Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials

Objective: To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR). Methods: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. Results: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61–78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57–82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68–91%)) and TRUFFLE (77% (95% CI, 70–84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80–89%)) (P < 0.01 for trend). Conclusions: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment. Trial Registration: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499

A randomised trial of timed delivery for the compromised preterm fetus:Short term outcomes and bayesian interpretation

Objectives. To compare the effect of delivering early to pre-empt terminal hypoxaemia with delaying for as long as possible to increase maturity. Design. A randomised controlled trial. Setting. 69 hospitals in 13 European countries. Participants. Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated. Methods. The interventions were 'immediate delivery' or 'delay until the obstetrician is no longer uncertain'. The data monitoring and analysis were Bayesian. Main outcome measures. 'Survival to hospital discharge' and 'developmental quotient at two years of age', this latter to be reported later. Results. Of 548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies). The median time-to-delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group. Total deaths prior to discharge were 29 (10%) in the immediate group versus 27 (9%) in the delay group (odds ratio 1.1, 95% CI 0.61-1.8). Total caesarean sections were 249 (91%) in the immediate group versus 217 (79%) in the delay group: (OR 2.7; 95% CI 1.6-4.5). These odds ratios were similar for those randomised at gestational ages above or below 30 weeks. Interpretation. The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to randomise at about the correct equivocal threshold between delivery and delay. However, there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong