priya rajan, md northwestern university september 13, 2013

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Priya Rajan, MD Northwestern University September 13, 2013

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Page 1: Priya Rajan, MD Northwestern University September 13, 2013

Priya Rajan, MD Northwestern University September 13, 2013

Page 2: Priya Rajan, MD Northwestern University September 13, 2013
Page 3: Priya Rajan, MD Northwestern University September 13, 2013

o “Study Finds Benefits in Delaying Severing of Umbilical Cord” • nytimes.com, 7/10/13

o “Delay cord clamping for baby health, say experts” • bbc.com.uk, 11/15/11

o “Birth Injuries Related to Umbilical Cord Clamping: Autism, cerebral palsy…neural, behavioral and developmental disorders” • cordclamp.org, accessed 9/11/13

Page 4: Priya Rajan, MD Northwestern University September 13, 2013

o Normal fetal circulation o Studies in preterm infants o Studies in term infants o What should we do?

Page 5: Priya Rajan, MD Northwestern University September 13, 2013
Page 6: Priya Rajan, MD Northwestern University September 13, 2013

o Umbilical cord clamping is typically performed within 15–20 seconds after birth

o Commonly part of a combination of actions that comprise active management of the 3rd stage of labor

Page 7: Priya Rajan, MD Northwestern University September 13, 2013

o Alveolar expansion o pulmonary vascular resistance o R atrial pressure, in L atrial pressure

• Closure of foramen ovale o Constriction of umbilical arteries and then

umbilical vein

Page 8: Priya Rajan, MD Northwestern University September 13, 2013

o 30-50% blood volume in placenta o Factors that affect this exchange

• Extrauterine breathing • Position of infant • Uterine contractions • Timing of cord

Page 9: Priya Rajan, MD Northwestern University September 13, 2013

o In 3 minutes after delivery 80-100mL blood may be shifted from placenta to neonate • Around 90% at 1st minute • 50mg/kg iron • Minimize relative hypoperfusion

Page 10: Priya Rajan, MD Northwestern University September 13, 2013

Preterm o Lower rates

• Bronchopulmonary dysplasia (BPD)

• Necrotising enterocolitis (NEC) • Late onset sepsis (LOS) • Intraventricular hemorrhage

(IVH) o Less need for transfusion

• Anemia • Hypotension

o Hematopoetic stem cells

Term o Lower rates

• Anemia • Iron deficiency

o Hematopoetic stem cells

Page 11: Priya Rajan, MD Northwestern University September 13, 2013

Preterm o Delaying resuscitation o Hypothermia o Polycythemia o Hyperbilirubinemia o Postpartum hemorrhage

Term o Polycythemia o Hyperbilirubinemia o Lower volumes with banked

cord blood o Postpartum hemorrhage

Page 12: Priya Rajan, MD Northwestern University September 13, 2013

60-80% preterm infants require transfusions

Page 13: Priya Rajan, MD Northwestern University September 13, 2013

o Rhode Island o 24wod-31w6d o Exclusion

• major anomaly, abruption, previa, severe maternal illness, mult gest, provider refusal

o ICC (5-10sec) or DCC (30-45sec) o Infants held 10-15 inches below introitus at

VD, below incision at CD o Primary outcome BPD

Mercer et al Pediatrics. 2006. 117(4): 1237

Page 14: Priya Rajan, MD Northwestern University September 13, 2013

o 72 randomized • 296 infants admitted w PTL • 7 protocol violations (6 DCC, 1 ICC)

o No difference in rates of BPD, NEC o Lower rate of LOS (3% v 22%), IVH (14% v

36%) • Adjusted OR for IVH w ICC 3.5

Mercer et al Pediatrics. 2006. 117(4): 1237

Page 15: Priya Rajan, MD Northwestern University September 13, 2013

o Oregon o Before-after comparison o 2010 DCC protocol

• < 35w, 45 seconds • 10-20cm below introitus or between legs in

warm towel • Exclusions: mult gestation, cong anomalies, no

resp effort and bradycardia

Kaempf et al. 2012. 120(2): 325

Page 16: Priya Rajan, MD Northwestern University September 13, 2013

o resuscitation in delivery room for VLBW o Hct but no difference in transfusion rate o No difference in rates of IVH, NEC, LOS, or

use of phototherapy

Kaempf et al. 2012. 120(2): 325

Page 17: Priya Rajan, MD Northwestern University September 13, 2013

o 15 studies o 24-36w gestation o Variation in definition of control and

intervention, position of infant, modes of delivery studied • DCC 30-180s

Rabe et al. Cochrane Database of Systematic Reviews 2012 (8)

Page 18: Priya Rajan, MD Northwestern University September 13, 2013

o IVH (RR 0.59) • Grade III/IV IVH (RR 0.68)

o NEC (RR 0.62) o transfusion for anemia (RR 0.61) o jaundice

• No difference in phototherapy use o No clear difference in RDS, need for oxygen o No reported maternal outcomes

Rabe et al. Cochrane Database of Systematic Reviews 2012 (8)

Page 19: Priya Rajan, MD Northwestern University September 13, 2013

o Wide confidence intervals o No study reported outcome at 2-3y age o Suggestion that increased neonatal blood

volume at birth improves blood pressure, and reduces need for transfusion, risk for IVH, and risk for NEC

Rabe et al. Cochrane Database of Systematic Reviews 2012 (8)

Page 20: Priya Rajan, MD Northwestern University September 13, 2013

High incidence of childhood anemia in resource-poor countries

Page 21: Priya Rajan, MD Northwestern University September 13, 2013

o Argentina o Singleton pregnancy at term

• Exclusions: maternal disease, major congenital malformations, IUGR

o ICC compared to DCC at 1’ and at 3’ • Infant held in mothers’ arms if VD and placed

on legs if CD

Cernadas et al. Pediatrics 2006. 117(4): e779

Page 22: Priya Rajan, MD Northwestern University September 13, 2013

o 276 women enrolled o Average clamping times were 12.7s, 59.8s,

and 169.5s in respective groups o No difference in mean Hct at 6h o anemic infants at 6h and 24-28h in ICC

group o polycythemia w 3’ at 6h but not 24-48h o No difference in secondary neonatal

outcomes or maternal PPH

Cernadas et al. Pediatrics 2006. 117(4): e779

Page 23: Priya Rajan, MD Northwestern University September 13, 2013

o Mexico o 37-41w6d

• Exclusions: CD, mult gestation, mat medical condition, major congenital anomalies, not planning to breastfeed to 6mo, smoker

o ICC (10s) v DCC at 2 min after delivery of shoulders

o At level of mother’s uterus

Chaparro et al. Lancet 2006. 367: 1997

Page 24: Priya Rajan, MD Northwestern University September 13, 2013

o 476 mother-infant pairs randomized • 75% completed the 6 month follow-up • Differed w respect to maternal Hgb and BMI

o No increase in clinical jaundice o No difference in maternal bleeding o Fe def anemia o ferritin and total body iron at 6mo

• > in infants born to mothers w low ferritin, exclusively breastfed infants, BW 2500-3000g

Chaparro et al. Lancet 2006. 367: 1997

Page 25: Priya Rajan, MD Northwestern University September 13, 2013

o Sweden o 37-41w6d

• Exclusions: congenital malformations or diseases

o DCC 180s o 20cm below for 1st 30s then on abdomen o Oxytocin after cord clamping

Andersson et al. BMJ 2011. 343:d7157

Page 26: Priya Rajan, MD Northwestern University September 13, 2013

o 382 mother-infant pairs randomized • 87% received their allotted allocation • 92% followed up at 4mo

o No difference in Hgb levels or prevalence of anemia at 4mo • anemia at 2mo

o ferritin level, total body iron, iron deficiency

o No difference in phototherapy or respiratory symptoms

Andersson et al. BMJ 2011. 343:d7157

Page 27: Priya Rajan, MD Northwestern University September 13, 2013

o 15 trials, 1912 newborns • 8 in countries w low perinatal mortality, 2 w

moderate, 5 w high • Variation in position of neonate and use/timing

of uterotonics o 37w or greater o DCC at least 2’

Hutton et al. JAMA 2007. 171:202.

Page 28: Priya Rajan, MD Northwestern University September 13, 2013

o Hct up to 2mo (47%), but no difference at 6mo • Same true for rate of anemia

o No difference in mean bilirubin levels, clinical jaundice, or phototherapy

o ferritin levels (33%)

Hutton et al. JAMA 2007. 171:202.

Page 29: Priya Rajan, MD Northwestern University September 13, 2013

o 15 studies • 37 excluded, most for lack of randomization

o Majority delivered vaginally o Substantial heterogeneity

• Variation in duration of DCC (1-3’), timing of uterotonic, and position of infant

McDonald et al. Cochrane Database of Systematic Reviews 2013 (7)

Page 30: Priya Rajan, MD Northwestern University September 13, 2013

o No increase in PPH (RR 1.17) o newborn Hgb (~2g/dL)

• No difference in Hgb at 3-6 months but iron stores

o jaundice requiring phototherapy (RR w early 0.62)

o One trial evaluated neurodevelopment • No difference at 4 months

McDonald et al. Cochrane Database of Systematic Reviews 2013 (7)

Page 31: Priya Rajan, MD Northwestern University September 13, 2013

o DCC may be beneficial with respect to increased iron stores in settings where phototherapy is readily available

McDonald et al. Cochrane Database of Systematic Reviews 2013 (7)

Page 32: Priya Rajan, MD Northwestern University September 13, 2013

Active placental transfusion by milking cord towards infant

Page 33: Priya Rajan, MD Northwestern University September 13, 2013

o United Kingdom o 24-32w6d

• Exclusions: multiple gestation, fetal hydrops, Rh alloimmunization, major congenital abnormalities

o DCC 30s or milking umbilical cord 4 times • Infant held in plastic bags 20cm below the level

of the placenta

Rabe et al. Obstet Gyn 2011. 171:202.

Page 34: Priya Rajan, MD Northwestern University September 13, 2013

o 58 infants randomized • Of 212 PTL admissions

o Similar Hgb at delivery • Slightly higher in milking group at 6w

o No difference in number of transfusions o Timing of cord clamping not recorded

Rabe et al. Obstet Gyn 2011. 117:205.

Page 35: Priya Rajan, MD Northwestern University September 13, 2013

o Virginia o 24-28w admitted for possible PTD

• Exclusions: major congenital anomaly, possible fetal anemia

o Video demonstrating technique • Extended hand’s width length of cord (~20cm) • At or below level of placenta • Milked three times before clamping

March et al. J Perinat 2013. 1-5.

Page 36: Priya Rajan, MD Northwestern University September 13, 2013

o 113 subjects randomized • 75 included in final analysis • Excluded subjects didn’t deliver before 28w

o trend transfusion in first 28d (83% v 97%, RR 0.86) • Higher initial Hgb

o IVH (25% v 51%, RR 0.49) • Higher rate of chorio/infection in control group

o No increase in need for phototherapy

March et al. J Perinat 2013. 1-5.

Page 37: Priya Rajan, MD Northwestern University September 13, 2013

o Rhode Island o 37-41w6d GA for scheduled elective CD

• Exclusions: multiple gestation, maternal medical and obstetric complications, severe maternal anemia, smokers

o Hold cord near placental insertion site • Milk entire length 5 times w other hand • Below level of placenta

Erickson-Owens et al. J Perinat 2012. 35:580

Page 38: Priya Rajan, MD Northwestern University September 13, 2013

o 24 infants randomized o Average time for milking 18s o Hgb levels at 36-48h (19.4 v 17.2g/dL) o No difference in hyperbilirubinemia or

phototherapy

Erickson-Owens et al. J Perinat 2012. 35:580

Page 39: Priya Rajan, MD Northwestern University September 13, 2013

o May be minimal difference in cord gas parameters of term infants

o Slightly higher rate of inability to collect sample

o No information on preterm infants

Wiberg et al. BJOG 2008. 115(6): 697. DePaco et al, Arch Gynecol Obstet 2011. 283:1011

Andersson et al. Acta Obstet Gynecol Scand 2013. 92(5): 567

Page 40: Priya Rajan, MD Northwestern University September 13, 2013
Page 41: Priya Rajan, MD Northwestern University September 13, 2013

o Royal College of Obstetricians and Gynaecologists • May be a benefit but better trials needed • Do not lift infant significantly above placenta

o World Health Organization • Clamping and cutting cord 1-3 min

• Low cost, easy to implement intervention • Weak recommendation, low quality evidence

RCOG Scientific Paper 14 2009 Abalos. WHO Reproductive Library. Rev Mar 2009

Page 42: Priya Rajan, MD Northwestern University September 13, 2013

o European Consensus Guidelines • DCC 30-45s • Infant held below mother

o Society of Obstetricians and Gynaecologists of Canada • DCC 60s

Page 43: Priya Rajan, MD Northwestern University September 13, 2013

o Insufficient evidence in term infants • May be of greater value in low-resource

settings o Benefit in preterm infants

• Decreased transfusions, better transition, nearly 50% reduction in IVH

• 30-60 seconds, below the placenta • Independent of wishes for cord blood banking

o Insufficient evidence regarding cord milking

ACOG Committee Opinion 543. Obstet Gyn 2012. 120:1522

Page 44: Priya Rajan, MD Northwestern University September 13, 2013

o More optimal blood and O2 transport • Increased blood flow in SVC • Reduced inotropic support • Higher cerebral oxygenation

o Fewer transfusions o Lower rate IVH

Raju et al. Clin Perinat 2012. 39:889

Page 45: Priya Rajan, MD Northwestern University September 13, 2013

o Higher Hgb in first few months after delivery o Improved survival from malaria o Better iron status up to 6mo o Increased phototherapy?

Raju et al. Clin Perinat 2012. 39:889

Page 46: Priya Rajan, MD Northwestern University September 13, 2013

o Optimal timing (30-180s) o Role in active management of 3rd stage o Mode of delivery (cesarean v vaginal) o 24-28w o Where to hold infant (above, at, or below

level of placenta) o Setting (high- v low-resource settings)

ACOG Committee Opinion 543. Obstet Gyn 2012. 120:1522

Raju et al. Clin Perinat 2012. 39:889 Rabe et al. Cochrane Database of Systematic Reviews 2012 (8)

McDonald et al. Cochrane Database of Systematic Reviews 2013 (7)

Page 47: Priya Rajan, MD Northwestern University September 13, 2013

o Inclusion • < 32w gestation • Preterm delivery

o Exclusion • Multiple gestation • General anesthesia • Major congenital anomaly • Discretion of obstetrician or neonatologists

Page 48: Priya Rajan, MD Northwestern University September 13, 2013

o Pre-delivery confirmation of plan with team o Vaginal delivery

• Wrap infant in warm sterile towel and hold at introitus

o Cesarean delivery • Wrap infant in warm sterile towel and hold on

lower maternal abdomen/legs

Page 49: Priya Rajan, MD Northwestern University September 13, 2013

o RN counts 10s intervals o Clamp at 30s o Hold oxytocin until cord clamped o Cord gases, cord blood collection after o Procedure may be terminated prematurely

at obstetrician or neonatologist’s discretion

Page 50: Priya Rajan, MD Northwestern University September 13, 2013

Raju et al. Clin Perinatol 2012. 39:889

Ka

Page 51: Priya Rajan, MD Northwestern University September 13, 2013
Page 52: Priya Rajan, MD Northwestern University September 13, 2013

o Switzerland o 39 neonates between 29-32w o DCC 60-90s o Infant as low as possible for VD and 15cm

below placenta for CD o Uterotonic given as soon as infant delivered o Higher

Baenziger et al. Pediatrics 2007. 119:455.