Cerebroplacental ratio-based management versus care as usual in non-small-for-gestational-age fetuses at term with maternal perceived reduced fetal movements (CEPRA)
Lancet O&G study published this month
Citation
Lens, L. A., Posthuma, S., Damhuis, S. E., Burger, R. J., Groen, H., Duijnhoven, R. G., Kumar, S., Heazell, A. E. P., Khalil, A., Ganzevoort, W., & Gordijn, S. J.; CEPRA Investigators. (2025). Cerebroplacental ratio-based management versus care as usual in non-small-for-gestational-age fetuses at term with maternal perceived reduced fetal movements (CEPRA): A multicentre, cluster-randomised controlled trial. Lancet Obstetrics & Gynaecology, 10(7), 123–134.
The CEPRA trial provides high-level evidence that management guided by the cerebroplacental ratio (CPR) in term non-small-for-gestational-age fetuses presenting with reduced movements reduces a composite of stillbirth, neonatal mortality, low Apgar score, umbilical artery acidosis and emergency birth for distress from 15 % to 12 % (RR 0.76; 95 % CI 0.58–0.99; NNS 27; 95 % CI 15–216). CPR values below 1.1 triggered expedited delivery within 16 hours and were associated with a marked reduction in severe neonatal morbidity (RR 0.27; 95 % CI 0.10–0.73) without increasing overall maternal complications. Implementation of routine Doppler assessment of the middle cerebral and umbilical arteries in women reporting reduced fetal movements at term enables earlier identification of placental dysfunction in ostensibly low-risk pregnancies.
Background and rationale for the CEPRA study
Reduced fetal movements occur in up to 15 % of term pregnancies and signal a 2- to 5-fold increase in stillbirth and neurodevelopmental impairment risk. Placental dysfunction often presents subclinically in non-SGA fetuses and escapes routine assessment protocols focused on growth centiles alone. The cerebroplacental ratio, defined as MCA-PI / UA-PI, offers a validated surrogate for fetal hypoxia and placental insufficiency. Prior to CEPRA no randomised trial had addressed CPR-guided management in non-SGA fetuses with reduced movements. CEPRA aimed to determine whether CPR-based expedited birth versus usual care could improve perinatal outcomes in term non-SGA pregnancies.
Study design and cluster randomisation
CEPRA was a pragmatic multicentre cluster-randomised trial across 22 Dutch and 1 Australian hospitals. Hospitals were allocated 1:1 to a revealed (CPR-based) or concealed (care as usual) arm, stratified by country and expected recruitment volume. Inclusion required singleton cephalic gestations at 37 + 0 to 40 + 6 weeks, estimated fetal weight ≥ 10th centile, and perceived reduced movements. Randomisation employed computer-generated sequences in Castor EDC; analysis followed a modified intention-to-treat principle. The intracluster correlation for the primary outcome was 0.003, minimising bias from cluster imbalances.
Doppler methodology and CPR threshold All participants underwent MCA and UA Doppler with at least three consistent waveforms, insonation angle < 15°. CPR was calculated in real time and abnormality defined as an absolute value < 1.1, corresponding approximately to the 5th percentile at term. In revealed centres clinicians received CPR results and expedited birth was recommended within 16 hours if CPR < 1.1. Concealed centres masked CPR results; management followed local protocols, typically expectant monitoring. Validity of pulsatility indices was ensured by training sonographers and standardising measurement sites in the cord loop and circle of Willis.
Primary outcome and statistical findings
The composite primary outcome occurred in 99 / 853 (11.6 %) of the revealed group versus 127 / 831 (15.3 %) of the concealed group. The relative risk of adverse perinatal outcome was 0.76 (95 % CI 0.58–0.99; p = 0.042), with NNS 27 (95 % CI 15–216) to prevent one event. No stillbirths occurred; neonatal mortality was equal at one case per group. Risk reduction was driven by severe neonatal morbidity (RR 0.27; 95 % CI 0.10–0.73), notably respiratory distress syndrome (RR 0.19; 95 % CI 0.04–0.89) and sepsis (RR 0.14; 95 % CI 0.02–1.13). Generalised linear mixed-effects models accounted for hospital clustering with complete case analysis due to < 5 % missing primary data.
Secondary outcomes and subgroup analyses
Postpartum haemorrhage was reduced in the revealed group (7 % vs 10 %; RR 0.63; 95 % CI 0.45–0.88). Maternal hypertensive disorders and mild neonatal morbidity (hypoglycaemia, hypothermia, neonatal ward admission) did not differ significantly. Subgroup analysis by normal versus abnormal CPR at recruitment showed benefit primarily in normal CPR fetuses (RR 0.74; 95 % CI 0.56–0.96). Women with abnormal CPR had shorter time to birth in the revealed group (median 2.0 days vs 7.0 days; p < 0.001) but small numbers (23 vs 38) limited precision. Sensitivity analyses by country and high-recruitment clusters and a post-hoc covariate-adjusted model yielded consistent effect estimates.
Clinical management implications
Incorporate routine MCA and UA Doppler assessment into evaluation algorithms for reduced fetal movements at term. Adopt CPR < 1.1 as a trigger for expedited delivery planning, ideally within 16 hours of presentation. Balance risks of iatrogenic prematurity against placental insufficiency-driven compromise by individualised counselling. Educate multidisciplinary teams on CPR interpretation, timely documentation and escalation pathways in labour units. Implement audit cycles to monitor CPR measurement adherence, perinatal outcomes and unintended intervention rates.
Integration with care pathways and guideline alignment
CEPRA findings align with RATIO37 (Lancet 2024) and ISUOG recommendations for utilising CPR in term planned birth. National guidelines on reduced fetal movements should be updated to consider CPR measurement alongside CTG and fetal biometry in the setting of RFM. Local protocols must specify roles of obstetricians, sonographers and midwives in obtaining and acting on Doppler results. Integrate electronic alerts in maternity records when reduced movements are reported to prompt CPR assessment as part of overall fetal evaluation.
Maternal and neonatal morbidity impacts
CPR-based management did not increase rates of caesarean section (5 % prelabour; 11 % emergency) compared with usual care. No significant difference in induction of labour (41 % vs 40 %) or gestational age at birth (median 40 + 0 weeks in both groups). Reduction in postpartum haemorrhage suggests potential benefits beyond perinatal outcomes when CRT-prompted interventions are optimised. No increase in neonatal ward admissions (12.8 % vs 20.6 %; RR 0.76; 95 % CI 0.47–1.22) despite targeted expedited deliveries. Findings support a favourable maternal risk profile for CPR-guided interventions in term non-SGA pregnancies.
Limitations and directions for future research
Open-label design may have introduced performance bias through clinician and patient awareness of CPR status. Abnormal CPR prevalence was lower than anticipated (4 % overall), limiting power to assess outcomes in that subgroup. Inter-rater variability of Doppler measurements by routine sonographers warrants dedicated reproducibility studies. Generalisation to low-resource settings requires caution given the high education level and resource availability in CEPRA centres. Long-term neurodevelopmental follow-up and cost-effectiveness analyses are needed to fully define the impact of CPR-guided management.