Intact-cord Stabilisation and Physiology-based Cord Clamping in Caesarean Sections (INTACT-1)

Feasibility-testing of Extra-uterine Placental Transfusion to Facilitate Intact-cord Stabilisation and Physiology-based Cord Clamping for Term and Preterm Infants Delivered by Acute or Planned Caesarean Section

This is a feasibility study with historical control designed to evaluate whether delivery of the placenta prior to umbilical cord clamping at caesarean sections is a feasible, safe and acceptable way of facilitating intact-cord stabilisation of preterm and term newborn infants.

Study Overview

• Status: Recruiting
• Conditions: Infant Conditions; Cesarean Section
• Intervention / Treatment: Procedure: Extrauterine placental transfusion and physiology-based umbilical cord clamping; Procedure: Extrauterine placental transfusion, intact cord stabilisation and physiology-based umbilical cord clamping; Procedure: Delayed umbilical cord clamping

Detailed Description

Standard procedure when an infant is delivered by caesarean section is to wait to clamp the umbilical cord for approximately one minute, and then transfer the infant to a designated area for assessment and stabilisation. If the infant needs immediate resuscitation, the umbilical cord is cut earlier to expedite transfer to resuscitation equipment and qualified care (including stimulation, clearing airways and respiratory support).

It has been suggested in several pilot and clinical studies that keeping the umbilical cord intact during the infant's transition from intra- to extrauterine life may improve outcomes and survival, especially for preterm infants. Since length of the umbilical cord is limited, finding ways to avoid cutting the cord while initiating stabilisation and care is warranted. To date, most studies have reported on interventions that involve mobile resuscitation equipment; thus keeping the infant in close proximity to the mother. This may be extra challenging in caesareans sections, especially due to space constraints and maintenance of sterility.

The objective of this study to determine whether extra-uterine placental transfusion to facilitate intact-cord stabilisation and physiology-based cord clamping for infants delivered by caesarean section is feasible, safe and acceptable for infants and their mothers, as well as for involved personnel.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Elisabeth Sæther, RNM/MSc; Phone Number: +4792889455; Email: elisabeth.sether@helse-mr.no
• Study Contact Backup: Name: Beate H Eriksen, MD/PhD; Phone Number: +4747238508; Email: beate.horsberg.eriksen@helse-mr.no

Study Locations

• Norway
  • Møre And Romsdal
    • Ålesund, Møre And Romsdal, Norway, 6026
      • Recruiting
      • Møre and Romsdal Hospital Trust
      • Contact: Beate H Eriksen, MD/PhD; Phone Number: +4747238508; Email: beate.horsberg.eriksen@helse-mr.no
      • Contact: Elisabeth Saether, RNM/MSc; Phone Number: +4792889455; Email: elisabeth.sether@helse-mr.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 9 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Women planning to give birth at Clinic Ålesund are candidates for enrolment in this clinical study. Pregnant women will be invited to participate when called for second trimester routine ultrasound scan. They will be asked for preliminary consent in the event of intrapartum or planned cesarean section and fullfilment of inclusion cirteria. Women having ultrasound scans done elsewhere, who are later referred to Clinic Ålesund, may be invited to participate after admission, but will not be approached for consent if delivery is imminent. Both parents (if applicable) must consent on behalf of their infant

Description

Inclusion Criteria:

• live infants (singletons or dichorionic twins) born in gestational week 32+0 to 42+0
• delivered by CS in regional anaesthesia
• immediate care may be planned with involved personnel prior to delivery
• informed maternal consent is obtained (parental consent on behalf of the unborn child).

Exclusion Criteria:

• twins, triplets
• significant congenital malformations
• placenta complications with high risk of abnormal maternal blood loss
• severe fetal distress requiring cesarean section in general anaesthesia (crash CS)
• participation in any other clinical study within the last month
• not sufficient time for preparations or collection of maternal/parental consent
• mother does not comprehend Norwegian or English

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Self-breathing infants; Vigorous infants with spontaneous onset of respiration within one minute after delivery by cesarean section, receiving extra-uterine placental transfusion and physiology-based cord clamping	Procedure: Extrauterine placental transfusion and physiology-based umbilical cord clamping; Placenta is delivered prior to umbilical cord clamping to facilitate placental transfusion. Infant and placenta are transferred to a warmer in an adjacent room, the umbilical cord is clamped and cut when the cord is white, pulsations have ceased and the infants is breathing regularly (within 10 minutes after delivery)
Infants with respiratory support; Infants with no or poor spontaneous onset of respiration after delivery by cesarean section, receiving extra-uterine placental transfusion, intact-cord stabilisation (any respiratory support) and physiology-based cord clamping after transfer to resuscitation table	Procedure: Extrauterine placental transfusion, intact cord stabilisation and physiology-based umbilical cord clamping; Placenta is delivered prior to umbilical cord clamping to facilitate placental transfusion. Infant and placenta are transferred to a warmer in an adjacent room and necessary respiratory support is initiated (CPAP or PPV) by a neonatal team. The umbilical cord is clamped and cut when the cord is white, pulsations have ceased and the infant is breathing regularly with or without support (at maximum 10 minutes after delivery)
Historical control group; Infants delivered by cesarean section in a time period when delayed cord clamping after 1-3 minutes was default procedure. Less-than-vigorous infants needing respiratory support or full resuscitation had their umbilical cords cut early (within 30 seconds)	Procedure: Delayed umbilical cord clamping; Umbilical cord is clamped and cut minimum 60 seconds after delivery to facilitate placental transfusion. Placenta is delivered after cord clamping. Infants needing respiratory support or other stabilisation are transferred to a warmer in the adjacent room where a neonatal team is waiting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention fidelity (cohort 1)	Extra-uterine placental transfusion + physiology-based cord clamping applied (for vigorous infants), measured as proportion of completed checklists. Registered by staff, using checklists in the operating room.	First 10 minutes after delivery
Intervention fidelity (cohort 2)	Extra-uterine placental transfusion + intact-cord stabilisation + physiology-based cord clamping applied (for infants needing any respiratory support), measured as proportion of completed checklists. Registered by staff, using checklists in the operating room.	First 10 minutes after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First cry or breathing effort (cohort 1+2)	Time from birth to infant's first cry or attempt of spontaneous breathing (measured in minutes and seconds). Assessed by attending midwife or pediatric registrar. Registered on a checklist by a time-keeper in the operating room.	Within 10 minutes after birth
Apgar score (cohort 1+2)	Composite of heart rate, breathing effort, skin colour, muscle tone and reflexes (each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Assessed by the attending midwife or pediatric registrar, registered on a special data collection sheet by a timekeeper in the operating room	At 1 minute after birth
Delivery of placenta (cohort 1+2)	Time from birth to delivery of the placenta (measured in minutes ans seconds), registered on checklist by a time-keeper in the operating room	At 1 minute (+/- 10 seconds) after birth
Duration of respiratory support (cohort 2)	Duration of respiratory support (CPAP or PPV), measured in minutes and seconds. Registered on a special data collection sheet by the attending neonatal team or midwife	First 10-15 minutes after birth
Apgar score	Composite of heart rate, breathing effort, skin colour, muscle tone and reflexes (each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Assessed and registered on a special data collection sheet by the attending midwife or neonatal nurse	At 5 minutes after birth (cohort 1+2)
Stabilisation (cohort 2)	Time from birth to stabilisation achieved (regular breathing, heartrate (HR) >100, Saturation (SpO2) >85%, inspired oxygen fraction (FiO2) <40%. Measured in minutes and seconds. Assessed and registered on a special data collection sheet by the attending midwife or neonatal nurse	Within 10-20 minutes after birth
Cord clamping time (cohort 1+2)	Time from birth to umbilical cord clamping (measured in minutes and seconds), registered on a special data collection sheet by the attending midwife	Within 10 minutes after birth
Apgar score (cohort 1+2)	Composite of heart rate, breathing effort, skin colour, muscle tone and reflexes (each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Assessed and registered on a special data collection sheet by the attending midwife or neonatal nurse	At 10 minutes after birth
Skin-to-skin-contact (cohort 1+2)	Time from birth to continuous skin-to-skin contact between infant and mother (or other parent), measured in minutes. Registered on a checklist by the attending midwife or neonatal nurse	Within 2 hours after birth
Residual placenta volume (cohort 1+2)	Drained and weighed residual blood volume from placenta and umbilical cord after cord clamping (measured in grams, converted to milliliters by a ratio of 1.05:1). Registered by the attending midwife or assistant nurse	Within 10-15 minutes after birth
Dry-electrode ECG attached (cohort 1+2)	Time from birth to dry-electrode ECG (NeoBeat) is attached to the infant's chest or abdomen (measured in seconds). Registered on a checklist by a time-keeper in the operating room.	Within 10 seconds after birth
Heart rate (cohort 1+2)	Infant's heart rate after birth measured by a dry-electrode ECG (NeoBeat). Registered on a special data collection sheet by a timekeeper or attending midwife. Data are transferred wirelessly from the NeoBeat device to the Liveborn App (installed on a designated tablet) for storage and further analysis.	First 10 -15 minutes after birth
Umbilical cord blood samples (cohort 1+2)	Time from birth to sampling for umbilical cord blood gas analysis (arterial and venous) completed (measured in seconds). Registered on a checklist by a time-keeper in the operating room.	Within 40-60 seconds after birth
Respiratory support (cohort 2)	Type of respiratory support applied. Alternatives are: CPAP (Continuous Positive Airway Pressure) or PPV (Positive Pressure Ventilation) Registered on a special data collection sheet by the attending neonatal team or midwife	First 10-15 minutes after birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-cesarean infection (all cohorts)	Prevalence of maternal post-operative wound infection needing antibiotic therapy. Registered in a dedicated paper form in the patient's record by the attending obstetrician	Within14 days after surgery (cesarean section)
Abnormal blood loss (all cohorts)	Prevalence of abnormal maternal blood-loss during surgery and wound closure (more than 1000 ml). Estimated by staff by visual inspection and count of blood-soaked compresses. Registered in the patient's record by the attending obstetrician	45 minutes from incision time
Low Apgar score (all cohorts)	Prevalence of infant Apgar score less than 7 (mild asphyxia), composite of heart rate, breathing effort, skin colour, muscle tone and reflexes (subscale range from 0-2). Assessed and registered on a special data collection sheet and in the patient's record by the attending midwife or neonatal team	At 5 minutes after birth
Infant hypothermia (all cohorts)	Prevalence of infant rectal temperature less than 36.5 degrees celsius, measured by a thermometer and registered on a special data collection form and in the patient's record by the attending midwife or neonatal team	Within 2 hours after birth
Pre-operative maternal Hemoglobin	Maternal Hemoglobin value from a venous blood sample taken before cesarean section, measured in grams per 100 ml. Registered on a checklist and in the patient's record by the midwife	Within 48 hours before cesarean section
Post-operative maternal Hemoglobin	Maternal Hemoglobin value from a venous blood sample taken after cesarean section, measured in grams per 100 ml. Registered on a checklist and in the patient's record by the midwife	Within 24 hours after cesarean section
Admittance to Neonatal Intensive Care Unit (NICU) (all cohorts)	Indication for infant's admittance to neonatal intensive care unit after birth. Assessed by the attending pediatric registrar or neonatologist. Registered in a special data collection sheet and in the patient's record	Within 24 hours after birth
Days in NICU (all cohorts)	Infant's length of stay i neonatal intensive care unit, measured in days. Registered on a checklist and in the patient's record by the neonatal team	Maximum 2 months

Collaborators and Investigators

• Sponsor: Helse Møre og Romsdal HF
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Beate H Eriksen, MD/PhD, Møre and Romsdal Hosptal Trust / Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: cesarean section; umbilical cord clamping; placental transfusion; infant stabilisation; intact umbilical cord
• Other Study ID Numbers: 399101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No