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

BackgroundAntenatal 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 findingsThis 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.ConclusionsIn 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 registrationThis trial is registered with the ISRCTN registry, ISRCTN67698474.

Matias C Vieira and colleagues evaluate the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age in the DESiGN cluster randomised trial.     

An improved histochemical method for measuring nitric oxide synthase activity

The previous quantitative histochemical method for measuring nitric oxide synthase (NOS) activity in tissue sections involved the loss of about 15 per cent of the NOS, presumably from the section into the reaction medium. Two changes are now described. The first is concerned with the preparation in the laboratory of the active reagent, lead ammonium citrate/acetate (LACA). The second change involves an improvement of the procedure for measuring NOS activity. The new method appears to retain all the measurable NOS activity inside the section. Copyright © 1999 John Wiley & Sons, Ltd.     

Nest covering in plovers: How modifying the visual environment influences egg camouflage

Camouflage is one of the most widespread antipredator defences, and its mechanistic basis has attracted considerable interest in recent years. The effectiveness of camouflage depends on the interaction between an animal's appearance and its background. Concealment can therefore be improved by changes to an animal's own appearance, by behaviorally selecting an optimal background, or by modifying the background to better match the animal's own appearance. Research to date has largely focussed on the first of these mechanisms, whereas there has been little work on the second and almost none on the third. Even though a number of animal species may potentially modify their environment to improve individual‐specific camouflage, this has rarely if ever been quantitatively investigated, or its adaptive value tested. Kittlitz's plovers (Charadrius pecuarius) use material (stones and vegetation) to cover their nests when predators approach, providing concealment that is independent of the inflexible appearance of the adult or eggs, and that can be adjusted to suit the local surrounding background. We used digital imaging and predator vision modeling to investigate the camouflage properties of covered nests, and whether their camouflage affected their survival. The plovers' nest‐covering materials were consistent with a trade‐off between selecting materials that matched the color of the eggs, while resulting in poorer nest pattern and contrast matching to the nest surroundings. Alternatively, the systematic use of materials with high‐contrast and small‐pattern grain sizes could reflect a deliberate disruptive coloration strategy, whereby high‐contrast material breaks up the telltale outline of the clutch. No camouflage variables predicted nest survival. Our study highlights the potential for camouflage to be enhanced by background modification. This provides a flexible system for modifying an animal's conspicuousness, to which the main limitation may be the available materials rather than the animal's appearance.     

Insect infestations, incidence of viral plant diseases, and yield of winter wheat in relation to planting date in the northern Great Plains

Planting date effects on arthropod infestation and viral plant disease are undocumented for winter wheat, Triticum aestivum L., in South Dakota and the northern Great Plains. Winter wheat was planted over three dates (early, middle, and late; generally from late August to late September) to determine the effect on abundance of insect pests, incidence of plant damage, incidence of viral plant disease, and grain yield. The study was conducted simultaneously at two sites in South Dakota over three consecutive cropping seasons for a total of six site yr. Cereal aphids (Homoptera: Aphididae) were abundant in three site yr. Rhopalosiphum padi (L.), bird cherry-oat aphid, was the most abundant cereal aphid at the Brookings site, whereas Schizaphis graminum (Rondani), greenbug, predominated at Highmore. Aphid-days were greater in early versus late plantings. Aphid abundance in middle plantings depended on aphid species and site, but it usually did not differ from that in early plantings. Incidence of Barley yellow dwarf virus (family Luteoviridae, genus Luteovirus, BYDV) declined with later planting and was correlated with autumnal abundance of cereal aphids. Incidence of BYDV ranged from 24 to 81% among 1999 plantings and was < 8% in other years. Damage to seedling wheat by chewing insects varied for two site-years, with greater incidence in early and middle plantings. Wheat streak mosaic virus, spring infestations of cereal aphids, wheat stem maggot, and grasshoppers were insignificant. Yield at Brookings was negatively correlated with BYDV incidence but not cereal aphid abundance, whereas yield at Highmore was negatively correlated with aphid abundance but not BYDV incidence. Planting on 20 September or later reduced damage from chewing insects and reduced cereal aphid infestations and resulting BYDV incidence.     

Are Frontal Cognitive and Atrophy Patterns Different in PSP and bvFTD? A Comparative Neuropsychological and VBM Study

Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD) are two clinicohistological entities that share a severe prefrontal syndrome. To what extent do the cognitive syndrome and the location of the underlying brain atrophy unify or segregate these entities? Here, we examined the clinical and radiological patterns of frontal involvement and the neural bases of the cognitive dysfunctions observed in the Richardson form of PSP and the behavioral variant of FTD (bvFTD). The cognitive profile and grey and white matter volume of PSP (n = 19) and bvFTD (n = 16) patients and control participants (n = 18) were compared using a standard battery of neuropsychological tests and voxel-based morphometry (VBM), respectively. Analyses of correlations between neuropsychological and morphometric data were additionally performed. The severity and qualitative pattern of cognitive dysfunction was globally similar between the two patient groups. Grey matter volume was decreased in widespread frontal areas and in the temporal uncus in bvFTD, while it was decreased in the frontal and temporal lobes as well as in the thalamus in PSP. We also found an unexpected involvement of the frontal rectal gyrus in PSP patients compared to controls. Correlation analyses yielded different results in the two groups, with no area showing significant correlations in PSP patients, while several frontal and some temporal areas did so in bvFTD patients. In spite of minor neuropsychological and morphological differences, this study shows that the patterns of cognitive dysfunction and atrophy are very similar in PSP and bvFTD. However, executive dysfunction in these diseases may stem from partially divergent cortical and subcortical neural circuits.