The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study

BMC Pregnancy Childbirth. 2021 Apr 9;21(1):285. doi: 10.1186/s12884-021-03760-2.

Abstract

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable 'over treatment' of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes.

Methods: International multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score < 7 at 5 min, cord pH < 7.10, emergency delivery for fetal distress, and severe neonatal morbidity.

Discussion: The CEPRA trial will identify whether the CPR is a good indicator for delivery in women with perceived reduced fetal movements.

Trial registration: Dutch trial registry (NTR), trial NL7557 . Registered 25 February 2019.

Keywords: CPR; Cerebroplacental ratio; Decreased fetal movements; Fetal hypoxia; Neonatal morbidity; Placental insufficiency; Reduced fetal movements; Stillbirth.

Publication types

  • Clinical Trial Protocol
  • Comparative Study

MeSH terms

  • Adult
  • Apgar Score
  • Clinical Decision-Making / methods
  • Female
  • Fetal Distress / etiology
  • Fetal Distress / physiopathology
  • Fetal Distress / prevention & control*
  • Fetal Movement / physiology*
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Labor, Induced / standards*
  • Middle Cerebral Artery / diagnostic imaging*
  • Middle Cerebral Artery / physiopathology
  • Multicenter Studies as Topic
  • Perinatal Mortality
  • Placental Insufficiency / diagnosis*
  • Placental Insufficiency / physiopathology
  • Practice Guidelines as Topic
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Trimester, Third
  • Pulsatile Flow / physiology
  • Randomized Controlled Trials as Topic
  • Risk Assessment / methods
  • Stillbirth
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Prenatal
  • Umbilical Arteries / diagnostic imaging*
  • Umbilical Arteries / physiopathology