A study to improve the outcomes of mothers and babies through safe and appropriate caesarean sections

1. Not yet submitted 26/06/2025, University of Liverpool Research Ethics Committee (University of Liverpool, Liverpool, L69 7ZX, United Kingdom; +44 (0) 151 794 8290; ethics@liverpool.ac.uk), ref: -

2. Approved 29/10/2023, Fernandez Foundation Institutional Ethics Committee (4-1-1230, Bogulkunta, Off Abid Road, Hyderabad – 500001, Telangana, Hyderabad, -, India; +91 (0)40 40222300; irb@fernandez.foundation), ref: 47_2023

3. Not yet submitted, Mbeya Medical Research and Ethics Committee (PO Box 2410, Hospital Hill Road, Mbeya, PO Box 2410, Tanzania)

4. Not yet submitted, National Institute for Medical Research (3 Barack Obama Drive, PO Box 9653, Dar es Salaam, 11101, Tanzania; info@nimr.or.tz)

Current primary outcome measures as of 24/06/2025:
The main outcomes are those measuring the change in practice and are likely to lead to improvements in clinical practice.
Co-Primary outcomes are:
1. Caesarean section rate measured as the number of caesarean section births out of the number of total births in Robson groups (1-4), which are defined as:
Group 1: Number of nulliparous women, with a singleton fetus with a cephalic presentation at term gestation (≥37+0 weeks) in spontaneous labour
Group 2: Nulliparous, singleton, cephalic, term births with induced labour or prelabour caesarean section
Group 3: Multiparous, singleton, cephalic, term births without previous caesarean section in spontaneous labour
Group 4: Multiparous, singleton, cephalic, term births without previous caesarean section with induced labour or prelabour caesarean section
2. Adherence to safe perioperative measures during caesarean section which is defined as adherence to 4 out of 5 C-Op components (prospective us of the WHO CS modified Surgical Safety checklist, administration of prophylactic antibiotics 30-60 minutes before skin incision, vaginal cleansing before procedure, administration of prophylactic uterotonics immediately after birth of baby, and changing of gloves and instruments prior to sheath closure).




Previous primary outcome measures:
The main outcomes are those measuring the change in practice, and likely to lead to improvements in clinical practice. Changes in more than one process outcome will be required to improve maternal and perinatal clinical outcomes, therefore the main outcomes include the following:
1. Caesarean section rate measured as the number of caesarean section births out of the number of total births taking place per month
2. Assisted vaginal birth rate measured as the number of assisted vaginal births out of the number of total births taking place per month
3. Spontaneous vaginal birth rate (not including assisted vaginal births) measured as the number of (unassisted) vaginal births out of the number of total births taking place per month
4. Rates of the mode of birth in Robson groups (1-4) measured as 1. The Caesarean section rate in each of the Robson groups is listed below; 2. The Assisted vaginal birth rate in each of the Robson groups listed below; and, 3. The Spontaneous vaginal birth rate in each of the Robsons groups listed below
Robson groups are defined as:
Group 1: Number of women who are nulliparous, with a singleton fetus with a cephalic presentation at term gestation (≥37+0 weeks) in spontaneous labour;
Group 2: Nulliparous, singleton, cephalic, term births with induced labour or prelabour caesarean section;
Group 3: Multiparous, singleton, cephalic, term births without previous caesarean section in spontaneous labour;
Group 4: Multiparous, singleton, cephalic, term births without previous caesarean section with induced labour or prelabour caesarean section;
5. Indications for caesarean sections measured using main and associated indications recorded according to the C-Why classification system using the C-Why audit tool looking at a percentage of total CS per month.
6. Use of C-Safe checklists measured as partial or total completion of C-Op checklists per month out of all CS birth and C-Non (AVB) checklists per month out of all assisted vaginal births
7. Delivery of the C-Safe packages measured as partial or total administration of the C-Op package components out of all CS birth and C-Non package components out of all assisted vaginal births.

Current secondary outcome measures as of 24/06/2025:
Implementation, acceptability, equity and maternal and perinatal mortality and morbidity (clinical outcomes).

Implementation outcomes include the following:
1. Reach (measured as the proportion of women who receive the C-Safe intervention at 3 months after implementation)
2. Adoption (measured as the proportion of healthcare professionals trained at 3 months after implementation)
3. Fidelity (measured as the proportion of individual intervention components given as specified at 3 months after implementation)
4. Adaption (measured as the number of intervention components modified at 3 months after implementation)
5. Appropriateness (measured as perceived fit of the intervention at 3 months after implementation)

Acceptability and equity outcomes include the following:
1. Acceptability to women and healthcare providers measured using interviews, surveys and observations at baseline, end of month 6 and month 12
2. Barriers to intervention delivery or study conduct measured using interviews, surveys and observations at baseline, end of month 6 and month 12
3. Patient-reported outcomes such as dignity, information sharing, and positive birth experience, measured using interviews, surveys and observations at baseline, end of month 6 and month 12

Clinical outcomes include the following and will be collected monthly throughout the trial period:
Maternal:
1. Postpartum haemorrhage (defined as blood loss ≥500 ml after birth) measured for all births
2. Surgical site infection (defined as an infection that occurs within 30 days after the operation and involves the skin and subcutaneous tissue of the incision (superficial incisional) and/or the deep soft tissue (for example, fascia, muscle) of the incision (deep incisional) and/or any part of the anatomy (for example, organs and spaces) other than the incision that was opened or manipulated during an operation (organ/space), measured until discharge from hospital.
3. Number of instrumental births (defined as the number of babies whose birth was facilitated by an instrument) as a proportion of total vaginal births and total births
4. Number of spontaneous vaginal births (defined as the number of babies birthed vaginally without assistance of an instrument) as a proportion of total births and total vaginal births
5. Major organ injury (defined as damage to bladder, bowel or ureters) during caesarean section surgery
6. Perineal tear (1st, 2rd, 3rd or 4th degree tear (defined as a tear that extends into the anal sphincter or the lining of the anus or rectum)) occurring in vaginal births
7. Oasis - defined as 3rd degree tear (extending into anal sphincter muscles) or 4th degree tear (further involving the lining of rectum or anus) occurrence in vaginal births.
8. Episiotomy (defined as a cut made at the opening of the vagina during birth to aid a difficult delivery) measure in all vaginal births
9. Length of hospital stay (defined as length of time a woman was in hospital following birth (vaginal or CS)), calculated in days and hours
10. Maternal death (death of a mother from any cause during and after CS up until discharge) as a proportion of women having CS
11. Return to theatre (defined as mother returning to theatre for further surgical procedure following CS), recording until discharge, or on admission within 30 days
12. Hysterectomy (required for any cause during or after CS until discharge) as a proportion of women having CS.
13. Admission to ITU (defined as a woman requiring admission to ITU for higher-level care after CS) was recorded until discharge in all women having CS.

Neonatal composite components:
1. Total number of stillbirths (defined as the death of a baby after 28 weeks of gestation (defined by WHO), but before or during birth. Includes total numbers of fresh and macerated stillbirths in babies born vaginally and by CS.
2. Neonatal death (defined as the death of a baby who is born alive but dies during the first 28 days of life), measured until discharge from the hospital.
3. Admission to the neonatal unit for more than 24 hours of treatment (defined as the admission of a baby to receive additional neonatal care or observation), measured until discharge from the hospital

Uptake of C-Non components (in all vaginal births), including:
1. Reviewed birth preference (was there a discussion around women's birthing choices and available options)
2. Presence of a birth companion (is the woman offered or allowed the option of having a person of her choosing present during labour, where possible and desired)
3. Information about birth analgesia provided (was there a discussion about available pain relief options (both pharmacological and non-pharmacological))
4. Mobilisation in labour (was the woman encouraged to mobilise and change position to aid labour progress; what positions were tried?)
5. Hydration and nutrition (was the woman offered food and drink throughout labour)
6. Initiation of breastfeeding (was breastfeeding initiated within one hour after birth); also measured in CS births.
7. Delayed cord clamping (defined as a practice where the umbilical cord is not clamped and cut immediately after birth, but delayed a minimum of 30 seconds); also measured in CS births.
8. Skin-to-skin (defined as a baby being put onto their mother's skin immediately, or very shortly, after birth); also measured in CS births.




Previous secondary outcome measures:
Implementation, acceptability, equity and maternal and perinatal mortality and morbidity (clinical outcomes).

Implementation outcomes include the following:
1. Reach (measured as the proportion of women who receive the C-Safe intervention at 3 months after implementation)
2. Adoption (measured as the proportion of healthcare professionals trained at 3 months after implementation)
3. Fidelity (measured as the proportion of individual intervention components given as specified at 3 months after implementation)
4. Adaption (measured as number of intervention components modified at 3 months after implementation)
5. Dose (measured as proportion of individual intervention components delivered at 3 months after implementation)
6. Appropriateness (measured as perceived fit of the intervention at 3 months after implementation)

Acceptability and equity outcomes include the following:
1. Acceptability to women and healthcare providers measured using interviews, surveys and observations at baseline, end of month 6 and month 12
2. Barriers to intervention delivery or study conduct measured using interviews, surveys and observations at baseline, end of month 6 and month 12
3. Patient-reported outcomes such as dignity, information sharing, and positive birth experience, measured using interviews, surveys and observations at baseline, end of month 6 and month 12

Clinical outcomes include the following and will collected monthly throughout the trial period:
Maternal:
1. Postpartum haemorrhage (defined as blood loss ≥500 ml after birth)
2. Surgical site infection (defined as an infection that occurs within 30 days after the operation and involves the skin and subcutaneous tissue of the incision (superficial incisional) and/or the deep soft tissue (for example, fascia, muscle) of the incision (deep incisional) and/or any part of the anatomy (for example, organs and spaces) other than the incision that was opened or manipulated during an operation (organ/space), measured until discharge from hospital.
3. Sepsis (defined as organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion, or postpartum period) measured until discharge from hospital.
4. Death (defined as death from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy), measured until discharge from hospital.
5. Caesarean hysterectomy (defined as the removal of the uterus at the time of caesarean section)
6. Major organ injury (defined as major organs such as bladder or bowel damaged during caesarean section surgery)
7. 3rd/4th degree tear (defined as a tear that extends into the anal sphincter or the lining of the anus or rectum)
8. Admission to intensive care (defined as admission of an acutely unwell mother to receive critical medical care), measured until discharge from hospital

Perinatal:
1. Stillbirth (defined as the death of a baby after 28 weeks of pregnancy, but before or during birth)
2. Neonatal death (defined as the death of a baby who is born alive but dies during the first 28 days of life), measured until discharge from hospital.
3. Apgar score (defined as standardised assessment for infants after birth using five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which receive a score of 0, 1, or 2, reported at 1 minute and 5 minutes after birth)
4. Admission to neonatal unit (defined as the admission of a baby to receive additional neonatal care or observation), measured until discharge from hospital
5. Seizures (defined as fits in the baby from birth), measured until discharge from the hospital