The enhanced antenatal care bundle to improve maternal and newborn outcomes in Malawi and Zambia: a multi-country, parallel cluster-randomized trial
| ISRCTN | ISRCTN16218936 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16218936 |
| Secondary identifying numbers | University of Liverpool Sponsor UoL001883 |
- Submission date
- 03/03/2025
- Registration date
- 13/03/2025
- Last edited
- 08/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Even though many pregnant women in Malawi and Zambia receive regular healthcare during pregnancy and give birth in health centres, there are still many women who die from complications during childbirth. We have reliable evidence that these maternal deaths can be prevented with good quality healthcare that follows the guidance of the World Health Organisation (WHO). The WHO recommend that all pregnant women have regular health visits during pregnancy; the WHO also recommends that healthcare staff perform specific checks during each pregnancy visit so that any problems during pregnancy are found and treated before they become life-threatening to women or their babies.
This study will look at the healthcare pregnant women receive during their pregnancy and when they give birth in primary health centres in Malawi and Zambia. The researchers will compare important events during pregnancy and birth in facilities where staff provide women with standard pregnancy care versus those same important events in facilities where staff deliver an improved pregnancy healthcare service. The improved pregnancy health services include training for staff and pregnant women and supplies for health facilities.
Who can participate?
This study will include health facilities rather than individuals. The health centres will have 700 - 2000 visits per year from pregnant women. The health centres will also be able to provide emergency pregnancy care, provide services for free to pregnant women, and complete an assessment process to ensure that the site is ready for the trial.
What does the study involve?
The study will start with a baseline phase, where the researchers will measure key events during pregnancy and childbirth. Next, the facilities will be randomly assigned to either continue providing their standard pregnancy care with basic supplies or to deliver the study intervention to improve pregnancy care, with training for staff and pregnant women and with basic supplies.
What are the possible benefits of participating?
The researchers expect that the health centres receiving the study intervention to improve pregnancy will be better able to provide care that meets WHO standards. They expect these health facilities to have better results for women and babies in terms of avoiding complications during pregnancy that lead to preventable deaths amongst women.
Where is the study run from?
This study is run from the Malawi Liverpool Wellcome Institute in Blantyre (Malawi) and from Lusaka Apex Medical University in Lusaka (Zambia). The study teams also have support from the University of Liverpool (UK).
When is the study starting and how long will it run for?
August 2022 to July 2026
Who is funding the study?
National Institute for Health and Social Care Research (UK)
Who is the main contact?
safemotherhood@liverpool.ac.uk
Contact information
Principal Investigator
Liverpool Women's Hospital - First Floor
University of Liverpool Dept. of Women's and Children's Health
Crown Street
Liverpool
L8 7SS
United Kingdom
 ORCID ID |
0000-0002-7878-2327 |
|---|---|
| Phone | +44 (0)1517942064 |
| david.lissauer@liverpool.ac.uk |
Scientific
Private Bag 360
Chichiri
Blantyre
BT3
Malawi
| ORCID ID |
0000-0002-3572-3810 |
|---|---|
| Phone | +265 (0)1810911 |
| lmipando@kuhes.ac.mw |
Public
Liverpool Women's Hospital
University of Liverpool Dept. of Women's and Children's Health
Crown Street
Liverpool
L8 7SS
United Kingdom
| Phone | +44 (0)1517942064 |
|---|---|
| nmedley2@liverpool.ac.uk |
Study information
| Study design | Parallel cluster-randomized trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Cluster randomised trial |
| Study setting(s) | GP practice, Hospital, Medical and other records |
| Study type | Prevention, Treatment |
| Participant information sheet | Not available in web format. Please use contact details to request a participant information sheet. |
| Scientific title | The enhanced antenatal care bundle to improve maternal and newborn outcomes in pregnant women attending maternity health services in Malawi and Zambia: a multi-country, parallel cluster-randomised trial |
| Study acronym | ENHANCE |
| Study objectives | ENHANCE will provide a comprehensive bundle of measures carefully developed for primary health centres in resource-limited settings, to support the consistent and comprehensive delivery of all aspects of antenatal care according to WHO guidelines. ENHANCE includes tools, leadership, mentorship, task shifting and basic antenatal care supplies. This study will determine whether an ENHANCE strategy compared with standard antenatal care is acceptable to pregnant women and healthcare staff; whether ENHANCE improves the implementation of antenatal care services according to WHO guidance; and whether ENHANCE improves both the quality of antenatal care and the maternal and neonatal clinical outcomes for women and babies who receive the intervention. |
| Ethics approval(s) |
1. Approved 24/02/2025, The University of Liverpool Ethics Committee (Foundation Building, Liverpool, L69 7ZX, United Kingdom; +44 (0)151 794 2000; research.ethics@liverpool.ac.uk), ref: 15682 2. Approved 05/12/2024, College of Medicine Research Ethics Committee (Private Bag 360 Chichiri, Blantyre, 3, Malawi; +265 (0)1874377; comrec@medcol.mw), ref: P.10/24-1155 3. Approved 25/10/2024, Lusaka Apex Medical University Biomedical Research Ethics Committee (Foxdale Campus Plot No. 3073, Lusaka, PO Box 31909, Zambia; +260 (0)979452488; lamubrec@lamu.edu.zm), ref: 0294/25/10/2024 4. Approved 23/01/2025, National Health Research Authority (Lot No. 18961/M off Kasama Rd, Chalala Lusaka, PO Box 30075, Zambia; +260 (0)211250309; znhrasec@nhra.org.zm), ref: NHRA-1849/09/01/2025 |
| Health condition(s) or problem(s) studied | Delivery of antenatal care services |
| Intervention | The study will implement a package designed to improve the quality and content of antenatal care delivered in resource-limited settings and compare this with the standard antenatal care offered to pregnant women in Malawi and Zambia. This is a multi-country, parallel cluster-randomised controlled trial with a baseline period. There is an integrated implementation evaluation and health economic evaluation. The trial will include primary healthcare centres in Malawi and Zambia as clusters. During the first 3 months each cluster will provide standard care to establish weekly rates of maternal and newborn outcomes. After the baseline, the clusters will be randomly allocated in a 1:1 ratio to ENHANCE or standard care with the provision of basic ANC supplies, using a minimisation algorithm to account for the imbalance in location, hospital deliveries volume and distance to referral facility. Both quantitative and qualitative approaches will gather the data required to meet the objectives. The researchers will conduct an intention-to-treat analysis of the composite primary outcome. Descriptive statistics for continuous (mean and standard deviations), discrete (median and range or interquartile range) and categorical (frequency counts and percentages) variables will summarize baseline characteristics (demographic and clinical data) and outcome variables. Process evaluation surveys will be summarised using descriptive statistics as appropriate, and responses compared across PHCs and countries. Interviews will be analysed using combined deductive framework and inductive thematic analysis. |
| Intervention type | Mixed |
| Primary outcome measure | 1. Maternal mortality: 1.1. Maternal deaths 2. Newborn mortality: 2.1. Stillbirths 2.2. Neonatal deaths 3. Maternal morbidity: 3.1. (Pre)-eclampsia 3.2. Uterine rupture 3.3. Antepartum haemorrhage 3.4. Postpartum haemorrhage 3.5. Maternal sepsis 4. Newborn morbidity: 4.1. Birth asphyxia 4.2. Prematurity (born before 37 weeks gestation) 4.3. Low birthweight (weight less than 2500 g) 5. Emergency obstetric referrals 6. Appropriate emergency referrals Measured by monthly collection of routine health facility records for maternity ward records from the baseline phase to the end of cluster participation. In addition to the primary and secondary outcomes listed here, the researchers may evaluate general process outcomes as described in the protocol attached. |
| Secondary outcome measures | 1. Proportion of women with the following obstetric complications: 1.1. (Pre)-eclampsia 1.2. Anaemia (Hb less than 7g/dl) 1.3. Syphilis 2. Proportion of women referred out for any cause, or due to pre/eclampsia, anaemia and risk for obstruction of labour 3. Proportion of newborns with the following complications: neonatal sepsis 4. Proportion of neonatal unit (NNU) admission for any cause 5. Proportion of newborn breastfeeding initiated within 60 minutes of birth 6. Proportion Kangaroo Mother Care (KMC) admissions 7. Proportion of newborns resuscitated 8. Proportion of newborns received antibiotics 9. Proportion of women starting antenatal care (ANC) visit in the first trimester (<12 weeks) 10. Average total ANC visits per woman 11. Proportion of women who received required doses of the following (data from registers): 11.1. Tetanus toxoid vaccination (TTV) (≥2 doses) 11.2. Sulphadoxine-pyrimethamine (SP) (≥3 doses) Measured by monthly collection of routine health facility maternity and neonatal records and cohort records (6 months prior to reporting month) for ANC data records, from the baseline to the end of cluster participation. In addition to the primary and secondary outcomes listed here, the researchers may evaluate general process outcomes as described in the protocol attached. |
| Overall study start date | 01/08/2022 |
| Completion date | 31/07/2026 |
Eligibility
| Participant type(s) | Patient, Health professional |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 32 total facilities (clusters) with at least 1600 women per trial arm |
| Key inclusion criteria | Clusters: Primary Health Centre facilities offering maternity care will be included as a cluster following the completion of a successful feasibility report with the minimum prerequisites of: 1. A minimum of 700 ANC initial visits to a maximum of 2000 per year 2. Providers of basic emergency obstetric care 3. Public primary facility 4. Completed the site readiness assessment process Participants: clients (in process evaluation interviews and survey): 1. ≤ 20 weeks of gestation at the initial visit to ANC 2. Able to provide informed consent 3. Willing to participate in the study 4. Aged 18 years and above Participants: HCWs (in process evaluation interviews and survey): 1. Healthcare workers responsible for the care of women during pregnancy 2. Willing to participate in the study 3. Able to provide informed consent |
| Key exclusion criteria | Clusters: 1. PHC with less than 700 initial ANC visits per year 2. PHCs with more than 2000 initial ANC visits per year-outliers to other facilities 3. PHCs not willing to participate in the study 4. High risk of contamination (geographically close to another participating centre or site where similar interventions are already taking place) Participants: clients (in process evaluation - interviews and survey): 1. >20 weeks of gestation at the initial visit to ANC 2. Unable to provide informed consent 3. Medical and obstetric complications on the initial visit 4. Aged less than 18 years Participants: HCWs (in process evaluation - interviews and survey): 1. Not willing to participate in process evaluation 2. Unable to provide informed consent |
| Date of first enrolment | 01/08/2025 |
| Date of final enrolment | 31/05/2026 |
Locations
Countries of recruitment
- Malawi
- Zambia
Study participating centres
Lilongwe
207201
Malawi
Mangochi
301400
Malawi
Kafue
None
Zambia
Chongwe Lusaka
None
Zambia
Chisamba
None
Zambia
Mumbwa
None
Zambia
Sponsor information
Research organisation
Institute of Life Course and Medical Sciences
William Henry Duncan Building
Liverpool
L7 8TX
England
United Kingdom
| Phone | +44 (0)1517942064 |
|---|---|
| sponsor@liverpool.ac.uk | |
| Website | http://liverpool.ac.uk |
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. The researchers expect the data sets generated from this study to be available upon request. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.0 | 12/11/2024 | 12/03/2025 | No | No |
Additional files
Editorial Notes
08/07/2025: The date of first enrolment was changed from 01/07/2025 to 01/08/2025.
19/06/2025: The recruitment start date was changed from 01/06/2025 to 01/07/2025.
09/04/2025: The following changes were made to the trial record:
1. The recruitment start date was changed from 15/04/2025 to 01/06/2025.
2. The recruitment end date was changed from 02/03/2026 to 31/05/2026.
12/03/2025: Study's existence confirmed by the NIHR.
