Intact-cord Stabilisation and Physiology-based Cord Clamping in Caesarean Sections

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cesarean Section, Infant Conditions

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 32 Weeks
Maximum Age: 42 Weeks

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Self-breathing infants<br>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<br>* 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)<br>|
| Infants with respiratory support<br>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<br>* 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)<br>|
| Historical control group<br>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<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infant stabilisation, intact umbilical cord, umbilical cord clamping, placental transfusion, cesarean section