The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0 weeks’ gestation

Abstract

Background Stillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth. Methods PLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman’s pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians. Discussion Our aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus. Trial registration ISRCTN58254381. Registered on 4 July 2019

Ultrasound and biochemical predictors of pregnancy outcome at diagnosis of early-onset fetal growth restriction

“…Future studies to identify and validate predictive models in early-onset SGA (EFW <10 th centile <32+0 weeks of gestation) would allow application to a wider population. This would complement the work currently being done in the PLANES study, which is investigating the impact of revealed PlGF in SGA from 32+0 weeks (63). Finally, our primary outcome of fetal or neonatal death provides only short-term information, and data collection for 2-year neurodevelopmental outcomes is on-going.…”

“…Future studies to identify and validate predictive models in early-onset SGA (EFW <10 th centile <32+0 weeks of gestation) would allow application to a wider population. This would complement the work currently being done in the PLANES study, which is investigating the impact of revealed PlGF in SGA from 32+0 weeks (63).…”

Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction

“…Future studies to identify and validate predictive models in early-onset SGA (EFW below the tenth centile, before 32+0 weeks of gestation) would allow application to a wider population. This would complement the work currently being done in the PLANES (placental growth factor led management of the small for gestational age fetus) study, which is investigating the effect of revealed PlGF in SGA from 32+0 weeks (60). Finally, our primary outcome of fetal or neonatal death provides only short-term information, and data collection for 2-year neurodevelopmental outcomes is ongoing.…”

The role of the PLGF in the prediction of the outcome in pregnancies complicated with fetal microsomia

“…PLGF awareness was associated with lower perinatal mortality and fewer low birth weight neonates at the expense of increasing respiratory neonatal morbidity without additional burden to the maternal outcome. The value of clinical management according to the PLGF result is currently under investigation by a randomized trial and it is likely that its results will have a strong in uence on the antenatal care [17].…”