Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. RESULTS: Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. CONCLUSION: The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Community-Level Factors are Predictors of Severe Maternal Morbidity Among American Indian and Alaska Native Pregnant People in the Pacific Northwest in a Multilevel Logistic Regression.

INTRODUCTION: American Indian/Alaska Native (AI/AN) pregnant people face barriers to health and healthcare that put them at risk of pregnancy complications. Rates of severe maternal morbidity (SMM) among Indigenous pregnant people are estimated to be twice that of non-Hispanic White (NHW) pregnant people. METHODS: Race-corrected Oregon Hospital Discharge and Washington Comprehensive Hospital Abstract Reporting System data were combined to create a joint dataset of births between 2012 and 2016. The analytic sample was composed of 12,535 AI/AN records and 313,046 NHW records. A multilevel logistic regression was used to assess the relationship between community-level, individual and pregnancy risk factors on SMM for AI/AN pregnant people. RESULTS: At the community level, AI/AN pregnant people were more likely than NHW to live in mostly or completely rural counties with low median household income and high uninsured rates. They were more likely to use Medicaid, be in a high-risk age category, and have diabetes or obesity. During pregnancy, AI/AN pregnant people were more likely to have insufficient prenatal care (PNC), gestational diabetes, and pre-eclampsia. In the multilevel model, county accounted for 6% of model variance. Hypertension pre-eclampsia, and county rurality were significant predictors of SMM among AI/AN pregnant people. High-risk age, insufficient PNC and a low county insured rate were near-significant at p < 0.10. DISCUSSION: Community-level factors are significant contributors to SMM risk for AI/AN pregnant people in addition to hypertension and pre-eclampsia. These findings demonstrate the need for targeted support in pregnancy to AI/AN pregnant people, particularly those who live in rural and underserved communities.

What is already known on this subject? American Indian and Alaska Native pregnant people face higher rates of severe maternal morbidity and mortality, and the risk is exacerbated for rural Indigenous pregnant people.What this study adds? This publication uses a multilevel model to assess the contribution of community-level factors in severe maternal morbidity risk for American Indian and Alaska Native pregnant people. This analysis highlights the important role that rurality, prenatal care adequacy and access to insurance play in maternal morbidity risk and discusses how those risks are disproportionately felt by American Indian and Alaska Native pregnant people in the Pacific Northwest.

Racial differences in healthcare utilization among patients with suspected or diagnosed preeclampsia: A retrospective cohort study.

OBJECTIVES: To analyze healthcare resource utilization and severe maternal morbidity (SMM) in Black and White patients with preeclampsia diagnosis versus signs/symptoms. STUDY DESIGN: This was a retrospective cohort study analyzing data from the IBM® Explorys Database between 7/31/2012-12/31/2020. Demographic, clinical, and laboratory data were extracted. Healthcare utilization and SMM were analyzed during the antepartum period (20 weeks of gestation until delivery) among Black and White patients with signs/symptoms of preeclampsia, with a diagnosis of preeclampsia, or neither (control). MAIN OUTCOME MEASURES: Healthcare utilization and SMM in those with a preeclampsia diagnosis or signs/symptoms of preeclampsia only were compared with a control group (White patients with no preeclampsia diagnosis or signs/symptoms). RESULTS: Data from 38,190 Black and 248,568 White patients were analyzed. Patients with preeclampsia diagnosis or signs/symptoms were more likely to visit the emergency room compared to those without diagnosis or signs/symptoms. Black patients with signs/symptoms of preeclampsia had the highest elevated risk (odds ratio [OR] = 3.4), followed by Black patients with a preeclampsia diagnosis (OR = 3.2), White patients with signs/symptoms (OR = 2.2), and White patients with a preeclampsia diagnosis (OR = 1.8). More Black patients experienced SMM (SMM rate 6.1% [Black with preeclampsia diagnosis] and 2.6% [Black with signs/symptoms]) than White patients (5.0% [White with preeclampsia diagnosis] and 2.0% [White with signs/symptoms]). SMM rates were higher for Black preeclampsia patients with severe features than for White preeclampsia patients with severe features (8.9% vs 7.3%). CONCLUSIONS: Compared with White patients, Black patients had higher rates of antepartum emergency care and antepartum SMM.

The Association of Race and Ethnicity with Severe Maternal Morbidity among Individuals Diagnosed with Hypertensive Disorders of Pregnancy.

OBJECTIVE: This study aimed to examine whether there are racial disparities in severe maternal morbidity (SMM) in patients with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: Secondary analysis of an observational study of 115,502 patients who had a live birth at ≥20 weeks in 25 hospitals in the United States from 2008 to 2011. Only patients with HDP were included in this analysis. Race and ethnicity were categorized as non-Hispanic White, non-Hispanic Black (NHB), and Hispanic and were abstracted from the medical charts. Patients of other races and ethnicities were excluded. Associations were estimated between race and ethnicity, and the primary outcome of SMM, defined as any of the following, was estimated by unadjusted logistic and multivariable backward logistic regressions: blood transfusion ≥4 units, unexpected surgical procedure, need for a ventilator ≥12 hours, intensive care unit (ICU) admission, or failure of ≥1 organ system. Multivariable models were run classifying HDP into three levels as follows: (1) gestational hypertension; (2) preeclampsia (mild, severe, or superimposed); and (3) eclampsia or HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. RESULTS: A total of 9,612 individuals with HDP met inclusion criteria. No maternal deaths occurred in this cohort. In univariable analysis, non-Hispanic White patients were more likely to present with gestational hypertension whereas NHB and Hispanic patients were more likely to present with preeclampsia. The frequency of the primary outcome, composite SMM, was higher in NHB patients compared with that in non-Hispanic White or Hispanic patients (11.8 vs. 4.5% in non-Hispanic White and 4.8% in Hispanic, p < 0.001). This difference was driven by a higher frequency of blood transfusions and ICU admissions among NHB individuals. Prior to adjusting the analysis for confounding factors, the odds ratio (OR) of primary composite outcomes in NHB individuals was 2.85 (95% confidence interval [CI]: 2.38, 3.42) compared with non-Hispanic White. After adjusting for sociodemographic and clinical factors, hospital site, and the severity of HDP, the OR of composite SMM did not differ between the groups (adjusted OR [aOR] = 1.26, 95% CI: 0.95, 1.67 for NHB, and aOR = 1.29, 95% CI: 0.94, 1.77 for Hispanic, compared with non-Hispanic White patients). Sensitivity analysis was done to exclude one single site that was an outliner with the highest ICU admissions and demonstrated no difference in ICU admission by maternal race and ethnicity. CONCLUSION: NHB patients with HDP had higher rates of the composite SMM compared with non-Hispanic White patients, driven mainly by a higher frequency of blood transfusions and ICU admissions. However, once severity and other confounding factors were taken into account, the differences did not persist. KEY POINTS: · Black patients with HDP had higher frequency of SMM compared with non-Hispanic White patients.. · The SMM disparities were driven by blood transfusions and ICU admissions.. · After adjustment for confounders, including HDP severity, the significant difference in SMM did not persist..

Risk of Adverse Pregnancy Outcomes Among Pregnant Individuals With Gestational Diabetes by Race and Ethnicity in the United States, 2014-2020.

Importance: Gestational diabetes, which increases the risk of adverse pregnancy outcomes, has been increasing in frequency across all racial and ethnic subgroups in the US. Objective: To assess whether the frequency of adverse pregnancy outcomes among those in the US with gestational diabetes changed over time and whether the risk of these outcomes differed by maternal race and ethnicity. Design, Setting, and Participants: Exploratory serial, cross-sectional, descriptive study using US National Center for Health Statistics natality data for 1 560 822 individuals with gestational diabetes aged 15 to 44 years with singleton nonanomalous live births from 2014 to 2020 in the US. Exposures: Year of delivery and race and ethnicity, as reported on the birth certificate, stratified as non-Hispanic American Indian, non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White (reference group). Main Outcomes and Measures: Maternal outcomes of interest included cesarean delivery, primary cesarean delivery, preeclampsia or gestational hypertension, intensive care unit (ICU) admission, and transfusion; neonatal outcomes included large for gestational age (LGA), macrosomia (>4000 g at birth), small for gestational age (SGA), preterm birth, and neonatal ICU (NICU) admission, as measured by the frequency (per 1000 live births) with estimation of mean annual percentage change (APC), disparity ratios, and adjusted risk ratios. Results: Of 1 560 822 included pregnant individuals with gestational diabetes (mean [SD] age, 31 [5.5] years), 1% were American Indian, 13% were Asian/Pacific Islander, 12% were Black, 27% were Hispanic/Latina, and 48% were White. From 2014 to 2020, there was a statistically significant increase in the overall frequency (mean APC per year) of preeclampsia or gestational hypertension (4.2% [95% CI, 3.3% to 5.2%]), transfusion (8.0% [95% CI, 3.8% to 12.4%]), preterm birth at less than 37 weeks (0.9% [95% CI, 0.3% to 1.5%]), and NICU admission (1.0% [95% CI, 0.3% to 1.7%]). There was a significant decrease in cesarean delivery (-1.4% [95% CI, -1.7% to -1.1%]), primary cesarean delivery (-1.2% [95% CI, -1.5% to -0.9%]), LGA (-2.3% [95% CI, -2.8% to -1.8%]), and macrosomia (-4.7% [95% CI, -5.3% to -4.0%]). There was no significant change in maternal ICU admission and SGA. In comparison with White individuals, Black individuals were at significantly increased risk of all assessed outcomes, except LGA and macrosomia; American Indian individuals were at significantly increased risk of all assessed outcomes except cesarean delivery and SGA; and Hispanic/Latina and Asian/Pacific Islander individuals were at significantly increased risk of maternal ICU admission, preterm birth, NICU admission, and SGA. Differences in adverse outcomes by race and ethnicity persisted through these years. Conclusions and Relevance: From 2014 through 2020, the frequency of multiple adverse pregnancy outcomes in the US increased among pregnant individuals with gestational diabetes. Differences in adverse outcomes by race and ethnicity persisted.

Does race or ethnicity play a role in the origin, pathophysiology, and outcomes of preeclampsia? An expert review of the literature.

The burden of preeclampsia, a substantial contributor to perinatal morbidity and mortality, is not born equally across the population. Although the prevalence of preeclampsia has been reported to be 3% to 5%, racial and ethnic minority groups such as non-Hispanic Black women and American Indian or Alaskan Native women are widely reported to be disproportionately affected by preeclampsia. However, studies that add clarity to the causes of the racial and ethnic differences in preeclampsia are limited. Race is a social construct, is often self-assigned, is variable across settings, and fails to account for subgroups. Studies of the genetic structure of human populations continue to find more variations within racial groups than among them. Efforts to examine the role of race and ethnicity in biomedical research should consider these limitations and not use it as a biological construct. Furthermore, the use of race in decision making in clinical settings may worsen the disparity in health outcomes. Most of the existing data on disparities examine the differences between White and non-Hispanic Black women. Fewer studies have enough sample size to evaluate the outcomes in the Asian, American Indian or Alaskan Native, or mixed-race women. Racial differences are noted in the occurrence, presentation, and short-term and long-term outcomes of preeclampsia. Well-established clinical risk factors for preeclampsia such as obesity, diabetes, and chronic hypertension disproportionately affect non-Hispanic Black, American Indian or Alaskan Native, and Hispanic populations. However, with comparable clinical risk factors for preeclampsia among women of different race or ethnic groups, addressing modifiable risk factors has not been found to have the same protective effect for all women. Abnormalities of placental formation and development, immunologic factors, vascular changes, and inflammation have all been identified as contributing to the pathophysiology of preeclampsia. Few studies have examined race and the pathophysiology of preeclampsia. Despite attempts, a genetic basis for the disease has not been identified. A number of genetic variants, including apolipoprotein L1, have been identified as possible risk modifiers. Few studies have examined race and prevention of preeclampsia. Although low-dose aspirin for the prevention of preeclampsia is recommended by the US Preventive Service Task Force, a population-based study found racial and ethnic differences in preeclampsia recurrence after the implementation of low-dose aspirin supplementation. After implementation, recurrent preeclampsia reduced among Hispanic women (76.4% vs 49.6%; P<.001), but there was no difference in the recurrent preeclampsia in non-Hispanic Black women (13.7 vs 18.1; P=.252). Future research incorporating the National Institute on Minority Health and Health Disparities multilevel framework, specifically examining the role of racism on the burden of the disease, may help in the quest for effective strategies to reduce the disproportionate burden of preeclampsia on a minority population. In this model, a multilevel framework provides a more comprehensive approach and takes into account the influence of behavioral factors, environmental factors, and healthcare systems, not just on the individual.

Disparities in Obstetric Readmissions: A Multistate Analysis, 2007-2014.

OBJECTIVE: Hospital readmissions are generally higher among racial-ethnic minorities and patients of lower socioeconomic status. However, this has not been widely studied in obstetrics. The aim of the study is to determine 30-day postpartum readmission rates by patient-level social determinants of health: race ethnicity, primary insurance payer, and median income, independently and as effect modifiers. STUDY DESIGN: Using state inpatient databases from the health care cost and utilization project from 2007 to 2014, we queried all deliveries. To produce accurate estimates of the effects of parturients' social determinants of health on readmission odds while controlling for confounders, generalized linear mixed models (GLMMs) were used. Additional models were generated with interaction terms to highlight any associations and their effect on the outcome. Adjusted odds ratios (aOR) with 95% confidence intervals are reported. RESULTS: There were 5,129,867 deliveries with 79,260 (1.5%) 30-day readmissions. Of these, 947 (1.2%) were missing race ethnicity. Black and Hispanic patients were more likely to be readmitted within 30 days of delivery, as compared with White patients (p < 0.001 and p < 0.05, respectively). Patients with government insurance were more likely to be readmitted than those with private insurance (p < 0.001). Patients living in the second quartile of median income were also more likely to be readmitted than those living in other quartiles (p < 0.05). Using GLMMs, we observed that Black patients with Medicare were significantly more likely to get readmitted as compared with White patients with private insurance (aOR 2.78, 95% CI 2.50-3.09, p < 0.001). Similarly, Black patients living in the fourth (richest) quartile of median income were more likely to get readmitted, even when compared with White patients living in the first (poorest) quartile of median income (aOR 1.48, 95% CI 1.40-1.57, p < 0.001). CONCLUSION: Significant racial-ethnic disparities in obstetric readmissions were observed, particularly in Black patients with government insurance and even in Black patients living in the richest quartile of median income. KEY POINTS: · Using generalized linear mixed models, we observed significant interactions.. · Government-insured Black patients were 2.78X more likely to be readmitted.. · The wealthiest Black patients were still 1.48X more likely to be readmitted..

Nativity-Related Disparities in Preeclampsia and Cardiovascular Disease Risk Among a Racially Diverse Cohort of US Women.

Importance: Preeclampsia is an independent risk factor for future cardiovascular disease and disproportionally affects non-Hispanic Black women. The association of maternal nativity and duration of US residence with preeclampsia and other cardiovascular risk factors is well described among non-Hispanic Black women but not among women of other racial and ethnic groups. Objective: To examine differences in cardiovascular risk factors and preeclampsia prevalence by race and ethnicity, nativity, and duration of US residence among Hispanic, non-Hispanic Black, and non-Hispanic White women. Design, Setting, and Participants: This cross-sectional analysis of the Boston Birth Cohort included a racially diverse cohort of women who had singleton deliveries at the Boston Medical Center from October 1, 1998, to February 15, 2016. Participants self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. Data were analyzed from March 1 to March 31, 2021. Exposures: Maternal nativity and duration of US residence (<10 vs ≥10 years) were self-reported. Main Outcome and Measures: Diagnosis of preeclampsia, the outcome of interest, was retrieved from maternal medical records. Results: A total of 6096 women (2400 Hispanic, 2699 non-Hispanic Black, and 997 non-Hispanic White) with a mean (SD) age of 27.5 (6.3) years were included in the study sample. Compared with Hispanic and non-Hispanic White women, non-Hispanic Black women had the highest prevalence of chronic hypertension (204 of 2699 [7.5%] vs 65 of 2400 [2.7%] and 28 of 997 [2.8%], respectively), obesity (658 of 2699 [24.4%] vs 380 of 2400 [15.8%] and 152 of 997 [15.2%], respectively), and preeclampsia (297 of 2699 [11.0%] vs 212 of 2400 [8.8%] and 71 of 997 [7.1%], respectively). Compared with their counterparts born outside the US, US-born women in all 3 racial and ethnic groups had a significantly higher prevalence of obesity (Hispanic women, 132 of 556 [23.7%] vs 248 of 1844 [13.4%]; non-Hispanic Black women, 444 of 1607 [27.6%] vs 214 of 1092 [19.6%]; non-Hispanic White women, 132 of 776 [17.0%] vs 20 of 221 [9.0%]), smoking (Hispanic women, 98 of 556 [17.6%] vs 30 of 1844 [1.6%]; non-Hispanic Black women, 330 of 1607 [20.5%] vs 53 of 1092 [4.9%]; non-Hispanic White women, 382 of 776 [49.2%] vs 42 of 221 [19.0%]), and severe stress (Hispanic women, 76 of 556 [13.7%] vs 85 of 1844 [4.6%]; non-Hispanic Black women, 231 of 1607 [14.4%] vs 120 of 1092 [11.0%]; non-Hispanic White women, 164 of 776 [21.1%] vs 26 of 221 [11.8%]). After adjusting for sociodemographic and cardiovascular risk factors, birth status outside the US (adjusted odds ratio [aOR], 0.74 [95% CI, 0.55-1.00]) and shorter duration of US residence (aOR, 0.62 [95% CI, 0.41-0.93]) were associated with lower odds of preeclampsia among non-Hispanic Black women. However, among Hispanic and non-Hispanic White women, maternal nativity (aOR for Hispanic women, 1.07 [95% CI, 0.72-1.60]; aOR for non-Hispanic White women, 0.98 [95% CI, 0.49-1.96]) and duration of US residence (aOR for Hispanic women <10 years, 1.04 [95% CI, 0.67-1.59]; aOR for non-Hispanic White women <10 years, 1.20 [95% CI, 0.48-3.02]) were not associated with preeclampsia. Conclusions and Relevance: Nativity-related disparities in preeclampsia persisted among non-Hispanic Black women but not among Hispanic and non-Hispanic White women after adjusting for sociodemographic and cardiovascular risk factors. Further research is needed to explore the interplay of factors contributing to nativity-related disparities in preeclampsia, particularly among non-Hispanic Black women.

Performance of Fetal Medicine Foundation algorithm for first trimester preeclampsia screening in an indigenous south Asian population.

BACKGROUND: To evaluate the performance of the Fetal Medicine Foundation (FMF) preterm preeclampsia (PE) screening algorithm in an indigenous South Asian population. METHODS: This was a prospective observational cohort study conducted in a tertiary maternal fetal unit in Delhi, India over 2 years. The study population comprised of 1863 women carrying a singleton pregnancy and of South Asian ethnicity who were screened for preterm pre-eclampsia (PE) between 11 and 14 weeks of gestation using Mean Arterial Pressure (MAP), transvaginal Mean Uterine Artery Pulsatility Index (UtAPI) and biochemical markers - Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor.. Absolutemeasurements of noted biomarkers were converted to multiples of the expected gestational median (MoMS) which were then used to estimate risk for preterm PE < 37 weeks using Astraia software. Women with preterm PE risk of ≥1:100 was classified as as high risk. Detection rates (DR) at 10% false positive rate were calculated after adjusting for prophylactic aspirin use (either 75 or 150 mg). RESULTS: The incidence of PE and preterm PE were 3.17% (59/1863) and 1.34% (25/1863) respectively. PAPP-A and PlGF MoM distribution medians were 0.86 and 0.87 MoM and significantly deviated from 1 MoM. 431 (23.1%) women had a risk of ≥1:100, 75 (17.8%) of who received aspirin. Unadjusted DR using ≥1:100 threshold was 76%.Estimated DRs for a fixed 10% FPR ranged from 52.5 to 80% depending on biomarker combination after recentering MoMs and adjusting for aspirin use. CONCLUSION: The FMF algorithm whilst performing satisfactorily could still be further improved to ensure that biophysical and biochemical markers are correctly adjusted for indigenous South Asian women.

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population.

The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe.

BACKGROUND: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care. METHODS: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model. RESULTS: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy. CONCLUSIONS: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.

Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: US Preventive Services Task Force Recommendation Statement.

Importance: Preeclampsia is one of the most serious health problems that affect pregnant persons. It is a complication in approximately 4% of pregnancies in the US and contributes to both maternal and infant morbidity and mortality. Preeclampsia also accounts for 6% of preterm births and 19% of medically indicated preterm births in the US. There are racial and ethnic disparities in the prevalence of and mortality from preeclampsia. Non-Hispanic Black women are at greater risk for developing preeclampsia than other women and experience higher rates of maternal and infant morbidity and perinatal mortality. Objective: To update its 2014 recommendation, the USPSTF commissioned a systematic review to evaluate the effectiveness of low-dose aspirin use to prevent preeclampsia. Population: Pregnant persons at high risk for preeclampsia who have no prior adverse effects with or contraindications to low-dose aspirin. Evidence Assessment: The USPSTF concludes with moderate certainty that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality in pregnant persons at high risk for preeclampsia. Recommendation: The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia. (B recommendation).

Placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a stepped wedge cluster randomised control trial (PARROT Ireland).

OBJECTIVE: To determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity. DESIGN: Stepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019. SETTING: National multisite trial in seven maternity hospitals throughout the island of Ireland PARTICIPANTS: Women with a singleton pregnancy between 20+0 to 36+6 weeks' gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate. INTERVENTION: Participants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment. MAIN OUTCOMES MEASURES: Co-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat. RESULTS: Of the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity-457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)-or in neonatal morbidity-527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67). CONCLUSIONS: This was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881073.

Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China.

Importance: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Within-country studies have reported racial differences in the presentation and outcome, but little is known about differences between countries. Objective: To compare preeclampsia prevalence, risk factors, and pregnancy outcomes between the Swedish and Chinese populations. Design, Setting, and Participants: This cross-sectional study compared deliveries from the Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015-2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and these data were reweighted to enable national comparisons. Participants included 555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis was conducted from November 2018 to August 2020 and revised in February to March 2021. Exposures: Maternal characteristics, parity, multiple gestation, chronic and gestational diabetes, cesarean delivery. Main Outcomes and Measures: Preeclampsia prevalence and risk factors, overall and for mild and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no gestational hypertension. Results: The 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in China. Obesity (defined as BMI ≥28 in China and BMI ≥30 in Sweden) was a stronger risk factor in China compared with Sweden (China: odds ratio [OR], 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49; 95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/77 512[1.1%] vs 1753/547 219 [0.3%], P < .001), and 10-fold higher among women with preeclampsia (66/1652 [4.6%] vs 60/14 499[0.4%], P < .001). Conclusions and Relevance: In this study, the prevalence rates of preeclampsia in Sweden and China were similar, but women in China had more severe disease and worse pregnancy outcomes than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role for lifestyle and health care factors but may reflect some differences in pathophysiology. These findings have relevance for current efforts to identify high-risk pregnancies and early serum markers because the value of risk prediction models and biomarkers may be population specific.

Soluble Flt1 levels are associated with cardiac dysfunction in Black women with and without severe preeclampsia.

Background: We evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) levels and cardiac function during pregnancy and postpartum among Black women with and without preeclampsia. Study design: Prospective longitudinal cohort study from 2015 to 2017 of Black women with preterm severe preeclampsia and normotensive pregnant controls.We obtained echocardiograms and sFlt-1 levels during pregnancy and postpartum. Results: 93 Black women were included (43 cases, 50 controls). Higher sFlt1 levels were correlated with worse longitudinal strain, diastolic dysfunction, decreased ventricular-arterial coupling, and increased chamber and arterial elastance at the time of preeclampsia diagnosis and postpartum. Conclusions: Higher sFlt1 levels are associated with cardiovascular dysfunction during pregnancy and postpartum.

Trends and Racial/Ethnic Disparities in the Rates of Pre-eclampsia by HIV Status in the US.

BACKGROUND: Preeclampsia and HIV account for a significant proportion of the global burden of disease and pose severe maternal-fetal risks. There is a dearth of literature regarding racial/ethnic disparities in preeclampsia associated with HIV/AIDS in the US. METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) database from 2002 to 2015 on a cohort of hospitalized pregnant women with or without preeclampsia and HIV. Joinpoint regression models were used to identify trends in the rates of preeclampsia among pregnant women living with or without HIV, stratified by race/ethnicity over the study period. We also assessed the association between preeclampsia and various socio-demographic factors. RESULTS: We analyzed over 60 million pregnancy-related hospitalizations, of which 3665 had diagnoses of preeclampsia and HIV, corresponding to a rate of 0.61 per 10,000. There was an increasing trend in the diagnosis of preeclampsia among hospitalized, pregnant women without HIV across each racial/ethnic category. The highest prevalence of preeclampsia was among non-Hispanic (NH) Blacks, regardless of HIV status. CONCLUSION: The increase in rates of pre-eclampsia between 2002 and 2015 was mostly noted among pregnant women without HIV. Regardless of HIV status, NH-Blacks experienced the highest discharge prevalence of preeclampsia.

Exploration of CYP21A2 and CYP17A1 polymorphisms and preeclampsia risk among Chinese Han population: a large-scale case-control study based on 5021 subjects.

BACKGROUND: Several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs), such as rs4409766, rs1004467, and rs3824755 in CYP17A1 and rs2021783 in CYP21A2, as new hypertension susceptibility genetic variants in the Chinese population. This study aimed to look into the relationship between preeclampsia (PE) and these SNPs in Chinese Han women. METHODS: Overall, 5021 unrelated pregnant women were recruited, including 2002 patients with PE and 3019 normal healthy controls. The real-time PCR (TaqMan) method was applied to genotype these four polymorphisms. RESULTS: A statistically obvious difference in the allelic frequencies was observed in CYP21A2 rs2021783 between cases and controls (χ2 = 7.201, Pc = 0.028 by allele), and the T allele was associated with the occurrence and development of PE (OR = 1.151, 95% CI 1.039-1.275). We also found a significant association between rs2021783 and the development of early-onset PE (Pc = 0.008 by genotype, Pc = 0.004 by allele). For rs1004467 and rs3824755, the distribution of allelic frequencies differed markedly between mild PE and control groups (χ2 = 6.843, Pc = 0.036; χ2 = 6.869, Pc = 0.036), and patients with the TT genotype of rs1004467 were less easy to develop mild PE than were those carrying the CT or CC genotype (χ2 = 7.002, Pc = 0.032, OR = 1.306, 95% CI 1.071-1.593). The GG genotype of rs3824755 appeared to a protective effect on the occurrence of mild PE (OR = 0.766, 95% CI 0.629-0.934). CONCLUSIONS: CYP21A2 rs2021783 appears to be closely related to PE susceptibility, and CYP17A1 rs1004467 and rs3824755 seem to be closely associated with mild PE in Han women.

Comparative risks and predictors of preeclamptic pregnancy in the Eastern, Western and developing world.

Preeclampsia (PE) is a complication of pregnancy characterized by hypertension (HTN-Preg), and often proteinuria. If not managed promptly, PE could lead to eclampsia and seizures. PE could also lead to intrauterine growth restriction (IUGR) and prematurity at birth. Although PE is a major cause of maternal and fetal morbidity and mortality, the underlying mechanisms are unclear. Also, there is a wide variability in the incidence of PE, ranging between 2 and 8% of pregnancies in the Eastern, Western and Developing world, suggesting regional differences in the risk factors and predictors of the pregnancy-related disorder. Several demographic, genetic, dietary and environmental factors, as well as maternal circulating biomarkers have been associated with PE. Demographic factors such as maternal race and ethnicity could play a role in PE. Specific genetic polymorphisms have been identified in PE. Maternal age, parity, education and socioeconomic status could be involved in PE. Dietary fat, protein, calcium and vitamins, body weight, and environmental factors including climate changes and air pollutants could also play a role in PE. Several circulating cytoactive factors including anti-angiogenic factors and cytokines have also been associated with PE. Traditional midwifery care is a common practice in local maternity care units, while advanced perinatal care and new diagnostic tools such as uterine artery Doppler velocimetry have been useful in predicting early PE in major medical centers. These PE risk factors, early predictors and diagnostic tools vary vastly in different regions of the Eastern, Western and Developing world. Further understanding of the differences in the demographic, genetic, dietary and environmental factors among pregnant women in different world regions should help in designing a region-specific cluster of risk factors and predictors of PE, and in turn provide better guidance for region-specific tools for early detection and management of PE.

Assessment of insertion/deletion polymorphism of ACE gene as a genetic risk marker for preeclampsia in pregnant women.

OBJECTIVE: To investigate the possible associations of angiotensin converting enzyme insertion or deletion genotypes and alleles with the risk of preeclampsia in Arab women. METHODS: The case-control study was conducted from January 2016 to December 2017 at King Abdulaziz University Hospital and Maternity & Children Hospital, Jeddah, Saudi Arabia, and comprised pregnant women withpreeclampsia as cases and normal pregnant women as controls. Deoxyribonucleic acid was extracted and angiotensin-converting enzyme gene was amplified by polymerase chain reaction analysis and characterised through gel electrophoresis. RESULTS: Of the 162 women, 68(42%) were cases and 94(58%) controls. The mean values of age, body mass index, and systolic and diastolic blood pressure were significantly different among the cases than the controls (p<0.05), but mean gestational age did not significantly differ between the groups (p>0.05). The distribution of the polymorphic variants of the angiotensin converting enz yme gene insertion/deletion was not significantly different between the groups (p>0.05). Also, genotype distribution and allelic frequencies were not significantly different between the groups (p>0.05). CONCLUSIONS: For insertion/deletion polymorphism, no significant differences were detected in the genotype and allele frequencies or any of the inheritance models between preeclampsia patients and controls.