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Effects of delayed cord clamping in intrauterine growth–restricted neonates: a randomized controlled trial

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Abstract

The time of cord clamping in intrauterine growth–restricted (IUGR) neonates remains an area of uncertainty. This assessor-blinded randomized controlled trial compared the effects of delayed cord clamping (DCC) with early cord clamping (ECC) on the systemic blood flow (SBF) and cerebral hemodynamics in IUGR neonates of gestational age ≥28 weeks, not requiring resuscitation. Eligible newborns were randomized to DCC (cord clamping after 60 s; n=55) or ECC (cord clamping within 30 s; n=55) group immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24±2 h. The secondary outcome variables were right ventricular output (RVO), anterior cerebral artery (ACA) blood flow velocity (BFV), superior mesenteric artery (SMA)-BFV and venous hematocrit at 24±2 h, peak total serum bilirubin (TSB), incidences of polycythemia, intraventricular hemorrhage, respiratory distress, feeding intolerance, and necrotizing enterocolitis, outcome, duration of hospital stay, screening audiometry, and serum ferritin levels at the postnatal age of 3 months. Compared to ECC, DCC was associated with significantly higher SVC flow (101.22±21.02 and 81.27±19.12 mL/kg/min, in DCC and ECC groups, respectively; p<0.0001), and significantly increased RVO, SMA-BFV, venous hematocrit, and serum ferritin levels. Though peak TSB was significantly higher with DCC, duration of phototherapy was comparable. ACA-BFV, incidence of polycythemia, and other outcomes were comparable between the groups.

Conclusions: DCC was a safe and beneficial intervention in IUGR infants with an improved SBF and SMA-BFV and an increased hematocrit and serum ferritin levels without higher incidences of polycythemia and requirement of phototherapy for significant hyperbilirubinemia.

Trial registration: Clinical Trials Registry of India (CTRI/2019/05/018904)

What is Known:

• Delayed cord clamping (DCC) increases superior vena cava (SVC) blood flow in preterm neonates.

• DCC increases hematocrit and serum ferritin in intrauterine growth–restricted (IUGR) neonates, but there may be an associated risk of polycythemia and neonatal hyperbilirubinemia.

What is New:

• DCC increases SVC blood flow, right ventricular output, superior mesenteric artery blood flow velocity, venous hematocrit, and serum ferritin in IUGR neonates.

• Incidences of polycythemia and duration of phototherapy for significant neonatal hyperbilirubinemia do not increase with DCC.

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Data availability

Deidentified individual participant data (including data dictionaries) will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to drkanhu.ped@gmail.com.

Abbreviations

ACA:

Anterior cerebral artery

ASSR:

Auditory Steady-State Response Audiometry

ANOVA:

Analysis of variance

BFV:

Blood flow velocity

BW:

Birth weight

BERA:

Brainstem-evoked response audiometry

CC:

Cord clamping

CI:

Confidence interval

CPAP:

Continuous positive airway pressure

CTRI:

Clinical Trial Registry of India

EDV:

End-diastolic velocity

GA:

Gestational age

DCC:

Delayed cord clamping

ECC:

Early cord clamping

HHHFNC:

Heated humidified high flow nasal cannula

IVH:

Intraventricular hemorrhage

IUGR:

Intrauterine growth restriction

IQR:

Interquartile range

LED:

Light-emitting diode

MD:

Mean difference

n :

Number

N :

Total number in that population

NEC:

Necrotizing enterocolitis

NNH:

Neonatal hyperbilirubinemia

NNTB:

Number needed to treat for benefit

NNTH:

Number needed to treat to harm

NS:

Non-significant

LAMA:

Left against medical advice

PET:

Partial exchange transfusion

PSV:

Peak-systolic velocity

RCT:

Randomized controlled trial

RI:

Resistive index

RR:

Relative risk

RVO:

Right ventricular output

SD:

Standard deviation

SMA:

Superior mesenteric artery

SVC:

Superior vena cava

TSB:

Total serum bilirubin

TcB:

Transcutaneous bilirubinometer

UA:

Umbilical artery

VTI:

Velocity time integral

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Acknowledgments

We would like to thank all the study infants and their families who accepted joining this study.

Author information

Authors and Affiliations

  1. Department of Neonatology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India

    Kanhu Charan Digal, Poonam Singh & Sriparna Basu

  2. Department of Pediatrics , Cardiology. Division, All India Institute of Medical Sciences, Rishikesh, India

    Yash Srivastava

  3. Department of Gyne & Obstetrics, All India Institute of Medical Sciences, Rishikesh, India

    Jaya Chaturvedi

  4. Department of Otolaryngology, All India Institute of Medical Sciences, Rishikesh, India

    Amit Kumar Tyagi

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  1. Kanhu Charan Digal
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Contributions

Prof Sriparna Basu, Dr. Kanhu Charan Digal, Dr. Poonam Singh, and Dr. Yash Srivastava conceptualized and designed the study, coordinated and supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Yash Srivastava performed the echocardiography and color Doppler procedures. Prof Jaya Charurvedi helped in data collection and reviewed the manuscript. Dr. Amit Kumar Tyagi performed the hearing assessment and reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sriparna Basu.

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Ethics approval and consent to participate

The trial was ethically approved by the institute ethics committee of All India Institute of Medical Sciences, Rishikesh, India. Written informed consent was obtained from all the parents of the study participants.

Consent for publication

Written informed consent was obtained from all the parents of the study participants for publication of their data.

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The authors declare no competing interests.

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Digal, K.C., Singh, P., Srivastava, Y. et al. Effects of delayed cord clamping in intrauterine growth–restricted neonates: a randomized controlled trial. Eur J Pediatr 180, 1701–1710 (2021). https://doi.org/10.1007/s00431-021-03959-7

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  • DOI: https://doi.org/10.1007/s00431-021-03959-7

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