The mechanical force of blood flow is a fundamental determinant of vascular homeostasis. This frictional stimulation of cells, fluid shear stress (FSS), is increasingly recognised as being essential to placental development and function. Here, we focus on the role of FSS in regulating fetoplacental circulatory flow, both in normal pregnancy and that affected by fetal growth restriction (FGR). The fetus is reliant on placental perfusion to meet its circulatory and metabolic demands. Failure of normal vascular adaptation and the mechanisms enabling responsive interaction between fetoplacental and maternal circulations can result in FGR. FSS generates vasodilatation at least partly through the release of endothelial nitric oxide, a process thought to be vital for adequate blood flow. Where FGR is caused by placental dysfunction, placental vascular anatomy is altered, alongside endothelial dysfunction and hypoxia, each impacting upon the complex balance of FSS forces. Identifying specific mechanical sensors and the mechanisms governing how FSS force is converted into biochemical signals is a fast-paced area of research. Here, we raise awareness of Piezo1 proteins, recently discovered to be FSS-sensitive in fetoplacental endothelium, and with emerging roles in NO generation, vascular tone and angiogenesis. We discuss the emerging concept that activating mechanosensors such as Piezo1 ultimately results in the orchestrated processes of placental vascular adaptation. Piecing together the mechanisms governing endothelial responses to FSS in placental insufficiency is an important step towards developing new treatments for FGR.

Blood flow, and the force it generates, is critical to placental development and function throughout pregnancy. This mechanical stimulation of cells by the friction generated from flow is called shear stress (SS) and is a fundamental determinant of vascular homeostasis, regulating remodelling and vasomotor tone. This review describes how SS is fundamental to the establishment and regulation of the blood flow through the uteroplacental and fetoplacental circulations. Amongst the most recent findings is that alongside the endothelium, embryonic stem cells and the villous trophoblast are mechanically sensitive. A complex balance of forces is required to enable effective establishment of the uteroplacental circulation, while protecting the embryo and placental villi. SS also generates flow-mediated vasodilatation through the release of endothelial nitric oxide, a process vital for adequate placental blood flow. The identification of SS sensors and the mechanisms governing how the force is converted into biochemical signals is a fast-paced area of research, with multiple cellular components under investigation. For example, the Piezo1 ion channel is mechanosensitive in a variety of tissues including the fetoplacental endothelium. Enhanced Piezo1 activity has been demonstrated in response to the Yoda1 agonist molecule, suggesting the possibility for developing tools to manipulate these channels. Whether such agents might progress to novel therapeutics to improve blood flow through the placenta requires further consideration and research.

ObjectiveTo determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2).DesignRetrospective cohort study.SettingMultiple centres (in Australia, Ireland, New Zealand, and the UK).PopulationFive thousand five hundred and nineteen low‐risk nulliparous pregnant women.MethodsData on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log‐normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors.Main outcome measuresTime to pregnancy and infertility.ResultsOf the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15–1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0–3.3 months) versus 4.1 months (3.6–4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15–2.29) or not (adjusted RR 1.73; 95% CI 1.33–2.23). Reduced high‐density lipoprotein cholesterol (HDL‐C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility.ConclusionMetabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification.Tweetable abstractMetabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

STUDY QUESTION: Does the shear stress sensing ion channel subunit Piezol have an important mechanotransduction role in human fetoplacental endothelium? SUMMARY ANSWER: Piezol is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezol prevents the normal response to shear stress. WHAT IS KNOWN ALREADY: Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezol channels are Ca2+ -permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We investigated the relevance of Piezol to placental vasculature by studying human fetoplacental endothelial cells (FpECs) from healthy pregnancies. Endothelial cells were isolated from placental cotyledons and cultured, for the study of tube formation and cell alignment to shear stress. In addition, human placental arterial endothelial cells were isolated and studied immediately by patch-damp electrophysiology. MAIN RESULTS AND THE ROLE OF CHANCE: The synthetic Piezol channel agonist Yoda I caused strong elevation of the intracellular Ca2+ concentration with a 50% effect occurring at about 5.4 mu M. Knockdown of Piezol by RNA interference suppressed the Yoda I response, consistent with it being mediated by Piezol channels. Alignment of cells to the direction of shear stress was also suppressed by Piezol knockdown without loss of cell viability. Patch-clamp recordings from freshly isolated endothelium showed shear stress-activated single channels which were characteristic of Piezol. LIMITATIONS, REASONS FOR CAUTION: The in vitro nature of fetoplacental endothelial cell isolation and subsequent culture may affect FpEC characteristics and PIEZOl expression. In addition to Piezol, alternative shear stress sensing mechanisms have been suggested in other systems and might also contribute in the placenta. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that Piezol is an important molecular determinant of blood flow sensitivity in the placenta. Establishing and manipulating the molecular mechanisms regulating shear stress sensing could lead to novel therapeutic strategies to improve blood flow in the placenta. LARGE-SCALE DATA: Not applicable.

Background: Obesity has been associated with increased risk of antenatal depression, but little is known about this relationship. This study tested whether socio-economic status (SES) influences the relationship between obesity and antenatal depression.Methods: Data were taken from the Screening for Pregnancy Endpoints (SCOPE) cohort. BMI was calculated from measured height and weight at 15 +/- 1 weeks' gestation. Underweight women were excluded. SES was indicated by self-reported household income (dichotomised around the median: low SES < 45,000; pound high SES > 45,000) pound. Antenatal depression was defined as scoring >= 13 on the Edinburgh Postnatal Depression Scale at both 15 +/- 1 and 20 +/- 1 weeks' gestation, to identify persistently elevated symptoms of depression.Results: Five thousand five hundred and twenty two women were included in these analyses and 5.5% had persistently elevated antenatal depression symptoms. There was a significant interaction between SES and BMI on the risk of antenatal depression (p=0.042). Among high SES women, obese women had approximately double the odds of antenatal depression than normal weight controls (AOR 2.11, 95%Cl 1.16-3.83, p=0.014, adjusted for confounders). Among low SES women there was no association between obesity and antenatal depression. The interaction effect was robust to alternative indicators of SES in sensitivity analyses. Limitations: 1) Antenatal depression was assessed with a self-reported screening measure; and 2) potential mediators such as stigma and poor body-image could not be examined.Conclusions: Obesity was only associated with increased risk of antenatal depression among high SES women in this sample. Healthcare professionals should be aware that antenatal depression is more common among low SES women, regardless of BMI category. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background The effect of prenatal distress on the risk of a small for gestational age (SGA) infant is uncertain. We have addressed the influences of prenatal stress, anxiety and depression on the risk of SGA. We also examined the effects of infant sex and timing of distress during pregnancy on any observed associations. Method The study population comprised 5606 healthy nulliparous pregnant women who participated in the international prospective Screening for Obstetric and Pregnancy Endpoints (SCOPE) study. Women completed the Perceived Stress Scale (PSS), the short form of the Spielberger State–Trait Anxiety Inventory (STAI) and the Edinburgh Postnatal Depression Scale (EPDS) at 15 ± 1 and 20 ± 1 weeks' gestation. SGA was defined as birthweight below the 10th customized percentile. Logistic regression was used for data analysis, adjusting for several potential confounders such as maternal age, body mass index (BMI), smoking, socio-economic status and physical exercise. Results The risk of SGA was increased in relation to mild [adjusted odds ratio (aOR) 1.35, 95% confidence interval (CI) 1.07–1.71], moderate (aOR 1.26, 95% CI 1.06–1.49), high (aOR 1.45, 95% CI 1.08–1.95) and very high stress scores (aOR 1.56, 95% CI 1.03–2.37); very high anxiety score (aOR 1.45, 95% CI 1.13–1.86); and very high depression score (aOR 1.14, 95% CI 1.05–1.24) at 20 ± 1 weeks' gestation. Sensitivity analyses showed that very high anxiety and very high depression increases the risk of SGA in males but not in females whereas stress increases the risk of SGA in both males and females. Conclusions These findings suggest that prenatal stress, anxiety and depression measured at 20 weeks' gestation increase the risk of SGA. The effects of maternal anxiety and depression on SGA were strongest in male infants.

PURPOSE To document the radiologic abnormalities seen in the central nervous system (CNS) during and after treatment of childhood leukemia. METHODS MR images (19 patients) and CT scans (12 patients) were reviewed retrospectively in 19 children and adolescents with neurologic complications of leukemia or its treatment. Patients were divided into two groups: the first included those with disease-related complications of leukemia, such as meningeal and parenchymal leukemia, chloroma, and cerebrovascular disorders; the second included patients with treatment-related neurotoxicity and infection caused by immunocompromised states. Pathologic confirmation of the CNS lesions was obtained in eight patients. Factors that predisposed to the development of tumor-related or treatment-related complications were determined by reviewing the medical records. RESULTS Among the 19 patients, 10 had two or more different CNS abnormalities found on CT scans or MR images. The imaging abnormalities seen in 12 patients during treatment included sinus thrombosis (n = 3), transient gray or white matter ischemia (n = 2), presumed disseminated microinfarcts (n = 1), cerebral hemorrhage or infarct (n = 3), inflammatory demyelinating polyradiculoneuropathy (n = 1), infections (n = 4, 2 bacterial and 2 fungal), and meningeal leukemia (n = 2). After therapy, seven patients had CNS imaging abnormalities, including secondary brain tumors (2 malignant gliomas and 1 CNS lymphoma), spinal chloroma (n = 1), necrotizing leukoencephalopathy and mineralizing microangiopathy (n = 3), cerebral mucormycosis (n = 1), spontaneous intracranial hemorrhage (n = 3), and spinal meningeal leukemia (n = 1). CONCLUSION The wide spectrum of CNS abnormalities that occur during and after treatment for leukemia is related to the inherent risk of the leukemia itself, to the treatment method, and to the duration of survival. Because many neurologic complications of leukemia are treatable, early diagnosis is essential.

Objective Preterm birth is a global public health issue. In women considered high risk, insertion of a cervical cerclage has been shown to reduce this risk. We present findings from a retrospective cohort evaluating the success of different cerclage procedures (Shirodkar, McDonald and Transabdominal) in a tertiary level obstetric unit. Study design Retrospective data was collected for 200 women who underwent a cerclage procedure at Leeds Teaching Hospitals NHS Trust between August 2000 and October 2010. Exclusion criteria for the study included multiple pregnancy, insertion of more than one cerclage in a single pregnancy, or an incomplete data record. Success was measured by delivery of a live baby ≥ 34 weeks. Mean gestational age (MGA) for each group was also calculated. Statistical analysis was performed using Fisher’s exact test. Results The Shirodkar cerclage produced a significantly greater MGA at delivery (36.3 weeks), compared to both McDonald (33.5 weeks; p = 0.004) and transabdominal cerclage (33.3 weeks; p = 0.007). Elective insertion of Shirodkar, McDonald and Transabdominal cerclage was carried out in 70, 37, 25 women respectively. These produced success rates of 81.4%, 70.3% and 72% (Shirodkar vs McDonald p = 0.226, Shirodkar vs Transabdominal p = 0.393). Ultrasound-indicated sutures were placed in 48 women (Shirodkar n = 24, McDonald n = 24). The success rates were 92.7% and 66.7% respectively, however these were not significantly different (p = 0.0723). Conclusion These results demonstrate consistent rates in births greater than 34 weeks gestation following insertion of cervical cerclage. Although Shirodkar cerclage appears preferable in elective and ultrasound-indicated procedures, prospective randomised trials such as MAVRIC1 need to be completed to confirm this. Reference http://www.medscinet.net/mavric/default.aspx

The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.

Log in or Register Subscribe to journalSubscribe Get new issue alertsGet alerts Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Secondary Logo Journal Logo All Articles Images Videos Podcasts Blogs Advanced Search Toggle navigation Subscribe Register Login Articles & Issues Current IssuePrevious Issues Collections Obstetric Airway ManagementMaternal EmbolismRegional Anesthesia for Cesarean SectionGeneral Anesthesia for Cesarean SectionAnalgesia for LaborObstetric HemorrhagePre-Eclampsia/EclampsiaPharmacologyTraumaInfection and SepsisMaternal ObesityMaternl Morbidity and MortalityNeonatal Morbidity and MortalityObstetric ComplicationsAnesthetic ComplicationsNon-Obstetric Maternal DiseaseCritical CareDrug Abuse in PregnancyEthicsSystems Based Practice For Authors Information for AuthorsLanguage Editing Services Journal Info About the JournalEditorial BoardAdvertisingOpen AccessSubscription ServicesReprintsRights and Permissions All Articles Images Videos Podcasts Blogs Advanced Search

Background There is little evidence for modifiable factors for normal pregnancy. Most work has focused on prediction of complicated pregnancy. Methods Data from 3513 healthy nulliparous women with a singleton pregnancy participating in the SCreening fOr Pregnancy Endpoints study from six centers in New Zealand (Auckland), Australia (Adelaide), UK (London, Manchester, Leeds) and Ireland (Cork) were analysed using logistic regression to identify risk and protective factors for uncomplicated pregnancy in nulliparous women. Main outcome measure Uncomplicated normotensive pregnancy, delivered at >37 weeks, with a liveborn baby not SGA, excluding pregnancies with significant other complication. Results Of the 3513 women, 1973 (56%) had an uncomplicated pregnancy and 1540 (44%) had a complicated pregnancy. Potentially modifiable factors were identified (table 1). Non-modifiable risk factors included participant9s birthweight, Indian ethnicity, hypertension on oral contraception, asthma, family history of pregnancy hypertension, paternal history of heart disease, two vaginal bleeds in current pregnancy, gastroenteritis, uterine artery resistance index and femur length. Conclusions These results provide firm evidence on which to base recommendations for pre- and early pregnancy counselling to improve the likelihood of having a normal uncomplicated pregnancy.

Introduction In women at risk of midtrimester loss or extreme preterm birth (PTB), insertion of a cervical cerclage has been shown to reduce that risk.1 Three common techniques are used. We present the findings of an audit on our results following insertion of McDonald, Shirodkar and Transabdominal cervicoisthmic sutures. Methods Retrospective data were collected from the Leeds Teaching Hospitals maternity database on 178 women who had had a cervical suture over the past 5 years. Success was defined as the discharge of a live baby from hospital (whether term or preterm). Comparisons were made between the three cerclage techniques using Fisher9s exact test. Results Elective insertion of McDonald, Shirodkar and Transabdominal sutures was carried out in 54, 63 and 24 women respectively. These produced success rates of 83%, 97% and 84% respectively (Shirodkar vs McDonald p=0.02; Shirodkar vs Transabdominal p=0.05). Ultrasound-indicated sutures were placed in 19 women (McDonald n=5; Shirodkar n=14). The success rates (60% vs 93%) were not significantly different (p=0.15), although the numbers were small. Discussion These results demonstrate excellent live baby rates following insertion of cervical cerclage in patients at high risk of PTB. These figures may be used when counselling women who may be suitable for cervical cerclage. Although the Shirodkar procedure was associated with greater success, this was not a randomised trial and the optimal route for elective cerclage remains to be established through multicentre studies such as MAVRIC.2

Please cite this paper as: Howarth LA, Walker JJ. The role of family planning in South Asia. BJOG 2011;118 (Suppl. 2):31–35.

From the earliest days of medical practice, when surgeons used cadavers to explore the possibilities of surgical intervention, simulation has been employed to advance the practice of health care. In the last 10 years, technological advances have allowed for a wider availability and greater realism of simulation, and this has encouraged a great expansion in its use. Simulation aims to create a virtuous cycle of professional development to improve patient outcomes. Although it seems eminently logical to believe that simulation will result in better outcomes, there is a need to test these new training interventions rigorously to be sure of their worth and to understand any limitations. The purpose of this BJOG supplement is to examine in depth several paradigms of medical simulation within maternity care and gynaecology, in different settings, looking at what can be achieved and how. In this opening review, we look at the potential use of medical simulation in broad terms and describe the types of evidence that can be employed to support its use.

No individual can claim credit for all the advances made during his lifetime. However, certain individuals have a far greater influence than others. Prof. Christopher Redman has had a huge role to play in increasing the understanding of the aetiology, pathology, progression and management of preeclampsia. The work he did personally, led in others and stimulated in colleagues, both friend and foe, has helped to progress preeclampsia from a disease that came from nowhere to one that is more understood and safely managed. In this paper, it is the work in immunology that will be concentrated on in a chronological way but this will be linked to other relevant research and clinical practice. The understanding that preeclampsia is a two-stage disease starting in the placenta and progressing systemically has led to greater understanding as well as more questions. The universal role of immunology first as an acceptor within the placental bed then as a disease driver in the systemic circulation emphasises the good and the bad in physiological systems. Prof. Redman has been present in all these areas of discovery and enlightenment as will be described.

Hiby, SE, Apps, R., Sharkey, AM, Farrell, LE, Gardner, L., Mulder, A., Claas, FH, Walker, JJ, Redman, CW, Morgan, L., Tower, C., Regan, L., Moore, GE, Carrington, M., & Moffett, A. (2011). Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2 (Journal of Clinical Investigation (2010) 120, 11 (4102-4110) DOI: 10.1172/JCI43998). Journal of Clinical Investigation, 121(1), 455–455 … Hiby, SE, et al. “Maternal Activating KIRs Protect against Human Reproductive Failure Mediated by Fetal HLA-C2 (Journal of Clinical Investigation (2010) 120, 11 (4102-4110) DOI: 10.1172/JCI43998).” Journal of Clinical Investigation, vol. 121, no. 1, Journal of Clinical Investigation, 2011, pp. 455–55 … Hiby, SE, R Apps, AM Sharkey, LE Farrell, L Gardner, A Mulder, FH Claas, et al. 2011. “Maternal Activating KIRs Protect against Human Reproductive Failure Mediated by Fetal HLA-C2 (Journal of …

Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)‐4 −590 (C>T), toll‐like receptor (TLR)‐2 +2258 (G>A) and matrix metalloproteinase (MMP)‐9 −1562 (C>T) were examined by polymerase chain reaction–restriction fragment length polymorphism to identify their merit as genetic markers for pre‐eclampsia. One hundred and seventeen pre‐eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James’s University Hospital. While the TLR‐2 +2258 (G>A) and MMP‐9 −1562 (C>T) SNPs failed to present any significant association with pre‐eclampsia, there was a marked trend for an association between the IL‐4 −590 (C>T) SNP and pre‐eclampsia (χ2= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286–15.350).

The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1 beta IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1 beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (SEM). PET featured significantly higher IL-1, IL-2, IL-10, IL-13, G-CSF, IFN-gamma MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.