Search

Objectives Urinary incontinence (UI) is highly prevalent peri-partum. To gain more understanding regarding the gap between the prevalence of UI and actual help seeking behaviour of peri-partum women, this study aims to understand, (1) how peri-partum women experience UI and which factors influence these experiences and (2) the perspective of health care professionals on UI during pregnancy, and the first year after childbirth. Methods A qualitative approach was used, using semi-structured interviews with adult pregnant and up to 1 year post-partum women and a focus group with health care professionals (HCP’s) involved in the care of pregnant and post-partum women. Thematic analysis was used to analyse the data. Results Six pregnant and seven post-partum women were included. Nearly all of these women expressed to be not, or only slightly bothered by their UI and accept it as a result of pregnancy and/or delivery. They were surprised because they were unaware that UI could be a problem. None of the HCP’s routinely asked about the presence of UI during pregnancy. At the post-natal check at 6 weeks post-partum, UI is still not a standard question for the majority of the gynecologists and registrars in contrast to the midwives. Conclusions for Practice The interviewed women with UI during pregnancy and the first year after childbirth were surprised but hardly bothered by their UI and accept it as part of being pregnant or as a result of the delivery. HCP’s do not routinely discuss UI during pregnancy or post-partum.

Objectives Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE. Study design: In this cross-sectional study, women with a history of normotensive HELLP (n=32), PE without HELLP (n=59), and PE with HELLP (n=101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Main outcome measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and “double product” (to approximate energy consumption), indexed to LVM. Results LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals. Conclusions Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population.

PROBLEM: NK cells are important for healthy pregnancy and aberrant phenotypes or effector functions have been associated with RPL. We compared expression of a broad panel of NK cell receptors, including immune checkpoint receptors, and investigated their clinical association with RPL as this might improve patient stratification and prediction of RPL.METHOD OF STUDY: Peripheral blood mononuclear cells were isolated from fifty-two women with RPL and from twenty-two women with an uncomplicated pregnancy for flowcytometric analysis and plasma was used to determine anti-CMV IgG antibodies.RESULTS: Between RPL and controls, we observed no difference in frequencies of T-, NKT or NK cells, in CD56dimCD16+ or CD56brightCD16- NK cell subsets or in the expression of KIRs, NKG2A, NKG2C, NKG2D, NKp30, NKp44, NKp46 or DNAM1. NK cells from women with RPL had a higher expression of LILRB1 and TACTILE and this was associated with the number of losses. The immune checkpoint receptors PD1, TIM3 and LAG3 were not expressed on peripheral blood NK cells. In RPL patients, there was a large variation in NKG2C expression and higher levels could be explained by CMV seropositivity.CONCLUSIONS: Our study identified LILRB1 and TACTILE as NK cell receptors associated with RPL. Moreover, we provide first support for the potential role of CMV in RPL via its impact on the NK cell compartment. Thereby our study could guide future studies to confirm the clinical association of LILRB1, TACTILE and NKG2C with RPL in a larger cohort and to explore their functional relevance in reproductive success. This article is protected by copyright. All rights reserved.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage.METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2 * degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue.CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Introduction and hypothesis Post-partum, women often experience urinary incontinence (UI). However, the association between experienced UI bother and UI beliefs and help-seeking behavior is less known. Therefore, we aim to investigate the prevalence of self-reported UI, the level of experienced bother and beliefs, to explain help-seeking behavior for UI in women in the Netherlands from 6 weeks to one year post-partum. Methods A digital survey among post-partum women, shared on social media, was used for recruitment. The survey consists of: 1. demographic variables, 2. International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), 3. ICIQ Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and 4. questions on beliefs and help-seeking behavior. For analysis, descriptive statistics and the independent samples t-test were used to determine differences between help- and non-help-seekers. Results 415 women filled in the survey. The mean age was 30.6 years (SD 4.0, range 21–40) of which 48.2% was primiparous. The overall prevalence of UI was 57.1% (95% confidence interval (CI) (52.3–61.8)). Primiparous women reported a statistically significantly lower overall prevalence than multiparous women, 52.0% and 61.9% respectively (p = .043). UI was reported as bothersome in 38% of women, 25% of all women sought help. Help-seeking women showed significantly higher scores for bother, measured by the ICIQ-UI SF, than non-help seekers (p = .001). Conclusions More than half of all post-partum women in the Netherlands from 6 weeks to one year post childbirth experience UI (57.1%), 38% classified their UI as bothersome. In total 25% of UI women sought professional help.

Introduction: An antepartum screening method to determine normal and abnormal placental function is desirable in the prevention of maternal and fetal pregnancy complications. Placental appearance can easily be obtained and evaluated using 2D ultrasonography, but surprisingly little is known about the change in placental appearance during gestation. Aim of this systematic review was to describe the antepartum placental appearance in placenta syndrome (PS) pregnancies, and to compare this to the appearance in healthy pregnancies.Methods: A systematic review investigating placental thickness, -lakes and/or -calcifications by ultrasound examination in both uncomplicated (reference group) and PS pregnancies in relation to gestational age was performed. English literature was searched using PubMed (NCBI), EMBASE (Ovid) and the Cochrane Library, from database inception until September 2020. Data on placental thickness was presented as a continuous variable or as the proportion of abnormal placental thickness. Data on placental lakes and -calcifications was presented as prevalence (%). There was no restriction applied on the definition of placental lakes or -calcifications. Due to heterogeneity, pooling of the results was not performed.Results: A total of 28 studies were included describing 1719 PS cases; consisting of 370 (21 %) cases with preeclampsia or pregnancy induced hypertension, 1341 (78 %) cases with fetal growth restriction (FGR) or small for gestational age (SGA), and 8 (1%) cases with combined clinical expressions. In addition, the reference group comprised 3315 pregnant women. Placental thickness showed an increase between the first and second trimester, which was higher in PS- compared to uncomplicated pregnancies. Placental lakes were frequently observed in FGR and SGA pregnancies, especially in the second trimester. Grade 3 calcifications were most prominent in the PS pregnancies, specifically in the late second and third trimester. Moreover, in the reference group, no grade 3 calcifications were reported before 35 weeks of gestation.Conclusion: Placental appearance in PS-pregnancies shows higher placental thickness and greater presence of placental lakes and -calcifications compared to uncomplicated pregnancies. Standardized definitions of (ab-)normal placental appearance and longitudinal research in both healthy and complicated pregnancies are needed to improve personalized obstetric care. (C) 2021 Published by Elsevier B.V.

Purpose In early-onset preeclampsia, each additional day of pregnancy prolongation reduces offspring infant mortality about 9%. We evaluated if maternal stress at admission to hospital for early-onset preeclampsia predicted admission-to-delivery intervals in days. Methods This prospective, longitudinal cohort-study involved 15 singleton pregnancies with a diagnosis of preeclampsia before 34 weeks gestation with intended expectant management. Upon hospital admission, maternal psychological stress was assessed with questionnaires and physiological stress with hair cortisol. Hair samples were analyzed in three hair segments representing the preconception period, and the first and second trimester of pregnancy. Results Mean pregnancy prolongation was 16.2 days. Higher maternal anxiety at hospital admission significantly correlated with shorter admission-to-delivery intervals (r = − 0.54, p = 0.04). Chronically increased hair cortisol concentrations (i.e. from preconception through the second trimester) of pregnancy tended to be related to shorter admission-to-delivery intervals (p Conclusion Higher reported anxiety is, and chronically high hair cortisol tended to be, related with fewer days of prolongation from admission to delivery in women with early-onset preeclampsia. These findings suggest that maternal stress might be a potential determinant of disease progression. Future research into early innovative stress-reducing interventions for early-onset preeclampsia may shed more light on the etiology and treatment of this disease.

In early-onset preeclampsia, each additional day of pregnancy prolongation reduces offspring infant mortality about 9%. We evaluated if maternal stress at admission to hospital for early-onset preeclampsia predicted admission-to-delivery intervals in days.This prospective, longitudinal cohort-study involved 15 singleton pregnancies with a diagnosis of preeclampsia before 34 weeks gestation with intended expectant management. Upon hospital admission, maternal psychological stress was assessed with questionnaires and physiological stress with hair cortisol. Hair samples were analyzed in three hair segments representing the preconception period, and the first and second trimester of pregnancy.Mean pregnancy prolongation was 16.2 days. Higher maternal anxiety at hospital admission significantly correlated with shorter admission-to-delivery intervals (r = - 0.54, p = 0.04). Chronically increased hair cortisol concentrations (i.e. from preconception through the second trimester) of pregnancy tended to be related to shorter admission-to-delivery intervals (p . 10).Higher reported anxiety is, and chronically high hair cortisol tended to be, related with fewer days of prolongation from admission to delivery in women with early-onset preeclampsia. These findings suggest that maternal stress might be a potential determinant of disease progression. Future research into early innovative stress-reducing interventions for early-onset preeclampsia may shed more light on the etiology and treatment of this disease.

Preeclampsia is often preceded by abnormal hemodynamic changes with heterogeneous patterns in the first half of pregnancy. We assessed the effect of timely tailored correction of nonphysiological hemodynamic changes on preventing preeclampsia in a high-risk population. Primiparous women with a history of preeclampsia were invited to participate in a longitudinal program in their next pregnancy, including repeated hemodynamic assessments at 12-, 16-, 20- and 30-week gestation additional to regular pregnancy checkups. When at least 2 of the hemodynamic variables were not within physiological reference values, the hemodynamic imbalance between cardiac output and peripheral vascular resistance was counteracted with either labetalol, methyldopa, or nifedipine using a simple treatment algorithm. Normogram-guided women (n=157) were matched to 157 women receiving care as usual (power, 80%; α=0.05). Risk of recurrent preeclampsia was analyzed with logistic regression adjusted for daily low-dose aspirin or calcium supplementation. Hemodynamic changes were considered nonphysiological in 90% of women in the normogram-guided group. Twelve percent of these women developed recurrent preeclampsia compared with 22% in the care-as-usual group (adjusted odds ratio, 0.47 [95% CI, 0.25–0.88]). There were no differences between groups in gestational age at delivery (38 1 and 38 2 weeks in the normogram-guided and care-as-usual groups, respectively) and neonatal birth weight (3148 and 3180 g in the normogram-guided and care-as-usual groups, respectively). Tailored circulatory normalization of nonphysiological hemodynamic changes during pregnancy halves the risk of recurrent preeclampsia, without disadvantageous effects on offspring outcome. This simple and innovative treatment strategy may also be beneficial to other women at increased risk for preeclampsia in pregnancy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04216706.

Introduction and hypothesis Pregnancy and delivery are thought to induce urinary incontinence (UI), but its clinical impact is less known. Therefore, we investigated the prevalence of self-reported UI, level of experience of bother, and beliefs to gain a greater understanding of help-seeking behavior in adult pregnant women. Methods A digital survey shared on social media was used for recruitment. The survey consists of: (1) demographic variables, (2) International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), (3) ICIQ Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and (4) questions on beliefs and help-seeking behavior. For analysis, descriptive statistics and the independent samples t-test were used to determine differences between help- and non-help-seekers. Results Four hundred seven women were eligible for data analysis. The prevalence of UI rises from 55.1% in the first to 70.1% in the third trimester, with an overall prevalence of 66.8%. Nearly 43.0% of the respondents reported UI occurring once a week or less; 92.5% of women lost a small amount; 90% reported slight to moderate impact on quality of life. Only 13.1% of the respondents sought help for their UI. The main reasons for not seeking help were: minimal bother and the idea that UI would resolve by itself. Help-seeking women showed significantly higher scores than non-help-seeking women regarding ICIQ-UI SF (p p ≤ 0.001), and interference in daily life (p Conclusions During pregnancy, UI affects two out of three women, but only one in eight women sought professional help. Non-help-seeking women experience less bother.

Preeclampsia (PE) is strongly associated with heart failure (HF) later in life. The aberrant cardiac remodelling is likely initiated or amplified during preeclamptic pregnancy. Aberrant remodelling often persists after delivery and is known to relate strongly to cardiac fibrosis. This review provides an overview of pro- and anti- fibrotic circulating effector molecules that are involved in cardiac fibrosis and their association with PE. Women with PE complicated pregnancies show increased ANG-II sensitivity and elevated levels of the pro-fibrotic factors IL-6, TNF-alpha, TGs and FFAs compared to uncomplicated pregnancies. In the postpartum period, PE pregnancies compared to uncomplicated pregnancies have increased ANG-II sensitivity, elevated levels of the pro-fibrotic factors IL-6, TNF-alpha, LDL cholesterol and leptin, as well as decreased levels of the anti-fibrotic factor adiponectin. The review revealed several profibrotic molecules that associate to cardiac fibrosis during and after PE. The role that these fibrotic factors have on the heart during and after PE may improve the understanding of the link between PE and HF. Furthermore they may provide insight into the pathways in which the relation between both diseases can be understood as potential mechanisms which interfere in the process of cardiovascular disease (CVD). Unravelling the molecular mechanism and pathways involved might bring the diagnostic and therapeutic abilities of those factors a step closer.

Contains fulltext : 235325.pdf (Publisher’s version ) (Open Access) BACKGROUND: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. OBJECTIVE: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. SEARCH STRATEGY: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. SELECTION CRITERIA: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis. MAIN RESULTS: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P

Introduction and hypothesis Urinary incontinence (UI) is a common and embarrassing complaint for pregnant women. Reported prevalence and incidence figures show a large range, due to varying case definitions, recruited population and study methodology. Precise prevalence and incidence figures on (bothersome) UI are of relevance for health care providers, policy makers and researchers. Therefore, we conducted a systematic review and meta-analysis to investigate the prevalence and incidence of UI in pregnancy in the general population for relevant subgroups and assessed experienced bother. Methods All observational studies published between January 1998 and October 2018 reporting on prevalence and/or incidence of UI during pregnancy were included. All women, regardless of weeks of gestation and type of UI presented in all settings, were of interest. A random-effects model was used. Subgroup analyses were conducted by parity, trimester and subtype of UI. Results The mean (weighted) prevalence based on 44 included studies, containing a total of 88.305 women, was 41.0% (range of 9–75%). Stress urinary incontinence (63%) is the most prevalent type of UI; 26% of the women reported daily loss, whereas 40% reported loss on a monthly basis. Bother was experienced as mild to moderate. Conclusions UI is very prevalent and rising with the weeks of gestation in pregnancy. SUI is the most common type and in most cases it was a small amount. Bother for UI is heterogeneously assessed and experienced as mild to moderate by pregnant women.

Background Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed. Methods A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. Results In healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70–0.89) and 0.50 (95% CI: 0.47–0.54) in the first trimester to 0.50 (95% CI: 0.45–0.55, p p p = 0.752) and 0.36 (95% CI: 0.35–0.38, p = 0.037) in the third trimester, respectively. In parallel, PSV altered from 0.22 m/s (95% CI: 0.13–0.30 m/s) to 0.28 m/s (95% CI: 0.17–0.40 m/s, p = 0.377) and to 0.25 m/s (95% CI: 0.20–0.30 m/s, p = 0.560) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.80, p p = 0.349). Conclusions This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI was found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

Contains fulltext : 229273.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR. METHODS: For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity. RESULTS: Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR. CONCLUSION: Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.

Contains fulltext : 229268.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Low-dose aspirin (LDA) prophylaxis has been shown to reduce women's preeclampsia risk. Evidence regarding LDA adherence rates of pregnant women is based almost exclusively on clinical trials, giving a potentially biased picture. Moreover, these studies do not report on determinants of adherence. Since 2017, obstetric healthcare professionals in a Dutch region have assessed women's preeclampsia risk by means of a prediction tool and counseled those with an above-population average risk on LDA as a prophylactic measure. MATERIAL AND METHODS: From 2017 to 2018, 865 women were recruited in multiple centers and prospectively followed using web-based surveys (Expect Study II). Rates and determinants of LDA usage among women with an increased preeclampsia risk in daily practice were assessed. Results were compared with findings in a similar cohort from a care-as-usual setting lacking risk-based counseling (Expect Study I, n = 2614). Netherlands Trial Register NTR4143. RESULTS: In total, 306 women had a predicted increased preeclampsia risk. LDA usage was higher for women receiving risk-based care than care-as-usual (29.4% vs 1.5%, odds ratio 19.1, 95% confidence interval 11.2-32.5). Daily LDA usage was positively correlated with both predicted risk and women's concerns regarding preeclampsia. Most reported reasons for non- or incomplete use were unawareness of LDA as a preventive intervention, concerns about potential adverse effects and doubts regarding the benefits. CONCLUSIONS: Risk-based counseling was associated with a higher prevalence of LDA usage, but general usage rates were low. Future research regarding potential factors improving the usage of LDA during pregnancy is necessary.

Background: Satisfaction of pregnancy and childbirth is an important quality measure of maternity care. Satisfaction questionnaires generally result in high scores. However, it has been argued that dissatisfaction relies on a different construct. In response to a worldwide call for obstetric care that is more woman-centered, we identified and described the contributors to suboptimal satisfaction with pregnancy and childbirth.Methods: A prospective subcohort of 739 women from a larger cohort (Expect Study I, n = 2614) received a pregnancy and childbirth satisfaction questionnaire. Scores were transformed to a binary outcome whereby a score

Contains fulltext : 229383.pdf (Publisher’s version ) (Open Access) Obesity leads to an amplified risk of disease and contributes to the occurrence of type 2 diabetes, fatty liver disease, coronary heart disease, stroke, chronic kidney disease and various types of cancer. MicroRNAs (miRNAs), small non-coding RNA molecules of 20-25 nucleotides, can remain stable in plasma and have been studied as potential (predictive) biomarkers for obesity and related metabolic disorders. The aim of this study was to identify circulating miRNAs as biomarkers for obesity status and metabolic alterations in women. Circulating miR-216a and miR-155-5p were selected by miRNA expression profiling and validated by real time quantitative PCR in a validation cohort of 60 obese women and 60 normal weight-age-matched control women. This was supplemented by correlation analysis of the candidate miRNA and anthropometric variables, blood biochemistry and lipid profile markers. Circulating miR-216a was validated as a biomarker of obesity status with significantly reduced levels in obese women. Interestingly, this was associated with a negative correlation between the plasma miR-216a content and body mass index (BMI), waist circumference, mean arterial pressure (MAP), triglycerides, ratio of total cholesterol/high density lipoprotein (HDL)-cholesterol and high sensitivity-C reactive protein (hs-CRP).Taken together, we provide evidence for an abnormally expressed circulating miRNA, miR-216a, with additive value as a predictive marker for obesity that correlates with metabolic alterations presented by lipid profile and inflammatory markers.

One out of four women with a history of preeclampsia shows abnormal cardiac remodeling consistent with subclinical heart failure (HF) in the first decade postpartum. Since these women are susceptible for developing remote symptomatic HF, development of a model for aberrant cardiac geometry as a first screening tool after delivery, is urgently needed. In this cross-sectional study, 752 preeclamptic women were included. Cardiovascular evaluation was conducted between six months and five years postpartum including cardiac ultrasound, systolic and diastolic blood pressure (SBP and DBP), plasma volume (PV) and biomarker assessment. We developed a multimarker model using uni- and multivariable linear regression and used the regression coefficients (RC) to develop a formula and estimate the aberrant cardiac remodeling in our population. Both SBP and PV were shown to be independently correlated with relative wall thickness (RWT) and left ventricular mass index (LVMi). C-reactive protein (CRP) and uric acid were independently correlated with RWT. Fibrinogen did not relate to either LVMi or RWT. This study displays markers of abnormal cardiac remodeling in former preeclamptic women, suggesting a combination of mechanical and biochemical factors that should be involved in worrisome chamber remodeling before clinical symptoms arise.

Background and Objectives: The aim of this study was to evaluate the value of adding fetal growth velocity and first trimester maternal biomarkers to baseline screening, for the prediction of small-for-gestational age (SGA) and adverse neonatal outcomes. Method: A retrospective cohort study was conducted of singleton pregnancies in the Maastricht University Medical Centre between 2012 and 2016. The biomarkers PAPP-A, β-hCG, PlGF, and sFlt-1 were measured at 11–13 weeks of gestational age (GA) and two fetal growth scans were performed (18–22 and 30–34 weeks of GA). Differences in biomarkers and growth velocities were compared between appropriate-for-gestational age (AGA; birth weight percentile 10–90) and SGA (birth weight percentile Results: We included 296 singleton pregnancies. Compared to AGA (n = 251), SGA neonates (n = 45) had significantly lower growth velocities in the abdominal circumference (mm/week): 10.1 ± 0.98 versus 10.8 ± 0.98, p = 0.001. Compared with AGA, the SGA neonates had higher sFlt-1 multiples of the median (MoM): 0.89 (0.55) versus 0.76 (0.44), p = 0.023, and a higher sFlt-1/PlGF MoM ratio: 1.09 (1.03) versus 0.90 (0.64), p = 0.027. For a 15% false-positive rate, the prediction of SGA neonates increased from 44.8% for the baseline screening model to 56.5% after the addition of fetal growth velocities, and to 73.9% after the further addition of maternal biomarkers (PPV 9.6%, NPV 82.4%). The corresponding AUC for the three models were 0.722, 0.804, and 0.839, respectively. In addition, AGA neonates with reduced fetal growth velocity had more adverse neonatal outcomes compared to the AGA reference group (12.4 vs. 3.9%, p = 0.013). Conclusions: Combining fetal growth velocity with first trimester biomarkers resulted in a better prediction of SGA compared to baseline screening parameters alone. This approach could possibly result in reduced adverse neonatal outcomes in neonates, who are at a potential risk due to late mild placental dysfunction.

OBJECTIVES: Overwhelming clinical evidence exists on disturbed vascular and endothelial function in the pathophysiology of preeclampsia (PE). In a non-pregnant (NP) population, L-FMC (low-flow mediated constriction) provides insight in the 'resting' endothelial capacity in contrast to the gold standard of flow mediated dilatation (FMD), reflecting endothelial nitric oxide bioavailability.STUDY DESIGN: Longitudinal follow-up of 100 healthy pregnant (HP) women, 33 PE women and 16 NP controls with non-invasive vascular assessments. HP women were evaluated at 12 and 35 weeks of gestation and at 6 months postpartum. PE patients were assessed at diagnosis (mean 30 weeks) and 6 months postpartum.MAIN OUTCOME MEASURES: Endothelial function (L-FMC, FMD, peripheral arterial tonometry (PAT)) and arterial stiffness (pulse wave velocity (PWV) and analysis (PWA)) were measured at the different visits and compared between groups.RESULTS: Overall endothelial dysfunction is present in PE (FMD HP 9.09 ± 4.20 vs PE 5.21 ± 4.47, p = 0.0004; L-FMC HP -1.90 ± 2.66 vs PE -0.40 ± 2.09, p = 0.03). L-FMC gradually elevates during the course of a HP (1st trim -0.31 ± 1.75 vs 3rd trim -1.97 ± 3.02, p 0.05).CONCLUSION: PE is characterized by dysfunction of both resting and recruitable endothelial capacity. This study offers new insights in different aspects of endothelial function in pregnancy, since L-FMC reflects an adaptation in HP that is absent in PE.

Background Fetal growth restriction is, despite advances in neonatal care and uptake of antenatal ultrasound scanning, still a major cause of perinatal morbidity. Neonates with birth weight > 10th percentile are assumed to be appropriate-for-gestational-age (AGA), although many are at increased risk of perinatal morbidity, because of undetected mild restriction of growth potential. We hypothesized that within AGA neonates, reduced fetal growth velocities are associated with adverse neonatal outcome. Methods A retrospective cohort study of singleton pregnancies, in the Maastricht University Medical Centre (MUMC) between 2010 and 2016. Women had two fetal biometry scans (18–22 weeks and 30–34 weeks of gestational age) and delivered a newborn with a birth weight between the 10th–80th percentile. Differences in growth velocities of the abdominal circumference (AC), biparietal diameter (BPD), head circumference (HC) and femur length (FL) were compared between the suboptimal AGA (sAGA) (birth weight centiles 10–50) and optimal AGA (oAGA) (birth weight centiles 50–80) group. We assessed the association between velocities and neonatal outcomes. Results We included 934 singleton pregnancies. In the suboptimal AGA group, fetal growth velocities were lower (in mm/week): AC 10.72 ± 1.00 vs 11.23 ± 1.00 (p

Objective To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. Methods This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index >= 30 kg/m(2); dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. Results The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e(-LP)), where LP is linear predictor = -8.693 + (0.312 x SGA (yes = 1)) + (0.507 x EO-PE (yes = 1)) + (0.053 x systolic blood pressure). Conclusions The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome. Methods In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Results Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group. Conclusions In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management.

Introduction and hypothesis Urinary incontinence (UI) is a common complaint for post-partum women. Reported prevalence and incidence figures show a large range due to varying study methodology. The crude prevalence of post-partum UI may differ when accounting for bother. Precise prevalence and incidence figures on (bothersome) UI are of relevance for health care providers, research planning, and policy makers. Therefore, we conducted a systematic review and meta-analysis to investigate the prevalence and incidence of UI in post-partum women in the Western world for relevant subgroups and assessed experienced bother in relation to UI. Methods Observational studies, published between January 1998 and March 2020 and reporting on prevalence and incidence between 6 weeks and 1 year post-partum, were included, regardless of type of UI or setting. We used a random effects model with subgroup analyses for post-partum period, parity and subtype of UI. Results The mean (weighted) prevalence based on 24 included studies, containing a total of 35.064 women, was 31.0%. After an initial drop in prevalence at 3 months post-partum, prevalence rises up to nearly the same level as in the third trimester of pregnancy at 1 year post-partum (32%). Stress UI (54%) is the most prevalent type. UI prevalence is equal among primi- and multiparous women. Experienced bother of UI is heterogeneously assessed and reported to be mild to moderate. Conclusions Post-partum UI is highly prevalent in women in the Western world. After an initial drop it rises again at 1 year post-partum. Experienced bother is mild to moderate.

Objective The best screening strategy for gestational diabetes mellitus (GDM) remains a topic of debate. Several organizations made a statement in favor of universal screening, but the volume of oral glucose tolerance tests (OGTT) required may burden healthcare systems. As a result, many countries still rely on selective screening using a checklist of risk factors, but reported diagnostic characteristics vary. Moreover, women's discomfort due to an OGTT is often neglected. Since 2017, obstetric healthcare professionals in a Dutch region assessed women's GDM risk with a prediction model and counseled those with an increased risk regarding an OGTT. Methods From 2017 to 2018, 865 women were recruited in a multicenter prospective cohort. Results In total, 385 women (48%) had an increased predicted GDM risk. Of all women, 78% reported that their healthcare professional discussed their GDM risk. Predicted GDM risks were positively correlated with conducting an OGTT. Conclusion Implementation of a GDM prediction model resulted in moderate rates of OGTTs performed in general, but high rates in high‐risk women. As 25% of women experienced discomfort from the OGTT, a selective screening strategy based on a prediction model with a high detection rate may be an interesting alternative to universal screening. Study cohort registration Netherlands Trial Register: NTR4143; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4143., Synopsis Implementing a gestational diabetes mellitus prediction model resulted in a majority of high‐risk women receiving an oral glucose tolerance test within the recommended gestational window.

Contains fulltext : 232397.pdf (Publisher’s version ) (Closed access) Objective. To determine the prevalence of metabolic syndrome in formerly preeclamptic women according to three definitions of metabolic syndrome (World Health Organization [WHO], International Diabetes Federation [IDF], and Third Adult Treatment Panel updated [ATPIII]), to evaluate agreement amongst definitions and to compare the risk of recurrent preeclampsia. Methods. In 197 women with a history of preeclampsia, we determined presence of metabolic syndrome using WHO, IDF, and ATPIII criteria. We evaluated agreement amongst definitions by using Kappa statistics. The prevalence of recurrent preeclampsia was compared between women with and without inter-pregnancy metabolic syndrome, according to the three definitions. Results. A total of 40 (20%), 46 (23%), and 31 (16%) of women with previous preeclampsia were classified as having metabolic syndrome postpartum according to WHO, IDF, and ATPIII criteria, respectively. Agreement among criteria was considered substantial between WHO and IDF (κ = 0.64, 95% CI 0.53-0.79), WHO and ATPIII (κ = 0.74, 95% CI 0.62-0.86), and IDF and ATPIII (κ = 0.66, 95% CI 0.51-0.77). The prevalence of recurrent preeclampsia was 45% versus 17% in women with and without inter-pregnancy metabolic syndrome according to the WHO definition (P

Contains fulltext : 238866.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies. METHODS: Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model. RESULTS: We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to -18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e' ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks. CONCLUSION: LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy.

Background In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. Methods Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. Discussion This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. Trial registration NCT02531490, registered on 24 August 2015.