Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.

PPARγ alleviates preeclampsia development by regulating lipid metabolism and ferroptosis.

The study aims to explore the effect of PPARγ signaling on ferroptosis and preeclampsia (PE) development. Serum and placental tissue are collected from healthy subjects and PE patients. The PPARγ and Nrf2 decreases in the PE. Rosiglitazone intervention reverses hypoxia-induced trophoblast ferroptosis and decreases lipid synthesis by regulating Nfr2 and SREBP1. Compared to the Hypoxia group, the migratory and invasive abilities enhance after rosiglitazone and ferr1 treatment. Rosiglitazone reduces the effect of hypoxia and erastin. The si-Nrf2 treatment attenuats the effects of rosiglitazone on proliferation, migration, and invasion. The si-Nrf2 does not affect SREBP1 expression. PPARγ agonists alleviates ferroptosis in the placenta of the PE rats. The study confirms that PPARγ signaling and ferroptosis-related indicators were dysregulated in PE. PPARγ/Nrf2 signaling affects ferroptosis by regulating lipid oxidation rather than SREBP1-mediated lipid synthesis. In conclusion, our study find that PPARγ can alleviate PE development by regulating lipid oxidation and ferroptosis.

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

BACKGROUND: Behavior 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. METHODS: We 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. RESULTS: One 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. CONCLUSION: While 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.

Hypertensive states of pregnancy.

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.

Protective Effects of Aspirin Supplemented With Quercetin in L-NAME-Induced Preeclampsia-Like Rats.

Aspirin supplemented with quercetin was reported to enhance the therapeutic effects of aspirin in a rat model of preeclampsia. In this study, the underlying mechanisms were further explored. Preeclampsia was induced by L-NAME (50 mg/kg/day) via oral gavage from gestation day (GD)14 to GD19. Aspirin (1.5 mg/kg/day) administration was performed using aspirin mixed with rodent dough from GD0 to GD19. The administration of quercetin (2 mg/kg/day) was performed by intraperitoneal infusion from GD0 to GD19. Protein levels were evaluated using ELISA or Western blot, and microRNA (miRNA) level was evaluated by RT-PCR. Aspirin supplemented with quercetin ameliorated the increase of systolic blood pressure (SBP), proteinuria, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and improved the pregnancy outcomes in preeclampsia rats. Aspirin supplemented with quercetin inhibited miR-155 expression in preeclampsia rats. The decreased miR-155 level in placenta further increased the protein level of SOCS1 and inhibited the phosphorylation of p65. In this study, we demonstrated that aspirin supplemented with quercetin enhanced the effects of aspirin for the treatment of preeclampsia.

Assessing pre-eclampsia awareness among pregnant women in Syria: a cross-sectional study on knowledge and perceptions.

BACKGROUND: Pre-eclampsia (PE) is a major contributor to morbidity and mortality in mothers worldwide. Adequate understanding of this condition improves treatment, control, and prevention. This study evaluated preeclampsia awareness among pregnant women in Syria, and the characteristics related to awareness adequacy. METHODS: This national cross-sectional study was conducted in Syria between 25 October and November 19, 2022. We included pregnant females of all age groups from all Syrian governorates. The questionnaire consisted of sociodemographic characteristics and knowledge of pre-eclampsia and its associated factors, symptoms, and complications. RESULTS: Overall, 706 participants were involved in this research, with a mean age of 38.22. Only 52.1% of them reported that they had heard of preeclampsia. Among the participants, 56.5% stated that they would not terminate a pregnancy if they were determined to be likely to develop preeclampsia, while nearly 55.2% agreed to continue the pregnancy rather than deliver prematurely even if their where a potential risk on their health risks. Participants who reported a family history of PE or had already experienced PE were more likely to have appropriate preeclampsia knowledge than those who did not (OR = 2.27, OR = 3.18, respectively). Respondents aged 25 to 35 years had the highest knowledge scores, and participants living in cities scored higher knowledge than rural residents. CONCLUSION: According to our findings, pregnant women in Syria have a awareness gaps regarding the PE topic. This highlights the need to enhance women's preeclampsia understanding for better pregnancy outcomes. Education through organizations, the media, and national programs is a significant aspect that promotes an adequate understanding of preeclampsia.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

BACKGROUND: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin. METHODS: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage and the effects of chemerin in chorionic plate arteries. RESULTS: Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and the fetal/maternal concentration ratio of pravastatin was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate arteries. In explants, statins upregulated low-density lipoprotein receptor expression, which relies on the same transcription factor as chemerin, and NO release. CONCLUSIONS: Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO and low-density lipoprotein receptor-dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offers an attractive mechanism by which statins may prevent or treat preeclampsia.

Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort.

BACKGROUND: Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women. METHODS AND RESULTS: The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff-administered 24-hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest-to-lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44-11.0]; Ptrend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; Ptrend=0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10-0.99]; Ptrend=0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both Pinteractions=0.017). Healthy Eating Index 2015 findings were generally nonsignificant. CONCLUSIONS: While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low-income Hispanic/Latina women.

Integrating evidence and causal mapping of factors that influence medication decision-making by pregnant women at risk of hypertensive disorder: protocol for a scoping review.

INTRODUCTION: In 2018, the American College of Obstetricians and Gynecologists recommended low-dose aspirin to prevent the onset of pre-eclampsia among women who were at high risk. Factors influencing women's acceptance of this recommendation span multiple sectors and levels. Understanding how these factors interact will help stakeholders design effective population-level intervention strategies. Our study aims to identify and map relationships among factors influencing the medication decisions of pregnant women at risk of hypertensive disorders. METHODS AND ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines will be followed for this review. A research librarian developed a comprehensive search strategy to retrieve published and unpublished English studies after 1 January 1980, involving factors that influence pregnant women's uptake and adherence to medication for gestational hypertensive disorders. This literature includes perceptions, patterns, acceptance, refusal, tendencies, probability and service utilisation. We will search PubMed, Embase, Web of Science and CINAHL. Reference lists of the selected papers will be searched manually to identify more relevant studies. A two-stage independent screening, consisting of title and abstract screening, followed by full-text screening, will be conducted by two independent reviewers to identify eligible articles. Extracted data will be recorded in a customised variable extraction form and input into a Microsoft Access database. The PRISMA-ScR will be used to guide the presentation of the results, which will be presented in a table and causal map to demonstrate the relationships between extracted variables and medication uptake and adherence. A conceptual simulation model will be formulated to validate the logic of the relationships between variables and identify knowledge gaps. Lastly, experts and stakeholders will be invited to critique and comment on the results. ETHICS AND DISSEMINATION: This study does not require ethical approval. The full review results will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication.

AT1-AA Is Produced in Offspring in Response to Placental Ischemia and Is Lowered by B-Cell Depletion Without Compromising Overall Offspring Health.

BACKGROUND: Preeclampsia, new-onset hypertension during pregnancy alongside other organ dysfunction, is the leading cause of mortality for the mother and low birth weight for the baby. Low birth weight contributes to high risk of cardiovascular disorders later in life. Women with preeclampsia have activated B cells producing agonistic autoantibodies to AT1-AA (angiotensin II type I receptor). We hypothesize that rituximab, a B cell-depleting chemotherapeutic, will deplete maternal B cells in reduced uterine perfusion pressure (RUPP) rats without worsening the effect of placental ischemia on pup growth and survival. METHODS AND RESULTS: To test this hypothesis, the RUPP procedure was performed, and rituximab was continuously infused via miniosmotic pump. Maternal blood and tissues were collected. A separate group of dams were allowed to deliver, pup weights were recorded, and at 4 months of age, tissues were collected from offspring. Immune cells were measured via flow cytometry, and AT1-AA was quantified using a contraction bioassay. Blood pressure increased in RUPP rats and was normalized with rituximab treatment. RUPP offspring also had increased circulating B cells, cytolytic natural killer cells, and increased circulating AT1-AA, which were normalized with maternal rituximab treatment. This is the first study to analyze the AT1-AA in RUPP offspring, which was normalized with rituximab. CONCLUSIONS: Our findings indicate that perinatal rituximab lowers maternal mean arterial pressure in RUPP rats and improves birth weight, circulating AT1-AA, and circulating natural killer cells, indicating that rituximab improves adverse fetal outcomes in response to placental ischemia.

Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women: a randomised clinical trial in Eastern Democratic Republic of the Congo.

BACKGROUND: Previous studies have reported the association between maternal vitamin D deficiency and preeclampsia. However, the efficacy of vitamin D supplementation in reducing the occurrence of preeclampsia remains unclear. The objective of this study was to evaluate the effect of cholecalciferol supplementation on the incidence of preeclampsia in primigravid women and its related maternal and foetal outcomes. METHODS: A single-blinded clinical trial was conducted in fourteen antenatal care health facilities in the North (Goma, Mwesso, Nyiragongo) and South Kivu (Bukavu-Panzi) provinces of the Democratic Republic of Congo from March 1, 2020, to June 30, 2021. A total of 1300 primigravid women not exceeding 16 weeks of gestation were randomised with a 1:1 ratio to either the supplemented (A) or control (B) group. Each pregnant woman (A) presenting for antenatal care received a single monthly dose of cholecalciferol (60,000 IU) orally for 6 months. The control group received no vitamin D supplementation or placebo. Serum 25(OH)D was measured at recruitment and at 34 weeks of gestation. Outcomes were assessed monthly until delivery. RESULTS: The median maternal age was 21 years (14-40), while the median gestational age was 15 weeks (5.4-29.0). A significant reduction in the risk of preeclampsia [RR = 0.36 (0.19-0.69); p = 0.001] and preterm delivery [RR = 0.5 (0.32-0.78); p = 0.002] was observed in the intervention group. An RR of 0.43 [(0.27-0.67); p < 0.001] was found for low birth weight. The RR for caesarean section was 0.63 [(0.52-0.75); p < 0.001]. The APGAR score at the 5th minute (p = 0.021) and the size of the newborn were significantly higher in the supplemented group (p = 0.005). CONCLUSION: A single monthly dose (60,000 IU) of vitamin D supplementation, started in earlypregnancy, significantly reduced the incidence of preeclampsia and its maternal and foetal complications. TRIAL REGISTRATION: ISRCTN Register with ISRCTN46539495 on 17 November 2020.

Prevention of preeclampsia.

Preeclampsia is a relatively common pregnancy complication and constitutes a major cause of morbidity and mortality for mothers and children worldwide. It disproportionally affects low-resource countries. Appropriate identification of individuals at increased risk and prevention of the disease and its complications remain healthcare and research priorities, and the investigation of potential interventions to prevent preeclampsia has driven much of the obstetric research in recent decades. In this article, we review the scientific literature on the topic, highlighting established benefits and remaining questions regarding different non-pharmacological and pharmacological strategies, including exercise, the timing of birth, aspirin and calcium use, among others, as well as potential novel therapies under investigation.

Impact of preeclampsia on infant and maternal health among women with rheumatic diseases.

OBJECTIVES: We sought to identify the impact of preeclampsia on infant and maternal health among women with rheumatic diseases. METHODS: A retrospective single-center cohort study was conducted to describe pregnancy and infant outcomes among women with systemic lupus erythematosus (SLE) with and without preeclampsia as compared to women with other rheumatic diseases with and without preeclampsia. RESULTS: We identified 263 singleton deliveries born to 226 individual mothers (mean age 31 years, 35% non-Hispanic Black). Overall, 14% of women had preeclampsia; preeclampsia was more common among women with SLE than other rheumatic diseases (27% vs 8%). Women with preeclampsia had a longer hospital stay post-delivery. Infants born to mothers with preeclampsia were delivered an average of 3.3 weeks earlier than those without preeclampsia, were 4 times more likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. The large majority of women with SLE in this cohort were prescribed hydroxychloroquine and aspirin, with no clear association of these medications with preeclampsia. CONCLUSIONS: We found preeclampsia was an important driver of adverse infant and maternal outcomes. While preeclampsia was particularly common among women with SLE in this cohort, the impact of preeclampsia on the infants of all women with rheumatic diseases was similarly severe. In order to improve infant outcomes for women with rheumatic diseases, attention must be paid to preventing, identifying, and managing preeclampsia.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Pregnancy-An Ideal Period to Identify Women at Risk for Chronic Hypertension.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy. METHODS: Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks' gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed. RESULTS: In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%-58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1-79.3) of future CH. CONCLUSIONS: Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide.

Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.