The Role of ARTificial Uterine CONtractions in Perinatal Respiratory Morbidity of Term Infants Delivered by Elective Caesarean Section

Study Overview
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Brief Summary
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In this study, the investigators aim to investigate if artificial uterine contractions prior to elective caesarean section delivery may have an impact on the respiratory morbidity of term neonates.

Detailed Description
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Accumulating evidence suggests that the respiratory morbidity of infants is lower if delivered by caesarean section after the spontaneous onset of uterine contractions, or after oxytocin exposure. Moreover, benefits for the mother due to stretching of the lower uterine segment and possible lower blood loss are plausible. In obstetrics, there is a well described and standardized way to induce artificial uterine contractions in order to predict fetal wellbeing and tolerance of labor, without inducing the labor itself. This is the oxytocin challenge test (OCT). Although the OCT has not been performed previously in the context of planned elective caesarean section deliveries, it is generally considered a safe procedure if appropriate monitoring is granted. Hence evaluation of the role of artificial uterine contractions in perinatal respiratory morbidity of term infants delivered by elective caesarean section is possible and of interest.

Official Title
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A Prospective, Randomized and Placebo Controlled Trial Comparing the Role of ARTificial Uterine CONtractions and no Intervention in Perinatal Respiratory Morbidity of Term Infants Delivered by Elective Caesarean Section - ARTCON Study

Conditions
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Neonatal Respiratory Distress

Intervention / Treatment
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* Drug: Oxytocin
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term/near-term pregnancy (36+0 - 41+6 weeks of gestation) Planned delivery by elective caesarean section Absence of any exclusion criteria Informed consent obtained Exclusion Criteria: Term premature rupture of membranes (TPROM) Spontaneous onset of uterine contractions Known serious congenital malformations Placenta praevia/vasa praevia Abnormal placental attachment Intrauterine growth restriction (birth weight below 3rd centile for given gestational age and gender)
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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: artificial contractions (ARTCON) group<br>All participating patients in the intervention (ARTCON) group will undergo oxytocin exposure in the form of a continuous intravenous infusion according to dosage guidelines of The Czech Society of Obstetrics and Gynaecology. The exposure will take two hours to complete and should be finished at least one hour before elective caesarean section is performed in order for the assumed effects of physiological stress associated with labor to occur. | Drug: Oxytocin<br>* The intervention group (ARTCON) will receive the standard assignment for the elective caesarean section, but at least one hour before surgery oxytocin exposure will be performed with cardiotocographic (CTG) monitoring and obstetrical supervision.<br>|
| Placebo Comparator: standard approach (SA) group<br>All participating patients in the control (SA) group will undergo placebo exposure in the form of a continuous intravenous infusion. The exposure will take two hours to complete and should be finished at least one hour before elective caesarean section is performed. | Other: Normal saline<br>* The control group (SA) will receive the standard assignment for the elective caesarean section, but at least one hour before surgery placebo exposure will be performed with cardiotocographic (CTG) monitoring and obstetrical supervision.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of neonatal respiratory morbidity | Neonatal respiratory morbidity during the first 24 hours after delivery is defined as presence of transitory tachypnoea of the newborn, or respiratory distress syndrome, and/or persistent pulmonary hypertension of the newborn. | First 24 hours after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxytocin challenge test effectivity | Contractions being induced (felt or CTG recorded) before elective caesarean section | Before elective caesarean section | 
| Oxytocin challenge test safety and feasibility | CTG trace suggestive of hypoxia during oxytocin exposure. Subjectively unbearable pain and discomfort during oxytocin exposure. | Before elective caesarean section | 
| Maternal blood loss | Defined as the difference in hemoglobin levels before and after surgery | During caesarean section | 
| Total duration of surgery | Minutes | Time of caesarean section | 
| Lamellar body count in amniotic fluid | Particles per microlitre | During caesarean section | 
| Incidence of transitory tachypnoea of the newborn | Breathing rate above 60 per minute at least for 3 hours (3 consecutive measurements) and /or dyspnoea for at least two hours in the follow-up period (consecutive) and /or the need for oxygen therapy during the first 24 hours after birth. | First 24 hours after delivery | 
| Incidence of respiratory distress syndrome | Defined by need for ventilatory support in the first 24 hours after birth (nasal continuous positive airway pressure, mechanical ventilation) and X-ray examination results consistent with RDS diagnosis. | First 24 hours after delivery | 
| Incidence of perinatal hypoxia | Presence of diagnostic criteria of hypoxic-ischaemic encephalopathy: 5-min Apgar score of less than 5, need for delivery room intubation or CPR, umbilical cord arterial pH less than 7.00 and abnormal neurological signs such as hypotonic muscles or lack of sucking reflex | First 24 hours after delivery | 
| Incidence of early onset sepsis | Clinical or proven (positive blood culture) | First 48 hours after delivery | 
| Incidence of significantly increased neonatal pulmonary vascular resistance | Pulmonary vascular resistance measurements consist of measuring the right ventricular systolic pressure (RVSP), pulmonary artery pressure (PAP) and persistent ductus arteriosus (PDA) shunting (if present). | First 72 hours after delivery | 
| Incidence of persistent pulmonary hypertension of the newborn | Defined by marked pulmonary hypertension that causes hypoxemia secondary to right-to-left shunting of blood at the foramen ovale and ductus arteriosus. | First 24 hours after delivery |