Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

BACKGROUND: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling. METHODS: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed. RESULTS: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07-0.05; P<0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m2; 95% CI, -7.99 to -4.74; P<0.001), end-diastolic volume (-3.87 mL/m2; 95% CI, -6.77 to -0.98; P=0.009), and end-systolic volume (-3.25 mL/m2; 95% CI, 4.87 to -1.63; P<0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P<0.001) and 2.8% (95% CI, 1.4-4.1; P<0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P=0.024) and a reduction in left atrial volumes of -4.33 mL/m2 (95% CI, -5.52 to -3.21; P<0.001) between baseline and follow-up when adjusted for baseline differences in measures. CONCLUSIONS: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04273854.

Slavery, Home Ownership, and Contemporary Perinatal Outcomes in the Southeast: A Test of Mediation and Moderation.

OBJECTIVE: To estimate the effect of geographic variation in historic slavery on perinatal outcomes [chronic hypertension, hypertensive disorders of pregnancy (HDP), very preterm birth (VPTB), or very low birth weight birth (VLBW)] among Black people living in states where slavery was legal in 1860 and test mediation by Black homeownership. METHODS: We linked data from the 1860 census (the proportion of enslaved residents) to natality data on outcomes (2013-2021) using resident county. The percent of Black residents in a county who owned their home was a potential mediator. We fit log binomial models to estimate risk ratios (RRs) representing total and controlled direct effects (accounting for Black homeownership) of proportion enslaved on outcomes, accounting for potential confounding using marginal structural models. RESULTS: Among 2,443,198 included births, 8.8% (213,829) experienced HDP, 4.1% (100,549) chronic hypertension, 3.3% (81,072) VPTB, and 2.6% (62,538) VLBW. There was an increase in chronic hypertension and VPTB risk, but not HDP or VLBW, in counties with a 10% greater proportion enslaved in 1860 [adjusted RR: 1.06, 95% CI: (1.02, 1.1); 1.02 (1.00, 1.05); 1.00 (0.98, 1.02); 1.01 (1.00, 1.03)]. There was not evidence of mediation by Black homeownership. CONCLUSIONS: Historic slavery remains relevant for perinatal health.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Serum levels of sirtuins, leptin and adiponectin in women with pregnancy-induced hypertension.

INTRODUCTION: Pregnancy-induced hypertension (PIH) and preeclampsia (PE) are associated with disturbed maternal inflammatory response, oxidative stress and vascular endothelial cell dysfunction. Obesity is one of risk factors of PE. Leptin is elevated in obesity and its level correlates positively with the amount of adipose tissue. In contrast, adiponectin levels are decreased in obesity. Sirtuins are expressed in the placenta, however their role in pregnancy-related pathology in humans is not known. AIM OF THE STUDY: The aim of our study was to measure serum concentrations of selected sirtuins, adiponectin and leptin in healthy pregnancy and in women with PIH. MATERIALS AND METHODS: The study included 70 women: 38 healthy pregnant women and 32 women with PIH. Blood samples were obtained between the 20th and 40th week of gestation. Serum levels of sirtuins 1, 3, 6, leptin and adiponectin were measured with ELISA. RESULTS: Leptin levels were significantly higher in PIH group as compared to the controls and correlated positively with BMI. Highest leptin levels were observed in women who needed a cesarean section. Levels of sirtuins 1, 3 and 6 were similar in both groups and did not correlate with BMI. CONCLUSIONS: High leptin levels in PIH women during 3rd trimester might be helpful to predict the necessity for a caesarian section. Blood levels of sirtuins 1, 3 and 6 measured after the 20th week of gestation cannot be regarded as a single diagnostic test for PIH or preeclampsia. More studies to clarify significance of sirtuins in PIH and PE development and diagnosis are needed.

DNA methylation landscape in pregnancy-induced hypertension: progress and challenges.

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

Telemedicine in the treatment of gestational diabetes: An observational cohort study on pregnancy outcomes and maternal satisfaction.

AIMS: Gestational diabetes treatment requires several outpatient consultations from diagnosis until delivery in order to prevent hyperglycaemia, which is associated with maternal and fetal complications. There is limited evidence in the literature about telemedicine superiority in improving pregnancy outcomes for women with gestational diabetes. The primary aim of the study was to evaluate maternal and fetal outcomes, while the secondary aim was to estimate the degree of satisfaction with gestational diabetes treatment, comparing telemedicine versus outpatient care. METHODS: This observational cohort study involved 60 consecutive women with gestational diabetes treated at the Diabetology Unit of Ferrara: 27 were followed up through a weekly remote control method (telemedicine group) and 33 in ambulatory clinics every 2 or 3 weeks (conventional group). After giving birth, 56 women responded to the modified Oxford Maternity Diabetes Treatment Satisfaction Questionnaire to assess their satisfaction with diabetes care. RESULTS: No statistically significant differences were found in most of the maternal and neonatal parameters evaluated in both groups. The questionnaire scores were positive in all areas investigated. Telemedicine follow-up made women feel more controlled (p = 0.045) and fit better with their lifestyle (p = 0.005). It also emerged that almost all women treated with telemedicine would recommend this method to a relative or a friend. CONCLUSIONS: Telemedicine follow-up proved to be safe both in terms of metabolic control and pregnancy outcomes; furthermore, it significantly decreased the need for outpatient consultations and increased women's satisfaction. Studying the impact of telemedicine is also necessary, considering the current difficulties associated with the Sars-COV-2 pandemic.

The association between human chorionic gonadotropin and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. DATA SOURCES: Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words. STUDY ELIGIBILITY CRITERIA: This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus). METHODS: Studies were extracted using REDCap software. The Newcastle-Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. RESULTS: A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia. CONCLUSION: Human chorionic gonadotropin levels are associated with placenta-mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values.

Microvascular dysfunction in women with a history of hypertensive disorders of pregnancy: A population-based retrospective cohort study.

OBJECTIVE: To evaluate microvascular function in women with previous hypertensive disorders of pregnancy (HDP). DESIGN: Retrospective population-based cohort study. SETTING: Linköping, Sweden. POPULATION: Women aged 50-65 years, participating in the Swedish CArdioPulmonary bioImage Study (SCAPIS) at one site (Linköping) 2016-18, who underwent microcirculatory assessment (N = 1222). METHODS: Forearm skin comprehensive microcirculatory assessment was performed with a PeriFlux PF6000 EPOS (Enhanced Perfusion and Oxygen Saturation) system measuring oxygen saturation and total speed resolved perfusion. Obstetric records were reviewed to identify women with previous HDP. Data on cardiovascular risk factors, comorbidities, medication, lifestyle, anthropometric data, and biochemical analyses were obtained from SCAPIS. The microcirculatory data were compared between women with and without previous HDP. MAIN OUTCOME MEASURES: Skin microcirculatory oxygen saturation and total speed resolved perfusion at baseline and post-ischaemic peak. RESULTS: Women with previous pre-eclampsia displayed impaired post-ischaemic peak oxygen saturation compared with women with normotensive pregnancies (88%, interquartile range [IQR] 84-89% vs 91%, IQR 87-94%, p = 0.001) 6-30 years after pregnancy. The difference remained after multivariable adjustment (ß -2.69, 95% CI -4.93 to -0.45). CONCLUSIONS: The findings reveal microvascular dysfunction at long-term follow up in women with previous pre-eclampsia and strengthen the possible role of endothelial dysfunction as a link to the increased risk of cardiovascular disease in women with HDP.

Environmental exposure to metal(loid)s and hypertensive disorders of pregnancy: A systematic review.

BACKGROUND: Environmental exposure to metal(loid)s has been associated with adverse effects on human health, but the systemic repercussion of these elements on the development of hypertensive disorders of pregnancy (HDP) is still poorly understood. OBJECTIVE: To summarize evidence published about the influence of environmental exposure to aluminum, arsenic, barium, cadmium, lead, strontium and mercury on the development of HDP. METHODS: We conducted a systematic literature review according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search strategy was validated by the Peer Review of Electronic Search Strategies. We searched for articles published up to February 2023 in seven databases without language restriction. Two researchers conducted the steps for selection, data extraction and evaluation of the methodological quality of the instruments for epidemiological studies of the Joanna Briggs Institute. Any disagreements were resolved by a third researcher. RESULTS: We obtained 5076 records, of which 37 articles met the inclusion criteria moderate to high methodological quality. Single exposure to metal(loid)s was predominant, and the leading biological matrix analyzed to detect the concentrations from exposure was maternal blood. Lead was the metal investigated the most, and had the largest number of studies showing positive association with HDP. In relation to the other metal(loid)s, higher levels were found in women with HDP in comparison with healthy women, but the finding of a cause-effect relationship was inconsistent. CONCLUSIONS: Although we found evidence of harmful effects of the metal(loid)s studied on human health, the results were inconclusive with regard to HDP. Longitudinal studies that consider prospective investigation, adjustment of confounding factors and the interference of other contaminants in the exacerbation of oxidative stress in women from the preconception phase to the puerperal period should be encouraged.

Pregnancy induced hypertension and umbilical cord blood DNA methylation in newborns: an epigenome-wide DNA methylation study.

OBJECTIVIES: Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother. METHODS: Whole-genome bisulfite sequencing (WGBS) was used to examine the changes in whole genome DNA methylation in the umbilical cord blood of three healthy (NC) and four PIH individuals. Using methylKit, we discovered Hypo- and hyper- differentially methylated probes (DMPs) or methylated regions (DMRs) in the PIH patients' cord blood DNA. Pathway enrichments were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays. DMPs or DMRs relevant to the immunological, neurological, and circulatory systems were also employed for enrichment assay, Metascape analysis and PPI network analysis. RESULTS: 520 hyper- and 224 hypo-DMPs, and 374 hyper- and 186 hypo-DMRs between NC and PIH group, respectively. Both DMPs and DMRs have enhanced pathways for cardiovascular, neurological system, and immune system development. Further investigation of DMPs or DMRs related to immunological, neurological, and circulatory system development revealed that TBK1 served as a hub gene for all three developmental pathways. CONCLUSION: PIH-associated DMPs or DMRs in umbilical cord blood DNA may play a role in immunological, neurological, and circulatory system development. Abnormal DNA methylation in the immune system may also contribute to the development of CVDs and neurodevelopment disorders.

MicroRNA-195-5p Attenuates Pregnancy-Induced Hypertension by Inhibiting Oxidative Stress via OTX1/MAPK Signaling Pathway.

Pregnancy-induced hypertension (PIH) is a hypertensive disorder during pregnancy and can induce perinatal death of human infants. MicroRNA (miR)-195-5p was validated to display low expression in severe preeclampsia placentas, but the role of miR-195-5p in pregnancy-induced hypertension (PIH) has not been investigated. The study emphasized on the functions and mechanism of miR-195-5p in PIH. A reduced uterine perfusion pressure (RUPP) rat model was established to mimic PIH in vivo. Adenovirus (Ad)-miR-195-5p agomir and/or Ad-OTX1 were further injected into some model rats. RT-qPCR was conducted to assess the expression of miR-195-5p and orthodenticle homeobox 1 (OTX1) in rat placental tissues, the isolated aortic endothelial cells (AECs), and in serum samples of PIH patients. Western blot analysis was implemented to measure the protein levels of OTX1, VEGFA, and key factors involved in the MAPK signaling pathway. The concentrations of oxidative stress markers (superoxide dismutase, catalase, and lipid hydroperoxide) in AECs and placental tissues of RUPP rats were measured by corresponding kits. The binding relation between miR-195-5p and OTX1 was verified using the dual-luciferase reporter assay. Hematoxylin-eosin staining was conducted to evaluate the pathological features of rat placental tissues. MiR-195-5p was downregulated, while OTX1 was upregulated in rat placental tissues and human serum samples of PIH patients. MiR-195-5p could target OTX1 and inversely regulate OTX1 expression in AECs and rat placental tissues. In addition, miR-195-5p can negatively regulate VEGFA level. Furthermore, miR-195-5p inactivates oxidative stress and the MAPK signaling by downregulating OTX1 in AECs. In vivo experiments revealed that OTX1 overexpression reversed the protective effect of miR-195-5p overexpression on placental damage and oxidative stress. MiR-195-5p alleviates PIH by inhibiting oxidative stress via targeting OTX1 and inactivating MAPK signaling.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats.

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

Strategies to improve postpartum engagement in healthcare after high-risk conditions diagnosed in pregnancy: a narrative review.

Transition from antepartum to postpartum care is important, but often fragmented, and attendance at postpartum visits can be poor. Access to care is especially important for individuals diagnosed antepartum with conditions associated with longer-term implications, including gestational diabetes (GDM) and hypertensive disorders in pregnancy (HDP). Strategies to link and strengthen this transition are essential to support people to attend recommended appointments and testing. This narrative review evaluates what is known about postpartum transition of care after higher-risk antepartum conditions, discusses barriers and facilitators to uptake of recommended testing, and outlines strategies trialled to increase both postpartum attendance and testing. Barriers to attendance frequently overlap with general barriers to accessing healthcare. Specific postpartum challenges include difficulties with transport, coordinating breastfeeding and childcare access. Systemic challenges include inadequate communication to women around implications of health conditions diagnosed in pregnancy, and the importance of postpartum follow up. Uptake of recommended testing after a diagnosis of GDM and HDP is variable but generally suboptimal. Strategies which demonstrate promise include the use of patient navigators, focused education and specialised clinics. Reminder systems have had variable impact. Telehealth and technology are under-utilised in this field but offer promising options particularly with the expansion of virtual healthcare into routine maternity care. Strategies to improve both attendance rates and uptake of testing must be designed to address disparities in healthcare access and tailored to the needs of the community. This review provides a starting point to develop such strategies from the community level to the population level.

Association between fetal fraction of cell-free DNA and adverse pregnancy outcomes.

PURPOSE: To determine the association between fetal fraction (FF) levels in cell-free fetal DNA (cffDNA) testing and adverse pregnancy outcomes. METHODS: This retrospective cohort study, conducted at a single center, involved 2063 pregnant women with normal 1st and 2nd trimester non-invasive prenatal test (NIPT) results between 2016 and 2021. Pregnancy outcomes were examined by determining the < 4% and < 5th percentile (3.6%) cut-off values for low fetal fraction (LFF). Pregnancy outcomes were also examined by dividing the FF into population-based quartiles. Adverse pregnancy outcomes were pregnancy-induced hypertensive diseases (PIHD), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), intrahepatic cholestasis of pregnancy (ICP), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, and 1st and 5th minutes low APGAR scores (< 7). RESULTS: PIHD was significantly higher in LFF (< 4% and < 5th percentile) cases (p = 0.015 and p < 0.001, respectively). However, in population-based quartiles of FF, PIHD did not differ significantly between groups. Composite adverse maternal outcomes were significantly higher in the FF < 4% group (p = 0.042). When analyzes were adjusted for maternal age, BMI, and gestational age at NIPT, significance was maintained at < 4%, < 5th percentile LFF for PIHD, and < 4% LFF for composite adverse maternal outcomes. However, there was no significant relationship between LFF with GDM, ICP and PTB. Additionally, there was no significant association between low APGAR scores, SGA, LGA, LBW, macrosomia, and LFF concerning neonatal outcomes. CONCLUSION: Our study showed that LFF in pregnant women with normal NIPT results may be a predictor of subsequent PIHD.

Pregnancy-induced hypertension awareness, knowledge and its risk factors: A cross-sectional study.

Background and Objective: Pregnancy-induced hypertension (PIH) has severe implications for maternal morbidity and mortality; thus, boosting pregnant women's awareness and knowledge of this medical condition is crucial for improving the mother's and foetus's health. This study assessed the awareness and knowledge of PIH and its risk factors among pregnant women in Mdantsane, South Africa. Methods: This cross-sectional study involved 249 conveniently selected and consenting pregnant women attending antenatal care clinics in Mdantsane, Buffalo City Metropolitan Municipality, South Africa. A self-designed questionnaire was utilised to collect data. Descriptive statistics, chi-square (χ2) test and multivariate logistic regression analysis were performed. The significance level was 0.05. Results: Over 50% of the women were knowledgeable about PIH and associated risk factors ((χ2=4.92; p = 0.04). The prevalence of PIH was 51.8%, and married women were more aware of the PIH risk factors (71.1%). Women with previous pregnancies were more likely to be aware of PIH (OR = 17.1, 95%; CI = 9.09 to 32.15) compared to first time mothers. Women in age group 36-45 were 2.5 times more likely to be aware of PIH (OR = 2.5, 95% CI: 1.19-3.24) compared to women aged <35 years. Likewise, women aged 36-45 years were two times more likely to be knowledgeable about risk factors for PIH (OR = 2.3, 95% CI: 1.14-2.81) compared to women aged <35 years. Married women were more likely to be aware of PIH risk factors (OR = 2.70, 95% CI = 1.35-5.47) than unmarried women. Moreover, pregnancy increases the likelihood (OR=12.8, 95% CI: 6.97-23.58) of being aware of PIH risk factors. There was a significant difference between the mean ages of women who knew about PIH risk factors and those who do not (t=3.49, Mean difference = 3.49, p=0.0001, 95% CI (2.54; 4.44)). Conclusion: The prevalence of PIH was high. Age, history of PIH, previous pregnancy, and marital status were predictors of PIH knowledge/awareness and risk factors for PIH. Context-specific health education programmes during prenatal visits are crucial to improving pregnant women's knowledge of PIH.

Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study.

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2-1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5-3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

The genetic risk factors for pregnancy-induced hypertension: Evidence from genetic polymorphisms.

Pregnancy-induced hypertension (PIH) is a multifactorial and severe pregnancy complication including preeclampsia/eclampsia, gestational hypertension, chronic (pre-existing) hypertension, and preeclampsia/eclampsia variants superimposed on chronic hypertension. PIH-induced maternal mortality accounts for approximately 9% of all maternal deaths over the world. A large number of case-control studies have established the importance of various genetic factors in the occurrence and development of PIH. In this narrative review, we summarized the genetic risk factors involved in the renin-angiotensin system, endothelin system, inflammatory factors, oxidative stress, and other functional networks, with the aim of sorting out the genetic factors that may play a potential role in PIH and providing new ideas to elucidate the pathogenesis of PIH.

First-trimester glycaemic markers as predictors of gestational diabetes and its associated adverse outcomes: A prospective cohort study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with excessive fetal growth in later gestation. Recent data suggest accelerated growth may begin before 28 weeks' gestation when GDM is typically diagnosed. The identification of pregnancies at risk of early fetal growth would enable early intervention. We assessed the use of early pregnancy HbA1c in predicting excessive fetal growth. RESEARCH DESIGN AND METHODS: Women were recruited at antenatal booking from a major maternity unit in the UK. HbA1c was measured at <14 weeks gestation in 1243 women at risk of GDM as defined by UK NICE risk factors of whom 1115 underwent OGTT. Women with previous GDM were excluded. Comprehensive fetal ultrasound was performed at 28 weeks' gestation alongside 75 g OGTT in 976 of these women. GDM was defined using WHO criteria. Pregnancy outcomes were extracted from the regional maternity care database. RESULTS: Two hundred and thirty-six women screened positive for GDM. At diagnosis, GDM pregnancies demonstrated higher adjusted fetal weight percentile than non-GDM pregnancies: (51.8 vs. 46.3, p = 0.008). This was driven by increases in the fetal abdominal circumference percentile in GDM compared with non-GDM pregnancies (55.3 vs. 46.2, p = <0.001). Early pregnancy HbA1c was higher in the GDM versus non-GDM group: (35.7 mmol/mol vs. 32.9 mmol/mol p = <0.01). A threshold for predicting excessive fetal growth was not identified in this cohort. CONCLUSIONS: Accelerated fetal growth is evident prior to the diagnosis of GDM. There remains a need for suitable methods of early identification of pregnancies at high risk for early accelerated fetal growth due to GDM. First-trimester HbA1c was not useful in identifying these pregnancies. NOVELTY STATEMENT: WHAT IS ALREADY KNOWN?: Recent research suggests excessive growth associated with GDM may begin prior to 28 weeks' gestation, when GDM is typically tested for WHAT THIS STUDY HAS FOUND?: Pregnancies affected by GDM are already subject to accelerated fetal growth in comparison to non-GDM pregnancies by way of higher estimated fetal weight and fetal abdominal circumference Neither first-trimester HbA1c nor plasma glucose was useful predictors of these outcomes WHAT ARE THE IMPLICATIONS OF THIS STUDY?: Highlights the emergence of excessive growth prior to detection of GDM Reinforces need for suitable methods of identifying such pregnancies in earlier gestation.

Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

American College of Cardiology and American Heart Association blood pressure categories-a systematic review of the relationship with adverse pregnancy outcomes in the first half of pregnancy.

OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs. DATA SOURCES: We systematically searched electronic databases (from 2017 to 2021) for reports of blood pressure measurements in pregnancy, classified according to 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at <20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated. RESULTS: Of 23 studies included, there was a stepwise relationship between the American College of Cardiology and American Heart Association blood pressure category (when compared with normal blood pressure of <120/80 mmHg) and the strength of the association with preeclampsia. The category of elevated blood pressure had a risk ratio of 2.0 (95% prediction interval, 0.8-4.8), the stage 1 hypertension category had a risk ratio of 3.0 (95% prediction interval, 1.1-8.5), and the stage 2 hypertension category had a risk ratio of 7.9 (95% prediction interval, 1.8-35.1). Between-study variability was related to the magnitude of the association with stronger relationships in larger studies at low risk of bias and with unselected populations with multiple routine blood pressure measurements. None of the systolic blood pressure measurements of <120 mmHg, <130/80 mmHg, or <140/90 mmHg were useful to rule out the development of preeclampsia (all negative likelihood ratios >0.2). Only a blood pressure measurement of ≥140/90 mmHg was a good predictor for the development of preeclampsia (positive likelihood ratio, 5.95). The findings were similar for other outcomes. CONCLUSION: Although a blood pressure of 120 to 140 over 80 to 90 mmHg at <20 weeks gestation is associated with a heightened risk for preeclampsia and adverse pregnancy outcomes and may assist in risk prediction in multivariable modelling, lowering the diagnostic threshold for chronic hypertension would not assist clinicians in identifying women at heightened risk.