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AbstractObjectiveTo determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity.DesignStepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019.SettingNational multisite trial in seven maternity hospitals throughout the island of IrelandParticipantsWomen with a singleton pregnancy between 20+0 to 36+6 weeks’ gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate.InterventionParticipants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment.Main outcomes measuresCo-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat.ResultsOf the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity—457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)—or in neonatal morbidity—527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67).ConclusionsThis was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit.Trial registrationClinicalTrials.gov NCT02881073.

Objective To explore pregnant women's views of participation in a clinical research trial while pregnant. Design Prospective nested qualitative cohort study embedded within a national, multi‐site randomized controlled trial of a diagnostic test for preeclampsia: Placental Growth Factor. One‐to‐one in‐depth semi‐structured interviews were undertaken with 19 women who had recently participated in the trial at a single recruiting site. The interviews were conducted in private, recorded digitally and transcribed verbatim. Setting Single tertiary maternity hospital currently recruiting eligible women onto an on‐going randomized controlled trial (NCT 02881073). Participants Women who had participated in the PARROT Ireland randomized controlled trial during their recent pregnancy. Methods Thematic analysis was utilized. Each line of the transcribed interviews was coded into a category by two researchers. The resultant categories were reviewed, and those with similarities were pooled allowing the development of themes. Main Outcome Measures Women's opinions and experience of participation in a randomized controlled trial of an interventional diagnostic test during their pregnancy. Results Four major themes were identified as follows: (a) Understanding of preeclampsia, (b) Motivators for clinical trial participation, (c) Barriers to decision making and (d) Influence of PARROT Ireland on pregnancy experience. Conclusions Women are generally interested and positively inclined to participate in research during pregnancy. The potential of risk is an important consideration for eligible pregnant woman. Information and support by both researchers and clinicians are paramount in aiding women's understanding of a research trial.

Women presenting with suspected pre-eclampsia are currently triaged on the basis of hypertension and dipstick proteinuria. This may result in significant false positive and negative diagnoses resulting in increased morbidity or unnecessary intervention. Recent data suggest that placental growth factor testing may be a useful adjunct in the management of women presenting with preterm pre-eclampsia. The primary objective of this trial is to determine if the addition of placental growth factor testing to the current clinical assessment of women with suspected preterm pre-eclampsia, is beneficial for both mothers and babies. This is a multicentre, stepped wedge cluster, randomised trial aiming to recruit 4000 women presenting with symptoms suggestive of preterm pre-eclampsia between 20 and 36+6 weeks' gestation. The intervention of an unblinded point of care test, performed at enrolment, will quantify maternal levels of circulating plasma placental growth factor. The intervention will be rolled out sequentially, based on randomisation, in the seven largest maternity units on the island of Ireland. Primary outcome is a composite outcome of maternal morbidity (derived from the modified fullPIERS model). To ensure we are not reducing maternal morbidity at the expense of earlier delivery and worse neonatal outcomes, we have established a co-primary outcome which will examine the effect of the intervention on neonatal morbidity, assessed using a composite neonatal score. Secondary analyses will examine further clinical outcomes (such as mode of delivery, antenatal detection of growth restriction and use of antihypertensive agents) as well as a health economic analysis, of incorporation of placental growth factor testing into routine care. Ethical approval has been granted from each of the seven maternity hospitals involved in the trial. The results of the trial will be presented both nationally and internationally at conference and published in an international peer-reviewed journal. NCT02881073.

Thromboembolic disease (TED) has consistently been identified as one of the leading causes of direct maternal mortality in the CEMACH report, with a reported mortality of 1.94/100 000 maternities.1 In November 2009 the RCOG published a guideline on TED that involves risk assessment of women at booking visit, during any antenatal admission and at delivery and assigns them into low, intermediate or high risk groups. The aim of our study was to determine how the implementation of these guidelines would affect our obstetric population. A retrospective review of the first 100 women who delivered at the CWIUH in 2010 was conducted and risk stratification applied at the relevant time points. 51 women (i.e., more than half) were deemed to be at intermediate or high risk of TED at some point during pregnancy. 35 of the 51 women (70%) had an increased risk of thrombosis determined by either age > greater than 35, parity ≥3, body mass index (BMI) >30 kg/m2 or history of smoking. The adjusted odds ratio for thrombosis with these risk factors ranges from 1.3 to 3.4 in case controlled studies and there is no evidence that they have an additive or synergistic effect in increasing risk. In our obstetric population, the percentage of women > 35 years is 25.5%, parity ≥3 is 8.5%, BMI >30 kg/m2 is 19% and smoke cigarettes is 16.7%.2 Identification of women at increased risk of TED in pregnancy and administering appropriate thrombophrophylaxis remains paramount. The strategy of accumulating factors that individually have a low risk to assign the category of intermediate or high risk needs to be re-visited especially when these risk factors are prevalent in the population.

We present a very unusual case of a set of twins delivering 87 days apart and with a birth weight difference of 1990 g with survival of both. A 33 year old woman with 2 previous full term vaginal deliveries presented to the EPAU of out department at 6 weeks gestation with light PV bleeding. Ultrasound confirmed DCDA twin pregnancy. Follow-up ultrasound 10 days later confirmed an ongoing pregnancy. She had formal booking appointment at 12 weeks and an uncomplicated pregnancy with regular review until 23 + 5 gestation when she presented with brown PV watery loss. PPROM of Twin 1 was confirmed. She was afebrile with normal BP and HR. HVS was taken, oral erythromycin commenced and bethamethasone administered. She was retained for inpatient monitoring and counselled about the associated risks of preterm delivery. 24 hours following admission she began contracting and had a quick spontaneous breech vaginal delivery of twin 1, a female, at 24 + 0 weeks weighing 550 g. Twin 2 was Cephalic with normal liquor volume on ultrasound. A trial of conservative management was agreed. She was retained in hospital for 4 hourly temperature, HR and BP cheques as well as weekly HVS, CRP and FBC monitoring and ultrasound surveillance. Her inpatient management period was uneventful and she was induced at 36 + 3 gestation with 1 mg of Prostaglandin PV and went on a few hours later to have a spontaneous vaginal delivery of Twin 2, a female, weighing 2.54 Kg as well as the retained placenta of Twin 1.

We report a case of a 32 year old para 0+0 transferred from a peripheral unit at 24+1 with PPROM. Ultrasound showed estimated fetal weight 615g, breech, anhydramnious and upper placenta. At 25+3 she developed severe lower back pain and antepartum haemorrhage >500mls. She underwent emergency caesarean for suspected placental abruption with consultant present. The uterus was markedly abnormal looking; the pregnancy lay below the anatomical uterus in a distended, thin walled segment. A female weighing 700g was delivered in good condition through a transverse lower uterine incision. A massive post partum haemorrhage of 6 litres followed and attempts at stabilisation of the patient were unsuccessful. Emergency hysterectomy was performed. Histology confirmed a cervical pregnancy. The patient had a further PPH 17 days later and underwent embolisation via interventional radiology but thereafter made a good recovery. Cervical pregnancy is a very rare form of ectopic pregnancy with an incidence of approximately 1 in 9000 deliveries. On a very rare occasion, a cervical pregnancy results in the birth of a live baby, typically the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity. The most effective treatment of cervical pregnancy is still unclear, with medical rather than surgical therapy recommended with multidose methotrexate in patients who are hemodynamically stable.

Background The latest confidential enquiry in maternal mortality highlighted that uncontrolled severe hypertension and fluid overload and pulmonary oedema were significant contributors to death from pre-eclampsia. The aim of this study was to examine standards of care of women with severe PET in our institution, to identify areas of potential improvement and to implement change to facilitate this improvement. Methods In 2007 over an 8 month period a retrospective audit of 52 admissions with severe PET to the High Dependency Unit (HDU) of our hospital was performed. 16 standards of care were examined based on published guidelines, with 5 standards identified as requiring major improvement. A HDU flow chart was designed incorporating an early warning scoring system (EWSS) with the aim of improving patient care. The flow chart was introduced in October 2010 and standard of care has been audited for 22 women with severe pre-eclampsia to date. Results & Conclusions Introduction of a HDU flow sheet with EWSS has resulted in significant improvement in the monitoring and appropriate response to severe hypertension and in appropriate fluid restriction in cases of severe PET.

Background Perennial ryegrass is a premier forage and turf grass, a genomic model organism for cool-season perennial grasses, but has relatively poor persistence under drought stress. The cultivar ‘Manhattan’ is an heirloom turf-type cultivar, and ancestral to many current turf cultivars and breeding lines in the USA. To improve turf-type perennial ryegrass genome resources, we assembled and compared two haplotypes of ‘Manhattan’ and extracted late embryogenesis abundant (LEA) gene families. Results Both haplotypes resolved into 2.3 Gb genome assemblies of 7 chromosomes each, with Gypsy-like retrotransposon concentrations in putative centromere regions. Repeat content was 83%, and the two haplotypes were syntenic with each other as well as published forage-type perennial ryegrass genomes. Annotations resulted in 43,000 genes for each haplotype with over 95% complete, 89% as single copy genes, and 86% with functional annotation. Seventy-two LEA genes were identified in haplotype-1 and fitted into 8 Pfam-based families, with 46 exhibiting expression evidence in vegetative tissues and 39 showing differential expression upon drought stress. Conclusions Broad synteny but high heterozygosity characterized the ‘Manhattan’ perennial ryegrass genome haplotypes. Repeat content, including long terminal repeat genes with annotation support, were high and indicative of cool-season Poaceae grasses. The identification of LEA genes differentially expressed upon drought stress provide candidate genes for further drought tolerance studies.

The vascular wilt fungi Verticillium dahliae and V. albo-atrum infect over 200 plant species, causing billions of dollars in annual crop losses. The characteristic wilt symptoms are a result of colonization and proliferation of the pathogens in the xylem vessels, which undergo fluctuations in osmolarity. To gain insights into the mechanisms that confer the organisms' pathogenicity and enable them to proliferate in the unique ecological niche of the plant vascular system, we sequenced the genomes of V. dahliae and V. albo-atrum and compared them to each other, and to the genome of Fusarium oxysporum, another fungal wilt pathogen. Our analyses identified a set of proteins that are shared among all three wilt pathogens, and present in few other fungal species. One of these is a homolog of a bacterial glucosyltransferase that synthesizes virulence-related osmoregulated periplasmic glucans in bacteria. Pathogenicity tests of the corresponding V. dahliae glucosyltransferase gene deletion mutants indicate that the gene is required for full virulence in the Australian tobacco species Nicotiana benthamiana. Compared to other fungi, the two sequenced Verticillium genomes encode more pectin-degrading enzymes and other carbohydrate-active enzymes, suggesting an extraordinary capacity to degrade plant pectin barricades. The high level of synteny between the two Verticillium assemblies highlighted four flexible genomic islands in V. dahliae that are enriched for transposable elements, and contain duplicated genes and genes that are important in signaling/transcriptional regulation and iron/lipid metabolism. Coupled with an enhanced capacity to degrade plant materials, these genomic islands may contribute to the expanded genetic diversity and virulence of V. dahliae, the primary causal agent of Verticillium wilts. Significantly, our study reveals insights into the genetic mechanisms of niche adaptation of fungal wilt pathogens, advances our understanding of the evolution and development of their pathogenesis, and sheds light on potential avenues for the development of novel disease management strategies to combat destructive wilt diseases.

Key messageTwo QTLs for resistance to lettuce drop, qLDR1.1 and qLDR5.1, were identified. Associated SNPs will be useful in breeding for lettuce drop and provide the foundation for future molecular analysis.Lettuce drop, caused by Sclerotinia minor and S. sclerotiorum, is an economically important disease of lettuce. The association of resistance to lettuce drop with the commercially undesirable trait of fast bolting has hindered the integration of host resistance in control of this disease. Eruption is a slow-bolting cultivar that exhibits a high level of resistance to lettuce drop. Eruption also is completely resistant to Verticillium wilt caused by race 1 of Verticillium dahliae. A recombinant inbred line population from the cross Reine des Glaces × Eruption was genotyped by sequencing and evaluated for lettuce drop and bolting in separate fields infested with either S. minor or V. dahliae. Two quantitative trait loci (QTLs) for lettuce drop resistance were consistently detected in at least two experiments, and two other QTLs were identified in another experiment; the alleles for resistance at all four QTLs originated from Eruption. A QTL for lettuce drop resistance on linkage group (LG) 5, qLDR5.1, was consistently detected in all experiments and explained 11 to 25% of phenotypic variation. On LG1, qLDR1.1 was detected in two experiments explaining 9 to 12% of the phenotypic variation. Three out of four resistance QTLs are distinct from QTLs for bolting; qLDR5.1 is pleiotropic or closely linked with a QTL for early bolting; however, the rate of bolting shows only a small effect on the variance in resistance observed at this locus. The SNP markers linked with these QTLs will be useful in breeding for resistance through marker-assisted selection.