Priya Rajan, MD Northwestern University September 13, 2013

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

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

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

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

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

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

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

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

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

60-80% preterm infants require transfusions

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

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

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

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

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)

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)

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)

High incidence of childhood anemia in resource-poor countries

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

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

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

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

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

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

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.

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.

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)

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)

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)

Active placental transfusion by milking cord towards infant

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.

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.

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.

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.

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

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

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

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

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

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

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

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

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

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)

o Inclusion • < 32w gestation • Preterm delivery

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

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

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

Raju et al. Clin Perinatol 2012. 39:889

Ka

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.