Publications by authors named "Marc E A Spaanderman"

102 Publications

Inappropriate left ventricular mass after HELLP syndrome inappropriate LVM after HELLP syndrome.

Pregnancy Hypertens 2021 Nov 12;27:16-22. Epub 2021 Nov 12.

Department of Obstetrics and Gynecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands; Department of Cardiology, Heart & Vascular Centre, Maastricht University Medical Center (MUMC), the Netherlands.

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.
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http://dx.doi.org/10.1016/j.preghy.2021.11.003DOI Listing
November 2021

Maternal myocardial dysfunction after hemolysis, elevated liver enzymes, and low platelets syndrome: a speckle-tracking study.

J Hypertens 2021 10;39(10):1956-1963

Department of Obstetrics and Gynecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), The Netherlands.

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.
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http://dx.doi.org/10.1097/HJH.0000000000002901DOI Listing
October 2021

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

J Neuroimaging 2021 09 23;31(5):902-911. Epub 2021 Jun 23.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.

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 T degradation effects. With the Patlak graphical approach, the leakage rate (K ) and blood plasma volume fraction (v ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.

Results: K and v were significantly higher in gray matter compared to white matter of all participants. These K 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 K values.
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http://dx.doi.org/10.1111/jon.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519128PMC
September 2021

Prevalence, incidence and bothersomeness of urinary incontinence between 6 weeks and 1 year post-partum: a systematic review and meta-analysis.

Int Urogynecol J 2021 07 17;32(7):1675-1693. Epub 2021 Jun 17.

Faculty of Health, Medicine and Life Sciences, Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, P.O. Box 616, 6200, MD, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00192-021-04877-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295150PMC
July 2021

Adaptation of left ventricular diastolic function to pregnancy: a systematic review and meta-analysis.

J Hypertens 2021 10;39(10):1934-1941

Department of Cardiology, Maastricht University Medical Center (MUMC+), The Netherlands.

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.
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http://dx.doi.org/10.1097/HJH.0000000000002886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452327PMC
October 2021

Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy.

Hypertension 2021 06 5;77(6):2045-2053. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology (E.G.M., E.C., V.A.L.v.B., V.M.M.M.S., R.J.A., M.E.A.S.), Maastricht University Medical Centre, the Netherlands.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16502DOI Listing
June 2021

Urinary incontinence 6 weeks to 1 year post-partum: prevalence, experience of bother, beliefs, and help-seeking behavior.

Int Urogynecol J 2021 07 23;32(7):1817-1824. Epub 2021 Jan 23.

Care and Public Health Research Institute (CAPHRI), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00192-020-04644-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295159PMC
July 2021

Comparison of three definitions of metabolic syndrome and relation to risk of recurrent preeclampsia.

Hypertens Pregnancy 2021 Feb 18;40(1):97-108. Epub 2021 Jan 18.

Department of Obstetrics and Gynaecology, Radboud University Medical Center , Nijmegen, The Netherlands.

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. 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. 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 (= 0.64, 95% CI 0.53-0.79), WHO and ATPIII (= 0.74, 95% CI 0.62-0.86), and IDF and ATPIII (= 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 ( < 0.001), 26% versus 21% according to the IDF criteria (P = 0.16), and 39% versus 20% according to the ATPIII definition (P = 0.02). Agreement among WHO, IDF, and ATPIII criteria of metabolic syndrome in women after preeclampsia is considered substantial. The risk of recurrent preeclampsia is almost one out of two in women with inter-pregnancy metabolic syndrome according to the WHO criteria.
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http://dx.doi.org/10.1080/10641955.2021.1872614DOI Listing
February 2021

Prevalence, incidence and bothersomeness of urinary incontinence in pregnancy: a systematic review and meta-analysis.

Int Urogynecol J 2021 07 13;32(7):1633-1652. Epub 2021 Jan 13.

Care and Public Health Research Institute (CAPHRI), Maastricht University, P.O. Box 616, 6200, MD, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00192-020-04636-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295103PMC
July 2021

Cardiac dysfunction after preeclampsia; an overview of pro- and anti-fibrotic circulating effector molecules.

Pregnancy Hypertens 2021 Mar 24;23:140-154. Epub 2020 Dec 24.

Department of Obstetrics and Gynecology, Maastricht University Medical Centre (MUMC+), The Netherlands; Department of Cardiology, Maastricht University Medical Centre (MUMC+), The Netherlands.

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-α, 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-α, 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.
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http://dx.doi.org/10.1016/j.preghy.2020.12.001DOI Listing
March 2021

The "sex gap" in COVID-19 trials: a scoping review.

EClinicalMedicine 2020 Dec 30;29:100652. Epub 2020 Nov 30.

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.

Background: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses.

Methods: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated.

Findings: 30 studies were eligible for inclusion, investigating remdesivir ( = 2), lopinavir/ritonavir ( = 5), favipiravir ( = 1), umifenovir ( = 1), hydroxychloroquine/chloroquine ( = 8), convalescent plasma ( = 6), interleukin-6 (IL-6) pathway inhibitors ( = 5), interleukin-1 (IL-1) pathway inhibitors ( = 1) and corticosteroids ( = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females.

Interpretation: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2020.100652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701906PMC
December 2020

Adherence rates to a prediction tool identifying women with an increased gestational diabetes risk: An implementation study.

Int J Gynaecol Obstet 2021 Jul 5;154(1):85-91. Epub 2021 Jan 5.

Department of Epidemiology, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1002/ijgo.13517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247415PMC
July 2021

Urinary incontinence during pregnancy: prevalence, experience of bother, beliefs, and help-seeking behavior.

Int Urogynecol J 2021 Mar 20;32(3):695-701. Epub 2020 Oct 20.

Faculty of Health, Medicine and Life Sciences, Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, P.O. Box 616, 6200, MD, Maastricht, The Netherlands.

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 < 0.001), ICIQ-LUTSqol (p ≤ 0.001), and interference in daily life (p < 0.001).

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.
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http://dx.doi.org/10.1007/s00192-020-04566-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902563PMC
March 2021

Circulating miR-216a as a biomarker of metabolic alterations and obesity in women.

Noncoding RNA Res 2020 Sep 22;5(3):144-152. Epub 2020 Aug 22.

Department of Obstetrics and Gynecology, School for Oncology & Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre (MUMC+), the Netherlands.

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.
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http://dx.doi.org/10.1016/j.ncrna.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479169PMC
September 2020

Low Plasma Volume and Increased Pressure Load Relate to Concentric Left Ventricular Remodeling After Preeclampsia: A Longitudinal Study.

J Am Heart Assoc 2020 10 13;9(19):e015043. Epub 2020 Sep 13.

Department of Obstetrics and Gynecology Research School GROW Maastricht University Medical Center Maastricht the Netherlands.

Background During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling. Methods and Results In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m. We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06-17.40; and adjusted OR, 4.67; 95% CI, 1.02-21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99-1.35]; OR, 1.24 [95% CI, 0.98-1.58]; and OR, 1.20 [95% CI, 0.98-1.47], respectively). Conclusions In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.
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http://dx.doi.org/10.1161/JAHA.119.015043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792392PMC
October 2020

Maternal myocardial dysfunction after normotensive fetal growth restriction compared with hypertensive pregnancies: a speckle-tracking study.

J Hypertens 2020 10;38(10):1955-1963

Department of Obstetrics and Gynecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), The Netherlands.

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.
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http://dx.doi.org/10.1097/HJH.0000000000002496DOI Listing
October 2020

Sex-specific microRNAs in women with diabetes and left ventricular diastolic dysfunction or HFpEF associate with microvascular injury.

Sci Rep 2020 08 18;10(1):13945. Epub 2020 Aug 18.

Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.

Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the presence of sex-differences in plasma miRs and Ang-2 in diabetic (female) patients with LVDD or HFpEF. After a pilot study, we assessed 16 plasma miRs in patients with LVDD (n = 122), controls (n = 244) and female diabetic patients (n = 10). Subsequently, among these miRs we selected and measured plasma miR-34a, -224 and -452 in diabetic HFpEF patients (n = 53) and controls (n = 52). In LVDD patients, miR-34a associated with Ang-2 levels (R 0.04, R = 0.21, p = 0.001, 95% CI 0.103-0.312), with plasma levels being diminished in patients with DM, while women with an eGFR < 60 ml/min and LVDD had lower levels of miR-34a, -224 and -452 compared to women without an eGFR < 60 ml/min without LVDD. In diabetic HFpEF women (n = 28), plasma Ang-2 levels and the X-chromosome located miR-224/452 cluster increased compared to men. We conclude that plasma miR-34a, -224 and -452 display an association with the microvascular injury marker Ang-2 and are particularly targeted to women with LVDD or HFpEF.
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http://dx.doi.org/10.1038/s41598-020-70848-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435264PMC
August 2020

Gestational Weight Gain by Maternal Pre-pregnancy BMI and Childhood Problem Behaviours in School-Age Years: A Pooled Analysis of Two European Birth Cohorts.

Matern Child Health J 2020 Oct;24(10):1288-1298

Department of Complex Genetics, Care and Public Health Research Institute, Maastricht University, 6200 MD, Maastricht, The Netherlands.

Objectives: Maternal pre-pregnancy weight is known to affect foetal development. However, it has not yet been clarified if gestational weight gain is associated with childhood behavioural development.

Methods: We performed a pooled analysis of two prospective birth cohorts to investigate the association between gestational weight gain and childhood problem behaviours, and the effect modification of maternal pre-pregnancy BMI. In total, 378 mother-child pairs from the Maastricht Essential Fatty Acids Birth cohort (MEFAB) and 414 pairs from the Rhea Mother-Child cohort were followed up from early pregnancy to 6-7 years post-partum. At follow up, parents assessed their children's behaviour, measured as total problems, internalizing and externalizing behaviours, with the Child Behaviour Checklist. We computed cohort- and subject-specific gestational weight gain trajectories using mixed-effect linear regression models. Fractional polynomial regressions, stratified by maternal pre-pregnancy BMI status, were then used to examine the association between gestational weight gain and childhood problem behaviours.

Results: In the pre-pregnancy overweight/obese group, greater gestational weight gain was associated with higher problem behaviours. On average, children of women with overweight/obesity who gained 0.5 kg/week scored 25 points higher (on a 0-100 scale) in total problems and internalizing behaviours, and about 18 points higher in externalizing behaviours than children whose mothers gained 0.2 kg/week. Inconsistent results were found in the pre-pregnancy normal weight group.

Conclusions For Practice: Excessive gestational weight gain in women with pre-pregnancy overweight/obesity might increase problem behaviours in school-age children. Particular attention should be granted to avoid excessive weight gain in women with a pre-pregnancy overweight or obesity.
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http://dx.doi.org/10.1007/s10995-020-02962-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476966PMC
October 2020

The natural course of pregnancies in women with primary atypical haemolytic uraemic syndrome and asymptomatic relatives.

Br J Haematol 2020 08 27;190(3):442-449. Epub 2020 Apr 27.

Department of Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, the Netherlands.

Pregnancy has been linked to various microangiopathies, including primary atypical haemolytic uraemic syndrome (aHUS). Complement dysregulation, often linked to rare variants in complement genes, is key for primary aHUS to manifest and may play a role in pregnancy complications of the mother and fetus. The burden of such complications is unknown, making counselling of women with primary aHUS and asymptomatic relatives difficult. We analyzed the maternal and fetal outcomes of 39 pregnancies from 17 women with primary aHUS and two asymptomatic relatives. Seven out of 39 pregnancies were complicated by pregnancy-associated aHUS. Five out of 32 pregnancies not linked to pregnancy-associated aHUS were complicated by pre-eclampsia or HELLP. Rare genetic variants were identified in 10 women (asymptomatic relatives, n = 2) who had a total of 14 pregnancies, including 10 uncomplicated pregnancies. Thirty-five out of 39 pregnancies resulted in live birth. Eight out of 19 women had progressed to end-stage kidney disease, with an incidence of 2·95 (95% confidence interval, 1·37-5·61) per 100 person-years after the first pregnancy. Thus, we emphasized the frequency of successful pregnancies in women with primary aHUS and asymptomatic relatives. Pregnancies should be monitored closely. Rare genetic variants cannot predict the risk of a given pregnancy.
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http://dx.doi.org/10.1111/bjh.16626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496636PMC
August 2020

Impact on perinatal health and cost-effectiveness of risk-based care in obstetrics: a before-after study.

Am J Obstet Gynecol 2020 09 26;223(3):431.e1-431.e18. Epub 2020 Feb 26.

Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

Background: Obstetric health care relies on an adequate antepartum risk selection. Most guidelines used for risk stratification, however, do not assess absolute risks. In 2017, a prediction tool was implemented in a Dutch region. This tool combines first trimester prediction models with obstetric care paths tailored to the individual risk profile, enabling risk-based care.

Objective: To assess impact and cost-effectiveness of risk-based care compared to care-as-usual in a general population.

Methods: A before-after study was conducted using 2 multicenter prospective cohorts. The first cohort (2013-2015) received care-as-usual; the second cohort (2017-2018) received risk-based care. Health outcomes were (1) a composite of adverse perinatal outcomes and (2) maternal quality-adjusted life-years. Costs were estimated using a health care perspective from conception to 6 weeks after the due date. Mean costs per woman, cost differences between the 2 groups, and incremental cost effectiveness ratios were calculated. Sensitivity analyses were performed to evaluate the robustness of the findings.

Results: In total 3425 women were included. In nulliparous women there was a significant reduction of perinatal adverse outcomes among the risk-based care group (adjusted odds ratio, 0.56; 95% confidence interval, 0.32-0.94), but not in multiparous women. Mean costs per pregnant woman were significantly lower for risk-based care (mean difference, -€2766; 95% confidence interval, -€3700 to -€1825). No differences in maternal quality of life, adjusted for baseline health, were observed.

Conclusion: In the Netherlands, risk-based care in nulliparous women was associated with improved perinatal outcomes as compared to care-as-usual. Furthermore, risk-based care was cost-effective compared to care-as-usual and resulted in lower health care costs.
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http://dx.doi.org/10.1016/j.ajog.2020.02.036DOI Listing
September 2020

External validation and clinical utility of prognostic prediction models for gestational diabetes mellitus: A prospective cohort study.

Acta Obstet Gynecol Scand 2020 07 14;99(7):891-900. Epub 2020 Feb 14.

Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

Introduction: We performed an independent validation study of all published first trimester prediction models, containing non-invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated.

Material And Methods: Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies.

Results: The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models.

Conclusions: The best performing prediction models showed acceptable performance measures and may enable more personalized medicine-based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies.
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http://dx.doi.org/10.1111/aogs.13811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317858PMC
July 2020

Low-dose-aspirin usage among women with an increased preeclampsia risk: A prospective cohort study.

Acta Obstet Gynecol Scand 2020 07 31;99(7):875-883. Epub 2020 Jan 31.

Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1111/aogs.13808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317843PMC
July 2020

Perinatal factors related to pregnancy and childbirth satisfaction: a prospective cohort study.

J Psychosom Obstet Gynaecol 2021 09 8;42(3):181-189. Epub 2020 Jan 8.

Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

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,  = 2614) received a pregnancy and childbirth satisfaction questionnaire. Scores were transformed to a binary outcome whereby a score <100 points corresponded with less satisfied women. We performed a multiple logistic regression analysis to define independent perinatal factors related to suboptimal satisfaction.

Results: Decreased perceived personal well-being, antenatal anxiety, and obstetrician-led care during labor were all independently associated with suboptimal pregnancy and childbirth satisfaction. No difference in satisfaction was found between antenatal care led by a midwife or an obstetrician, but midwife-led antenatal care reduced the odds of suboptimal satisfaction compared to women who were transferred to an obstetrician in the antenatal period. Antenatal anxiety was experienced by 25% of all women and is associated with decreased satisfaction scores.

Discussion: Screening and treatment of women suffering from anxiety might improve pregnancy and childbirth satisfaction, but further research is necessary. Women's birthing experience may improve by reducing unnecessary secondary obstetric care.
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http://dx.doi.org/10.1080/0167482X.2019.1708894DOI Listing
September 2021

Implementing a Preeclampsia Prediction Model in Obstetrics: Cutoff Determination and Health Care Professionals' Adherence.

Med Decis Making 2020 01 2;40(1):81-89. Epub 2019 Dec 2.

Department of Obstetrics and Gynecology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, Limburg, the Netherlands.

. Despite improved management, preeclampsia remains an important cause of maternal and neonatal mortality and morbidity. Low-dose aspirin (LDA) lowers the risk of preeclampsia. Although several guidelines recommend LDA prophylaxis in women at increased risk, they disagree about the definition of high risk. Recently, an externally validated prediction model for preeclampsia was implemented in a Dutch region combined with risk-based obstetric care paths. . To demonstrate the selection of a risk threshold and to evaluate the adherence of obstetric health care professionals to the prediction tool. . Using a survey ( = 136) and structured meetings among health care professionals, possible cutoff values at which LDA should be discussed were proposed. The prediction model, with chosen cutoff and corresponding risk-based care paths, was embedded in an online tool. Subsequently, a prospective multicenter cohort study ( = 850) was performed to analyze the adherence of health care professionals. Patient questionnaires, linked to the individual risk profiles calculated by the online tool, were used to evaluate adherence. . Health care professionals agreed upon employing a tool with a high detection rate (cutoff: 3.0%; sensitivity 75%, specificity 64%) followed by shared decision between patients and health care professionals on LDA prophylaxis. Of the 850 enrolled women, 364 women had an increased risk of preeclampsia. LDA was discussed with 273 of these women, resulting in an 81% adherence rate. . Consensus regarding a suitable risk cutoff threshold was reached. The adherence to this recommendation was 81%, indicating adequate implementation.
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http://dx.doi.org/10.1177/0272989X19889890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985995PMC
January 2020

The impact of interpregnancy weight change on perinatal outcomes in women and their children: A systematic review and meta-analysis.

Obes Rev 2020 03 21;21(3):e12974. Epub 2019 Nov 21.

Department of Pediatrics, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Prepregnancy overweight and obesity are associated with higher risk of perinatal complications. However, the effect of weight change prior to pregnancy on perinatal outcome is largely unknown. Therefore, it is aimed to examine the impact on perinatal outcomes of interpregnancy BMI change in women of different BMI categories. The MEDLINE, EMBASE, LILACS, and CINAHL databases were searched (1990-August 2019). Observational studies on interpregnancy BMI change were selected. Outcomes evaluated were gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension (GH), cesarean section, preterm birth, and newborns being large (LGA) or small (SGA) for gestational age. Meta-analyses and meta-regression analyses were executed. Thirty studies were included (n > 1 million). Interpregnancy BMI gain was associated with a higher risk of GDM (for BMI gain ≥3 kg/m : OR 2.21; [95%CI 1.53-3.19]), preeclampsia (1.77 [1.53-2.04]), GH (1.78 [1.61-1.97]), cesarean section (1.32 [1.24-1.39]), and LGA (1.54 [1.28-1.86]). The effects of BMI gain were most pronounced in women with BMI <25 kg/m before the first pregnancy regarding GDM, GH, and cesarean section. Except for LGA, interpregnancy BMI loss did not result in a decreased risk of perinatal complications. In this study, women of normal weight who gain weight before pregnancy were identified as a high-risk population for perinatal complications. This emphasizes that weight management is important for women of all BMI categories and a pregnancy wish.
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http://dx.doi.org/10.1111/obr.12974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050512PMC
March 2020

Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: study protocol for a randomised controlled trial in the Netherlands.

BMJ Open 2019 11 19;9(11):e030236. Epub 2019 Nov 19.

Department of Paediatrics, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands

Introduction: Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change.

Methods And Analysis: This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place.

Ethics And Dissemination: Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed.

Trial Registration Number: ClinicalTrials.gov NCT02703753.
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http://dx.doi.org/10.1136/bmjopen-2019-030236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886927PMC
November 2019

Longitudinal changes in placental biomarkers in women with early versus late placental dysfunction.

Hypertens Pregnancy 2019 Nov 27;38(4):268-277. Epub 2019 Sep 27.

Department of Obstetrics & Gynecology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.

: To evaluate longitudinal changes of angiogenic biomarkers in early- (EO-PD) versus late-onset (LO-PD) placental dysfunction. : Serum PlGF and sFlt-1 measured at different intervals in EO-PD (n= 43), LO-PD (n= 31) and controls (n = 133). : sFlt-1/PlGF ratio was higher at 16 weeks (30.6 vs 17.5), 20 weeks (29.3 vs 8.9) and 30 weeks (16.6 vs 6.7) in EO-PD vs controls (all p< 0.05), but not in LO-PD. Longitudinal changes for all intervals had higher AUC than single measurements. : Longitudinal biomarker change between 12 and 30 weeks could improve prediction of EO-PD compared to single measurements.
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http://dx.doi.org/10.1080/10641955.2019.1668948DOI Listing
November 2019

Can Fetal Growth Velocity and First Trimester Maternal Biomarkers Improve the Prediction of Small-for-Gestational Age and Adverse Neonatal Outcome?

Fetal Diagn Ther 2019 8;46(4):274-284. Epub 2019 May 8.

Department of Obstetrics and Gynecology, GROW School of Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.

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 <10). Combinations of the biomarkers and fetal growth velocity were added to baseline screening for the prediction of SGA and adverse neonatal outcome.

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.
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http://dx.doi.org/10.1159/000499580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878734PMC
March 2020

Long-term effects of motherfit group therapy in pre-(MOTHERFIT1) and post-partum women (MOTHERFIT2) with stress urinary incontinence compared to care-as-usual: study protocol of two multi-centred, randomised controlled trials.

Trials 2019 Apr 25;20(1):237. Epub 2019 Apr 25.

Maastricht University Medical Centre, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.

Background: Stress urinary incontinence (SUI) is highly prevalent during pregnancy and after delivery. It is often associated with a failing pelvic floor, sphincteric and/or supportive system. Pelvic-floor-muscle training (PFMT) peri-partum has been proven effective for up to 1 year post-partum; however, its long-term effects are unknown. Group PFMT, given by a physiotherapist, has been proven to be as equally effective as individual therapy. Motherfit is a group-PFMT therapy with an emphasis on pelvic floor exercises, adherence and general fitness. Care-as-usual (CAU), if guideline driven, should, as first treatment option, consist of PFMT. Cost-effective strategies are of relevance, given the rise of health care costs. Motherfit group therapy has the potential to be cost-effective in women with urinary incontinence. Therefore, the objectives of the two current studies are: (1) to investigate whether intensive, supervised, pre-partum (MOTHERFIT1) or post-partum (MOTHERFIT2) pelvic-floor-muscle group therapy reduces 18-month post-partum severity of SUI compared to CAU and (2) whether MOTHERFIT1 OR MOTHERFIT 2 is more (cost-)effective compared to CAU.

Methods: Two multi-centred, randomised controlled trials (MOTHERFIT1, n = 150, MOTHERFIT2, n = 90) will be performed. Participants will be recruited by their midwife or gynaecologist during their routine check. Participants with SUI will receive either motherfit group therapy or CAU. Motherfit group therapy consists of eight group sessions of 60 min each, instructed and supervised by a registered pelvic physiotherapist. Motherfit group therapy includes instructions on pelvic floor anatomy and how to contract, relax and train the pelvic-floor muscles correctly and is combined with general physical exercises. Adherence during and after motherfit will be stimulated by reinforcement techniques and a mobile app. The primary outcome measure is the absence of self-reported SUI based on the severity sum score of the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI-SF) at 18 months post-partum. Secondary outcomes evaluate quality of life, subjective improvement and health care costs.

Discussion: The motherfit studies are, to our knowledge, the first studies that evaluate both long-term results and health care costs compared to CAU in pregnant and post-partum women with SUI. If motherfit is shown to be (cost-)effective, implementation in peri-partum care should be considered.

Trial Registration: Netherlands Trial Register, ID: NL5816 . Registered on 18 July 2016.
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http://dx.doi.org/10.1186/s13063-019-3331-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485130PMC
April 2019

Inappropriate left ventricular mass after preeclampsia: another piece of the puzzle Inappropriate LVM and PE.

Hypertens Res 2019 04 14;42(4):522-529. Epub 2018 Dec 14.

Maternal Fetal Medicine Unit, Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.

Excessive left ventricular (LV) mass (LVM) increase results in inefficient LV work with high energy waste and a negative prognostic effect. We aimed to investigate the presence of inappropriate LVM and to calculate the myocardial mechanoenergetic efficiency index (MEEi) in asymptomatic women with a history of early-onset (EO) or late-onset (LO) pre-eclampsia (PE). Among all women diagnosed with PE in the years 2009-2013, after applying inclusion/exclusion criteria and cost-effectiveness analysis, we randomly selected thirty women who experienced EO-PE, thirty with a previous LO-PE and thirty healthy controls to undergo echocardiography from 6 months to 4 years after delivery. Data regarding gestational age (GA) and mean uterine artery (UtA) pulsatility index (PI) at PE onset were collected from medical records. All women were free from cardiovascular risk factors. LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was calculated as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM. Concentric remodeling was present in 60% of EO-PE and 53% of LO-PE. LVM excess was significantly more often present in the EO-PE group than in the control group. LVM was inappropriate in 52% of EO-PE and 17% of LO-PE. MEEi showed a tendency towards lower values in the EO-PE group. Multivariate regression analysis showed that both LVM excess and MEEi were independently associated with lower GA and higher mean UtA PI at PE onset. Inappropriate LVM with a tendency towards reduced MEEi in the first 4 years after delivery may partially explain the elevated cardiovascular risk in former pre-eclamptic women compared to the general population.
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http://dx.doi.org/10.1038/s41440-018-0163-9DOI Listing
April 2019
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