The primary outcome is the occurrence of neonatal respiratory morbidity within 24 hours after birth. Painful contractions. Progression of labour after stopping OCT. Nonreassuring fetal heart rate pattern during OCT.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
gezonde zwangerschap met sectio indicatie (electief)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be the rate of respiratory morbidity between infants
in the study group (OCT prior ECS) and the control group (no OCT prior ECS).
Neonatal respiratory morbidity is characterized by one or more of the following
criteria, tachypnea (more than 60 breaths per minute), expiratory grunting,
chest wall retractions, flaring of the nostrils, cyanosis, need for oxygen or
any positive pressure support present for at least two hours within the first
48 hours after birth. Corresponding diagnoses of neonatal respiratory morbidity
are usually but not exclusively respiratory distress syndrome (RDS) or
transient tachypnea of the newborn (TTN).
Positive pressure support includes continuous positive airway pressure (CPAP)
or high-flow nasal cannula or mechanical ventilation.
Neonatal death within 48 hours after delivery are also included in the
composite outcome as competing events.
Secondary outcome
* Any admission of the infant to a NICU within 48 hours irrespective of
diagnosis
* Fetal stress parameters:
* Copeptin and pH in arterial umbilical cord blood (serum tubes * stability
24-48h at room temperature
* Course of postnatal weight change and maximal postnatal weight loss
* Bilirubin at least one measurement including time point during postnatal
hospital stay (TCB, blood)
* Maternal total blood loss
* Duration of exclusive breastfeeding (up to 10 isolated formula feedings are
included)
* Duration of total breastfeeding (day of last breastfeeding)
* Retrospectively, antibiotics during pregnancy: when and how long
* Prospectively, antibiotics postpartum: when and what
* Basel, Zürich, St. Gallen: For microbiom analysis collection of infant*s
stool and mother*s milk * biobanking until end of study,
* Basel: Total nucleated cell count (TNC) and CD34+ cells in the umbilical cord
blood (The pregnant woman must agree to donate umbilical cord blood.
* All: Weight, length, BMI until 1 year (parent parameters as well)
* Any antibiotics during pregnancy and in childhood
Background summary
Caesarean section is a life-saving obstetrical operation for birth
complications and high risk deliveries. However, caesarean delivery rates are
rising worldwide and exceed in many countries by far the medical need 1. Every
pregnant woman should be informed about the benefits and risks of a caesarean
section and vaginal birth. Some women give more weight to the risks of vaginal
delivery than to those of a caesarean section. On the other hand, there are
pregnancies where vaginal delivery is not recommended but contractions are not
contraindicated. For this reason, the caesarean section rate will remain
significant even if no caesarean sections are performed without a medical
indication. High caesarean rates are associated with increased maternal and
neonatal morbidity, such as neonatal respiratory disorders 2*4, a significant
increase in the predisposition to allergic and autoimmune diseases 5,6 and
obesity 7.
Conversely, the process of vaginal birth prepares the fetus for the
extra-uterine environment and confers respiratory, cardiovascular and
homeostatic advantages to the newborn8, and is considered to play a critical
role in preparing the mother to bond with and breastfeed her infant9*11.
Vaginal delivery of a healthy infant provokes a unique surge in stress hormones
of the infant incommensurable with levels in children or adults measured in any
other situation, best described when measuring the stable by-product of
arginine vasopressin (AVP), copeptin8. In contrast, newborns delivered by
caesarean section performed before the onset of labour and rupture of the
membranes, also known as elective caesarean section (ECS), have low copeptin
concentrations at birth unless other stressors are present, including
chorioamnionitis or intrauterine growth restriction (IUGR)12,13. In newborns
delivered by caesarean section after a trial of labour, copeptin concentrations
rise between these two extremes14.
Copeptin is a nonspecific but highly sensitive plasma indicator of stress, and
a more sensitive marker than cortisol 15. It derives from the prohormone of AVP
and is secreted in equimolar ratio to AVP. Pulsatile secretion, platelet
binding and a short half-life make direct measurement of AVP unfeasible in the
clinical setting. Copeptin, however, remains stable in blood collection tubes
and is readily measured by sandwich immunoassay15. Animal studies suggest that
AVP regulates lung fluid secretion and reabsorption during transition from an
uterine to an air-breathing environment and that fetal AVP release is triggered
by uterine contractions8.
In a randomized, placebo-controlled trial, in women with singleton pregnancies
who were scheduled to undergo ECS, we found that a brief oxytocin challenge
test, also referred to as trial of labour, to mimic natural labour before
caesarean delivery triggered a mild fetal stress response16. We concluded that
the excellent acceptance of the induced labour and the absence of any safety
issues favour the project of a larger trial geared to clinical endpoints such
as neonatal respiratory morbidity and breastfeeding success.
Study objective
The primary outcome is the occurrence of neonatal respiratory morbidity within
24 hours after birth.
Painful contractions. Progression of labour after stopping OCT. Nonreassuring
fetal heart rate pattern during OCT.
Study design
This is a multicentre, prospective, open label randomised controlled trial
where pregnant women receive either oxytocin or the standard used ringers
lactate.
The effect of oxytocin is obvious, so blinding is not useful.
Intervention
OCT group: Oxytocin 5 IU/500 ml Ringer® lactate or NaCl will be infused at a
rate of 12 ml/h and doubled every 10 min until it induced five uterine
contractions per 15-min interval at which point it will stopped. The infusion
is stopped if no contractions develop after 40 minutes and the maximum infusion
rate of 96ml/h is given.
Control group: standard procedure prior ECS. Infusion with Ringer® lactate
Study burden and risks
The burden is low. We do not ask additional tests, but only data related from
standard of care and potentially a few additional questions. Mothers will have
labour related pain.
Risks are low, oxytocine is used in this group of patients to induce vaginal
delivery as standard of care.
Wytemaweg 90
Rotterdam 3015 CN
NL
Wytemaweg 90
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
* singleton pregnancy
* ECS without preceding contractions or rupture of the membranes
* Absence of a contraindication to oxytocin.
* Informed Consent as documented by signature.
Exclusion criteria
Non-inclusion criteria mother:
* Known or suspected unwillingness to follow the protocol
* Substance abuse (for example heroin, cocaine, amphetamine)
* Placenta praevia
* Clinical signs of infection
* Treated hypertension
* Preeclampsia
* Diabetes type I or II
* Steroid therapy during pregnancy
* Betablocker intake at inclusion
* Antenatal steroid administration for lung maturation
* A history of more than one previous caesarean section
Non-inclusion criteria fetus:
* Chromosomal aberration
* Malformation
* IUGR
* Nonreassuring fetal heart rate pattern
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003660-26-NL |
| ClinicalTrials.gov | NCT03693885 |
| CCMO | NL79417.000.21 |