Does placental growth factor testing improve outcomes for women with suspected preterm pre-eclampsia in low- and middle-income countries?

1. Approved 05/03/2025, King's College London Research Ethics Committee (5-11 Lavington Street, London, SE1 0NZ, United Kingdom; +44 (0) 20 7836 5454; rec@kcl.ac.uk), ref: HR/DP-24/25-46560

2. Approved 03/02/2025, University of Zambia Biomedical Research Ethics Committee (Ridgeway Campus, Lusaka, P.O. Box 50110, Zambia; +260 977925304; unzarec@unza.zm), ref: 6222-2024

3. Approved 24/02/2025, Sierra Leone Ethics and Scientific Review Committee (Directorate of Training and Research, Youyi Building, Brookfields, Freetown, FQG2+CP5, Sierra Leone; +23278366493; efoday@mohs.gov.sl), ref: 004/02/2025

4. Approved 20/01/2025, Institutional Ethics Committee of KLE Academy of Higher Education and Research (KLES Dr Prabhakar Kore Hospital, Nehru Nagar, Belagavi, 590010, India; +91-831-255 1876; kleclinicalresearch@gmail.com), ref: KAHER/EC/2025-26/D-21012501

The following primary outcome measures will be assessed from data collected from medical records at discharge, using data collected between recruitment and primary hospital discharge:
1. Primary maternal outcome: A composite of maternal mortality and morbidity (based on the miniPIERS composite of adverse maternal outcomes) during pregnancy and delivery until primary hospital discharge
2. Primary perinatal outcome: Composite of stillbirth and early neonatal death (<7 days) until primary hospital discharge

The following secondary outcome measures will be assessed from data collected from medical records at discharge, using data collected between recruitment and primary hospital discharge:

Tested Maternal Outcomes:
1. Maternal mortality according to clinical diagnosis
2. Eclampsia according to clinical diagnosis
3. Placental abruption according to clinical diagnosis
4. Termination pre-viability for maternal preeclampsia according to clinical diagnosis
5. Time to diagnosis of pre-eclampsia according to the International Society for the Study of Hypertension in Pregnancy definition
6. Proportion of women diagnosed with preeclampsia according to the International Society for the Study of Hypertension (ISSHP) in pregnancy definition
7. Time to delivery
8. Mode of birth (vaginal, assisted vaginal, caesarean section)

Descriptive Maternal Outcomes:
1. Stroke
2. Cortical blindness
3. Retinal detachment
4. Pulmonary oedema
5. Acute Kidney Injury and using laboratory creatinine measurements, definition according to the KIDIGO definitions
6. Liver capsule haematoma/rupture
7. Major post-partum haemorrhage
8. Hepatic dysfunction measured according to the hospital medical records and using laboratory AST/ALT measurements, definition according to ISSHP definitions
9. Low platelets measured according to the hospital medical records and using laboratory platelet measurements, definition according to ISSHP definitions
10. ICU admission
11. Intubation and ventilation (other than for delivery)
12. Glasgow coma score <13
13. Transient ischaemic attack
14. Posterior reversible encephalopathy
15. Positive inotropic support
16. Myocardial infarction/ischaemia
17. Blood oxygen saturation <90%
18. Requirement of ≥50% FiO2 for over one hour
19. Supplemental oxygen >50% for more than one hour
20. Dialysis required
21. HDU admission
22. Labour onset (spontaneous, induced or pre-labour caesarean section)
23. Indication for delivery
24. Use of MgSO4
25. Use of steroids
26. Use of antihypertensives
27. Parenteral infusion of third-line antihypertensives required

Perinatal Outcomes
Tested Perinatal Outcomes
1. Stillbirth
2. Early neonatal death (within 7 days of life)
3. Neonatal unit admission
4. Neonatal unit admission for more than 48 hours
5. Gestational age at delivery
6. Preterm birth before 37 weeks’ gestation
7. Preterm birth before 34 weeks’ gestation
8. Birthweight <10th centile (Intergrowth-21)

Descriptive Perinatal Outcomes
1. Late neonatal death (after 7 days of life, up to primary hospital discharge)
2. Respiratory support
3. Sepsis
4. Neonatal seizures
5. Birthweight
6. Birthweight <3rd centile (Intergrowth-21)
7. Antibiotics given
8. APGARs at 1 and 5 minutes
9. Hypoxic Ischaemic Encephalopathy and grade
10. Respiratory distress syndrome
11. Supplementary oxygen and duration
12. Administration of surfactant
13. Hypoglycaemia requiring intervention
14. Hypothermia (temperature < 35.6 °c)
15. Neonatal jaundice requiring phototherapy
16. Necrotising enterocolitis
17. Nasogastric feeding required
18. Umbilical artery and venous pH
19. Abnormal cerebral ultrasound
20. Fetal sex

Adherence Measures
Among the intervention group:
1. Valid PlGF test result obtained, measured using a point-of-care PlGF test
2. PlGF test result documented in patient notes

Among the control group:
3. PlGF test performed at any point

Health resource use outcomes for budget impact analysis:
1. Number of test cartridges used measured by the research team audit
2. Number of test cartridges wasted measured by the research team audit
3. Number of failed tests measured by the research team audit

Maternal:
1. Antenatal outpatient attendances
2. Formal ultrasound scans
3. Inpatient days
4. Intensive care unit days

Perinatal:
1. Total days in hospital
2. Total days in each level of care (intensive care, high dependency and special care unit days)