The study is to determine the prevelance of raised umbilical artery flow in unselected obstetric population at 28-34 weeks gestation in Kenya using a single screning with the Umbiflow device.

1 Background information and rationale

The global burden of stillbirth remains very high, with an estimated 2.6 million third trimester stillbirths worldwide in 2015, the vast majority occurring in low- and middle-income countries (LMICs)¹. It is estimated that a substantial proportion (30-50%) of fetal deaths are attributable to intrauterine growth restriction (IUGR)². Clinical techniques (such as history taking and serial physical assessments) to identify fetuses at increased risk of IUGR in LMICs have poor predictive values, and have not been shown to affect the rate of stillbirth or perinatal mortality^3-6.

In the early 1990s, it was recognised that the use of Doppler ultrasound for assessment of blood flow in fetal umbilical vessels could quantify placental function and be used to identify placental insufficiency. Abnormal flow indices as shown by Doppler ultrasound were shown to correlate with IUGR, and adverse fetal and neonatal outcomes, particularly when absent or reversed end diastolic flow was identified^7,8. Cochrane reviews have assessed the use of Doppler ultrasound in women with high- and low risk pregnancies. In high-risk pregnancies, use of Doppler - in conjunction with an appropriate follow-up - can reduce perinatal mortality and optimize the use of obstetric interventions⁹. However, there is insufficient evidence to establish whether the use of Doppler ultrasound benefits low-risk pregnant women in LMICs, as only five trials, from three high-income countries (HICs), have addressed this question. Based on the available evidence, the World Health Organization (WHO) does not currently recommend the routine use of Doppler velocimetry for low-risk antenatal populations. However, the recommendation remarks specify that the value of a routine single Doppler ultrasound examination of fetal blood vessels in the third trimester requires further evaluation, particularly in LMIC settings.

Continuous-wave Doppler ultrasound has been used since the 1980s but was slowly replaced by pulse-wave Doppler as ultrasound technology improved in the 1990s. Pulse-wave Doppler - available in most of the current obstetric ultrasound systems - is widely used in high-resource settings; however, it requires a high level of technical skill and has high financial costs. In the 1990s, researchers in South Africa developed a handheld, mobile continuous-wave Doppler ultrasound device called Umbiflow™¹⁰. Umbiflow has been validated against commercial ultrasound machines for the detection of fetal umbilical flow abnormalities¹¹. It can be performed by a range of health worker cadres (included midwives, nurses and non-specialist doctors) following a focused training. Studies have shown the potential benefits of Umbiflow in identifying at-risk fetuses at peripheral health care facilities by midwives without unnecessarily increasing the burden of referrals to hospitals. Interim analysis of an ongoing research study using the Umbiflow in an unselected population of women receiving antenatal care (ANC) in Mamelodi district, Pretoria, South Africa, has shown a higher than expected prevalence of fetal umbilical flow abnormalities that appears associated with a high risk of perinatal mortality¹². Women identified as “high-risk” through Umbiflow screening were referred and managed at the referral hospital using a standardized management protocol, which resulted in a 46% risk reduction (RR 0.54, 95% CI 0.31-0.94) in perinatal mortality¹². These findings have prompted the need for further observational research into the prevalence of umbilical flow abnormalities in unselected populations in other LMICs. This would establish the case for whether a trial of the effects of routine Doppler velocimetry in unselected or low-risk population in low-resource settings is warranted, as well as assess the capacity of health systems to apply this intervention at scale. If the rates of serious fetal umbilical flow abnormalities in low-resource settings are comparatively higher than what have been reported in high-resource settings (where the previous trials were conducted), then the use of Umbiflow in unselected obstetric populations in low-resource settings could optimize identification and management of at-risk fetuses, with a concomitant reduction in preventable perinatal deaths.

2 Study hypothesis and objectives

Hypothesis

Unselected pregnant women population in LMICs [Ghana, India, Kenya, Rwanda, and South Africa], have a similarly high prevalence of abnormal umbilical artery flow resistance indices, including absent end diastolic flow (AEDF), as the unselected antenatal population receiving care in Mamelodi district, Pretoria, South Africa.

Primary objective

To determine the prevalence of raised umbilical artery flow resistance indices, including AEDF, in unselected obstetric populations at 28 - 34 weeks gestation in Ghana, India, Kenya, Rwanda and South Africa, using a single screening with the Umbiflow device.

Secondary objectives

1. To assess the prevalence of raised RI by gestational age.
2. To determine the pregnancy outcomes of women screened with Umbiflow.
3. To assess the distribution of the RI in women identified as “high risk” and the RI thresholds associated with increased risk of perinatal mortality, among pregnant women screened with Umbiflow.
4. To assess the effect of Umbiflow device in screening unselected obstetric populations in antenatal care (ANC) settings on use of obstetric investigations, interventions and health system outcomes.

3 Study methods

Over a 12-month period, this multicountry, multi-centre prospective cohort study in five LMICs (Ghana, India, Kenya, Rwanda, and South Africa) will recruit and screen a population of 7,035 unselected pregnant women using a single screening with the Umbiflow device during ANC visit between 28 and 34 weeks’ gestation. Perinatal outcomes for all enrolled participants will be collected from medical records until 7 days postpartum (postnatal) or discharge (whichever comes first). The main outcomes of interest include: (1) prevalence of raised RI and AEDF, (2) perinatal mortality (stillbirth and early neonatal death) (3) perinatal morbidity (preterm birth and small for gestational age) (4) Health system contacts (number of ANC visits and hospital referrals).