Cord Clamping Among Neonates With Congenital Heart Disease

Official title

CORD-CHD: Clamp OR Delay Among Neonates With Congenital Heart Disease

Overview

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.

Detailed description

* AIM 1: Test the hypothesis that, among neonates with prenatally diagnosed significant CHD (ranking of 3 - 6 on the Fetal Cardiovascular Disease Severity Score \[FCDSS\]), DCC-120 results in lower global rank score (GRS), indicative of better health outcomes, compared with DCC-30. * AIM 2: Test the hypothesis that, among neonates with prenatally diagnosed significant CHD (ranking from 3 - 6 on the Fetal Cardiovascular Disease Severity Score \[FCDSS\]), DCC-120 will result in better neuromotor outcomes at 22-26 months postnatal than DCC-30.

Interventions

• Procedure Umbilical Cord Clamping at ~30 seconds
  Care team will wait to clamp the umbilical between 1-\<60 seconds after birth. 30 seconds is the ideal time of clamping.
• Procedure Umbilical Cord Clamping at ~120 seconds
  Care team will wait to clamp the umbilical cord between 60-180 seconds after birth.120 seconds is the ideal time of clamping
• Procedure Umbilical Cord Milking
  For infants who need their cord clamped before the target in the DCC-120 group. Care team may milk the umbilical cord towards the infant four times. Cord milking should NOT be performed if the delay meets or exceeds 60 seconds. Umbilical cord milking will not be provided among participant-infant dyads in the DCC-30 group.

Primary outcome measures

• Global Rank Score (Infant participant) [Time frame: Up to 30 days post-discharge following congenital heart disease intervention]

Secondary outcome measures (12)

• Neuromotor Outcomes at 3-4 months of age (Infant participant) [Time frame: 3-4 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 3-4 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 3-4 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 9-12 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 9-12 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 22-26 months after birth]
• Impact of infant's congenital heart disease (Parents / Caregivers) [Time frame: 22-26 months after birth]
• Neurodevelopmental Outcomes at 22-26 months (Infant participant) [Time frame: 22-26 months after birth]
• Neurodevelopmental Outcomes at 22-26 months (Infant participant) [Time frame: 22-26 months after birth]
• Parental perspectives of outcomes (Parents / Caregivers) [Time frame: 22-26 months after birth]
• Delivery Complications and Outcomes (Pregnant individual participant) [Time frame: Through hospital discharge (up to 1 month)]
• Delivery Complications and Outcomes (Pregnant individual participant) [Time frame: Through hospital discharge (up to 1 month)]

Eligibility criteria

Inclusion criteria are listed below and will be confirmed prior to randomization:

• Fetal diagnosis of congenital heart disease (CHD) by prenatal ultrasound / echocardiography from local fetal ECHO, conducted on or after 18 weeks of gestation and prior to randomization. The study fetal diagnosis of CHD must be rated as 3 - 6 on the Fetal Cardiovascular Disease Severity Score (FCDSS), as determined by independent evaluators at the CORD-CHD trial ECHO Core at the Children's Hospital of Philadelphia (to determine final FCDSS eligibility for randomization).

For each potential participant that has provided consent, the most relevant diagnostic prenatal ultrasound will be uploaded (shared) between 32 weeks of gestation and randomization for review by the ECHO Core. The ECHO Core will make the final FCDSS determination for eligibility status and stratification assignment.\]

\[NOTE: A fetal diagnosis of CHD rated as 3 - 6 FCDSS per local review, including borderline cases, will be used to determine preliminary eligibility for consent. Among borderline cases, eligible patients will be included if there is a reasonable expectation of the need for surgery or cardiac catheterization during the birth hospitalization.\]

• Singleton gestation.
• Gestational age at randomization for impending deliveries between 37 0/7 - 41 6/7 weeks of gestation inclusive based on clinical information and evaluation of the earliest ultrasound determined using criteria proposed by the American Congress of Obstetricians and Gynecologists (ACOG), the American Institute of Ultrasound in Medicine and the Society for Maternal-Fetal Medicine.

\[NOTE: Pregnant individuals who were admitted to the delivery hospital prior to 37 0/7 weeks of gestation remain eligible to randomize, provided they deliver within the 37 0/7 and 41 6/7 weeks "eligibility window". Alternatively, if an eligible dyad is randomized at or just prior to 41 6/7 weeks, they remain in trial.\]

• Consent for the participant and their infant

Exclusion criteria are listed below and will be confirmed prior to randomization:

Exclusion Criteria for Pregnant Individuals:

• Pregnant individual is a gestational carrier or surrogate.
• Compromise of the pregnant individual (e.g., vasa previa, placental accreta with hypotension, placental abruption, amniotic fluid embolism, uterine rupture, uterine inversion, disseminated intravascular coagulation), as determined by local care team

\[NOTE: There is no limitation on pregnant individual's age\]

Fetal Exclusion Criteria:

• Fetal demise or planned termination of pregnancy prior to randomization
• Tachyarrhythmia requiring transplacental therapy
• Fetal hydrops, severe
• Planned fetal surgery
• Diaphragmatic hernia, omphalocele, gastroschisis, intestinal atresia
• Major chromosomal defects (e.g., Trisomy 13, 18) identified prenatally; Trisomy 21 is allowed
• Disease or disorder impacting candidacy for neonatal cardiac interventions
• Parents choosing to limit treatment

Pregnancy Exclusion Criteria:

• Delivery planned at an institution not affiliated with or does not refer to a CORD-CHD participating site
• Participation in another prenatal interventional study that influences cord clamping or perinatal morbidity or mortality

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

United States · 18 centers

• Children's of Alabama — Birmingham
• Cedars-Sinai Medical Center — Los Angeles
• Children's Hospital of Orange County — Orange
• Lucile Packard Children's Hospital Stanford — Palo Alto
• Sharp Mary Birch Hospital for Woman and Newborns — San Diego
• UF Health Shands Children's Hospital — Gainesville
• Johns Hopkins Children's Center — Baltimore
• Children's of Mississippi — Jackson
• … and 10 more centers

Canada · 3 centers

• Stollery Children's Hospital, University of Alberta — Edmonton
• IWK Health Centre — Halifax
• The Hospital for Sick Children — Toronto

Publications

• Marzec L, Zettler E, Cua CL, Rivera BK, Pasquali S, Katheria A, Backes CH. Timing of umbilical cord clamping among infants with congenital heart disease. Prog Pediatr Cardiol. 2020 Dec;59:101318. doi: 10.1016/j.ppedcard.2020.101318. Epub 2020 Oct 28. PMID 34113067
• Backes CH, Huang H, Cua CL, Garg V, Smith CV, Yin H, Galantowicz M, Bauer JA, Hoffman TM. Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial. J Perinatol. 2015 Oct;35(10):826-31. doi: 10.1038/jp.2015.89. Epub 2015 Jul 30. PMID 26226244
• Fite EL, Rivera BK, McNabb R, Smith CV, Hill KD, Katheria A, Maitre N, Backes CH. Umbilical cord clamping among infants with a prenatal diagnosis of congenital heart disease. Semin Perinatol. 2023 Jun;47(4):151747. doi: 10.1016/j.semperi.2023.151747. Epub 2023 Mar 18. No abstract available. PMID 37002126

Identifiers

NCT: NCT06153459 · STUDY00003337 · UG3HL166794 · UG3HL166799

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗