Objective
To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early‐onset fetal growth restriction.
Design
A randomised placebo‐controlled trial.
Setting
Thirteen ...maternal–fetal medicine units across New Zealand and Australia.
Population
Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks.
Methods
Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first).
Main Outcome Measures
The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre‐eclampsia.
Results
Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil‐treated, 39/57 (68.4%) placebo‐treated adjusted odds ratio (OR) 0.49, 95% CI 0.23–1.05 and had no effect on abdominal circumference Z‐scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil‐treated and 47/59 (79.7%) for placebo‐treated (adjusted OR 2.50, 95% CI 0.80–7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil‐treated and 33/59 (55.9%) for placebo‐treated (adjusted OR 1.93, 95% CI 0.84–4.45); and new‐onset pre‐eclampsia was 9/51 (17.7%) for sildenafil‐treated and 14/55 (25.5%) for placebo‐treated (OR 0.67, 95% CI 0.26–1.75).
Conclusions
Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta‐analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.
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Maternal sildenafil use has no beneficial effect on growth in early‐onset FGR, but also no evidence of harm.
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Maternal sildenafil use has no beneficial effect on growth in early‐onset FGR, but also no evidence of harm.
Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain ...unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses.
A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115).
Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I
= 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I
= 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I
= 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I
= 84%). The overall quality of the evidence was low-moderate.
For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.
Objective
The My Baby’s Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (the MBM intervention).
Design
Stepped‐wedge cluster‐randomised ...controlled trial.
Setting
Twenty‐seven maternity hospitals in Australia and New Zealand.
Population
Women with a singleton pregnancy without major fetal anomaly at ≥28 weeks of gestation from August 2016 to May 2019.
Methods
The MBM intervention was implemented at randomly assigned time points, with the sequential introduction of eight groups of between three and five hospitals at 4‐monthly intervals. Using generalised linear mixed models, the stillbirth rate was compared in the control and the intervention periods, adjusting for calendar time, study population characteristics and hospital effects.
Main outcome measures
Stillbirth at ≥28 weeks of gestation.
Results
There were 304 850 births with 290 105 births meeting the inclusion criteria: 150 053 in the control and 140 052 in the intervention periods. The stillbirth rate was lower (although not statistically significantly so) during the intervention compared with the control period (2.2/1000 versus 2.4/1000 births; aOR 1.18, 95% CI 0.93–1.50; P = 0.18). The decrease in stillbirth rate was greater across calendar time: 2.7/1000 in the first versus 2.0/1000 in the last 18 months. No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident.
Conclusions
The MBM intervention did not reduce stillbirths beyond the downward trend over time. As a result of low uptake, the role of the intervention remains unclear, although the downward trend across time suggests some benefit in lowering the stillbirth rate. In this study setting, an awareness of the importance of fetal movements may have reached pregnant women and clinicians prior to the implementation of the intervention.
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The My Baby’s Movements intervention to raise awareness of decreased fetal movement did not significantly reduce stillbirth rates.
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The My Baby’s Movements intervention to raise awareness of decreased fetal movement did not significantly reduce stillbirth rates.
Linked article This article is commented on by Alexander E. P. Heazell, p. 42 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.16954.
Aim: Our aim was to quantify climatic influences on key leaf traits and relationships at the global scale. This knowledge provides insight into how plants have adapted to different environmental ...pressures, and will lead to better calibration of future vegetation-climate models. Location: The data set represents vegetation from 175 sites around the world. Methods: For more than 2500 vascular plant species, we compiled data on leaf mass per area (LMA), leaf life span (LL), nitrogen concentration (Nmass) and photosynthetic capacity (Amass). Site climate was described with several standard indices. Correlation and regression analyses were used for quantifying relationships between single leaf traits and climate. Standardized major axis (SMA) analyses were used for assessing the effect of climate on bivariate relationships between leaf traits. Principal components analysis (PCA) was used to summarize multidimensional trait variation. Results: At hotter, drier and higher irradiance sites, (1) mean LMA and leaf N per area were higher; (2) average LL was shorter at a given LMA, or the increase in LL was less for a given increase in LMA (LL-LMA relationships became less positive); and (3) Amasswas lower at a given Nmass, or the increase in Amasswas less for a given increase in Nmass. Considering all traits simultaneously, 18% of variation along the principal multivariate trait axis was explained by climate. Main conclusions: Trait-shifts with climate were of sufficient magnitude to have major implications for plant dry mass and nutrient economics, and represent substantial selective pressures associated with adaptation to different climatic regimes.
ObjectivesTo assess the feasibility of conducting a randomised placebo-controlled trial of corticosteroids prior to planned caesarean section from 35+0 to 39+6 weeks.DesignA triple-blind, ...placebo-controlled, parallel, trial randomised at the participant level (1:1 ratio). Additional feasibility data obtained by questionnaires from trial participants and women who declined trial participation, and focus groups with local site researchers and clinicians.SettingThree obstetric units in New Zealand including tertiary and secondary care; public and private care, and research active and non-active units.ParticipantsWomen undergoing a planned caesarean section from 35+0 to 39+6 weeks; local site researchers and clinicians.InterventionsTwo doses of 11.4 mg betamethasone or saline placebo. Questionnaires and focus group meetings.Primary and secondary outcome measuresPrimary outcome: trial recruitment rate of eligible women. Secondary outcomes: trial recruitment by gestational age, site and delivery indication; proportion of babies who completed measurements of blood glucose concentrations as per protocol; overall incidence neonatal respiratory distress requiring >60 min of respiratory support; overall incidence of neonatal hypoglycaemia, and barriers and enablers to trial participation by participants, researchers and clinicians.ResultsThe recruitment rate was 8.9% (88/987) overall and 11.2% (88/789) for those approached about the trial. Neonatal blood glucose concentrations were measured as per protocol in 87/92 (94.6%) babies. For potential participants, key enablers to participation were contributing to research, a feeling of relevance and a good understanding; key barriers were a lack of understanding and concerns over safety. For researchers and clinicians, themes representing enablers and barriers included relevance, communication and awareness, influences on women’s decision-making, resource challenges and trial process practicalities.ConclusionsSome women are willing to participate in a randomised placebo-controlled trial of corticosteroids prior to a planned caesarean section birth at late preterm and term gestations. Participation in such a trial can be enhanced.
Primary trophoblast cultures obtained from term placentae are an important research tool. Term trophoblasts, while isolated as mononuclear cells, spontaneously fuse to form multinucleated syncytial ...clusters. Since term trophoblast cells do not replicate in vitro, contaminating cells can overgrow the culture limiting the lifespan of primary trophoblast cultures to about seven days. We aimed to develop a method that would allow the prolonged culture of term trophoblasts.
Trophoblasts were isolated from term placentae, following vaginal or cesarean section delivery, using either trypsin/DNase or dispase/DNase to digest the tissue. Purity of the trophoblasts was confirmed using flow cytometry prior to plating and during culture using immunocytochemistry. Cell death was examined with propidium iodide and trophoblast fusion monitored using PKH67 membrane stain.
Digestion of term villous tissue with dispase/DNase resulted in the release of significantly more trophoblasts than digestion with trypsin/DNase (n = 8, p = 0.0051). Viability of the trophoblasts was unaffected by enzyme choice. The use of Advanced DMEM/F12 supplemented with 2% fetal bovine serum allowed culture of the trophoblasts with minimal cell death or contamination for 30 days. Despite prolonged culture over half of the trophoblasts remained mononuclear.
We report a simple, optimized method to isolate and culture trophoblasts from term placentae for prolonged periods without substantial contamination with other cell types. Consistent with previous findings, trophoblasts cultured using our method were able to syncytialise, forming multi-nucleated syncytia. This extended growth time allows long term in vitro experimentation to further understand the nature of trophoblasts.
•Dispase released significantly more trophoblasts from term placentae than trypsin.•Advanced DMEM/F12 plus 2% fetal bovine serum was the optimal medium for term trophoblasts.•Cultures of trophoblasts remained relatively free of contamination for 30 days.•Not all cytotrophoblasts underwent syncytialisation even in prolonged culture.
The ineffective implementation of evidence based practice guidelines can mean that the best health outcomes are not achieved. This study examined the barriers and enablers to the uptake and ...implementation of the new bi-national (Australia and New Zealand) antenatal corticosteroid clinical practice guidelines among health professionals, using the Theoretical Domains Framework.
Semi-structured interviews or online questionnaires were conducted across four health professional groups and three district health boards in Auckland, New Zealand. The questions were constructed to reflect the 14 behavioural domains from the Theoretical Domains Framework. Relevant domains were identified by the presence of conflicting beliefs within a domain; the frequency of beliefs; and the likely strength of the impact of a belief on the behaviour using thematic analysis. The influence of health professional group and organisation on the different barriers and enablers identified were explored.
Seventy-three health professionals completed either a semi-structured interview (n = 35) or on-line questionnaire (n = 38). Seven behavioural domains were identified as overarching enablers: belief about consequences; knowledge; social influences; environmental context and resource; belief about capabilities; social professional role and identity; and behavioural regulation. Five behavioural domains were identified as overarching barriers: environmental context and resources; knowledge; social influences; belief about consequences; and social professional role and identity. Differences in beliefs between individual health professional groups were identified within the domains: belief about consequences; social professional role and identity; and emotion. Organisational differences were identified within the domains: belief about consequences; social influences; and belief about capabilities.
This study has identified some of the enablers and barriers to implementation of the New Zealand and Australian Antenatal Corticosteroid Clinical Practice Guidelines using the validated Theoretical Domains Framework, as perceived by health professionals. We have identified differences between individual health professional groups and organisations. The identification of these behavioural determinants can be used to enhance an implementation strategy, assist in the design of interventions to achieve improved implementation and facilitate process evaluations to understand why or how change interventions are effective.
Abstract
The invasive hornet
Vespa velutina nigrithorax
is considered a proliferating threat to pollinators in Europe and Asia. While the impact of this species on managed honey bees is ...well-documented, effects upon other pollinator populations remain poorly understood. Nonetheless, dietary analyses indicate that the hornets consume a diversity of prey, fuelling concerns for at-risk taxa. Here, we quantify the impact of
V. velutina
upon standardised commercially-reared colonies of the European bumblebee,
Bombus terrestris terrestris
. Using a landscape-scale experimental design, we deploy colonies across a gradient of local
V. velutina
densities, utilising automated tracking to non-invasively observe bee and hornet behaviour, and quantify subsequent effects upon colony outcomes. Our results demonstrate that hornets frequently hunt at
B. terrestris
colonies, being preferentially attracted to those with high foraging traffic, and engaging in repeated—yet entirely unsuccessful—predation attempts at nest entrances. Notably however, we show that
B. terrestris
colony weights are negatively associated with local
V. velutina
densities, indicating potential indirect effects upon colony growth. Taken together, these findings provide the first empirical insight into impacts on bumblebees at the colony level, and inform future mitigation efforts for wild and managed pollinators.
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