Clinical trial NCT06278415: Physiologically Based Cord Clamping To Improve Neonatal Outcomes After Elective Cesarean Delivery
Official title: Pilot Prospective Unblinded Randomized Controlled Study Assessing the Efficacy and Safety of Physiologically Based Cord Clamping Versus Standard Delayed Cord Clamping After Elective Scheduled Cesarean Delivery of Full-term Newborn
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Transient Tachypnea of the Newborn
Keywords: Full-term baby
Scheduled c-section
Neonatal respiratory morbidity
Physiological based-cord clamping
Lead sponsor: Queen Fabiola Children's University Hospital
Sponsor class: OTHER
Collaborators: name: The Belgian Kids Fund
name: Fonds IRIS-Recherche
name: Ars Statistica
First posted: 2024-02-26
Enrollment: 50
Sex: ALL
Minimum age (years): 37
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Before birth, the baby's lungs are filled with fluid and babies do not use the lungs to breathe, as the oxygen comes from the placenta. As delivery approaches, the lungs begin to absorb the fluid. After vaginal delivery, the umbilical cord is clamped and cut after a delay that allows some of the blood in the umbilical cord and placenta to flow back into the baby. Meanwhile, as the baby breathes for the first time, the lungs fill with air and more fluid is pushed out. However, it does not always work out that way. Some babies need to be delivered via cesarean section, a surgical delivery requiring incisions through the abdominal and uterine walls. After cesarean section, the mother is often unable to hold the baby close right away as a result of her own post-surgical care. Moreover, a baby born by planned cesarean section may have breathing problems because of extra fluid staying in the lungs. Thus, the baby must breathe quicker and harder to get enough oxygen enter into the lungs. Although the baby is usually getting better within one or two days, the treatment requires close monitoring, breathing help, and nutritional help as the baby is too tired to suck and swallow milk. Sometimes, the baby cannot recover well and show greater trouble breathing needing intensive care. This further separates the mother and her baby. A possible mean to help the baby to adapt better after cesarean section while staying close to the mother is to delay cord clamping when efficient breathing is established, either spontaneously or after receiving breathing help at birth. In this study, we intend to test this procedure in term infants born by planned cesarean section and see whether the technique helps the baby to better adapt after birth and to better initiate a deep bond with the mother.

Detailed description: The successful transition from fetal to neonatal life is a major physiological challenge that requires the coordination of lung developmental processes, which culminate with the formation of a diffusible alveolar-capillary barrier, adequate pulmonary vasoreactivity, mature surfactant system, and clearance of lung fluid. During fetal life, gas exchange does not take place in fetal lungs but in the placenta. High pulmonary vascular resistance diverts blood flow to the left atrium through the foramen ovale and to the aorta via the ductus arteriosus. The placental circulation receives 30-50 % of the fetal cardiac output and is the major source of venous return to the fetal heart. Therefore, the umbilical venous return determines the preload for the left ventricle. Shortly before birth and during labor, the lungs undergo important transitional changes. The reabsorption of lung fluid within the airways is initiated during labor by adrenaline-induced activation of sodium channels. Uterine contractions during labor and the onset of inspiration after umbilical cord clamping generate a high transpulmonary pressure gradient leading to additional clearance of fluid from the airways into the surrounding tissue . Following the first breath and lung aeration, oxygen-induced vasodilation leads to a sudden rise in pulmonary blood flow and left atrial pressures, which closes the foramen ovale. Meanwhile, systemic vascular resistance increases above the level of pulmonary vascular resistance after placental removal, which reverses blood flow across the ductus arteriosus and induces ductal closure in response to high oxygen tension.

The route of delivery can impact the success of adaptation to extrauterine life. Over the past 30 years, the rate of cesarean deliveries has increased worldwide. In Belgium, this can be as high as 20% of all deliveries. A subset of cesarean deliveries is scheduled in term infants in the absence of spontaneous labor when vaginal delivery is considered as too risky for maternal and/or child health. The so-called iterative cesarean delivery, which is usually considered as a routine and harmless option, can however alter neonatal health. By contrast with vaginal delivery, infants born at term by iterative cesarean delivery have to adapt despite larger volumes of fluid within airways and interstitial tissue resulting from a limited rise in transpulmonary pressure and adrenaline-induced fluid reabsorption. Subsequently, the retention of lung fluid is responsible for transient tachypnea of the newborn, a respiratory distress that is usually considered as mild, transient, and without sequelae. Moreover, infants born by elective cesarean delivery exhibit a higher risk of positive pressure ventilation resuscitation at birth, admission to the neonatal intensive care unit (NICU), and severe hypoxic respiratory failure requiring mechanical ventilation in the most severe cases. In addition to increased neonatal morbidity, iterative cesarean section can impact mother-infant relationship. After vaginal delivery, immediate skin-to-skin contact during the first minute after birth is the natural process recommended to support mother-infant bonding and promote early onset of breastfeeding. Despite efforts made to start skin-to-skin contact as early as possible after cesarean delivery, immediate contact is practically difficult to implement. In our institution, the infant is usually shortly separated from the mother after umbilical cord clamping to provide first care by a pediatrician before returning on the mother's chest or on the father's chest depending on parental wishes and maternal well-being during the operation. The separation between the mother and her newborn can be further extended in the case of NICU admission for transient tachypnea.

Beside the route of delivery, the timing of umbilical cord clamping can profoundly affect the process of neonatal cardiorespiratory transition. Immediate cord clamping reduces the venous return to the heart, which transiently decreases heartbeats, cardiac output and cerebral blood flow before respiration initiates and pulmonary blood flow increases. Delayed cord clamping for longer than 60 seconds improves the transfusion of blood from the placenta to the newborn. Moreover, it can increase neonatal hemoglobin levels, improve long-term iron stores, and improve neurodevelopmental outcomes. Nevertheless, in both clinical research setting and daily practice, delayed cord clamping lasts rarely more than one minute during cesarean section. More recently, another approach, referred to as physiologically based cord clamping (PBCC), has been proposed to delay cord clamping up to 5 minutes after the onset of ventilation. PBCC allows to start lung aeration while on placental support and, therefore, promotes hemodynamic transition by increasing pulmonary blood flow and maintaining left ventricle preload. This strategy has been demonstrated efficient in preterm lambs and is feasible in very preterm infants, via the use of a purpose-designed resuscitation table that allows delayed cord clamping, maintenance of body temperature, and concomitant respiratory support where necessary. First experience has reported good parental acceptance of the procedure. Because PBCC has not been reported in term infants at risk of respiratory distress after birth, the present project aims to assess whether PBCC in term infants born by elective cesarean section would not be inferior to standard umbilical cord clamping with regards to adaptation to extrauterine life, respiratory morbidity, quality of mother-infant bonding, and maternal safety.

Eligibility criteria: Inclusion Criteria:

Pregnant women followed-up in Brugmann University Hospital will be eligible to participate if:

1. Scheduled for cesarean delivery (business days and daily working hours)
2. Singleton pregnancy
3. Cesarean section scheduled at or after 37 weeks gestational age

Exclusion Criteria:

1. Fetal anomalies (congenital malformations, anemia, growth restriction with abnormal Dopplers)
2. Abnormal placentation (placenta previa)
3. Signs of fetal distress necessitating an emergency cesarean section
4. Spontaneous labor before cesarean section
5. Maternal health issue including severe anemia (defined as hemoglobin level \< 7 g/dL), preeclampsia, and bleeding disorders
6. Maternal refusal of the use of blood products.
7. General anesthesia for cesarian section
8. Planned cord blood banking
9. Total language barrier without possibility of translation

Primary outcomes:
measure: Rate of neonatal mortality
timeFrame: within 28 days of delivery
measure: Rate of neonatal resuscitation
timeFrame: within first 10 minutes of life
measure: Rate of neonatal respiratory morbidity
timeFrame: within first 24 hours of life
measure: Number of admission to the NICU or special care baby unit
timeFrame: within first 72 hours of life
Secondary outcomes:
measure: Success of PBCC
timeFrame: within first 10 minutes of life
measure: Time to first breath/cry
timeFrame: post delivery
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Changes in physiological variables during neonatal transition
timeFrame: within first 10 minutes of life
measure: Early neonatal parameters
timeFrame: within the first 3 hours of life
measure: Early neonatal parameters
timeFrame: within first 24 hours of life
measure: Hemoglobin level
timeFrame: at 48 hours of life
measure: Bilirubin level
timeFrame: at 48 hours of life
measure: Number of neonatal adverse events
timeFrame: within first 72 hours of live
measure: Maternal perioperative parameters
timeFrame: at Day 1 post delivery
measure: Maternal perioperative parameters
timeFrame: at Day 1 post delivery
measure: Maternal perioperative parameters
timeFrame: at Day 1 post delivery
measure: Maternal perioperative parameters
timeFrame: at Day 1 post delivery
measure: Number of maternal adverse events
timeFrame: within first 2 weeks post delivery
measure: Rate of maternal-infant bonding
timeFrame: up to 2 weeks post delivery
measure: Rate of maternal-infant bonding
timeFrame: at 2 weeks post delivery
measure: Rate of maternal-infant bonding
timeFrame: at 2 weeks post delivery
measure: Child developmental assessment
timeFrame: at 2 weeks postnatally
measure: Parental satisfaction survey
timeFrame: at 2 weeks post delivery
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: Hôpital Universitair Des Enfants Reine Fabiola
Study officials:
affiliation: HUDERF
name: Anna AMORUSO
role: PRINCIPAL_INVESTIGATOR
References: