Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial

Abstract

Background Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. Methods and findings This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster–summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) −6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. Conclusions In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. Trial registration This trial is registered with the ISRCTN registry, ISRCTN67698474.

Improving antenatal detection of small‐for‐gestational‐age fetus: economic evaluation of Growth Assessment Protocol

“…The consort diagram, characteristics of women included during the pre-randomisation and outcome comparison phases, and results of the analysis for primary and secondary clinical outcomes have been published previously. 6 Model parameter values estimated from the trial data based on the primary outcome definition of small babies identified at birth are described in Table 1; parentheses contain corresponding values based on the secondary definition of SGA. Cost-effectiveness results relating to the primary definition of SGA status are presented in Table 2 (results pertaining to the secondary definition in parentheses).…”

“…Five remaining cluster sites actually implemented GAP. 6 All women giving birth in a cluster site were included in the trial database. Women with multiple births, babies with congenital fetal anomalies and those born before 24 +1 gestational weeks were excluded from the analysis.…”

“…The DESiGN trial (DEtection of the Small for GestatioNal age Fetus) was the first pragmatic randomised cluster control trial that compared the effect of GAP and standard care in the UK, 5 finding no statistically significant difference in the rate of ultrasound detection of SGA (primary outcome, 25•9% in the intervention and 27•7% in the standard care arm, adjusted difference 2•4%, 95% CI -6•1% to 10•8%; p=0•58) when implemented in this setting. 6 The inclusion of economic evaluations in healthcare research is recommended to assist decision making about the adoption or spread of implementation. 7 An economic evaluation studying the cost-effectiveness of GAP has not previously been published.…”

Effect of the Growth Assessment Protocol on the DEtection of Small for GestatioNal age fetus: process evaluation from the DESiGN cluster randomised trial

“…The DESiGN trial is the first and only randomised controlled trial comparing GAP to an alternative intervention. The clinical effectiveness trial found that GAP did not increase the rate of antenatal detection of SGA (the primary outcome), when compared to standard care [18]. This paper reports implementation outcome findings from the nested process evaluation and considers these in the light of the findings from the effectiveness study.…”

Detecting fetal growth restriction with customised assessment: Is the jury still out?

“…Strategies to improve the detection of abnormal fetal growth trajectories in the antenatal period have received deserved attention, and much effort has focused on the development of fetal growth centile charts. In an accompanying research study in PLOS Medicine , Vieira and colleagues assess customised growth charts devised as part of the Growth Assessment Protocol (GAP) against standard care across 13 hospitals in England, in the DESiGN cluster randomised trial [ 1 ].…”