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. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation.

Background: Severe pre-eclampsia can cause significant mortality and morbidity for both mother and child, particularly when it occurs remote from term, between 24 and 34 weeks' gestation. The only known cure for this disease is delivery. Some obstetricians advocate early delivery to ensure that the development of serious maternal complications, such as eclampsia (fits) and kidney failure are prevented. Others prefer a more expectant approach delaying delivery in an attempt to reduce the mortality and morbidity for the child associated with being born too early. Objectives: The objective of the review was to compare the effects of a policy of interventionist care and early delivery with a policy of expectant care and delayed delivery for women with early onset severe pre-eclampsia. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2013). Selection criteria: Randomised trials comparing the two intervention strategies for women with early onset severe pre-eclampsia. Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. Data were checked for accuracy. Main results: Four trials, with a total of 425 women are included in this review. Trials were at low risk of bias for methods of randomisation and allocation concealment; high risk for blinding; unclear risk for incomplete outcome data and other bias; and low risk for selective reporting. There are insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. For the baby, there is insufficient evidence for reliable conclusions about the effects on stillbirth or death after delivery (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.69 to 1.71; four studies; 425 women). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.82, 95% CI 1.06 to 3.14; one study; 262 women), more hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), require more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women) and were more likely to have a lower gestation at birth in days (average mean difference (MD) -9.91, 95% CI -16.37 to -3.45; four studies; 425 women), more likely to be admitted to neonatal intensive care (RR 1.35, 95% CI 1.16 to 1.58) and have a longer stay in the neonatal intensive care unit (average MD 11.14 days, 95% CI 1.57 to 20.72 days; two studies; 125 women) than those allocated an expectant policy. Nevertheless, babies allocated to the interventionist policy were less likely to be small-for-gestational age (RR 0.30, 95% CI 0.14 to 0.65; two studies; 125 women). Women who had been allocated to the interventionist group were more likely to have a caesarean section (RR 1.09, 95% CI 1.01 to 1.18; four studies; 425 women) than those allocated an expectant policy. There were no statistically significant differences between the two strategies for any other outcomes. Authors' conclusions: This review suggests that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence is based on data from only four trials. Further large trials are needed to confirm or refute these findings and establish if this approach is safe for the mother

Core Outcome Set for GROwth restriction: deVeloping Endpoints (COSGROVE).

BACKGROUND: Foetal growth restriction (FGR) refers to a foetus that does not reach its genetically predetermined growth potential. It is well recognised that growth-restricted foetuses are at increased risk of stillbirth, foetal compromise, early neonatal death and neonatal morbidity. Later in life, they are prone to health problems, including increased risk of cardiovascular diseases and neurodevelopmental disorders. Interventions for preventing and treating FGR have been studied in many trials, but evidence is often difficult to synthesise and compare because of differences in the selection and definition of outcomes. To enable future trials to measure similar, meaningful outcomes, we are developing two core outcome sets (COS) - one for prevention and the other for treatment of FGR. METHODS: We will review the literature to identify previously reported outcomes. An international panel of relevant stakeholders who have experience of FGR (parent or carer of a baby that was growth restricted, health professional involved in the care of mothers and babies affected by FGR, a person with expertise in FGR research) will rate the importance of each of those outcomes in a series of three sequential online rounds of a Delphi study. Participants will be able to add items to the proposed list in round 1. A final face-to-face consensus meeting will be held with representatives of each stakeholder group at which a final list of outcomes for inclusion in the COS will be agreed. DISCUSSION: The development of COSs in FGR will ensure the collection and reporting of a minimum dataset agreed by stakeholder consensus and will reduce inconsistencies in the reporting of outcomes across relevant trials. Such standardisation in the reporting of outcomes will improve synthesis of evidence and generalisability of knowledge in the future by reducing heterogeneity in outcomes between trials and thus improve the results of systematic reviews and meta-analyses. Ultimately, we hope that the COSs will lead to an improvement in the quality of evidence-based clinical practice, enhance patient care, and improve the quality and consistency of research. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness (COMET) database

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

Contains fulltext : 65628.pdf ( ) (Open Access)BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217

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

OBJECTIVE: To explore the influence on perinatal outcome of different fetal monitoring strategies for preterm fetal growth restriction (FGR). DESIGN: Cohort analysis of individual participant data from the Growth Restriction Intervention Study (GRIT) and Trial of Umbilical and Fetal Flow in Europe (TRUFFLE) studies. SETTING: European multi-centre trials. POPULATION: All women from GRIT (n=238) and TRUFFLE (n=503), randomized between 26 and 32 weeks. METHODS: Women were categorized according to their monitoring-intervention method: A. immediate delivery (from GRIT), B. delayed delivery using conventional cardiotocography (CTG, from GRIT), C. delayed delivery using computerized CTG only (cCTG, from GRIT), D delayed delivery using cCTG only (from TRUFFLE) and E. delayed delivery using cCTG and ductus venosus (DV) Doppler (from TRUFFLE). PRIMARY OUTCOME MEASURE: Survival without impairment at two years. RESULTS: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between GRIT and TRUFFLE, but neonatal and late death were more frequent in GRIT (18% vs. 6%; p<0.01). The primary outcome was least common in groups A (70%; 95% confidence interval [CI] 61-78), and B (69%; 95% CI 57-82), and increased with more advanced monitoring in C (80%; 95% CI 68-91) and D (77%; 95% CI 70-84) and was highest in E (84%; 95% CI 80-89); (p trend <0.01). CONCLUSIONS: This analysis supports that fetal monitoring for early FGR can best be performed by the combination of cCTG and DV Doppler assessment. TRIAL REGISTRATION: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. This article is protected by copyright. All rights reserved

Immediate versus deferred delivery of the preterm baby with suspected fetal compromise for improving outcomes

BACKGROUND: Immediate delivery of the preterm fetus with suspected compromise may decrease the risk of damage due to intrauterine hypoxia. However, it may also increase the risks of prematurity.OBJECTIVES: To assess the effects of immediate versus deferred delivery of preterm babies with suspected fetal compromise on neonatal, maternal and long-term outcomes.SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2016) and reference lists of retrieved studies.SELECTION CRITERIA: Randomised trials comparing a policy of immediate delivery with deferred delivery or expectant management in preterm fetuses with suspected in utero compromise. Quasi-randomised trials and trials employing a cluster-randomised design were eligible for inclusion but none were identified.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.MAIN RESULTS: We included one trial of 548 women (588 babies) in the review. Women with pregnancies between 24 and 36 weeks' gestation took part. The study took place in 13 European countries, between 1993 and 2001. The difference in the median randomisation to delivery interval between immediate delivery and deferred delivery was four days (median: 0.9 (inter-quartile range (IQR) 0.4 to 1.3) days for immediate delivery, median: 4.9 (IQR 2.0 to 10.8) days in the delay group).There was no clear difference in the primary outcomes of extended perinatal mortality (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.67 to 2.04, one trial, 587 babies, moderate-quality evidence) or the composite outcome of death or disability at or after two years of age (RR 1.22, 95% CI 0.85 to 1.75, one trial, 573 babies, moderate-quality evidence) with immediate delivery compared to deferred delivery. The results for these outcomes are consistent with both appreciable benefit and harm. More babies in the immediate delivery group were ventilated for more than 24 hours (RR 1.54, 95% CI 1.20 to 1.97, one trial, 576 babies). There were no differences between the immediate delivery and deferred delivery groups in any other infant mortality outcome (stillbirth, neonatal mortality, postneonatal mortality &gt; 28 days to discharge), individual neonatal morbidity or markers of neonatal morbidity (cord pH less than 7.00, Apgar less than seven at five minutes, convulsions, interventricular haemorrhage or germinal matrix haemorrhage, necrotising enterocolitis and periventricular leucomalacia or ventriculomegaly).Some important outcomes were not reported, in particular infant admission to neonatal intensive care or special care facility, and respiratory distress syndrome. We were not able to calculate composite rates of serious neonatal morbidity, even though individual morbidities were reported, due to the risk of double counting infants with more than one morbidity.More children in the immediate delivery group had cerebral palsy at or after two years of age (RR 5.88, 95% CI 1.33 to 26.02, one trial, 507 children). There were, however, no differences in neurodevelopment impairment at or after two years (RR 1.72, 95% CI 0.86 to 3.41, one trial, 507 children), death at or after two years of age (RR 1.04, 95% CI 0.66 to 1.63, one trial, 573 children), or death or disability in childhood (six to 13 years of age) (RR 0.82, 95% CI 0.48 to 1.40, one trial, 302 children). More women in the immediate delivery group had caesarean delivery than in the deferred delivery group (RR 1.15, 95% CI 1.07 to 1.24, one trial, 547 women, high-quality evidence). Data were not available on any other maternal outcomes.There were several methodological weaknesses in the included study, and the level of evidence for the primary outcomes was graded high for caesarean section and moderate for extended perinatal mortality and death or disability at or after two years. The evidence was downgraded because the CIs for these outcomes were wide, and were consistent with both appreciable benefit and harm. Bias may have been introduced by several factors: blinding was not possible due to the nature of the intervention, data for childhood follow-up were incomplete due to attrition, and no adjustment was made in the analysis for the non-independence of babies from multiple pregnancies (39 out of 548 pregnancies). This study only included cases of suspected fetal compromise where there was uncertainty whether immediate delivery was indicated, thus results must be interpreted with caution.AUTHORS' CONCLUSIONS: Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations. There is a lack of trials addressing this question, and limitations of the one included trial means that caution must be used in interpreting and generalising the findings. More research is needed to guide clinical practice.Although the included trial is relatively large, it has insufficient power to detect differences in neonatal mortality. It did not report any maternal outcomes other than mode of delivery, or evaluate maternal satisfaction or economic outcomes. The applicability of the findings is limited by several factors: Women with a wide range of obstetric complications and gestational ages were included, and subgroup analysis is currently limited. Advances in Doppler assessment techniques may diagnose severe compromise more accurately and help make decisions about the timing of delivery. The potential benefits of deferring delivery for longer or shorter periods cannot be presumed.Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby.There is a need for high-quality randomised controlled trials comparing immediate and deferred delivery where there is suspected fetal compromise at preterm gestations to guide clinical practice. Future trials should report all important outcomes, and should be adequately powered to detect differences in maternal and neonatal morbidity and mortality.</p