CRADLE 4

Background: 

Pre-eclampsia is one of the leading causes of maternal mortality worldwide. It complicates 2-8% of pregnancies and has the greatest impact in low and middle-income countries (LMIC) where a woman’s chance of dying from pre-eclampsia is 1 in 3000, compared to 1 in a million in the U.K.

The only cure for pre-eclampsia is delivery.

When is the best time to deliver?

The World Health Organisation (WHO) recommends that all women with pre-eclampsia at 37 weeks’ gestation onwards are delivered.

Before 34 weeks, expectant management (“watchful waiting”) is preferable, as it reduces the risk of complications of prematurity to the baby without increasing harm to the mother.

Guidance on the optimal timing of delivery for women between 34 and 37 weeks is less clear. It is likely that early delivery at this time would be beneficial to the mother and baby, particularly in a LMIC setting where morbidity and mortality from pre-eclampsia is high.

The CRADLE-4 Trial aims to find out whether planned early birth between 34 and 37 weeks of pregnancy in women with pre-eclampsia causes fewer complications to the mother and baby compared to waiting until 37 weeks.

This will be a randomised controlled trial across selected sites in India and Zambia. It is funded by the Medical Research Council in the United Kingdom.

Before designing the main intervention phase of the trial (due to begin in the summer of 2019) we are conducting a feasibility study (Phase 1). This will evaluate how acceptable planned early birth would be to women, their partners and healthcare workers.This is a critical step in ensuring that the views of local staff and patients inform the trial design and means that an understanding of the local context will be incorporated into the process of protocol development.

CRADLE-4 Phase 1 begun in January 2019 after gaining ethical approval from King’s College London, University of Zambia and K.L.E.S. Academy of Higher Education and Research. It is taking place across the three selected trial sites:

  • University Teaching Hospital, Lusaka, Zambia.
  • Ndola Teaching Hospital, Ndola, Zambia.
  • K.L.E.S JNMC Hospital, Belgaum, India.

To date we have completed 17 stakeholder interviews and 5 focus group discussions.

Christine Jere, one of our Research Assistants in Ndola, facilitating a focus group discussion with partners and relatives.

In addition to this qualitative work, a case notes audit is currently underway across all three sites.

The aim of this development work is to understand:

  • The existing local protocols for management of pre-eclampsia including diagnosis, referral pathways, management and timing of delivery.
  • The level of neonatal care at each of the trial sites, criteria for neonatal intensive care admission and gestation specific neonatal outcomes.
  • The methods used to determine gestational age, their availability and their accuracy.
  • How acceptable planned early delivery from 34 weeks is to local women, their partners and healthcare providers.

Setting:

India and Zambia have different health systems to one another and associated challenges, which will mean that the results are relevant to care of women with pre-eclampsia in various low and middle income country (LMIC) settings.

The inaugural CRADLE-4 team meeting in India

Ndola Teaching Hospital, Zambia – one of the three selected trial sites.

Outcome:

CRADLE 4 will be the first trial of its kind to be carried out in a low-income setting. By determining the optimal gestation for delivery in women with pre-eclampsia, this trial could impact on local, national and international guidelines relating to the care pathway of women in LMICs. This intervention, in conjunction with the CRADLE VSA, has the potential to significantly reduce the number of both maternal and neonatal deaths and improve access to care for women with pre-eclampsia.

Prof A Shennan, Dr A Beardmore-Gray and Dr Umesh Charanthimath visit one of the district health facilities in Belgaum, India. The CRADLE VSA Device is being used to monitor blood pressure at an ante-natal visit.