Objective This study evaluated pregnancy outcomes after history- and ultrasound-indicated cerclage and predictors of gestational age at delivery and pregnancy prolongation. Method 11-year retrospective cohort study in a tertiary center in the Netherlands. Women were included with singleton pregnancies receiving history- or ultrasound-indicated cerclage for suspected cervical insufficiency and/or short cervix <24+0 weeks. Analyses were stratified by cerclage indication. Ultrasound-indicated group was subdivided by obstetric history (with suspected prior cervical insufficiency [UIC-A] or without [UIC-B]). Kaplan–Meier analysis and univariable linear regression were used to assess associations between pre-/post-cerclage factors and gestational outcomes. Results A total of 272 women received history-indicated and 79 ultrasound-indicated cerclage (UIC-A: 36, UIC-B: 43). Median gestational age at delivery was comparable (37.9-38.4 weeks). Among women with suspected prior cervical insufficiency, spontaneous preterm birth <34 weeks was significantly less frequent after history-indicated than ultrasound-indicated cerclage (12% vs 25%), with comparable perinatal survival. Among ultrasound-indicated cases, UIC-A showed higher rates of spontaneous preterm birth <34 weeks (25% vs 7%) and preterm premature rupture of membranes (31% vs 9%). Greater post-cerclage distance between external os and cerclage was associated with higher gestational age at delivery and pregnancy prolongation, whereas pre-cerclage measures showed little association. Conclusions Pregnancy outcomes after cerclage differ according to clinical context and cerclage indication. In women with suspected prior cervical insufficiency, ultrasound-indicated cerclage after cervical shortening identified a subgroup at higher risk of spontaneous preterm birth and pregnancy complications. Post-cerclage cervical parameters were the strongest predictors. Optimizing cerclage placement height may be associated with improved outcomes.

AIMS:Cardiovascular risk increases progressively increases from lower blood pressure (BP) values in females than males, questioning current universal thresholds for hypertension. In this study, we established female- and age-specific thresholds for hypertension and assessed its association with subclinical cardiac aberrations in a high-risk female group of women after pre-eclampsia. METHODS:A standardized cross-sectional cardiovascular assessment was performed among former pregnant women, including 30-minutes BP measurement and transthoracic echocardiography to assess cardiac function and remodelling. Women with a history of normotensive pregnancy constituted the cardiovascular healthy reference group, in whom we established thresholds for elevated BP (≥95th percentile). The risk for subclinical cardiac aberrations in case of elevated BP was evaluated among former pre-eclamptic women. RESULTS:A number of 463 women were included in the healthy reference group and 951 formerly pre-eclamptic women (43 ± 8 and 39 ± 8 years, respectively). Female-specific thresholds defining hypertension were 132.8 mmHg systolic or 81.0 mmHg diastolic. Among former pre-eclamptic women, systolic BP levels above ≥132.8 mmHg but below current diagnostic threshold for hypertension (<140 mmHg) significantly associated with increased odds for left ventricular concentric remodelling [OR = 2.1, 95% confidence interval (CI) 1.1-4.2], diastolic dysfunction [OR = 4.5 (1.4-14.2)], and subclinical heart failure (OR = 2.3, 95% CI 1.2-4.2). CONCLUSION:For relatively young women, female-specific thresholds for hypertension are lower than ESC/ESH guidelines (≥133/81 vs. ≥140/90 mmHg), and associate with cardiac dysfunction in formerly pre-eclamptic women. Sex- and age-tailored interpretation of BP improves prevention of heart failure development and progression among high-risk women.

Introduction Despite being a leading cause of female morbidity and mortality, female-specific cardiovascular disease (CVD) is understudied, underdiagnosed and undertreated. Pregnancy complications involving the placenta, including pre-eclampsia, pregnancy-induced hypertension and foetal growth restriction, are thought to reflect global maternal vascular derangements that indicate a twofold to eightfold increased risk of future CVD. This calls for a better understanding of female cardiovascular pathophysiology to allow development of targeted screening and prevention strategies.Acute atherosis is a placental vascular lesion, which histologically resembles systemic atherosclerosis. The PlacEntal Acute atherosis RefLecting Subclinical atherosclerosis study investigates the association between placental acute atherosis lesions and subclinical systemic atherosclerosis up to 20 years postpartum.This study will improve our understanding of the relationship between pregnancy complications and CVD to identify potential prevention targets and treatments. In addition, it could determine whether the placenta can improve identification of young women at high risk of CVD. These women could benefit from risk-reducing interventions.Methods and analysis This longitudinal prospective cohort study will include women who are either currently pregnant or from a historical cohort. Both groups will have placental histopathology and a single postpartum CVD assessment. The CVD assessment will include medical history taking, blood tests, electrocardiography and echocardiography. Additionally, coronary CT angiography focusing on the presence of atherosclerotic plaques and calcium score will be carried out.The currently pregnant women will either have a pre-eclamptic pregnancy (pre-eclamptic group) or an uncomplicated normotensive pregnancy (uncomplicated group), and their placenta will be collected prospectively. The single CVD assessment will be carried out 6–36 months postpartum.Women from the historical cohort had a pre-eclamptic pregnancy 10–20 years ago. Placental tissue is available for reanalysis. The single CVD assessment will take place immediately and corresponds with 10–20 years postpartum.Exclusion criteria are contraindications to diagnostic assessment necessities: iodinated contrast, beta-blockers or glyceryl trinitrate. Women with uncomplicated pregnancies will be excluded if they have a pre-existing auto-immune condition, chronic hypertension or diabetes mellitus. In the pre-eclamptic group, there are no additional exclusion criteria.Ethics and dissemination Ethical approval was granted by the Medical Ethics Committee in Maastricht University Medical Centre+ (NL52556.068.15/METC152019). Participants will give written informed consent. Results will be shared in peer-reviewed journals and conference presentations.Trial registration number NCT05500989; ClinicalTrials.gov Identifier.

INTRODUCTION:To prevent extreme preterm birth, women with cervical insufficiency are eligible for transabdominal cerclage in case of prior failure or technical impossibility for transvaginal cerclage. This study aimed to identify patient characteristics that affect the success rate of transabdominal cerclage to prevent extreme preterm birth in women with cervical insufficiency. MATERIAL AND METHODS:Single-center retrospective cohort study in 87 women who underwent transabdominal cerclage by open laparotomy during first and early second trimester of pregnancy over a 20-year period. Participants were divided into subgroups according to indication for the intervention. Linear regression and meta-regression-analyses were performed to assess the effect of mean cervical length (before and after transabdominal cerclage placement) and gestational age of previous preterm birth, on gestational age at delivery. Kaplan-Meier analysis was performed to evaluate treatment effects on gestational age at delivery. RESULTS:Of 87 women, 62 women underwent a history-indicated and 25 an ultrasound-indicated transabdominal cerclage. Fetal survival was 92%: 91% in the history-indicated and 96% in the ultrasound-indicated group. Median gestational age at delivery was 37.3 weeks, with a median pregnancy prolongation of 163.0 days and with 92% of deliveries ≥34 weeks. Between groups, irrespective of singleton and twin pregnancies, outcomes were comparable. Gestational age at delivery was neither affected by cervical length before transabdominal cerclage, distance between transabdominal cerclage and external os, gestational age of previous preterm birth nor additional progesterone treatment. CONCLUSIONS:The efficacy of transvaginal cerclage placement via open laparotomy during high-risk pregnancy is favorable and relates to fetal survival of 92%. Regardless of indication, pregnancy outcomes after transabdominal cerclage are similar, and independent of gestational age at previous preterm birth, cervical length before transabdominal cerclage placement, distance between transabdominal cerclage and external os, and additional progesterone administration.

OBJECTIVE:To evaluate school performance at 12 years of age in children prenatally exposed to maintenance tocolysis with nifedipine versus placebo. DESIGN:12-year follow-up of the multicentre APOSTEL 2 trial, in which participants with threatened preterm birth between 26+0 and 32+2 weeks of gestation, who remained pregnant after initial 48-h tocolysis, were randomised to nifedipine maintenance tocolysis or placebo for up to 12 days. SETTING:The APOSTEL 2 trial was conducted in 11 Dutch hospitals from 2008 to 2010. School outcomes were assessed at age 12. PARTICIPANTS:Children from singleton and multiple pregnancies born to APOSTEL 2 participants. METHODS:School performance data were received through linkage with a national registry (Statistics Netherlands). MAIN OUTCOME MEASURES:A high track recommendation for secondary school, adjusted for maternal education level, socioeconomic status, and child's biological sex. RESULTS:Of 492 eligible children, 357 were included (follow-up rate 73%). In the nifedipine group, significantly fewer children received a high track recommendation for secondary school, 67/189 (35.4%), compared to 74/168 (44.0%) in the placebo group (adjusted risk ratio (aRR) 0.76; 95% confidence interval (CI) 0.61-0.95). Outcomes were significantly poorer in children with the longest nifedipine exposure (9-14 days) compared to those not exposed (aRR 0.58; 95% CI 0.41-0.83). CONCLUSIONS:Children prenatally exposed to maintenance tocolysis with nifedipine had significantly poorer school performance at 12 years of age compared to those exposed to placebo. These findings further discourage nifedipine's use for maintenance tocolysis, and more research is warranted regarding its long-term effects on child development.

IntroductionRecurrent pregnancy loss (RPL) is associated with altered immune phenotypes and functions. It has been proposed that physical exercise might impact the immune system. Therefore, we evaluated the effect of a personalized 3-month moderate-intensity aerobic exercise intervention on the immune system of women with unexplained RPL (uRPL). Given the suggested supportive role of Natural Killer (NK) cells during early pregnancy, we focused on numerical, phenotypic, and functional changes in peripheral NK (pNK) and uterine NK (uNK) cells.MethodsMononuclear cells were isolated from peripheral blood (PB) (n=23) and menstrual blood (MB) (n=22) of women with uRPL. NK cell phenotypes were assessed with comprehensive flow cytometry panels. NK cell function was assessed with degranulation assays and intracellular staining of interferon-γ (IFN-γ), perforin and granzyme-B in a subgroup of women due to lower availability of samples (n=12).ResultsAttendance to the exercise intervention was overall 95%, which resulted in effects on the phenotype and function of pNK cells. We found a significant reduction in the median fluorescent intensity of CD161 (464 vs 410, p=0.011), NKp30 (432 vs 376, p=0.018), and NKG2A (886 vs 732, p=0.039) in pNK cells after exercise, while no differences were observed in uNK cells. We also observed decreased percentages of IFN-γ+ pNK cells (49% vs 25.2%, p=0.027) after exercise.DiscussionOur study shows promising results, suggesting that exercise can impact pNK cell phenotype and function in women with uRPL. Following the changes in pNK phenotype and function suggest a lower pro-inflammatory state post-exercise. Whether these exercise-induced phenotypic and functional changes of pNK cells impact subsequent pregnancies remains to be studied. The study details are available through HYPERLINK “https://clinicaltrials.gov/”Home | ClinicalTrials.gov, trial ID: HMOVE

Women confronted with recurrent pregnancy loss (RPL) are often desperately searching for a possible explanation and hoping they will someday fulfill a healthy pregnancy. Unfortunately, in more than 50% of these women no cause for their losses can be identified after clinical investigations and therefore clinicians have no treatment options to help these women. Although adaptations in several systems such as the metabolic, the cardiovascular, and the immune system are highly important to support early pregnancy, especially the contribution of a specific subset of immune cells in the uterus known as CD56bright Natural Killer (NK) cells has gained a lot of interest, investigating separate RPL associated factors might not be the way forward. Moreover, a readily available and non-invasive exercise intervention might optimize all systems simultaneously, reducing metabolic, cardiovascular and immunological risk factors contributing to RPL. Therefore, we propose an aerobe exercise intervention and study the influence on the cardiovascular, the metabolic, and the immune system, with a particular focus on endometrial CD56bright NK cells, in women with unexplained RPL. In this exercise intervention study, women with unexplained RPL will receive two questionnaires to assess baseline characteristics. Moreover, they will receive (1) an immunological assessment (by sampling menstrual blood, peripheral blood and a vaginal swab) (2) an assessment of the cardiovascular system (by transvaginal ultrasound to assess uterine artery perfusion, by measuring hemodynamic and autonomic nerve system responses during a tilt test and by maximum stress test on a cycle ergometer) and (3) a metabolic assessment (by sampling peripheral blood, urine and by measuring body characteristics) before and after intervention. The intervention consists of 12-weeks moderate exercise training based on 50–65% of heart rate reserve. One year after the end of the intervention women will receive a final questionnaire regarding possible subsequent pregnancy outcome. This clinical trial with a multi-systemic approach can not only provide new insights by studying contribution and associations of the immune system, the cardiovascular system and the metabolic system in women with unexplained RPL, it also can support shared decision-making between clinicians and patients by evaluating the importance of a ready available exercise intervention strategy.

OBJECTIVE:Preeclampsia contributes to maternal cognitive problems, particularly involving executive functions. These higher-order cognitive functions-including working memory, organisation of materials, and task focus-are essential for adaptive, purposeful, and goal-directed behaviour. Similar cognitive problems are observed in metabolic syndrome and insulin resistance. This study investigates whether these conditions are also associated with executive function after preeclampsia. DESIGN:Nested case-control study. SETTING:Maastricht University Medical Centre+, a tertiary care hospital. POPULATION:Women 0.5 to 30 years after preeclampsia. METHODS:The Behaviour Rating Inventory of Executive Function for Adults provided a measure of executive function performance. The National Cholesterol Education Program Adult Treatment Panel III defined metabolic syndrome. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) quantified insulin resistance. Participants were matched on age, postpartum time, and educational attainment. Associations of attenuated executive function with metabolic syndrome, its constituents, and insulin resistance were examined with conditional logistic regression. MAIN OUTCOME MEASURES:Odds ratios and population attributable fractions for the associations of attenuated executive function with metabolic syndrome, its constituents, and insulin resistance. RESULTS:In 155 matched pairs, attenuated executive function was associated with metabolic syndrome (odds ratio 4.20 (95% confidence interval 1.58-11.14)), hyperglycaemia (2.96 (1.13-7.79)), and obesity (3.86 (2.00-7.47)). Attenuated executive function related to HOMA-IR (7.26 (3.75-14.07)), and was 13% (6%-20%) attributable to metabolic syndrome and 56% (49%-67%) to insulin resistance. CONCLUSIONS:Metabolic syndrome and insulin resistance are associated with attenuated executive function after preeclampsia. Our findings provide leads for future studies focused on improving post-preeclamptic cognitive performance.

ABSTRACTProblemNatural killer (NK) cells undergo education for full functionality via interactions between killer immunoglobulin‐like receptors (KIRs) or NKG2A and human leukocyte antigen (HLA) ligands. Presumably, education is important during early pregnancy as insufficient education has been associated with impaired vascular remodeling and restricted fetal growth in mice. NK cell education is influenced by receptor co‐expression patterns, human cytomegalovirus (CMV), the HLA‐ER107G dimorphism, and HLA‐B leader peptide variants. We hypothesized altered NK cell education status and differences in frequencies of HLA‐E genotypes and HLA‐B leader peptide variants in women with recurrent pregnancy loss (RPL) compared to women with previously uncomplicated pregnancies, and between CMV seropositive and seronegative RPL women.Methods of StudyPeripheral blood mononuclear cells were analyzed by flow cytometry. HLA‐ABC was typed by sequence‐specific oligonucleotide PCR, and HLA‐E by Sanger sequencing. CMV status was determined by anti‐CMV IgG immunoassay. NK cells were considered “educated” if the HLA ligand to a KIR or NKG2A was present.ResultsKIR/NKG2A co‐expression patterns and percentages of educated NK cells were similar between RPL and controls, and between seropositive and seronegative RPL women. Frequencies of HLA‐E genotypes and HLA‐B leader peptide variants were comparable. RPL women with the HLA‐B T/T variant had a lower percentage of NKG2A‐educated NK cells (47.8%) compared to controls (66.4%) (p = 0.025).ConclusionsHLA‐B leader peptide variants might impact NKG2A‐specific NK cell education in RPL, warranting validation in larger studies. Follow‐up studies are needed to investigate the education status of uterine NK cells and their role in pregnancy.

INTRODUCTION:Preterm prelabor rupture of membranes (PPROM) remains a major complication of fetal laser surgery in the treatment of twin-to-twin transfusion syndrome (TTTS). The aim of the study was to determine the impact of cannula size on pregnancy outcomes, with a particular focus on PPROM. MATERIAL AND METHODS:The protocol was developed and registered in the PROSPERO database under registration number CRD42022333630. The PubMed, Web of Science, and EMBASE databases were searched electronically on May 18, 2022, and updated on March 2, 2023, utilizing a combination of the relevant MeSH terms, keywords, and word variants for "TTTS" and "laser". Randomized controlled trials, prospective and retrospective cohorts, case-control studies, and case reports/series with more than five participants were considered eligible for inclusion. Studies reporting the cannula diameter and PPROM rate after laser surgery in the treatment of monochorionic pregnancies affected by TTTS between 16- and 26 weeks' gestation were included. Data was extracted independently, and when appropriate, a random-effects meta-analysis was undertaken to calculate pooled estimates and their confidence intervals. Heterogeneity in the effect estimates of the individual studies was calculated using the I2 statistic. The primary outcome was PPROM rate. Secondary outcomes were survival rate, preterm birth, and incomplete surgery. The quality of the included studies was assessed using a modified quality in prognosis study tool. RESULTS:We included a total of 22 studies, consisting of 3426 patients. Only one study was scored as low quality, seven as moderate quality, and the remaining 14 as high quality. The mean PPROM rate after laser surgery treating TTTS was 22.9%, ranging from 11.6% for 9 French (Fr) to 54.0% for 12 Fr. Subsequent meta-regression for the clinically relevant PPROM rate before 34 weeks of gestation, showed increased PPROM rates for increased cannula size (p-value 0.01). CONCLUSIONS:This systematic review confirmed PPROM as a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. A larger cannula diameter relates to a significant higher PPROM risk for PPROM before 34 weeks gestation. Hence, the ideal balance between optimal visualization requiring larger port diameters and shorter operation time and more complete procedures that benefit from larger diameters is crucial to reduce iatrogenic PPROM rates.

The purpose of the present study is to identify the impact of the postpartum menstrual cycle on aldosterone, renin, and their ratio of women with and without a preeclamptic pregnancy in the past. To this end, we analysed the data from 59 women with a history of preeclampsia and 39 healthy parous controls. Five to seven months post-partum, we measured aldosterone, renin, and the aldosterone-to-renin ratio during both the follicular and the luteal phase of the menstrual cycle. All measurements were taken in the supine position in the morning. Patients had maintained a standardized sodium diet in the week prior to the measurements. Our results show that in both post-partum women with recent preeclampsia and controls, average levels of renin and aldosterone are significantly elevated in the luteal phase as compared to the follicular phase. The aldosterone-to-renin ratio does not differ between the two phases in either group. Compared to controls, women with recent preeclampsia have significantly lower levels of renin, aldosterone, and aldosterone-to-renin ratio in the follicular phase. This remained consistent in the luteal phase, except for renin. A close correlation existed between the luteal and follicular aldosterone-to-renin ratio in the control group but not in the preeclampsia group. We conclude that both renin and aldosterone are significantly affected by the menstrual cycle whereas the resulting aldosterone-to-renin ratio is not. Post-partum women with recent preeclampsia tend to have lower values for aldosterone and the aldosterone-to-renin ratio than controls.

This chapter addresses the most common risk factors increasing maternal and offspring health disadvantages. Psychosocial vulnerability, including maternal stress and substance abuse, overweight and obesity, psychiatric disorders, chronic and acute infections, autoimmunity, chronic kidney disease and hypertension, cardiac disorders, either acquired or congenital, and diabetes mellitus are systematically evaluated on the effect of the condition on pregnancy and vice versa, and the possible effect of specific disease-modifying drugs.

Ultrasound speckle tracking is frequently used to quantify myocardial strain, and magnetic resonance imaging (MRI) feature tracking is rapidly gaining interest. Our aim is to validate cardiac MRI feature tracking by comparing it with the gold standard method (i.e., MRI tagging) in healthy subjects and patients. Furthermore, we aim to perform an indirect validation by comparing ultrasound speckle tracking with MRI feature tracking. Forty-two subjects (17 formerly preeclamptic women, three healthy women, and 22 left bundle branch block patients of both sexes) received 3-T cardiac MRI and echocardiography. Cine and tagged MRI, and B-mode ultrasound images, were acquired. Intrapatient global and segmental left ventricular circumferential (MRI tagging vs. MRI feature tracking) and longitudinal (MRI feature tracking vs. ultrasound speckle tracking) peak strain and time to peak strain were compared between the three techniques. Intraclass correlation coefficient (ICC) (< 0.50 = poor, 0.50-0.75 = moderate, > 0.75-0.90 = good, > 0.90 = excellent) and Bland-Altman analysis were used to assess correlation and bias; p less than 0.05 indicates a significant ICC or bias. Global peak strain parameters showed moderate-to-good correlations between methods (ICC = 0.71-0.83, p < 0.01) with no significant biases. Global time to peak strain parameters showed moderate-to-good correlations (ICC = 0.56-0.82, p < 0.01) with no significant biases. Segmental peak strains showed significant biases in all parameters and moderate-to-good correlation (ICC = 0.62-0.77, p < 0.01), except for lateral longitudinal peak strain (ICC = 0.23, p = 0.22). Segmental time to peak strain parameters showed moderate-to-good correlation (ICC = 0.58-0.74, p < 0.01) with no significant biases. MRI feature tracking is a valid method to examine myocardial strain, but there is bias in absolute segmental strain values between imaging techniques. MRI feature tracking shows adequate comparability with ultrasound speckle tracking.

OBJECTIVE:To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise.DESIGN:Experimental case-control pilot study.SETTING:University medical centre in the Netherlands.POPULATION:Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies.METHODS:In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training.MAIN OUTCOME MEASURES:Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss.RESULTS:Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss.CONCLUSIONS:Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (N ε -(carboxymethyl)lysine [CML], N ε -(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (−12%) and hypoxia-exposed placentas (−16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (−26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia.

Background Existing evidence suggests a relation between cardiovascular dysfunction and diminished ovarian reserve. While it is known that pre-existent cardiovascular dysfunction is also associated with the development of preeclampsia (PE) during pregnancy, we hypothesize that signs of diminished ovarian reserve may occur more frequently among women with a history of hypertensive disorders of pregnancy (HDP). The aim of our study was therefore to analyse if women with a history of HDP show signs of diminished ovarian reserve, represented by lower anti-Mullarian hormone (AMH) levels, compared to controls. For this retrospective observational case control study, patients included women with a history of HDP, whereas controls constituted of women with a history of an uncomplicated pregnancy. The study was conducted in a tertiary referral centre in which all women underwent a one-time cardiovascular and metabolic assessment. Ovarian reserve and markers of cardiovascular function were evaluated, adjusted for age and body mass index (BMI) using linear regression analyses. Results 163 patients and 81 controls were included over a time span of 3 years. No signs of diminished ovarian reserve i.e. lower AMH level were observed in the patient group versus controls. A subgroup analysis even showed higher AMH levels in late onset HDP as compared to controls (2.8 vs. 2.0 µg/L, p = 0.025). As expected, cardiovascular function markers were significantly less favourable in the patient group compared to controls; higher levels of systolic blood pressure (BP) (5%), diastolic BP (4%), triglycerides (29%), glucose (4%) and insulin levels (81%) (all p < 0.05), whereas high density lipid (HDL) cholesterol was 12% lower (NS). Conclusions Despite unfavourable cardiovascular risk profile, the present study does not substantiate the hypothesis that women with HDP show accelerated ovarian ageing as compared to healthy parous controls. Although HDP patients should be warned about their cardiovascular health, they shouldn’t be concerned about unfavourable ovarian reserve status.

Background Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory response may antedate or accompany vascular complicated pregnancy. We performed a systematic review and meta-analysis to delineate the trajectory of active plasma renin concentration (APRC) in healthy pregnancy and compare this to complicated pregnancy. Methods We performed a systematic review and meta-analysis on APRC during normotensive and hypertensive pregnancies, using PubMed (NCBI) and Embase (Ovid) databases. We included only studies reporting measurements during pregnancy together with a nonpregnant reference group measurement. Risk of bias was assessed with QUIPS. Ratio of the mean (ROM) and 95% confidence intervals (CI) of APRC values between pregnant and nonpregnant women were estimated for predefined intervals of gestational age using a random-effects model. Meta-regression was used to analyze APRC over time. Results In total, we included 18 studies. As compared to nonpregnant, APRC significantly increased as early as the first weeks of healthy pregnancy and stayed increased throughout the whole pregnancy (ROM 2.77; 95% CI 2.26–3.39). APRC in hypertensive complicated pregnancy was not significantly different from nonpregnancy (ROM 1.32; 95% CI 0.97–1.80). Conclusion Healthy pregnancy is accompanied by a profound rise in APRC in the first trimester that is maintained until term. In hypertensive complicated pregnancy, this increase in APRC is not observed.

Introduction Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance.Methods and analysis The cross-sectional ‘DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia’ (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood–brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses.Ethics and dissemination This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media.Trial registration number NCT02347540.