Priya Rajan, MD Northwestern University September 13, 2013

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1 Priya Rajan, MD Northwestern University September 13, 2013

2

3 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

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

5

6 o Umbilical cord clamping is typically performed within seconds after birth o Commonly part of a combination of actions that comprise active management of the 3 rd stage of labor

7 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

8 o 30-50% blood volume in placenta o Factors that affect this exchange Extrauterine breathing Position of infant Uterine contractions Timing of cord

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

10 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

11 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

12 60-80% preterm infants require transfusions

13 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 inches below introitus at VD, below incision at CD o Primary outcome BPD Mercer et al Pediatrics (4): 1237

14 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 (4): 1237

15 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 (2): 325

16 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 (2): 325

17 o 15 studies o 24-36w gestation o Variation in definition of control and intervention, position of infant, modes of delivery studied DCC s Rabe et al. Cochrane Database of Systematic Reviews 2012 (8)

18 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)

19 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)

20 High incidence of childhood anemia in resource-poor countries

21 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 (4): e779

22 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 (4): e779

23 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 : 1997

24 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 g Chaparro et al. Lancet : 1997

25 o Sweden o 37-41w6d Exclusions: congenital malformations or diseases o DCC 180s o 20cm below for 1 st 30s then on abdomen o Oxytocin after cord clamping Andersson et al. BMJ :d7157

26 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 :d7157

27 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 :202.

28 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 :202.

29 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)

30 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)

31 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)

32 Active placental transfusion by milking cord towards infant

33 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 :202.

34 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 :205.

35 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

36 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

37 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 :580

38 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 :580

39 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 (6): 697. DePaco et al, Arch Gynecol Obstet :1011 Andersson et al. Acta Obstet Gynecol Scand (5): 567

40

41 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 Abalos. WHO Reproductive Library. Rev Mar 2009

42 o European Consensus Guidelines DCC 30-45s Infant held below mother o Society of Obstetricians and Gynaecologists of Canada DCC 60s

43 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 seconds, below the placenta Independent of wishes for cord blood banking o Insufficient evidence regarding cord milking ACOG Committee Opinion 543. Obstet Gyn :1522

44 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 :889

45 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 :889

46 o Optimal timing (30-180s) o Role in active management of 3 rd 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 :1522 Raju et al. Clin Perinat :889 Rabe et al. Cochrane Database of Systematic Reviews 2012 (8) McDonald et al. Cochrane Database of Systematic Reviews 2013 (7)

47 o Inclusion < 32w gestation Preterm delivery o Exclusion Multiple gestation General anesthesia Major congenital anomaly Discretion of obstetrician or neonatologists

48 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

49 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

50 Raju et al. Clin Perinatol :889 Ka

51

52 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 :455.

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