Delayed Cord Clamping Techniques for Newborns with Congenital Heart Disease

(CORD-CHD Trial)

Recruiting at 20 trial locations

Overseen By Chelsea E Cobe, BA

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Carl Backes, MD

Disqualifiers: Gestational carrier, Fetal demise, Tachyarrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Immediate at birth

500 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of the treatment Delayed Cord Clamping Techniques for Newborns with Congenital Heart Disease?

Research shows that delayed cord clamping (waiting before cutting the umbilical cord) can increase hemoglobin levels, reduce the need for blood transfusions, and lower the risk of certain complications in newborns, such as brain bleeding and gut issues. These benefits have been observed in both preterm and full-term infants, suggesting potential advantages for newborns with congenital heart disease as well. ^{1 2 3 4 5}

Is delayed cord clamping safe for newborns?

Delayed cord clamping (DCC) is generally considered safe and may offer health benefits for newborns, including those with congenital heart disease, as well as preterm infants. Studies have shown that DCC can improve neonatal health without apparent safety issues, even in cesarean births and preterm infants. ^{2 3 4 6 7}

How does the treatment of delayed cord clamping differ from other treatments for newborns with congenital heart disease?

Delayed cord clamping (DCC) involves waiting longer before clamping the umbilical cord, allowing more blood to transfer from the placenta to the newborn, which may improve health outcomes. This approach is unique because it focuses on enhancing blood volume and oxygenation in newborns with congenital heart disease, unlike immediate clamping or other interventions that do not utilize this natural transfusion process. ^{2 3 4 6 8}

What is the purpose of this trial?

The goal of this clinical trial is to compare 2 different timepoints for clamping the umbilical cord at birth for term-born infants with a prenatal diagnosis of congenital heart disease (CHD). The main questions it aims to answer are: * Does Delayed Cord Clamping at 120 seconds (DCC-120) or Delayed Cord Clamping at 30 seconds (DCC-30) after birth lead to better health outcomes? * Does DCC-120 seconds or DCC-30 seconds after birth lead to better neuromotor outcomes at 22-26 months of infant age (postnatal)? Participants will be asked to do the following: * Participate in either DCC-120 or DCC-30 at birth (randomized assignment). * Complete General Movements Assessment (GMA) at 3-4 months of infant age (postnatal), complete questionnaires / surveys at this time. * Complete questionnaires / surveys at 9-12 months of infant age (postnatal). * Complete Hammersmith Infant Neurological Examination (HINE), Developmental Assessment of Young Children 2 Edition (DAYC-2), and questionnaires / surveys at 22-26 months of infant age (postnatal). * Permit data collection from electronic medical records for both the mother and infant study participants. Investigators will compare DCC-120 vs. DCC-30 to see which approach is more beneficial to both the mother and baby with CHD.

Research Team

Anup Katheria, MD

Principal Investigator

Sharp Mary Birch Hospital for Women & Newborns

Grecio (Greg) Sandoval, PhD

Principal Investigator

George Washington University Biostatistics Center

Scott Evans, PhD

Principal Investigator

George Washington University Biostatistics Center

Carl H. Backes, MD

Principal Investigator

Nationwide Children's Hospital

Kevin Hill, MD

Principal Investigator

Duke Children's Hospital

Madeline Rice, PhD

Principal Investigator

George Washington University Biostatistics Center

Eligibility Criteria

This trial is for term-born infants with a prenatal diagnosis of congenital heart disease, rated moderate to severe. The mother must be at 37-41 weeks of gestation and give informed consent. Exclusions include surrogacy, certain maternal or fetal health conditions, major chromosomal defects, neuromuscular disorders, and participation in another study affecting cord clamping.

Inclusion Criteria

My unborn baby has been diagnosed with a heart condition rated 3-6 on the FCDSS.

Singleton gestation

Gestational age at labor and delivery admission (randomization) between 37 0/7 - 41 6/7 weeks of gestation inclusive

Exclusion Criteria

Pregnant individual is a gestational carrier or surrogate

Compromise of the pregnant individual (e.g., vasa previa, placental accreta with hypotension)

Fetal demise or planned termination of pregnancy prior to randomization

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either Delayed Cord Clamping at 120 seconds (DCC-120) or Delayed Cord Clamping at 30 seconds (DCC-30) at birth

Immediate at birth

1 visit (in-person)

Follow-up

Participants complete General Movements Assessment (GMA) at 3-4 months, questionnaires at 9-12 months, and HINE, DAYC-2, and questionnaires at 22-26 months postnatal

26 months

Multiple visits (in-person and virtual)

Data Collection

Data collection from electronic medical records for both the mother and infant study participants

Ongoing

Treatment Details

Interventions

• Umbilical Cord Clamping at ~120 seconds
• Umbilical Cord Clamping at ~30 seconds
• Umbilical Cord Milking

Trial Overview The trial compares the effects of delaying umbilical cord clamping for ~120 seconds (DCC-120) versus ~30 seconds (DCC-30) on health and neuromotor outcomes in infants with CHD up to about two years old. It involves assessments at multiple stages postnatal and data collection from medical records.

Participant Groups

Group I: Delayed Cord Clamping at 30 Seconds (DCC-30) Active Control 1 Intervention

The umbilical cord will be clamped between 1 - \<60 seconds following delivery, with a goal of around 30 seconds.

Group II: Delayed Cord Clamping at 120 Seconds (DCC-120) Active Control 2 Interventions

The umbilical cord will be clamped at 60 - 180- seconds following delivery, with a goal of around 120 seconds. In the DCC-120 group, if there is concern for pregnant individual or baby and their doctor is not able to wait until at least 60 seconds, the doctor may do cord milking, which is four gentle squeezes of the umbilical cord pushing blood from the placenta to baby.

Umbilical Cord Clamping at ~120 seconds is already approved in United States, European Union for the following indications:

Approved in United States as Delayed Umbilical Cord Clamping for:

• Prevention of anemia in newborns
• Reduction of need for blood transfusions
• Improvement of iron levels
• Decrease in risk of necrotizing enterocolitis and intraventricular hemorrhage

Approved in European Union as Delayed Umbilical Cord Clamping for:

• Prevention of anemia in newborns
• Reduction of need for blood transfusions
• Improvement of iron levels
• Decrease in risk of necrotizing enterocolitis and intraventricular hemorrhage

Who Is Running the Clinical Trial?

Carl Backes, MD

Lead Sponsor

Trials

1

Recruited

500+

Duke Children's Hospital & Health Center

Collaborator

Trials

1

Recruited

500+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

University of Bristol

Collaborator

Trials

114

Recruited

25,030,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

The George Washington University Biostatistics Center

Collaborator

Trials

27

Recruited

111,000+

Findings from Research

Delayed cord clamping (DCC) significantly benefits newborns by improving hemoglobin levels and reducing the need for blood transfusions, as well as lowering the risk of serious conditions like necrotizing enterocolitis and intraventricular hemorrhage.

A quality improvement project at a university hospital successfully increased DCC rates from 12% to 96% through simple interventions such as provider education and the use of timers, demonstrating that these methods can be easily implemented in other healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Quality Improvement Project to Delay Umbilical Cord Clamping Time. Pauley, AN., Roy, A., Balfaqih, Y., et al.[2022]

In a study involving 260 preterm infants, umbilical cord milking (UCM) resulted in similar neonatal hemoglobin levels compared to delayed cord clamping (DCC), indicating that UCM is an effective alternative for placental transfusion.

UCM was associated with significantly lower rates of neonatal polycythemia and jaundice compared to DCC, suggesting it may be a safer option for preterm infants requiring resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of umbilical cord milking versus delayed cord clamping on preterm neonates in Kenya: A randomized controlled trial. Sura, M., Osoti, A., Gachuno, O., et al.[2021]

A survey of 327 healthcare professionals in Malaysia revealed that while most had positive knowledge about the benefits of delayed cord clamping (DCC) for both term and preterm infants, only 29% reported the existence of guidelines on umbilical cord clamping (UCC) at their workplaces.

Despite the awareness of DCC's benefits, such as increasing neonatal iron stores and reducing risks like intraventricular hemorrhage, this knowledge was not consistently applied in practice, highlighting the need for national guidelines to improve UCC practices in childbirth facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Survey on Current Practices of Umbilical Cord Clamping in Malaysia. Pong, KM., Puasa, N., Mahdy, ZA.[2022]

This pilot study involving 17 women demonstrated that delayed cord clamping (DCC) for at least 3 minutes during uncomplicated cesarean births is feasible, with a successful protocol completion rate of 94%.

There were no significant safety concerns noted, as maternal and neonatal outcomes were comparable to a historical control group, indicating that this method could be safely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing Delayed Umbilical Cord Clamping in Cesarean Birth Using a Novel Method: A Pilot Study of Feasibility and Safety. Welsh, S., Elwell, J., Manister, NN., et al.[2021]

In a study of 113 women undergoing scheduled cesarean deliveries, delayed umbilical cord clamping (at 60 seconds) did not significantly reduce maternal blood loss compared to immediate clamping (within 15 seconds), as measured by changes in hemoglobin levels postoperatively.

However, delayed cord clamping was associated with significantly higher neonatal hemoglobin levels at 24 to 72 hours after birth, suggesting a benefit for the newborns without negatively impacting maternal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Delayed vs Immediate Umbilical Cord Clamping on Maternal Blood Loss in Term Cesarean Delivery: A Randomized Clinical Trial. Purisch, SE., Ananth, CV., Arditi, B., et al.[2020]

Delayed umbilical cord clamping (DCC) in infants with congenital heart disease (CHD) was found to be safe and feasible, with no significant differences in safety measures compared to early clamping (ECC).

DCC resulted in a higher proportion of infants not requiring blood transfusions during hospitalization (43% vs 7% for ECC), suggesting potential benefits in reducing the need for transfusions in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial. Backes, CH., Huang, H., Cua, CL., et al.[2018]

Delayed cord clamping (DCC) for 120 seconds in preterm infants (born at less than 34 weeks' gestation) resulted in significantly higher hematocrit levels compared to early cord clamping (ECC) within 30 seconds, indicating better blood volume and oxygen delivery.

DCC did not increase the risk of hyperbilirubinemia, with lower mean total serum bilirubin levels in the DCC group (6.6 mg/dL) compared to the ECC group (8.7 mg/dL), suggesting that DCC is safe and beneficial for preterm neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of delayed umbilical cord clamping in preterm neonates of less than 34 weeks of gestation: a randomized controlled trial. Rana, A., Agarwal, K., Ramji, S., et al.[2022]

Delayed cord clamping (DCC) significantly improved hematocrit levels at 72 hours in vigorous neonates born via cesarean section compared to umbilical cord milking (UCM), indicating better placental transfusion benefits.

Despite the hematocrit improvement, there were no significant differences in other clinical outcomes such as serum ferritin, bilirubin levels, or the need for phototherapy between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed cord clamping versus cord milking in vigorous neonates ≥35 weeks gestation born via cesarean: A Randomized clinical trial. Murali, M., Sethuraman, G., Vasudevan, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Quality Improvement Project to Delay Umbilical Cord Clamping Time. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of umbilical cord milking versus delayed cord clamping on preterm neonates in Kenya: A randomized controlled trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Survey on Current Practices of Umbilical Cord Clamping in Malaysia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Implementing Delayed Umbilical Cord Clamping in Cesarean Birth Using a Novel Method: A Pilot Study of Feasibility and Safety. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Delayed vs Immediate Umbilical Cord Clamping on Maternal Blood Loss in Term Cesarean Delivery: A Randomized Clinical Trial. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial. [2018]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety of delayed umbilical cord clamping in preterm neonates of less than 34 weeks of gestation: a randomized controlled trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Delayed cord clamping versus cord milking in vigorous neonates ≥35 weeks gestation born via cesarean: A Randomized clinical trial. [2023]