Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Experience Counts: Unveiling Patients' Willingness to Pay for Remote Monitoring and Patient Self-Measurement.

OBJECTIVES: This study aimed to (1) estimate patients' willingness to pay (WTP) for remote monitoring (RM) and patient self-measurement (PSM) for pregnant women at risk of gestational hypertensive disorders, (2) assess the impact of experience with these technologies on WTP, and (3) determine their impact on health-related quality of life (HRQoL). METHODS: Data collection was part of a multicentric randomized controlled trial, Pregnancy Remote Monitoring II, with 2 interventions: RM and PSM. A contingent valuation survey, combining a payment card and open-ended question, was completed twice by 199 participants. Two-part models analyze the impact of experience on WTP, regression models estimated using ordinary least squares the impact of RM and PSM on HRQoL. RESULTS: The mean WTP amount was approximately €120 for RM and €80 for PSM. Compared with having no experience, WTP RM was €63 higher after a long-term exposure to RM (P = .01) and WTP PSM was €26 lower after a short-term exposure to RM (P = .07). No significant impact of RM or PSM on HRQoL was found. CONCLUSIONS: This study contributes to the discussion on the impact of experience on WTP. Those who had a long-term experience with RM, were willing to pay more for RM than those without experience. This confirms our hypothesis that involving patients without experience with the valued treatment, possibly underestimates WTP. A long-term experience has, however, no impact on the WTP for technologies for which the potential benefits are apparent without experiencing them, such as PSM.

Prediction of adverse pregnancy outcomes by first-trimester components of metabolic syndrome: a prospective longitudinal study.

PURPOSE: This study aimed to identify the optimal cutoff values of each component of metabolic syndrome (MetS) in the first trimester of pregnancy for predicting adverse pregnancy outcomes. METHODS: A total of 1076 pregnant women in the first trimester of gestation were recruited in this prospective longitudinal cohort study. Specifically, 993 pregnant women at 11-13 weeks of gestation who were followed up until the end of pregnancy were included in the final analysis. The cutoff values of each component of MetS in the occurrence of adverse pregnancy outcomes including gestational diabetes (GDM), gestational hypertensive disorders, and preterm birth were obtained via receiver operating characteristic (ROC) curve analysis using the Youden's index. RESULTS: Among the 993 pregnant women studied, the significant associations between the first trimester MetS components and adverse pregnancy outcomes were as follows: triglyceride (TG) and body mass index (BMI) with preterm birth; mean arterial pressure (MAP), TG, and high-density lipoprotein cholesterol (HDL-C) with gestational hypertensive disorders; BMI, fasting plasma glucose (FPG), and TG with GDM (all p values < 0.05). The cutoff point values for the above-mentioned MetS components were: TG > 138 mg/dl and BMI < 21 kg/m2 for the occurrence of preterm birth; TG > 148 mg/dL, MAP > 84, and HDL-C < 84 mg/dl for gestational hypertensive disorders; BMI > 25 kg/m2, FPG > 84 mg/dl, and TG > 161 mg/dl for GDM. CONCLUSION: The study findings imply the importance of early management of metabolic syndrome in pregnancy to improve maternal-fetal outcomes.

Maternal Iron Status in Early Pregnancy and Blood Pressure Throughout Pregnancy, Placental Hemodynamics, and the Risk of Gestational Hypertensive Disorders.

BACKGROUND: In nonpregnant populations, higher serum ferritin, which reflects high iron stores, is associated with an increased risk of hypertension. We hypothesized that a dysregulated maternal iron status in early pregnancy may lead to impaired gestational hemodynamic adaptations, leading to an increased risk of gestational hypertensive disorders. OBJECTIVES: We examined the associations of maternal iron status with maternal blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders. METHODS: In a population-based prospective cohort study among 5983 pregnant women, we measured maternal serum ferritin, transferrin saturation, serum iron, and transferrin concentrations at a median of 13.2 weeks gestation (95% range, 9.6-17.6). Maternal blood pressure was measured in early pregnancy, mid pregnancy, and late pregnancy, and placental hemodynamic parameters in mid pregnancy and late pregnancy were measured by ultrasound. Information on gestational hypertensive disorders was collected from medical records. We examined the associations of maternal early pregnancy iron status with maternal systolic and diastolic blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders using linear and logistic regression models. RESULTS: Higher maternal early pregnancy serum ferritin concentrations were associated with higher systolic and diastolic blood pressure throughout pregnancy in the basic models (P values < 0.05). After adjustment for maternal inflammation, sociodemographic and lifestyle factors, higher maternal early pregnancy serum ferritin concentrations were only associated with a higher early pregnancy diastolic blood pressure [0.27 (95% CI, 0.03-0.51) mmHg per SD score increase in serum ferritin] and with a higher mid pregnancy umbilical artery pulsatility index (P < 0.05). No associations with the risk of gestational hypertensive disorders were present. CONCLUSIONS: No consistent associations were present of maternal iron status in early pregnancy with gestational hemodynamic adaptations or the risks of gestational hypertensive disorders. Further studies are needed to examine the potential role of iron metabolism in the development of gestational hypertensive disorders within higher-risk populations.

Associations of dietary glycemic index and load during pregnancy with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders.

PURPOSE: The aim of this study was to examine the associations of dietary glycemic index and load with gestational blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. METHODS: In a population-based cohort among 3378 pregnant Dutch women, dietary glycemic index and load were assessed from food frequency questionnaires at median 13.4 (95% range 9.9-22.9) weeks gestation. Blood pressure was measured in early-, mid- and late-pregnancy. Placental hemodynamic parameters were measured in mid- and late-pregnancy by ultrasound. Data on gestational hypertensive disorders was acquired from medical records. RESULTS: Mean dietary glycemic index (SD) was 58 (3) and mean dietary glycemic load (SD) was 155 (47). Dietary glycemic index was not associated with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Higher dietary glycemic load SDS was associated with a higher diastolic blood pressure in early-pregnancy, remaining after adjustment for socio-demographic and lifestyle factors ((0.98 (95% CI 0.35-1.61) mmHg per SDS increase in glycemic load). No other associations of glycemic load with blood pressure or placental hemodynamic parameters and the risk of gestational hypertensive disorders were present. No significant associations of dietary glycemic index and load quartiles with longitudinal blood pressure patterns from early to late-pregnancy were present. CONCLUSION: Within this low-risk pregnant population, we did not find consistent associations of dietary glycemic index and load with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Further studies need to assess whether the effects on gestational hemodynamic adaptations are more pronounced among high-risk women with an impaired glucose metabolism.

[Clinical Confusion Concerning Increased D-Dimer Value during Pregnancy].

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy.

Design of the Pregnancy REmote MOnitoring II study (PREMOM II): a multicenter, randomized controlled trial of remote monitoring for gestational hypertensive disorders.

BACKGROUND: Observational data from the retrospective, non-randomized Pregnancy REmote MOnitoring I (PREMOM I) study showed that remote monitoring (RM) may be beneficial for prenatal observation of women at risk for gestational hypertensive disorders (GHD) in terms of clinical outcomes, health economics, and stakeholder perceptions. PREMOM II is a prospective, randomized, multicenter follow-up study that was performed to explore these promising results. METHODS: After providing written consent, 3922 pregnant women aged ≥18 years who are at increased risk of developing GHD will be randomized (1:1:1 ratio) to (a) conventional care (control group), (b) a patient self-monitoring group, and (c) a midwife-assisted RM group. The women in each group will be further divided (1:1 ratio) to evaluate the outcomes of targeted or non-targeted (conventional) antihypertensive medication. Women will be recruited in five hospitals in Flanders, Belgium: Ziekenhuis Oost-Limburg, Universitaire Ziekenhuis Antwerpen, Universitaire Ziekenhuis Leuven, AZ Sint Jan Brugge-Oostende, and AZ Sint Lucas Brugge. The primary outcomes are: (1) numbers and types of prenatal visits; (2) maternal outcomes; (3) neonatal outcomes; (4) the applicability and performance of RM; and (5) compliance with RM and self-monitoring. The secondary outcomes are: (1) cost-effectiveness and willingness to pay; (2) patient-reported outcome measures (PROMS) questionnaires on the experiences of the participants; and (3) the maternal and perinatal outcomes according to the type of antihypertensive medication. Demographic, and maternal and neonatal outcomes are collected from the patients' electronic records. Blood pressure and compliance rate will be obtained from an online digital coordination platform for remote data handling. Information about the healthcare-related costs will be obtained from the National Coordination Committee of Belgian Health Insurance Companies (Intermutualistisch Agentschap). PROMS will be assessed using validated questionnaires. DISCUSSION: To our knowledge, this is the first randomized trial comparing midwife-assisted RM and self-monitoring of prenatal blood pressure versus conventional management among women at increased risk of GHD. Positive results of this study may lead to a practical framework for caregivers, hospital management, and payers to introduce RM into the prenatal care programs of high-risk pregnancies. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov , identification number NCT04031430. Registered 24 July 2019, https://clinicaltrials.gov/ct2/show/NCT04031430?cond=premom+ii&draw=2&rank=1 .

HRG C633T polymorphism and risk of gestational hypertensive disorders: a pilot study.

BACKGROUND: Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders. METHODS: It was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP. RESULTS: The genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04-2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity. CONCLUSIONS: The HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.

Preconception Physical Exercise Is Associated with Phenotype-Specific Cardiovascular Alterations in Women at Risk for Gestational Hypertensive Disorders.

Background/Objectives: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy. Methods: A non-invasive hemodynamics assessment of arteries, veins, and the heart was performed on 40 non-pregnant women at risk for developing GHD in a subsequent pregnancy. Measurements of an electrocardiogram Doppler ultrasound, impedance cardiography and bio-impedance spectrum analysis were taken before and after they engaged in physical exercise (30-50 min, 3×/week, 4-6 months). Results: After a mean physical exercise period of 29.80 weeks, the total peripheral resistance (TPR), diastolic blood pressure and mean arterial pressure decreased in the total study population, without changing cardiac output (CO). However, in 42% (9/21) of women categorized with high or low baseline CO (>P75 or

Incidence of Heart Failure Related to Co-Occurrence of Gestational Hypertensive Disorders and Gestational Diabetes.

BACKGROUND: The extent to which their co-occurrence of gestational hypertensive disorders (GHTD) and gestational diabetes mellitus (GDM) influences heart failure (HF) risk is unclear. OBJECTIVES: The purpose of this study was to characterize the risk of HF related to concomitant GHTD and GDM. METHODS: We conducted a population-based cohort study using the Ministry of Health and Long-Term Care of Ontario (Canada) health care administrative databases. We included women with a livebirth singleton delivery between July 1, 2007, and March 31, 2018, and excluded those with prepregnancy diabetes, hypertension, HF, or coronary artery disease. GDM, GHTD, peripartum cardiomyopathy (at index pregnancy) were identified using diagnosis coding. Incident HF was assessed from index pregnancy until March 31, 2020. We estimated associations of GDM and/or GHTD with peripartum cardiomyopathy and incident HF. RESULTS: Among 885,873 women (mean age: 30 years, 54,015 with isolated GDM, 43,750 with isolated GHTD, 4,960 with GDM and GHTD), there were 489 HF events over 8 years. Compared to no-GDM and no-GHTD, isolated GDM (adjusted hazard ratio [aHR]: 1.44; 95% CI: 1.02-2.04) and isolated GHTD (aHR: 1.65; 95% CI: 1.17-2.31) were associated with a higher risk of incident HF. The co-occurrence of GDM and GHTD was associated with a higher HF risk (aHR: 2.64; 95% CI: 1.24-5.61). GDM and GHTD increased the risk of peripartum cardiomyopathy (adjusted risk ratio [aRR]: 7.30; 95% CI: 6.92-7.58), similarly to isolated GHTD (aRR: 7.40; 95% CI: 7.23-7.58). CONCLUSIONS: The co-occurrence of GDM and GHTD was associated with a significantly high risk of incident HF.

First-Trimester Normotension Is a Weak Indicator of Normal Maternal Cardiovascular Function.

BACKGROUND: As by definition, mean arterial pressure equals the product of cardiac output (CO) and total vascular resistance (TPR), we hypothesized that, irrespective of thresholds to define hypertension, a CO-TPR imbalance might exist in first-trimester normotensive pregnancies with altered risks for adverse gestational outcomes. METHODS: A standard protocol was used for automated blood pressure measurement combined with impedance cardiography assessment of CO and TPR (NICCOMO). First-trimester normotensive pregnant women were categorized into 3 groups relative to the reference 75th percentile (P75) of CO and TPR: (1) normal CO and TPR, (2) high CO, and (3) high TPR. These subgroups were compared at blood pressure thresholds 140/90, 130/85, and 130/80 mmHg. The gestational outcome was categorized after birth according to International Society for Studies of Hypertension in Pregnancy criteria. RESULTS: Compared with pregnancies with normal CO and TPR (≤P75), women with high TPR at blood pressure <140/90 mmHg are at risk for developing gestational hypertension (odds ratio, 3.795 [1.321-10.904]; P<0.010), late-onset preeclampsia (odds ratio, 3.137 [1.060-9.287]; P<0.050), and neonates small for gestational age (odds ratio, 1.780 [1.056-2.998]; P<0.050). CONCLUSIONS: Cardiovascular imbalance can present in normotensive women in the first trimester and is associated with increased risks for adverse gestational outcomes. This study illustrates the relevance of CO and TPR assessments as an adjunct to blood pressure measurement and invites for further exploring their value in screening algorithms for gestational hypertensive disorders and/or small for gestational age.

The clinical utility of D-dimer/platelet count ratio in pregnant women.

OBJECTIVE: We performed a retrospective study to assess the clinical utility of a new index, D-dimer/platelet count (DD/PLT) ratio, in discriminating preeclampsia from normal pregnancy and gestational hypertension during third trimester, compared to the biomarkers currently used, such as D-dimer (DD), platelet (PLT), lymphocyte (LIN) and neutrophil (NEU) counts, fibrinogen (FIB), PLT/NEU, NEU/LIN and PLT/LIN ratios. STUDY DESIGN: We retrospectively included 213 subjects. Of them, 163 and 50 were singleton pregnant and healthy non-pregnant women, respectively. Among pregnant women, 105 had normal pregnancy, 33 had gestational hypertension, and 25 had preeclampsia. RESULTS: Using Receiver Operating Curve (ROC) analysis, DD/PLT ratio showed significant higher area under the curve (AUC) (0.90; 95% confidence interval (CI) 0.84-0.95) in discriminating preeclampsia from normal pregnancy compared to those of DD, NEU, FIB, LIN, PLT/NEU, NEU/LIN and PLT/LIN ratios (p < .03). In discriminating preeclampsia from gestational hypertension, the DD/PLT AUC (0.90; 95% CI 0.79-0.96) was significantly higher than those of DD, NEU, FIB, LIN, NEU/LIN and PLT/LIN ratios (p < .03), and not statistically different from those of PLT (p = .22) and PLT/NEU ratio (p = .46). CONCLUSIONS: This study shows that DD/PLT ratio helps to discriminate preeclampsia from normal pregnancy and gestational hypertension. Large-scale studies are needed to verify its clinical usefulness, and to suggest more appropriate cutoff values for a widespread use.

Optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies: A single-center retrospective cohort study.

Objective: To explore the optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies. Methods: A retrospective cohort study in a university hospital which included twins delivered from February 2013 to September 2020. Restrictive cubic spline (RCS) model was applied to the trend of intertwin birthweight difference (BWD) with the risk of preeclampsia. Logistic regression and subgroup analysis were performed to find the cut-off with statistical significance and clinical meaningfulness. Results: A total of 2,631 women pregnant with twins were enrolled. RCS showed a nonlinear upward trend of preeclampsia with BWD, and the BWD of 15% was the initial rising point. With the confounders adjusted, only the group with BWD ≥ 25% was found to be significantly associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 2.44; 95% confidence interval [CI]: 1.74-3.42). Additionally, subgroup analysis showed that both monochorionic (MC) and small for gestational age (SGA) twins were more likely to complicate with preeclampsia. Conclusion: The growth discordance of 15% during pregnancy may be the preventive point of preeclampsia, and 25% may be the interventional point.

Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.

Blood pressure development plays a major role in both the etiology and prediction of gestational hypertensive disorders. Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography­mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values < 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value < 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.

Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders.

Background Offspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life. Methods and Results In a population-based cohort among 4777 mother-offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02-0.31] and 0.23 [95% CI, 0.08-0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (P values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (P values <0.05), with a comparable strength as maternal-offspring associations. Conclusions Gestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal-offspring and paternal-offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect.

Associations of DASH Diet in Pregnancy With Blood Pressure Patterns, Placental Hemodynamics, and Gestational Hypertensive Disorders.

Background The Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders. Methods and Results We examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population-based cohort study among 3414 Dutch women. We assessed DASH score using food-frequency questionnaires. We measured blood pressure in early-, mid-, and late pregnancy (medians, 95% range: 12.9 [9.8-17.9], 20.4 [16.6-23.2], 30.2 [28.6-32.6] weeks gestation, respectively), and placental hemodynamics in mid- and late pregnancy (medians, 95% range: 20.5 [18.7-23.1], 30.4 [28.5-32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile (P<0.05). No associations were present for early- and late pregnancy diastolic blood pressure and systolic blood pressure throughout pregnancy. Compared with the highest DASH score quartile, the lower DASH score quartiles were associated with a higher mid- and late pregnancy umbilical artery pulsatility index (P≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present. Conclusions A higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid- and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low-risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher-risk populations.

Associations of Maternal Early-Pregnancy Glucose Concentrations With Placental Hemodynamics, Blood Pressure, and Gestational Hypertensive Disorders.

BACKGROUND: Gestational diabetes mellitus is associated with increased risks of gestational hypertension and preeclampsia. We hypothesized that high maternal glucose concentrations in early pregnancy are associated with adverse placental adaptations and subsequently altered uteroplacental hemodynamics during pregnancy, predisposing to an increased risk of gestational hypertensive disorders. METHODS: In a population-based prospective cohort study from early pregnancy onwards, among 6,078 pregnant women, maternal early-pregnancy non-fasting glucose concentrations were measured. Mid and late pregnancy uterine and umbilical artery resistance indices were assessed by Doppler ultrasound. Maternal blood pressure was measured in early, mid, and late pregnancy and the occurrence of gestational hypertensive disorders was assessed using hospital registries. RESULTS: Maternal early-pregnancy glucose concentrations were not associated with mid or late pregnancy placental hemodynamic markers. A 1 mmol/l increase in maternal early-pregnancy glucose concentrations was associated with 0.71 mm Hg (95% confidence interval 0.22-1.22) and 0.48 mm Hg (95% confidence interval 0.10-0.86) higher systolic and diastolic blood pressure in early pregnancy, respectively, but not with blood pressure in later pregnancy. Also, maternal glucose concentrations were not associated with the risks of gestational hypertension or preeclampsia. CONCLUSIONS: Maternal early-pregnancy non-fasting glucose concentrations within the normal range are associated with blood pressure in early pregnancy, but do not seem to affect placental hemodynamics and the risks of gestational hypertensive disorders.

Sex differences in sympathetic activity in obesity and its related hypertension.

The prevalence of obesity is rapidly increasing in the United States, particularly among women. Approximately 60-70% of hypertension in adults may be directly attributed to obesity. In addition, maternal obesity is a major risk factor for hypertensive disorders during pregnancy. The underlying mechanisms for the association between obesity and cardiovascular risk are multifactorial, but activation of the sympathetic nervous system is one significant contributing factor. This brief review summarizes the current knowledge on sex differences in sympathetic activity in obesity and its related hypertension, with a focus on studies in humans. Evidence suggests that abdominal visceral fat, rather than subcutaneous fat, is related to augmented sympathetic activity regardless of sex. Race/ethnicity may affect the relationship between obesity and sympathetic activity. Obesity-related hypertension has an important neurogenic component, which is characterized by sympathetic overactivity. However, sex may influence the association between hypertension and sympathetic overactivity in obese people. Finally, both body weight and sympathetic overactivity seem to be involved in the development of gestational hypertensive disorders in women. Chronic hyperinsulinemia due to insulin resistance, high plasma levels of leptin, and/or obstructive sleep apnea may be responsible for sympathetic overactivity in obesity-related hypertension.

The impact of a remote monitoring program on the prenatal follow-up of women with gestational hypertensive disorders.

OBJECTIVES: In 2015, we showed the value of a remote monitoring (RM) follow-up program for women diagnosed with gestational hypertensive disorders (GHDs) compared with women who received conventional care (CC). We want to confirm or refute the conclusions drawn in 2015, by including data from 2016. STUDY DESIGN: A two year retrospective study in which all women diagnosed with GHD, who underwent prenatal follow-up at the outpatients prenatal clinic of Ziekenhuis Oost-Limburg (Genk, Belgium) during 2015 and 2016, were included. Of the 320 women diagnosed with GHD, ninety (28.13%) were monitored with RM. The other 230 (71.88%) GHD pregnancies were monitored with CC. Differences in continuous and categorical variables in maternal demographics and characteristics were tested using Unpaired Student's two sampled t-test or Mann Whitney U test and the c2 test. Both a univariate and multivariate analysis were performed for analyzing prenatal follow up and gestational outcomes. All statistical analyses are done at nominal level a = 0.05. RESULTS: The RM group had more women diagnosed with gestational hypertension but less with pre-eclampsia when compared to the CC group (69.77% versus 42.79% and 19.77% versus 44.19% respectively). In both uni- and multivariate analyses, the RM group had, when compared to the CC group, less prenatal admission (51.62% versus 71.63%), less prenatal admissions until the moment of the delivery (31.40% versus 57.67%), less induced starts of the birth process (43.00% versus 32.09%), more spontaneous starts of the birth process (32.86% versus 46.51%), more births after 37 weeks of gestational age in pregnancies complicated with gestational hypertension (91.67% versus 53.33%) and pregnancies complicated with pre-eclampsia (58.82% versus 53.33%). In multivariate analysis, a reduction in total number of prenatal visits was visible in the RM group when compared to the CC group (b = -1.76; CI = -2.74-0.77). Only in the univariate analysis was the mean gestational age at delivery between 34 and 37 weeks of gestation in pregnancies complicated with gestational hypertension higher in the CC group versus the RM group (35 w 4/7 (±0.49) versus 34 w 6/7 (±0.00).These conclusions were almost the same as in the analyses of 2015, except (1) there wasn't a difference anymore in NICU admissions between the RM and CC group in the analyses of 2015-2016 and (2) a significant decrease in total number of visits is reported in the RM group in the dataset of 2015-2016, which wasn't visible in the dataset of 2015. CONCLUSIONS: This study demonstrates that RM provides opportunities to offer timely interventions to pregnant women who require them.

Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort.

OBJECTIVE: Pregnancy and the obesity epidemic impacting women of reproductive age appear to predispose women to obstructive sleep apnea (OSA) in pregnancy. The aim of this study is to examine the association between OSA and adverse maternal outcomes in a national cohort. METHODS: The National Perinatal Information Center in the US was used to identify women with a delivery discharge diagnosis of OSA from 2010 to 2014. We used the International Classification of Diseases, ninth Revision to classify OSA diagnosis and maternal outcomes. MEASUREMENTS: The sample consisted of 1,577,632 gravidas with a rate of OSA of 0.12% (N = 1963). There was a significant association between OSA and preeclampsia (adjusted odds ratio (aOR) 2.22, 95% confidence interval (CI) 1.94-2.54), eclampsia (aOR 2.95, 1.08-8.02), and gestational diabetes (aOR 1.51, 1.34-1.72) after adjusting for a comprehensive list of covariates which includes maternal obesity. OSA status was also associated with a 2.5-3.5-fold increase in risk of severe complications such as cardiomyopathy, congestive heart failure, and hysterectomy. Length of hospital stay was significantly longer (5.1 + 5.6 vs 3.0 + 3.0 days, p < 0.001) and odds of an admission to an intensive care unit higher (aOR 2.74, 2.36-3.18) in women with OSA. CONCLUSIONS: Compared to pregnant women without OSA, pregnant women with OSA have a significantly higher risk of pregnancy-specific complications such as gestational hypertensive conditions and gestational diabetes, and rare medical and surgical complications such as cardiomyopathy, pulmonary edema, congestive heart failure, and hysterectomy. OSA diagnosis was also associated with a longer hospital stay and significantly increased odds for admission to the intensive care unit.