Prior Preeclampsia Research Articles

Left Ventricular Hypertrophy in Women With a History of Preeclampsia.

As a hypertensive disorder of pregnancy, preeclampsia is associated with increased cardiovascular morbidity and mortality later in life. Since early signs of myocardial affection could indicate a higher risk of future cardiovascular disease manifestations, we investigated whether women with prior preeclampsia have a higher prevalence of left ventricular hypertrophy compared with women from the general population and to what extent chronic hypertension affects any potential difference. In a cohort study, women aged 40 to 55 years with prior preeclampsia were compared with age- and parity-matched women from the general population. They underwent a research cardiac computed tomography, and the primary outcome was left ventricular hypertrophy, defined as a left ventricular mass index >30 g/m2.7. In 679 women with prior preeclampsia and 672 controls (median age, 47 years), we found a higher prevalence of left ventricular hypertrophy (14.0% versus 6.4%) in the preeclampsia group with an odds ratio of 1.62, 95% CI (1.07-2.46), P=0.024, median of 15 years (range, 0-28) after pregnancy, after adjustment for cardiovascular risk factors, including chronic hypertension. Left ventricular hypertrophy was more frequent among women with preeclampsia with (26.2% versus 15.6%) and without (5.5% versus 2.4%) chronic hypertension, and a mediation analysis showed that chronic hypertension explained 22% of the association between preeclampsia and left ventricular hypertrophy. Women with prior preeclampsia had a 2-fold higher prevalence of left ventricular hypertrophy compared with women from the general population, and preeclampsia was independently associated with left ventricular hypertrophy, regardless of the presence of cardiovascular risk factors, including chronic hypertension. URL: https://www.clinicalTrials.gov; Unique identifier: NCT03949829.

Frequent Use of Premenopausal Progestin in Prior Pre-Eclamptic Women.

Women with a history of pre-eclamptic pregnancy are predisposed to later occlusive vascular diseases. We compared the use of cyclic progestins or levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of menstrual cycle abnormalities between premenopausal women with and without a prior pre-eclamptic pregnancy. Register-based cohort study during 1994-2019 of oral progestin or levonorgestrel-releasing intrauterine device (LNG-IUD) in Finnish women with (n=31 688) and without (n=91 726) prior pre-eclampsia in 1969-1993. Cyclic progestin or LNG-IUD use and its association with future use of menopausal hormone therapy (MHT). Prior pre-eclamptic women had used cyclic progestins more often (23.5% vs. 9.1%; p<0.001) and initiated the use at younger ages (41.8 years [SD=6.3] vs. 45.9 years [3.1]; p<0.001) than control women. Also, LNG-IUD was inserted more frequently (p<0.001) in prior pre-eclamptic women (9.3%) than in controls (4.7%). Cyclic progestin or LNG-IUD use was accompanied by significant 37-90% elevations in future MHT use. Increased use of cyclic progestins and LNG-IUD in premenopausal women with a history of pre-eclamptic pregnancy can be seen as indirect evidence of earlier onset of ovulatory dysfunction. This may contribute to the elevated risk of endometrial cancer in these women. Our findings may indicate one additional late sequela of pre-eclamptic pregnancy.

Prediction of pre-eclampsia with machine learning approaches: Leveraging important information from routinely collected data

BackgroundGlobally, pre-eclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality. PE prediction using routinely collected data has the advantage of being widely applicable, particularly in low-resource settings. Early intervention for high-risk women might reduce PE incidence and related complications. We aimed to replicate our machine learning (ML) published work predicting another maternal condition (gestational diabetes) to (1) predict PE using routine health data, (2) identify the optimal ML model, and (3) compare it with logistic regression approach. MethodsData were from a large health service network with 48,250 singleton pregnancies between January 2016 and June 2021. Supervised ML models were employed. Maternal clinical and medical characteristics were the feature variables (predictors), and a 70/30 data split was used for training and testing the model. Predictive performance was assessed using area under the curve (AUC) and calibration plots. Shapley value analysis assessed the contribution of feature variables. ResultsThe random forest approach provided excellent discrimination with an AUC of 0.84 (95% CI: 0.82–0.86) and highest prediction accuracy (0.79); however, the calibration curve (slope of 1.21, 95% CI 1.13–1.30) was acceptable only for a threshold of 0.3 or less. The next best approach was extreme gradient boosting, which provided an AUC of 0.77 (95% CI: 0.76–0.79) and well-calibrated (slope of 0.93, 95% CI 0.85–1.01). Logistic regression provided good discrimination performance with an AUC of 0.75 (95% CI: 0.74–0.76) and perfect calibration. Nulliparous, pre-pregnancy body mass index, previous pregnancy with prior PE, maternal age, family history of hypertension, and pre-existing hypertension and diabetes were the top-ranked features in Shapley value analysis. ConclusionTwo ML models created the highest-performing prediction using routinely collected data to identify women at high risk of PE, with acceptable discrimination. However, to confirm this result and also examine model generalisability, external validation studies are needed in other settings, utilising standardised prognostic factors.

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension, cardiac dysfunction or both. In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated. At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all P<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all P<0.05). LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.

Externally validated prediction models for pre-eclampsia: systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the performance of existing externally validated prediction models for pre-eclampsia (PE) (specifically, any-onset, early-onset, late-onset and pretermPE). A systematic search was conducted in five databases (MEDLINE, EMBASE, Emcare, CINAHL and Maternity & Infant Care Database) and using Google Scholar/reference search to identify studies based on the Population, Index prediction model, Comparator, Outcome, Timing and Setting (PICOTS) approach until 20 May 2023. We extracted data using the CHARMS checklist and appraised the risk of bias using the PROBAST tool. A meta-analysis of discrimination and calibration performance was conducted when appropriate. Twenty-three studies reported 52 externally validated prediction models for PE (one preterm, 20 any-onset, 17 early-onset and 14 late-onset PE models). No model had the same set of predictors. Fifteen any-onset PE models were validated externally once, two were validated twice and three were validated three times, while the Fetal Medicine Foundation (FMF) competing-risks model for preterm PE prediction was validated widely in 16 different settings. The most common predictors were maternal characteristics (prepregnancy body mass index, prior PE, family history of PE, chronic medical conditions and ethnicity) and biomarkers (uterine artery pulsatility index and pregnancy-associated plasma protein-A). The FMF model for preterm PE (triple test plus maternal factors) had the best performance, with a pooled area under the receiver-operating-characteristics curve (AUC) of 0.90 (95% prediction interval (PI), 0.76-0.96), and was well calibrated. The other models generally had poor-to-good discrimination performance (median AUC, 0.66 (range, 0.53-0.77)) and were overfitted on external validation. Apart from the FMF model, only two models that were validated multiple times for any-onset PE prediction, which were based on maternal characteristics only, produced reasonable pooled AUCs of 0.71 (95% PI, 0.66-0.76) and 0.73 (95% PI, 0.55-0.86). Existing externally validated prediction models for any-, early- and late-onset PE have limited discrimination and calibration performance, and include inconsistent input variables. The triple-test FMF model had outstanding discrimination performance in predicting preterm PE in numerous settings, but the inclusion of specialized biomarkers may limit feasibility and implementation outside of high-resource settings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prepregnancy physiology and subsequent preterm preeclampsia

BackgroundPreeclampsia is a common pregnancy complication with debated etiology. ObjectiveTo evaluate the contribution of prepregnancy physiology, biochemistry and anthropometrics to the subsequent development of preterm preeclampsia. Study DesignOne-hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 non-pregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. ResultsPregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215+1143 vs. 1918+1510 grams (p=0.002), faster supine pulse, 77+7 vs. 67+10 beats per minute (p=0.001), higher supine diastolic blood pressure 82+6 vs. 68+6 mmHg (p< 0.001), increased cardiac output 5.6+1.1 vs. 4.6+1 L/min (p=0.002), faster aortic-popliteal pulse wave velocity 4.5+0.7 vs. 3.8+0.5 m/sec (p<0.001), and exaggerated cardiac output response to volume challenge 20+9 vs. 9+12 L/min (p=0.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86+0.08 vs. 0.97+0.12 (p=0.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7+12.5 vs. 4.1+5.8mg/mL (p=0.003) and greater insulin resistance, as assessed by HOMA-IR calculation 2.2+1.1 vs. 1.2+0.9 (p<0.001). ConclusionPrepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm pre-eclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance and increased android fat, all consistent with subclinical features of the metabolic syndrome.

Expectant management of preeclampsia with severe features diagnosed at less than 24 weeks

BackgroundThe recent ACOG practice bulletin offers no guidance on management of preeclampsia with severe features (PreE with SF) less than 24 weeks. Historically, immediate delivery was recommended due to poor perinatal outcomes and high maternal morbidity. Recently, advances in neonatal resuscitation have led to increased survival at peri-viable gestational ages. Study designWe aimed to report perinatal and maternal outcomes after expectant management of PreE with SF at < 24 weeks. MethodsThis was a retrospective case series of PreE with SF at < 24 weeks at a Level IV center between 2017-2023. Individuals requiring delivery within 24 hours of diagnosis were excluded. Perinatal and maternal outcomes were analyzed. Categorical variables from our database were compared to previously published data using chi squared tests. ResultsThere were 41 individuals diagnosed with PreE with SF < 24 weeks. After excluding for delivery within 24 hours, 30 individuals (73%) were evaluated. Median gestational age at diagnosis was 22 weeks (IQR 22-23 weeks). 16% had assisted reproductive technology, 27% had chronic hypertension, 13% had pregestational diabetes, 30% had prior preeclampsia, and 73% had BMI >30 kg/m2. Median latency at 22 and 23 weeks was 7 (IQR 4-23) and 8 days (IQR 4-13 days). Neonatal survival was 44% (95% CI 3-85%) for PreE with SF onset at 22 weeks and 29% (95% CI 1-56%) at 23 weeks. There were two cases of acute kidney injury (7%) and two cases of pericardial/pleural effusions (7%). Overall perinatal survival < 24 weeks was 30% in our current study versus 7% in previous reports (p=0.02). ConclusionFor cases of expectant management of PreE with SF at < 24 weeks, our findings show an increased rate of perinatal survival with decreased maternal morbidity compared to previously published data. This information may be used when counseling on expectant management of PreE with SF < 24 weeks.

Impact of early preeclampsia prediction on medication adherence and behavior change: a survey of pregnant and recently-delivered individuals

BackgroundBehavior change and medication adherence represent potential barriers to optimal prevention of pregnancy complications including preeclampsia. We sought to evaluate baseline sentiments on pregnancy care and medication amenability, and how these measures would be impacted by early predictive testing for preeclampsia.MethodsWe developed a digital survey to query participants’ baseline sentiments on pregnancy care, knowledge about pregnancy complications, and views on a hypothetical test to predict preeclampsia. The survey was administered online to pregnant and recently-delivered individuals in the United States. Survey data were analyzed using pooled two-sample proportion z-tests with adjustment for multiple comparisons.ResultsOne thousand and twenty-two people completed the survey. 84% reported they were satisfied with their pregnancy care. Self-assessed knowledge about preeclampsia was high, with 75% of respondents reporting they have a “good understanding” of preeclampsia, but measured knowledge was low, with only 10% able to identify five common signs/symptoms of preeclampsia. Notably, 40% of participants with prior preeclampsia believed they were at average or below-average risk for recurrence. 91% of participants desired early pregnancy predictive testing for preeclampsia. If found to be at high risk for preeclampsia, 88% reported they would be more motivated to follow their provider’s medication recommendations and 94% reported they would desire home blood pressure monitoring. Increased motivation to follow clinicians’ medication and monitoring recommendations was observed across the full spectrum of medication amenability. Individuals who are more medication-hesitant still reported high rates of motivation to change behavior and adhere to medication recommendations if predictive testing showed a high risk of preeclampsia. Importantly, a high proportion of medication-hesitant individuals reported that if a predictive test demonstrated they were at high risk of preeclampsia, they would feel more motivated to take medications (83.0%) and aspirin (75.9%) if recommended.ConclusionWhile satisfaction with care is high, participants desire more information about their pregnancy health, would value predictive testing for preeclampsia, and report they would act on this information. Improved detection of at-risk individuals through objective testing combined with increased adherence to their recommended care plan may be an important step to remedy the growing gap in prevention.

Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice-Brief Report.

Women with a history of preeclampsia have evidence of premature atherosclerosis and increased risk of myocardial infarction and stroke compared with women who had a normotensive pregnancy. Whether this is due to common risk factors or a direct impact of prior preeclampsia exposure has never been tested in a mouse atherosclerosis model. Pregnant LDLR-KO (low-density lipoprotein receptor knockout; n=35) female mice were randomized in midgestation to sFlt1 (soluble fms-like tyrosine kinase 1)-expressing adenovirus or identical control adenovirus. Postpartum, mice were fed high-fat diet for 8 weeks to induce atherogenesis. Comparison between the control and preeclampsia models was made for metabolic parameters, atherosclerosis burden and composition by histology, plaque inflammation by flow cytometry, and aortic cytokines and inflammatory markers using a cytokine array. In pregnant LDLR-KO mice, sFlt1 adenovirus significantly induced serum sFlt1, blood pressure, renal endotheliosis, and decreased pup viability. After 8 weeks of postpartum high fat feeding, body weight, fasting glucose, plasma cholesterol, HDL (high-density lipoprotein), and LDL (low-density lipoprotein) were not significantly different between groups with no change in aortic root plaque size, lipid content, or necrotic core area. Flow cytometry demonstrated significantly increased CD45+ aortic arch leukocytes and CD3+T cells and aortic lysate contained more CCL (CC motif chemokine ligand) 22 and fetuin A and decreased expression of IGFBP6 (insulin-like growth factor-binding protein 6) and CCL21 in preeclampsia-exposed mice compared with controls. In atherogenic LDLR-KO mice, exposure to sFlt1-induced preeclampsia during pregnancy increases future atherosclerotic plaque inflammation, supporting the concept that preeclampsia directly exacerbates atherosclerotic inflammation independent of preexisting risk factors. This mechanism may contribute to ischemic vascular disease in women after preeclampsia pregnancy.

Association Between Recurrent Preeclampsia and Attendance at the Blood Pressure Monitoring Appointment After Birth

ObjectiveTo examine the association between recurrent preeclampsia and attendance at the standard of care blood pressure monitoring appointment after birth. DesignRetrospective cohort. SettingSingle Magnet-accredited hospital affiliated with an academic medical center. ParticipantsMultiparous women who gave birth between 2010 and 2020 and were diagnosed with preeclampsia (N = 313). MethodsWe divided participants into two groups: those with prior preeclampsia (n = 119) and those without prior preeclampsia (n = 194). Using logistic regression, we calculated unadjusted and adjusted odds ratios to estimate the association between attendance at the postpartum blood pressure (PPBP) monitoring appointment and prior preeclampsia. We also explored the relationship between attendance at the PPBP monitoring appointment and use of magnesium sulfate during labor and birth and the relationship between attendance at the PPBP monitoring appointment and use of maintenance antihypertensive medications. ResultsIn adjusted analysis, participants with prior preeclampsia were 66.4% less likely to attend the PPBP monitoring appointment compared with those without prior preeclampsia, adjusted OR = 0.34, 95% CI [0.18, 0.62]. Administration of magnesium sulfate during delivery admission and use of maintenance antihypertensive medications were not associated with a change in attendance at the PPBP appointment. ConclusionFurther research on patient-perceived risk of recurrent preeclampsia and improvement of systems to facilitate postpartum follow-up is needed.

Assessing awareness of long-term health risks among women with a history of preeclampsia: a cross-sectional study.

Pregnancy complications, such as hypertensive disorders, present a substantial global public health challenge, with significant long-term implications for maternal and offspring health. This cross-sectional study aims to determine the level of awareness regarding long-term health risks among women who experienced preeclampsia during pregnancy in Cyprus and Greece. The study participants included adult women with a history of preeclampsia, while women with normal pregnancies were used as the comparison group. Data collection took place between June 2021 and February 2022, utilizing an online, self-administered questionnaire. The study included 355 women, with 139 (39.2%) in the preeclampsia group and 216 (60.8%) in the comparison group. Findings revealed that more than half of the women with prior preeclampsia (55.4%) were not aware of hypertensive disorders that can occur during pregnancy before their diagnosis, and a similar percentage (45.2%) had not received information about the long-term health risks following their diagnosis. Remarkably, only 3 participants (4.7%) with a history of preeclampsia were aware of the risk of developing cardiovascular diseases. There were no statistically significant differences between the preeclampsia and the comparison group regarding their concerns about long-term health risks, frequency of health checks, perceptions of factors influencing cardiovascular disease development, and doctor communication about different health topics, except from hypertension or high blood pressure. The study underscores the low level of awareness of long-term health risks among women with prior preeclampsia in Cyprus and Greece. This emphasizes the importance of implementing public health programs aimed at promoting cardiovascular risk assessment and effective management, both for clinicians and women with have experienced preeclampsia.

Abstract 023: Prior Sflt1 Induced Preeclampsia Exacerbates Post-partum Hypertension-mediated Aortic Stiffness And Hypercholesterolemia-induced Atherosclerotic Inflammation

Preeclampsia (PE) is new high blood pressure (BP) and organ damage occurring late in pregnancy in association with increased soluble VEGF receptor (sFlt1). PE survivors have increased risk of future hypertension and myocardial infarction/stroke. We hypothesized that exposure to high sFlt1 during pregnancy exacerbates hypertension and atherosclerosis post-partum. PE was induced by transient adenoviral expression of sFlt1 compared to control virus in pregnant mice. PE mice had elevated sFlt1, BP and kidney damage during pregnancy which resolve post partum. Two months post-partum, prior PE mice had significantly increased BP response to high salt diet. After high BP stimuli, we studied large and small artery function. Prior PE mice had diminished nitric oxide-mediated vasodilation and stiffer aortas with more fibrosis as measured by pulse wave velocity (Con:3.7 vs sFlt:5.9 mm/ms, p&lt;0.0001) and trichrome staining (Con:13.7% vs sFlt:33.9%, p=0.0009). Atherosclerosis studies exposed LDLR knockout mice to PE followed by high fat diet feeding for 8 weeks. Body weight, fasting glucose and cholesterol were not altered by prior PE. Aortic roots were histologically analyzed for plaque size and composition. Aortic root plaque size (Con:73.3 vs sFlt:78.0 AU, p=0.60) and necrotic core were not different between groups. Aortic arch plaque inflammation was quantified via flow cytometry showing significantly increased plaque CD45+ leukocytes (sFlt:1.6 fold, p=0.036) and T cells (sFlt:1.8 fold, p=0.031) from mice with prior PE. Atheroprone mice with prior PE had significantly increased aortic expression of CCL22 (sFlt:1.5 fold, p=0.047), providing a potential mechanism for increased T cell infiltration into atherosclerotic plaques. Experimental PE produces a state of enhanced sensitivity to hypertensive stimuli and increased vascular inflammation in atherosclerotic plaques supporting the concept that PE directly exacerbates hypertension, vascular stiffness, and atherosclerotic inflammation independent of pre-existing risk factors.

The severity of the recurrent preeclampsia compared with prior preeclampsia: A multicenter retrospective longitudinal cohort study

The severity of the recurrent preeclampsia compared with prior preeclampsia: A multicenter retrospective longitudinal cohort study

Early Pregnancy Systolic Blood Pressure Patterns Predict Early- and Later-Onset Preeclampsia and Gestational Hypertension Among Ostensibly Low-to-Moderate Risk Groups.

Background Clinical risk factors, a single blood pressure (BP) measurement, current biomarkers, and biophysical parameters can effectively identify risk of early-onset preeclampsia but have limited ability to predict later-onset preeclampsia and gestational hypertension. Clinical BP patterns hold promise to improve early risk stratification for hypertensive disorders of pregnancy. Methods and Results After excluding preexisting hypertension, heart, kidney, or liver disease, or prior preeclampsia, the retrospective cohort (n=249 892) all had systolic BP <140 mm Hg and diastolic BP <90 mm Hg or a single BP elevation ≤20 weeks' gestation, prenatal care at <14 weeks' gestation, and a still or live birth delivery at Kaiser Permanente Northern California hospitals (2009-2019). The sample was randomly split into development (N=174 925; 70%) and validation (n=74 967; 30%) data sets. Predictive performance of multinomial logistic regression models for early-onset (<34 weeks) preeclampsia, later-onset (≥34 weeks) preeclampsia, and gestational hypertension was evaluated in the validation data set. There were 1008 (0.4%), 10 766 (4.3%), and 11 514 (4.6%) patients with early-onset preeclampsia, later-onset preeclampsia, and gestation hypertension, respectively. Models with 6 systolic BP trajectory groups (0-20 weeks' gestation) plus standard clinical risk factors performed substantially better than risk factors alone to predict early- and later-onset preeclampsia and gestational hypertension, with C-statistics (95% CIs) of 0.747 (0.720-0.775), 0.730 (0.722-0.739), and 0.768 (0.761-0.776) versus 0.688 (0.659-0.717), 0.695 (0.686-0.704) and 0.692 (0.683-0.701), respectively, with excellent calibration (Hosmer-Lemeshow P=0.99, 0.99, and 0.74, respectively). Conclusions Early pregnancy BP patterns up to 20 weeks' gestation plus clinical, social, and behavioral factors more accurately discriminate hypertensive disorders of pregnancy risk among low-to-moderate risk pregnancies. Early pregnancy BP trajectories improve risk stratification to reveal higher-risk individuals hidden within ostensibly low-to-moderate risk groups and lower-risk individuals considered at higher risk by US Preventive Services Task Force criteria.

The Effects of Vitamin D Supplement on Prevention of Preeclampsia in Pregnant Women

Objective: To evaluate the role of vitamin D supplementation in preventing preeclampsia in pregnant women. Study Design: Randomized controlled trial. Place and Duration: The study was conducted in the Gynecology Department of Nishtar Hospital, Multan, from 1st January 2022 to 31 December 2022. Methodology: A total of 250 (N) pregnant patients with a history of prior pre-eclampsia were enrolled after taking informed consent. Patients in the control group were given a placebo, and in the intervention group, a vitamin-D supplement of 50000 IU after every two weeks was given. Primary variables of the study were systolic and diastolic blood pressure, proteinuria in 24 hours urine, termination of pregnancy results like cesarean section, spontaneous vaginal delivery or abortion, and development of preeclampsia. Results: In the intervention group, 62.4% of females had expected vaginal delivery, 33.6% had a cesarean section, and 4.0% had an abortion. Whereas 49.6% of females had a normal vaginal delivery, 45.6% had a cesarean section, and 4.8% had an abortion in the control group, which was statistically insignificant. The patients in the intervention group have significantly lower 23 (18.4%) presentation of preeclampsia than patients in the control group 31 (24.8%) (p&lt;0.001), which is statistically significant. Conclusion: Vitamin D supplementation during pregnancy helps prevent preeclampsia and gestational hypertension recurrence. Keywords: Vitamin D, Preeclampsia, Gestational Hypertension, Proteinuria, Pregnant Women. How to Cite This: Ashraf S, Khosa AF, Fatima K, Ibrahim M. The Effects of Vitamin D Supplement on Prevention of Preeclampsia in Pregnant Women. Isra Med J. 2023; 15(1): 11-14. DOI: https://doi.org/10.55282/imj.oa1370 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy

A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood. To disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy. This GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023. The association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes. A total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP). The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.

The Association of Race and Ethnicity With Adverse Outcomes in Women Treated for Mild Chronic Hypertension During Pregnancy [ID: 1381420

INTRODUCTION: The effect of race and ethnicity on outcomes in the treatment of mild chronic hypertension (cHTN) in pregnancy is unknown. METHODS: This was a secondary analysis of a multicenter randomized trial of pregnant patients with mild cHTN comparing antihypertensive therapy to goal blood pressure less than 140/90 mm Hg (Active) versus usual care. Log-binomial regression assessed differences in outcomes between racial and ethnic groups among Active participants. Outcomes included a composite (preeclampsia with severe features, medically indicated preterm birth [PTB]&lt;35 weeks, abruption, fetal/neonatal death), components of the composite, intensive care unit admission, HTN with end-organ dysfunction, low birth weight (LBW), PTB less than 37 weeks, neonatal intensive care unit admission, and small for gestational age (SGA). RESULTS: Baseline maternal characteristics of patients randomized to active treatment in the parent trial differed by race and ethnicity for age, married status, insurance, nulliparous, body mass index, tobacco use, aspirin, and prior preeclampsia. Models demonstrated increased risk of the primary composite (adjusted relative risk [aRR] 1.35 [1.05, 1.73]) among Black compared to White patients. Preeclampsia was not increased among Black (aRR 1.14 [0.87, 1.50]) or Hispanic patients (aRR 1.13 [0.82, 1.56]). Preterm birth was increased among Black (aRR 1.31 [1.02, 1.68]) and Hispanic patients (aRR 1.33 [1.00, 1.77]), and there was increased risk of LBW infants born to Black patients (aRR 1.54 [1.11, 2.14]), but not Hispanic (aRR 1.04 [0.69, 1.57]) compared to White. There was no difference in SGA between groups. CONCLUSION: Among women with mild cHTN treated to goal less than 140/90 mm Hg, baseline characteristics differed significantly, and Black and Hispanic women were at increased risk compared to White women for selected outcomes. Interventions to address disparities should further evaluate social determinants of health in addition to medical management.

Aspirin for the Prevention of Early and Severe Pre-Eclampsia Recurrence: A Real-World Population-Based Study.

Many clinical trials have reported that low-dose aspirin decreases the risk of pre-eclampsia in women with prior pre-eclampsia. However, its impact in a real-world population has not been fully assessed. To assess the rates of low-dose aspirin initiation during pregnancy in women with a history of pre-eclampsia, and to evaluate the impact of low-dose aspirin in prevention of pre-eclampsia recurrence in a real-world population. CONCEPTION is a French nationwide cohort study which uses data from the country's National Health Data System database. We included all women in France who gave birth at least twice between 2010-2018, and who had pre-eclampsia during their first pregnancy. Every dispensing of low-dose aspirin (75-300 mg) between the beginning of their second pregnancy and 36 weeks of gestation (WG) was identified. We used Poisson regression models to estimate the adjusted incidence rate ratios (aIRRs) of receiving aspirin at least once during their second pregnancy. In women who had early and/or severe pre-eclampsia during their first pregnancy, we estimated the IRRs of pre-eclampsia recurrence during their second pregnancy according to the aspirin therapy. In 28,467 women who were included in the study, the aspirin initiation rate during the second pregnancy ranged from 27.8% for women in whose first pregnancy the pre-eclampsia was mild and late, to 79.9% for those women whose pre-eclampsia was severe and early. Just over half (54.3%) of those treated with aspirin-initiated treatment before 16 WG and adhered to treatment. Compared with women with mild and late pre-eclampsia, the aIRRs (95% CI) for receiving aspirin at least once during the second pregnancy were 1.94 (1.86-2.03) for women with severe and late pre-eclampsia, 2.34 (2.17-2.52) for those with early and mild pre-eclampsia, and 2.87 [2.74-3.01] for those with early and severe pre-eclampsia E. Social deprivation was associated with a lower initiation of aspirin (IRR = 0.74 [0.70-0.78]). Aspirin was not associated with a lower risk of mild and late pre-eclampsia, severe and late pre-eclampsia, or mild and early pre-eclampsia during the second pregnancy. The aIRRs for severe and early pre-eclampsia during the second pregnancy were 0.77 (0.62-0.95) for women who received prescribed aspirin at least once, 0.71 (0.5-0.89) for those who initiated aspirin therapy before 16 WG, and 0.60 (0.47-0.77) for those who adhered to aspirin treatment throughout their second pregnancy. The risk of severe and early pre-eclampsia was lower only when the prescribed mean daily dose was ≥ 100 mg/day. In women with a history of pre-eclampsia, aspirin initiation during a second pregnancy and adherence to the prescribed dosage were largely insufficient, especially for women experiencing social deprivation. Aspirin initiated before 16 WG at a dose ≥ 100 mg/day was associated with a lower risk of severe and early pre-eclampsia.

Smooth Muscle Mineralocorticoid Receptor Promotes Hypertension After Preeclampsia.

Preeclampsia is a syndrome of high blood pressure (BP) with end organ damage in late pregnancy that is associated with high circulating soluble VEGF receptor (sFlt1 [soluble Fms-like tyrosine kinase 1]). Women exposed to preeclampsia have a substantially increased risk of hypertension after pregnancy, but the mechanism remains unknown, leaving a missed interventional opportunity. After preeclampsia, women have enhanced sensitivity to hypertensive stress. Since smooth muscle cell mineralocorticoid receptors (SMC-MR) are activated by hypertensive stimuli, we hypothesized that high sFlt1 exposure in pregnancy induces a postpartum state of enhanced SMC-MR responsiveness. Postpartum BP response to high salt intake was studied in women with prior preeclampsia. MR transcriptional activity was assessed in vitro in sFlt1-treated SMC by reporter assays and PCR. Preeclampsia was modeled by transient sFlt1 expression in pregnant mice. Two months post-partum, mice were exposed to high salt and then to AngII (angiotensin II) and BP and vasoconstriction were measured. Women exposed to preeclampsia had significantly enhanced salt sensitivity of BP verses those with a normotensive pregnancy. sFlt1 overexpression during pregnancy in mice induced elevated BP and glomerular endotheliosis, which resolved post-partum. The sFlt1 exposed post-partum mice had significantly increased BP response to 4% salt diet and to AngII infusion. In vitro, SMC-MR transcriptional activity in response to aldosterone or AngII was significantly increased after transient exposure to sFlt1 as was aldosterone-induced expression of AngII type 1 receptor. Post-partum, SMC-MR-KO mice were protected from the enhanced response to hypertensive stimuli after preeclampsia. Mechanistically, preeclampsia mice exposed to postpartum hypertensive stimuli develop enhanced aortic stiffness, microvascular myogenic tone, AngII constriction, and AngII type 1 receptor expression, all of which were prevented in SMC-MR-KO littermates. These data support that sFlt1-induced vascular injury during preeclampsia produces a persistent state of enhanced sensitivity of SMC-MR to activation. This contributes to postpartum hypertension in response to common stresses and supports testing of MR antagonism to mitigate the increased cardiovascular risk in women after PE.

JS-HR-4: PREECLAMPSIA UP TO DATE; WHAT WE SHOULD KNOW FOR MOTHER AND CHILD.

Preeclampsia (PE) is a systemic hypertensive disorder of pregnancy thought to arise from placental maladaptation and subsequent systemic inflammatory processes. PE is associated with significant maternal and fetal mortality with hypertensive disorder of pregnancy accounting for -14% of maternal deaths globally and also with increased maternal risks for chronic diseases in later life. In 2017, the American College of Cardiology/American Heart Association hypertension treatment guidelines identified hypertension as blood pressure (BP) 130/80 mmHg. The reference BP for hypertension during pregnancy as specified in international guidelines is still &gt; 140/90 mmHg. Also, recommended target BP level differs between these guidelines. A large number of studies have been examining the incidence of PE and fetal outcomes according to BP levels to figure out the optimal level for pregnant women. Given only termination of pregnancy has been proved to initiate the resolution of PE once it has developed, prevention of PE is a health care priority. However, the predictive value of BP and other clinical characteristics for PE is relatively low, and therefore, improved method for the prediction of PE and associated adverse outcomes is required. Past history of PE is now widely known to link with major chronic diseases such as hypertension, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease in later life. Since many cardiovascular risk factors are modifiable and related to lifestyle, all women with prior PE should be followed-up by physician even after resolution of PE (eg. hypertension, proteinuria). However, no long-term follow-up strategy for former-PE patient has yet been established. The 2019 Maternal Mortality update from the WHO report indicated the major contribution of PE and eclampsia to worldwide maternal deaths. Further investigation is needed to decrease PE related maternal and fetal deaths and also to reduce maternal risks for chronic diseases in later life. Participation of physicians is necessary to offer appropriate medical care to women with prior PE.