Publications by authors named "Edward Johnstone"

Computational models can be at the basis of new powerful technologies for studying and classifying disorders like pre-eclampsia, where it is difficult to distinguish pre-eclamptic patients from non-pre-eclamptic based on pressure when patients have a track record of hypertension. Computational models now enable a detailed analysis of how pregnancy affects the cardiovascular system. Therefore, new non-invasive biomarkers were developed that can aid the classification of pre-eclampsia through the integration of six different measured non-invasive cardiovascular signals.

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Introduction: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.

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Objective: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes.

Design: Superiority, double-blind randomised controlled trial.

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Article Synopsis
  • Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) can effectively map the oxygenation levels in the placenta, offering a new way to assess placental health in pregnant women.
  • In a study with twelve healthy pregnant subjects, both 2D and 3D imaging techniques were compared, revealing that 3D OE-MRI successfully covered the entire placenta without significant differences in average relaxation rates from the 2D scans.
  • While baseline measurements showed slight variances, no linkage was found between relaxation rates and gestational age, suggesting that the technique can detect detailed placental oxygenation changes during healthy pregnancies.
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Objective: We examined whether the risk of stillbirth was related to ambient air pollution in a UK population.

Design: Prospective case-control study.

Setting: Forty-one maternity units in the UK.

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Oral supplementation with L-citrulline, which is sequentially converted to L-arginine then nitric oxide, improves vascular biomarkers and reduces blood pressure in non-pregnant, hypertensive human cohorts and pregnant mice with a pre-eclampsia-like syndrome. This early-phase randomised feasibility trial assessed the acceptability of L-citrulline supplementation to pregnant women with chronic hypertension and its effects on maternal BP and other vascular outcomes. Pregnant women with chronic hypertension were randomised at 12-16 weeks to receive 3-g L-citrulline twice daily (n = 24) or placebo (n = 12) for 8 weeks.

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Maternal cardiovascular diseases, including hypertension and cardiac conditions, are associated with poor fetal outcomes. A range of adrenergic antihypertensive and cardioprotective medications are often prescribed to pregnant women to reduce major maternal complications during pregnancy. Although these treatments are not considered teratogenic, they may have detrimental effects on fetal growth and development, as they cross the fetoplacental barrier, and may contribute to placental vascular dysregulation.

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Background: Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation.

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Article Synopsis
  • The study investigates the link between pre-eclampsia and pre-existing cardiac dysfunction in pregnant women, finding no significant increase in overall pre-eclampsia rates.
  • A modest rise in cases of preterm pre-eclampsia and a significant increase in fetal growth restriction (FGR) were observed among women with cardiac issues.
  • The findings suggest that while there are concerns regarding pregnancy outcomes in this group, the relationship between cardiac dysfunction and pre-eclampsia is not clearly causal, and the use of β-blockers may have an impact on birthweight.
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Sphingolipids like sphingosine-1-phosphate (S1P) have been implicated in the pathophysiology of pre-eclampsia. We hypothesized that plasma S1P would be increased in women at high risk of developing pre-eclampsia who subsequently develop the disease. Low circulating placental growth factor (PlGF) is known to be associated with development of pre-eclampsia; so further, we hypothesized that increased S1P would be associated with concurrently low PlGF.

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Objective: To explore the nature of postnatal cardiovascular morbidity following pregnancies complicated by preterm pre-eclampsia and investigate associations between pregnancy characteristics and maternal postnatal cardiovascular function.

Study Design: This was an observational sub-study of a single-centre feasibility randomised double-blind placebo-controlled trial (https://www.

Clinicaltrials: gov; NCT03466333), involving women with preterm pre-eclampsia, delivering before 37 weeks.

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The purpose of this study is to characterise the sexual and reproductive health risks associated with mental illness among women. This was a retrospective cohort study of 2,680,149 women aged 14 to 45 years in the Clinical Practice Research Datalink, a UK primary care register, linked to 1,702,211 pregnancies that ended between the 1st January 1990 and 31st December 2017. Mental illness was identified in primary care and categorised into the following: common mental illness (depression/anxiety); addiction (alcohol/drug misuse); serious mental illness (affective/non-affective psychosis); other mental illness (eating/personality disorders).

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There is conflicting evidence regarding the effect of coronavirus disease (COVID-19) in pregnancy. Risk factors for COVID-19 overlap with risk factors for pregnancy complications. We aimed to assess the effects of the COVID-19 pandemic and confirmed SARS-CoV-2 infection on pregnancy outcomes.

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Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues.

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Background: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies.

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Introduction: Women with a history of stillbirth have an almost five-fold increased risk of stillbirth in a subsequent pregnancy, as well as increased risk of other adverse maternal and neonatal outcomes. The reasons for this association are not well understood but could relate to recurrent causes. We aimed to determine whether information from the time of index stillbirth, including cause, is associated with outcome of a subsequent pregnancy.

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Article Synopsis
  • Research shows that the birthweights of singleton babies conceived through IVF are increasing, but the specific treatment factors causing this change remain unclear.
  • Babies from fresh IVF transfers generally have lower birthweights compared to naturally conceived ones, while those from frozen embryo transfers have comparable or higher birthweights.
  • The study analyzed data from 7,588 births across five IVF centers, looking for links between treatment factors and birthweight, but found no significant associations, suggesting variability may be due to other unexplored factors.
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Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months' treatment with enalapril to improve postnatal cardiovascular function.

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Study Question: Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth?

Summary Answer: There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses.

What Is Known Already: In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health.

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Introduction: Late-gestation adverse pregnancy outcome is associated with reduced placental villous vascularity but rarely with a frankly abnormal umbilical artery Doppler waveform. The clinical utility of umbilical artery Doppler velocimetry in late gestation is limited by poor understanding of what aspect(s) of placental structure and function the impedance reflects. We hypothesized that placental arterial circulation impedance reflects placental vascularity and arterial function.

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Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy.

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