Delayed Versus Immediate Umbilical Cord Clamping

Shanterra Grable, Mercer University College of Pharmacy

Delayed umbilical cord clamping is performed from 25 seconds to five minutes after birth. The practice is thought to allow more blood to transfer from the placenta to the newborn, possibly increasing the baby’s blood volume by 30%. The American Congress of Obstetricians and Gynecologists (ACOG) supports delayed cord clamping in preterm infants but not in full term infants due to insufficient evidence showing benefits. The current standard during delivery  is to clamp the umbilical cord 10 to 30 seconds immediately after birth.  [1]

One of the associated benefits of delayed clamping is decreased risk of iron deficiency anemia due to transfer of additional 40 to 50 mg/kg of iron from the placenta to the infant. [1] Prior randomized controlled trials found that delayed cord clamping in preterm infants less than 32 weeks gestational age had lower instances of mortality, necrotizing enterocolitis, and infection than infants with immediate cord clamping; however, these studies did not show if delayed cord clamping is the sole factor leading to mortality and neurodevelopmental benefits. Despite the potential benefits, delayed clamping is not a universal practice due to concerns of delayed resuscitation and hyperbilirubinemia.  The following study was performed to add knowledge regarding the effects of delayed clamping on death and major morbidity in preterm infants. [2]

Delayed versus immediate cord clamping in preterm infants
Design Unblinded randomized control trial; N=1,566
Objective To determine the effects of delayed cord clamping on preterm infants
Study Groups Immediate clamping (n=782) or delayed clamping (n=784)
Methods Participants were randomized to immediate clamping within 10 seconds after delivery or delayed clamping 60 seconds or longer after delivery. The infants were held as low as possible below the placenta with no palpation of the umbilical cord. Variations to the interventions were made in the best interest of the mother and infant. Clinicians were allowed to use discretion in performing the intervention if the infant was considered nonvigorous (heart rate less than 100 beats per minute, low muscle tone, or lack of breathing or crying). Infants in multiple births were randomized individually.
Inclusion criteria: possible delivery before 30 weeks of gestation Exclusion criteria: fetal hemolytic disease, hydrops fetalis, twin-twin transfusion, genetic syndromes, potentially lethal malformations
Duration December 2010 to January 2017
Primary Outcome Measure Composite of death or major morbidity (severe brain injury, severe retinopathy, necrotizing enterocolitis, late onset sepsis)

*Chronic lung disease was removed from protocol as a major morbidity in 2013

Baseline Characteristics Immediate cord clamping (n=782) Delayed cord clamping (n=784)
Male sex- no. (%) 451 (57.7) 432 (55.1)
Gestational age- weeks 28 ± 2 28 ±2
Birth before 27 weeks of gestation- no. (%) 257 (32.9) 267 (34.1)
Presentation at birth- no. (%)
Cephalic 487 (62.3) 477 (60.8)
Breech 257 (32.9) 274 (34.9)
Other, including transverse 34 (4.3) 26 (3.3)
Unknown 4 (0.5) 7 (0.9)
Method of delivery- no. (%)
Vaginal with instruments 40 (5.1) 44 (5.6)
Vaginal without instruments 233 (29.8) 220 (28.1)
Cesarean in labor 165 (21.1) 160 (20.4)
Cesarean not in labor 344 (44.0) 360 (45.9)
Multiple birth status- no (%)
Single 588 (75.2) 588 (75.0)
Twin 168 (21.5) 176 (22.4)
Triplet 23 (2.9) 19 (2.4)
Quadruplet 3 (0.4) 1 (0.1)
White race, mother-no. (%) 575 (73.5) 568 (72.4)
Birth weight in grams 1000 ± 269 1018 ± 281
Birth weight <10th percentile for gestational age- no. (%) 83 (10.6) 94 (12.0)
Results
Outcome Ascertainment of outcome -% Immediate cord clamping- no./total no. (%) Delayed cord clamping- no./ total no. (%) Relative risk with delayed cord clamping (95% CI) p value
Primary outcome
Death or major morbidity 95.6 279/749 (37.2) 277/748 (37.0) 1.00 (0.88-1.13) 0.96
Death or major morbidity including chronic lung disease 96.0 498/748 (66.6) 520/756 (68.8) 1.03 (0.96-1.10) 0.45
Secondary outcomes
Death 100 70/782 (9.0) 50/784 (6.4) 0.69 (0.49-0.97) 0.45
Death or severe brain injury 95.5 115/754 (15.3) 101/741 (13.6) 0.85 (0.67-1.08) 0.18
Severe brain injury 95.1 45/684 (6.6) 51/691 (7.4) 1.07 (0.74-1.56) 0.71
Late cerebral abnormality on ultrasound 95.1 38/684 (5.6) 37/691 (5.4) 0.93 (0.61-1.42) 0.74
Intaventricular hemorrhage of grade three or four 100 17/712 (2.4) 24/734 (3.3) 1.35 (0.73-2.48) 0.34
Late onset sepsis 100 132/712 (2.4) 151/734 (20.6) 1.11 (0.90-1.36) 0.33
Necrotizing enterocolitis 100 44/712 (18.5) 41/734 (5.6) 0.91 (0.60-1.37) 0.64
Severe retinopathy of prematurity 98.3 48/700 (6.9) 38/721 (5.3) 0.75 (0.50-1.11) 0.16
Chronic lung disease 99.5 365/708 (51.6) 398/731 (54.4) 1.04 (0.95-1.14) 0.38
Patent ductus arteriosus requiring treatment 99.1 259/773 (33.5) 249/779 (32.0) 0.92 (0.81-1.06) 0.24
Adverse Events Common Adverse Events:

Polycythemia (hematocrit  65% or 70%): 52.1% in delayed vs. 60.5% in immediate; p= 0.001

Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions There was no difference in death or major morbidity seen at 36 weeks of postmenstrual age for infants in either the delayed cord clamping or immediate cord clamping group.

 

Because chronic lung disease was removed from the list of major morbidities halfway into the study, the relationship between chronic lung disease and intervention is unclear.  Additionally, how much statistical impact it had on the primary outcome results may also be datable; however, it is noted that analysis showed no difference when chronic lung disease was included. These results contradict prior studies that are used to support the recommendations for delayed cord clamping. One potential explanation is that included infants may have been less severely ill compared to previous trials; therefore, the differences may not be as significant between the two interventions. Since this was a short-term outcome study, follow up into childhood is planned to evaluate the long-term outcomes that may provide additional information to strengthen or change the current recommendations.  Although most current recommendations focus on preterm infants, it may be interesting to see  a similar study in full term infants as well since there is no clear consensus in that  population either. Nonetheless, at this time, given the lack of benefit or harm in preterm and full term infants, delayed cord clamping may be individualized when safety is not a concern.

 

References:

[1] Delayed cord clamping: what are the risks and benefits?. American Pregnancy Association website.  http://americanpregnancy.org/labor-and-birth/delayed-cord-clamping-risks-benefits/. Updated July 2017. Accessed December 14, 2017.

[2] Tarnow-Mordi W, Morris J, Kirby A, et al. Delayed versus immediate cord clamping in preterm infants. N Engl J Med. 2017;

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