Reducing Respiratory Distress After Elective Caesarean Birth Through Knee-chest-flexion: a Randomized Controlled Trial

Making Elective Caesarean Safer for Infant's Lungs by Reducing Respiratory Distress Using Knee-chest-flexion: a Randomized Controlled Trial

Planned caesarean birth is a risk factor for the development of neonatal respiratory distress commonly known as transient tachypnoea of the newborn. This is due to the absence of labor physiology which facilitates the clearance of fetal lung fluid. We hypothesized that by mimicking flexion induced by uterine contractions by manually performing knee-to-chest flexion directly at birth to achieve expulsion of excess lung liquid, we could reduce the incidence of respiratory distress in term children born by planned CS.

The goal of this clinical trial is to test whether performing a knee-to-chest flexion maneuver directly after elective caesarean section will decrease the incidence of respiratory distress in term infants when compared to the standard care

Study Overview

• Status: Recruiting
• Conditions: Transient Tachypnea of the Newborn
• Intervention / Treatment: Procedure: Knee-to-chest-flexion manoeuvre

Detailed Description

One of the major risk factors for term/near-term infants to develop respiratory distress (RD) is when they are born by elective caesarean section (CS). While this form of RD, commonly diagnosed as transient tachypnea of the newborn (TTN), is considered to be self-limiting, the severity of RD often leads to unexpected admission to the pediatric ward for respiratory support. TTN has also been associated and asthma, bronchiolitis, and other wheezing syndromes later in life. In low- and middle-income settings, where neonatal intensive care resources are limited, a considerable proportion of babies in need of respiratory support do not survive.

There is now strong physiological evidence that RD after elective cesarean section is caused by this greater volume of airway liquid present at birth, which is due to the absence of labor. During labor, uterine contractions contribute to the flexion of the fetus which increases abdominal and transpulmonary pressure. This elevates the diaphragm, resulting in lung liquid loss via nose and mouth. Flexion induced by uterine contractions could be mimicked by manually performing knee-to-chest flexion directly at birth, to achieve expulsion of excess lung liquid. When applying KCF, we essentially bring the newborn back into fetal position, similar to the holding position applied for performing lumbar puncture in neonates.

If this simple intervention has shown to improve neonatal outcome in the clinical setting, KCF will undoubtedly be an extremely cost-effective health care innovation. The maneuver is easy-to-teach to any clinician performing cesarean section. KCF will be performed conform standard gentle care and is likely to be entirely harmless. These advantages (easy-to-teach, no cost, no harm) are relevant across all settings, but may be particularly appealing in low-income settings, where neonatal follow-up and access to neonatal intensive care are often either impossible or limited. It is therefore of outmost importance to test this intervention in a larger institution adapted to performing high-quality clinical research in a low- or middle-income country.

We now hypothesize that performing a knee-to-chest flexion performed directly after birth will reduce the incidence of respiratory distress in term children born by elective caesarean section.

Objective: To test whether performing a knee-to-chest flexion (KCF) manoeuvre directly after elective CS will decrease the incidence of respiratory distress in term infants when compared to standard care.

Study design: Single-center randomized controlled trial Study population: Infants born by elective CS, 37-42 weeks gestational age. Simple randomization will be done to assign participants in either an interventional group or a control group Intervention: As soon as the infant is out of the uterus a KCF is performed for 30 seconds while the infant remains attached to the cord. Except for KCF, the infant will receive normal routine care and there are no co-interventions.

Control: As soon as the infant is out of the uterus normal routine care is given.

Study parameters: The primary outcome is the occurrence of respiratory distress

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

In the group of term infants born after elective caesarean there is a 7% risk for respiratory distress, of which 10% is complicated by PPHN. Although KCF is a new intervention performed directly after birth for 30 seconds, the technique used is similar to the way infants are held and positioned during a lumbar puncture. As the infants in this study population are in good condition before birth and would otherwise also have been exposed to large intrathoracic pressures generated by uterine contractions during labor, we expect that there is no added risk when the maneuver is performed gently and with care. We recently demonstrated that performing KCF directly after birth is feasible and safe after elective CS. As the percentages of elective CS are increasing worldwide both in developing and developed countries, there is a large potential to reduce morbidity, admissions at NICU and pediatric wards, and healthcare costs in this group of infants.

• Study Type: Interventional
• Enrollment (Estimated): 562
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Febronia L Shirima, MD; Phone Number: +255714143368; Email: febbylaw17@gmail.com
• Study Contact Backup: Name: Tupokigwe Jana; Phone Number: +255784734602; Email: t.jana@kcri.ac.tz

Study Locations

• Tanzania
  • Kilimanjaro
    • Moshi, Kilimanjaro, Tanzania, P.O.Box 3010
      • Recruiting
      • Kilimanjaro Christian Medical Centre
      • Contact: Febronia L Shirima, MD; Phone Number: +255714143368; Email: febbylaw17@gmail.com
      • Contact: Bariki Mchome, PhD; Phone Number: +255784280027; Email: barikimchome@gmail.com
      • Sub-Investigator: Febronia L Shirima, MD
      • Principal Investigator: Bariki Mchome, PhD
      • Principal Investigator: Blandina T Mmbaga, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants born by planned CS, 37-42 weeks gestational age

Exclusion Criteria:

• infants with significant congenital malformations influencing cardiopulmonary transition
• infants whose mother has gestational diabetes, pre-eclampsia, eclampsia
• infants where immediate cord clamping is needed due to resuscitation of the baby or mother
• when spontaneous contractions before the cesarean section is done.
• KCF will not be done to infants who will start breathing instantly after being extracted from the uterus so as not to interfere with their breathing efforts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: interventional arm; As soon as the infant is out of the uterus a Knee-to-chest flexion (KCF) maneuver is performed for 30 seconds while the infant remains attached to the cord. When applying KCF, we essentially bring the newborn back into the fetal position, flexing the knees to the chest. This is similar to the holding position applied for performing lumbar puncture in neonates. Except for KCF, the infant will receive normal routine care and there are no co-interventions.	Procedure: Knee-to-chest-flexion manoeuvre; The obstetrician will place one hand at the neck and shoulder of the baby and gently bend the infant into dorsiflexion while with the other hand bending the hips and knees against the abdomen and chest (squatting into fetal position). This holding position will be continued for 30 seconds, while compression of the umbilical cord is avoided to maintain an undisturbed umbilical circulation to and from the infant during KCF.
No Intervention: control; As soon as the infant is out of the uterus normal routine care is given

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
respiratory distress	newborns who have any signs of respiratory distress such as tachypnoea, nasal flaring, chest indrawing, grunting, cyanosis	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse outcome of knee-to-chest flexion maneuver	any signs of adverse outcomes from knee to chest flexion maneuver such as Hematoma on extremities, abdomen, or chest within 24 hours after birth	24hours

Collaborators and Investigators

• Sponsor: Kilimanjaro Clinical Research Institute
• Collaborators: Leiden University Medical Center
• Investigators: Principal Investigator: Bariki Mchome, PhD, Kilimanjaro Christian Medical Centre; Principal Investigator: Blandina T Mmbaga, PhD, Kilimanjaro Clinical Research Institute; Principal Investigator: Febronia L Shirima, MD, Kilimanjaro Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): February 14, 2025
• Study Completion (Estimated): February 14, 2025

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Estimated): February 21, 2024

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: planned caesarean birth
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Infant, Premature, Diseases; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome; Tachypnea; Transient Tachypnea of the Newborn
• Other Study ID Numbers: NIMR/HQ/R.8a/Vol.IX/4331

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual Participant Data that underlies results in a publication will be shared
• IPD Sharing Time Frame: Beginning 3 months following publication. No end date
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to A.B.te_Pas@lumc.nl. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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