Oxidative stress in pre-eclampsia; have we been looking in the wrong place?

Pre-eclampsia is a disorder of late pregnancy. It is a major cause of maternal and perinatal morbidity and mortality, accounting for nearly 18% of all maternal deaths worldwide; an estimated 77,000 maternal deaths per year [1]. Poor placentation is considered to be an initial cause of the placental ischemia [2]. Placental ischemia in turn gives rise to oxidative stress in the placenta and leads to shedding of syncytiotrophoblast debris into the maternal circulation provoking a systemic maternal inflammatory response and release of sFLT and sENG causing maternal vascular endothelial dysfunction. The ubiquitous nature of the maternal vascular endothelium accounts for the diverse multi-system nature of pre-eclampsia. Currently there is no treatment for pre-eclampsia except delivery of the placenta and the baby, with the attendant risk of iatrogenic prematurity and significant neonatal morbidity and mortality. As a result, intensive research endeavours have focused on defining the molecular mechanisms of pre-eclampsia and the identification of new pre-symptomatic biomarkers of the condition. This review focuses on the role of elevated oxidative stress in the pathology of pre-eclampsia and potential therapeutic agents targeting oxidative stress that may prevent or ameliorate this disorder

Hyperemesis gravidarum: current perspectives.

Hyperemesis gravidarum is a complex condition with a multifactorial etiology characterized by severe intractable nausea and vomiting. Despite a high prevalence, studies exploring underlying etiology and treatments are limited. We performed a literature review, focusing on articles published over the last 10 years, to examine current perspectives and recent developments in hyperemesis gravidarum

Prospective biomarkers in preterm preeclampsia: A review

Preterm pre-eclampsia (prior to 37 weeks’ gestation) remains a major cause of maternal and fetal morbidity and mortality particularly in low to middle income countries. Much research has focused on first and second trimester predictors of pre-eclampsia with the aim of allowing stratification of antenatal care and trialling of potential preventative and therapeutic agents. However, none have been shown to be of benefit in randomised controlled trials. In this literature review we critically evaluate predictive and diagnostic tests for preterm pre-eclampsia and discuss their clinical use and potential value in the management of preterm pre-eclampsia. We defined preterm pre-eclampsia as pre-eclampsia occurring prior to 37 weeks’ gestation. Substantial progress has been made in the development of predictive screening tests for preterm pre-eclampsia, but further research is needed prior to their introduction and integration into routine clinical practice. The performance of diagnostic tests mainly utilising angiogenic and anti-angiogenic factors for determining time to delivery in later pregnancy currently hold more promise than first trimester predictive tests, possible reflecting the heterogeneity of pre-eclampsia

Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records: A CALIBER Study.

BACKGROUND: The associations between pregnancy hypertensive disorders and common cardiovascular disorders have not been investigated at scale in a contemporaneous population. We aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders. METHODS: We used linked electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women, mean age at delivery 28 years, with nearly 1.9 million completed pregnancies. We used multivariable Cox models to determine the associations between hypertensive disorders of pregnancy, and preeclampsia alone (term and preterm), with 12 cardiovascular disorders in addition to chronic hypertension. We estimated the cumulative incidence of a composite end point of any cardiovascular disorder according to preeclampsia exposure. RESULTS: During the 20-year study period, 18 624 incident cardiovascular disorders were observed, 65% of which had occurred in women under 40 years. Compared to women without hypertension in pregnancy, women who had 1 or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% confidence interval 1.53-2.35) for any stroke, 1.67 (1.54-1.81) for cardiac atherosclerotic events, 1.82 (1.34-2.46) for peripheral events, 2.13 (1.64-2.76) for heart failure, 1.73 (1.38-2.16) for atrial fibrillation, 2.12 (1.49-2.99) for cardiovascular deaths, and 4.47 (4.32-4.62) for chronic hypertension. Differences in cumulative incidence curves, according to preeclampsia status, were apparent within 1 year of the first index pregnancy. Similar patterns of association were observed for hypertensive disorders of pregnancy, while preterm preeclampsia conferred slightly further elevated risks. CONCLUSIONS: Hypertensive disorders of pregnancy, including preeclampsia, have a similar pattern of increased risk across all 12 cardiovascular disorders and chronic hypertension, and the impact was evident soon after pregnancy. Hypertensive disorders of pregnancy should be considered as a natural screening tool for cardiovascular events, enabling cardiovascular risk prevention through national initiatives

The association between caesarean section and cognitive ability in childhood

Purpose: Global rates of caesarean section (CS) rates have increased rapidly in recent years. This is a growing public health concern as it has been proposed that CS may impact cognitive outcomes in childhood. However, the evidence for this association is limited and inconsistent. Therefore, the aim of this study was to investigate the relationship between obstetric mode of delivery and longitudinal cognitive outcomes in childhood. Methods: We examined this question using data from a longitudinal cohort study of 8845 participants from the Millennium Cohort Study, a nationally representative UK cohort, who completed a range of verbal and visual-spatial cognitive assessments at ages 3, 5, 7 and 11 years. Results: We found a statistically significant association between planned CS and visual-spatial cognitive delay in the pattern construction assessment at age 5 (OR 1.31, 95% CI 0.99–1.72) and age 7 (OR 1.42, 95% CI 1.12–1.81). Additionally planned CS was also associated with increased odds of “early childhood delay” (OR 1.70, 95% CI 1.15–2.50) and borderline increased odds of “persistent delay” (OR 1.37, 95% CI 0.99–1.89) in visual-spatial cognitive tests. Mode of delivery was not associated with verbal ability or with patterns of delay at any age point in verbal cognitive tests. Conclusion: We have reported a small association between planned CS and visual-spatial cognitive delay in childhood. However, while this result should be interpreted with caution, it highlights the need to further explore this potential relationship and the causal basis of such an association

Placental Growth Factor: A review of literature and future applications

Placental growth factor is an angiogenic protein, highly expressed during pregnancy, which correlates well with placental function. In this review, we highlight the origin, structure and function of Placental Growth Factor and its receptors. We discuss how their pro-angiogenic/anti-angiogenic synergism is critical for successful placentation and how their imbalance may be utilised as a diagnostic marker of disease or a potential therapeutic target for adverse pregnancy outcomes

Association between socioeconomic status with pregnancy and neonatal outcomes:An international multicenter cohort

Introduction: Previous evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland. Material and methods: The study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none. Results: A total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23–2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42–0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06–2.89). Conclusions: We did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes.</p

A Prospective Cohort Study Investigating Associations between Hyperemesis Gravidarum and Cognitive, Behavioural and Emotional Well-Being in Pregnancy

Objectives: To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy. Methods: The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15±1 weeks' gestation and at 20±1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6–24), Perceived Stress Scale score (PSS, range 0–30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0–30 or categories a–c) and behavioural responses to pregnancy score (limiting/resting [range 0–20] and all-or-nothing [range 0–28]). Results: During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15±1 and 20±1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]). Conclusion: This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial.Fergus P. McCarthy, Ali S. Khashan, Robyn A. North, Rona Moss-Morris, Philip N. Baker, Gus Dekker, Lucilla Poston, Louise C. Kenny on behalf of the SCOPE consortiu