hgb, Cerebral BV, regional tissue oxygenation 10
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