Per- and polyfluoroalkyl substances (PFAS) and Hypertensive disorders of Pregnancy- Integration of Epidemiological and Mechanistic Evidence.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a significant global health burden despite medical advancements. HDP prevalence appears to be rising, leading to increased maternal and fetal complications, mortality, and substantial healthcare costs. The etiology of HDP are complex and multifaceted, influenced by factors like nutrition, obesity, stress, metabolic disorders, and genetics. Emerging evidence suggests environmental pollutants, particularly Per- and polyfluoroalkyl substances (PFAS), may contribute to HDP development. OBJECTIVE: This review integrates epidemiological and mechanistic data to explore the intricate relationship between PFAS exposure and HDP. EPIDEMIOLOGICAL EVIDENCE: Studies show varying degrees of association between PFAS exposure and HDP, with some demonstrating positive correlations, particularly with preeclampsia. Meta-analyses suggest potential fetal sex-specific differences in these associations. MECHANISTIC INSIGHTS: Mechanistically, PFAS exposure appears to disrupt vascular hemodynamics, placental development, and critical processes like angiogenesis and sex steroid regulation. Experimental studies reveal alterations in the renin-angiotensin system, trophoblast invasion, oxidative stress, inflammation, and hormonal dysregulation - all of which contribute to HDP pathogenesis. Elucidating these mechanisms is crucial for developing preventive strategies. THERAPEUTIC POTENTIAL: Targeted interventions such as AT2R agonists, caspase inhibitors, and modulation of specific microRNAs show promise in mitigating adverse outcomes associated with PFAS exposure during pregnancy. KNOWLEDGE GAPS AND FUTURE DIRECTIONS: Further research is needed to comprehensively understand the full spectrum of PFAS-induced placental alterations and their long-term implications for maternal and fetal health. This knowledge will be instrumental in developing effective preventive and therapeutic strategies for HDP in a changing environmental landscape.

Expedited versus standard postpartum discharge in patients with hypertensive disorders of pregnancy and its effect on the postpartum course.

BACKGROUND: Hospital stay after an uncomplicated delivery is typically 2 days for vaginal birth and 3 days for cesarean birth. Health maintenance organizations and third-party payers have encouraged shorter maternity stays. The safety of earlier discharge is unclear particularly when it comes to patients diagnosed with hypertensive disorders of pregnancy (HDP). OBJECTIVE: To examine whether expedited discharge amongst patients with HDP will have a negative effect on postpartum readmission rate and blood pressure related complications. STUDY DESIGN: This was a single academic center retrospective cohort study of patients with HDP (gestational hypertension, preeclampsia, or chronic hypertension) during 2 epochs: 2015-2018, prior to implementation of an expedited discharge policy, and 2019-2020 after hospital wide implementation of expedited postpartum discharge. The expedited discharge policy entailed patients being discharged home as soon as day 1 after a vaginal delivery and day 2 after a cesarean delivery. The primary outcome was unplanned health care utilization postpartum, defined as Emergency Department (ED) visits, unscheduled clinic visits, and hospital readmission. Secondary outcomes were planned postpartum visits attendance, antihypertensive medication initiation after discharge, and blood pressure control throughout the first year. Bivariable and multivariable logistic regression analyses were run to evaluate the association between expedited discharge and primary and secondary outcomes. RESULTS: A total of 1,441 patients were included in the analysis. There were no statistically significant differences in the rate of unplanned health care utilization (11.3% in the standard postpartum discharge group vs. 13.8% in the expedited discharge group, p=0.17). Systolic and diastolic blood pressures did not differ between the groups at 1-2 weeks, six weeks, and one year postpartum. Patients in the expedited discharge group were more likely to attend the 1-2-week postpartum blood pressure check (58.7% vs. 51.7%, p=0.02, adjusted OR 1.33, 95% CI 1.08-1.77). Other secondary outcomes did not differ between the two cohort groups. CONCLUSION: In this single academic center study, expedited discharge after delivery in patients with HDP was not associated with a higher rate of unplanned healthcare utilization postpartum.

Exposure to organophosphate ester flame retardants and plasticizers and associations with preeclampsia and blood pressure in pregnancy.

BACKGROUND: Organophosphate esters (OPEs), flame retardants and plasticizers found widely in consumer products, may impact vascularization processes in pregnancy. Yet, the association between maternal exposure to OPEs and both preeclampsia and blood pressure during pregnancy remains understudied. METHODS: Within the LIFECODES Fetal Growth Study (N=900), we quantified 8 OPE metabolites from maternal urine collected at up to 3 time points during pregnancy and created within-subject geometric means. Outcomes included diagnosis of preeclampsia and longitudinal systolic (SBP) and diastolic (DBP) blood pressure measurements (mean=14 per participant). Cox proportional models were used to estimate associations between OPE metabolites and preeclampsia. Associations between average OPE metabolite concentrations and repeated blood pressure measurements were estimated using generalized estimating equations. RESULTS: Five OPE metabolites were detected in at least 60% of samples; 3 metabolites detected less frequently (5-39%) were examined in an exploratory analysis as ever vs. never detectable in pregnancy. There were 46 cases of preeclampsia in our study population. Associations between OPE metabolites and preeclampsia were null. We noted several divergent associations between OPE metabolites and longitudinal blood pressure measurements. An interquartile range (IQR) difference in average bis(2-chloroethyl) phosphate concentrations was associated with a decrease in SBP (-0.81 mmHg, 95% confidence interval [CI]: -1.62, 0.00), and, conversely, bis(1-chloro-2-propyl) phosphate was associated with a slight increase in SBP (0.94 mmHg, 95% CI: 0.28, 1.61). We also noted a decrease in SBP in association with several metabolites with low detection frequency. CONCLUSIONS: We observed null associations between OPE metabolites and preeclampsia, but some positive and some inverse associations with blood pressure in pregnancy. While our study was well-designed to assess associations with blood pressure, future studies with a larger number of preeclampsia cases may be better poised to investigate the association between OPE metabolites and phenotypes of this heterogenous hypertensive disorder of pregnancy.

The relationship between air pollution and the occurrence of hypertensive disorders of pregnancy: Evidence from a study in Wuhan, China.

Ambient air pollution has been reported to be a risk factor for hypertensive disorders of pregnancy (HDP). Past studies have reported supportive evidence, but evidence from China is scarce and does not integrate the different periods of the pregnancy course. In this study, 1945 pregnant women with HDP and healthy pregnancies between 2016 and 2022 from the Renmin Hospital of Wuhan University registry network database were analysed. The geographic information, biological information and demographic information of the case were fused in the analysis. Machine learning methods were used to obtain the weight of the variable. Then, we used the generalized linear mixed model to evaluate the relationship between increased exposure to each pollutant at different periods of HDP and examined it in different groups. The results showed that SO2 had the predominate impact (12.65 %) on HDP compared with other air pollutants. SO2 exposure was associated with an increased risk of HDP. Increased unit SO2 concentrations were accompanied by an increased risk of HDP (OR = 1.33, 95 % CI: 1.13, 1.566), and the susceptible window for this effect was mainly in the first trimester (OR = 1.242, 95 % CI: 1.092, 1.412). In addition, SO2 exposure was associated with an increased risk of HDP in urban maternity (OR = 1.356, 95 % CI: 1.112, 1.653), obese maternity (OR = 3.58, 95 % CI: 1.608, 7.971), no higher education maternity (OR = 1.348, 95 % CI: 1.065, 1.706), nonzero delivery maternity (OR = 1.981, 95 % CI: 1.439, 2.725), maternal with first time maternity (OR = 1.247, 95 % CI: 1.007, 1.544) and other groups. In summary, SO2 exposure in early pregnancy is one of the risk factors for HDP, and the increased risk of HDP due to increased SO2 exposure may be more pronounced in obese, urban, low-education, and nonzero delivery populations.

Prevalence of hypertension in pregnancy and its associated sociodemographic factors among mothers aged 15-49 years old in Malaysia.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) pose a substantial public health concern, ranking among the primary contributors to maternal and perinatal morbidity and mortality, impacting around 5-10% of pregnancies. This study aimed to determine the prevalence of HDP and its associated factors among mothers aged 15-49 who recently gave birth within the last two years, throughout Malaysia, informing effective public health and primary care interventions. METHODS: This study was a part of the national survey on maternal and child health (MCH) also known as the National Health and Morbidity Survey (NHMS) 2022: MCH. This was a cross-sectional study using two stage stratified random sampling design. Data of mothers aged 15-49 years old who recently gave birth within the last two years were selected in this study. This survey utilised a set of structured validated questionnaires administered via face-to-face interviews (using a mobile device). Multiple logistic regression analysis was employed to identify the associated factors for hypertension. RESULTS: Among 6 335 participants recruited for this study with an estimated population of 782, 550, the prevalence of HDP among Malaysian mothers aged 15-49 years old who recently gave birth within the last two years was 6.5% (95% CI: 5.76, 7.37). Multiple logistic regression showed that maternal age and ethnicity were significantly associated with hypertension. Advanced maternal age had higher odds of hypertension, with an aOR of 2.18 (95% CI = 1.75, 2.71). In addition, Other Bumiputera had higher odds of hypertension (aOR = 2.71, 95% CI = 1.25, 5.87). CONCLUSION: This study reveals the prevalence of HDP among Malaysian women with children under 2 years old, emphasizing advanced maternal age (above 35) and ethnicity as notable risk factors. It improves understanding of the epidemiology of HDP in Malaysia, offering valuable insights for the development of effective public health strategies and clinical interventions that can help with the control of HDP.

Protocol for a randomized controlled trial comparing phone-based prenatal mindfulness training to usual care for pregnant people at risk for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are the most common medical conditions in pregnancy and a leading cause of maternal morbidity and mortality in the United States. There are few interventions available to prevent HDP, and those currently available do not target underlying mechanisms of disease. Mindfulness training (MT) is effective at reducing blood pressure in non-pregnant patients with pre-hypertension and hypertension and has proven more effective at blood pressure reduction than other stress management interventions. MT thus holds great promise as a mind-body intervention to prevent HDP. This randomized trial will harness subjective and objective ecological momentary assessment methodology combined with wearable biosensor technology to capture psychological, physiological, and interpersonal processes through which MT may lead to improved maternal cardiovascular parameters. Pregnant women at risk for HDP will be randomized to an 8-week phone-delivered MT intervention or usual care. Through these methods, we will evaluate psychological, physiological, and interpersonal responses to daily experiences linking MT to cardiovascular parameters among women at risk for HDP.

Examining the predictive value of fetal fraction on hypertensive disorders of pregnancy.

BACKGROUND: Cell-free fetal DNA (cffDNA) screening is routinely performed in pregnancy. Abnormal fetal fraction has been associated with adverse pregnancy outcomes, including hypertensive disorders of pregnancy, which are associated with severe maternal and neonatal morbidity and mortality. OBJECTIVE: This study examined whether abnormal fetal fraction, defined in this study as fetal fraction either <6 or >15 on the basis of restricted-cubic-spline-plot within our study population, was associated with HDP in a retrospective sample, as well as whether fetal fraction improves the prediction of hypertensive disorders of pregnancy (HDP). We hypothesized that abnormal fetal fraction would be associated with HDP and that adding fetal fraction to a model would significantly improve its strength to predict HDP. STUDY DESIGN: This was a retrospective cohort study of 729 patients delivering singleton, non-anomalous pregnancies with conclusive cffDNA screening. The primary outcome was HDP. Logistic regression models tested associations between fetal fraction and HDP. We evaluated the impact of including fetal fraction on the prediction of hypertensive disorders of pregnancy (HDP) by comparing the area under the receiver operating characteristic (ROC) curve (AUC) between predictive models with and without fetal fraction. RESULTS: Among the study sample, there was an HDP rate of 11.5 %. Abnormal fetal fraction was defined as <6 % percentile and >15 %, HDP incidence was significantly higher in patients with fetal fraction <6 % compared to patients with fetal fraction in normal range (fetal fraction 6-15 %) (19.5 % vs 10.7 %, p = 0.006 on post hoc comparison). Model 1 had one predictor (fetal fraction) with an AUC of 0.59, Model 2 had three predictors (BMI, nulliparity, history of HDP) with an AUC of 0.71, and Model 3 had four predictors (BMI, nulliparity, history of HDP, and fetal fraction) with an AUC of 0.73. Models 2 and 3 were not significantly different (p = 0.18). CONCLUSIONS: More patients who developed HDP had low fetal fraction and fewer patients who developed HDP had high fetal fraction compared to those patients who did not develop HDP. Based on results from multivariable regression models, we cannot conclude that fetal fraction improves HDP prediction. However, developing standardized values for abnormal fetal fraction may be clinically useful.

Implementation of aspirin use during pregnancy in community midwifery-led care in the Netherlands: A pilot survey.

INTRODUCTION: Aspirin nowadays is widely used in pregnancy, but implementation among gynecologists took nearly four decades. For a complete insight in the implementation of aspirin, community midwives are to be involved. Community midwives do not have authority to prescribe aspirin and have to refer to a general practitioner or consultant obstetrician for a prescription. METHODS: The study was an online, national pilot survey about the implementation of aspirin use during pregnancy among independently practicing community midwives consisting of 29 items with five categories: background, advising, prescribing, possible indications, and clinical practice. RESULTS: Forty-seven community midwives completed the survey between April and May 2021. All respondents had experience on advising aspirin use in pregnancy. History of preterm pre-eclampsia or HELLP syndrome was identified as a risk factor for developing utero-placental complications by 97.9% of the community midwives. Moderate risk factors in women with otherwise low-risk pregnancy were identified by >75% of the participants. Practical issues in prescribing aspirin were experienced by one-third of the respondents. Suggestions were made to obtain authority for community midwives to prescribe aspirin and improve collaboration with consultant obstetricians and general practitioners. CONCLUSIONS: Community midwives seem to be adequate in identifying risk factors for developing utero-placental complications in women with otherwise low-risk pregnancy. Practical issues for prescribing aspirin occur often. Obtaining authority for community midwives to prescribe aspirin after education should be considered and consulting a consultant obstetrician should become more accessible to overcome the practical issues. Further educating community midwives and general practitioners might improve implementation rates and perinatal outcomes.

Antihypertensive Medication Prescription Dispensation Among Pregnant Women in the United States: A Cohort Study.

IMPORTANCE: Hypertension is increasingly common in pregnancy capable individuals, yet there is limited data on antihypertensive medication dispensation in peripartum individuals. OBJECTIVE: To describe antihypertensive medication dispensation from preconception through the first year postpartum. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Truven Health MarketScan administrative data from 2008 through 2014 to identify women in the United States with commercial or government health insurance, aged 15-54, free from heart disease, who experienced a pregnancy and filled at least one prescription for an antihypertensive medication between three months prior to conception and 12 months after the end of the pregnancy. MAIN OUTCOMES AND MEASURES: We describe antihypertensive dispensation patterns (continuation, initiation, and discontinuation) by medication class during five time periods: preconception, first, second, and third trimesters, and the first year postpartum. RESULTS: Of 1,058,521 pregnancies, 108,614 (10.3%) were exposed to at least one antihypertensive medication dispensation. The most commonly dispensed medications across all periods combined were adrenergic blockers, calcium channel blockers (CCBs), and diuretics. Renin-angiotensin-aldosterone system (RAAS) inhibitors were the third most dispensed medication class in the preconception period (26.4%), and fills decreased to 5.7% and 1.7% in the second and third trimesters, respectively. Of the women with chronic hypertension who filled at least one prescription prior to conception, 8.4% were not dispensed an antihypertensive medication during the first year after delivery. CONCLUSIONS AND RELEVANCE: Antihypertensive prescription dispensation of both preferred and potentially harmful agents is common in pregnancy capable individuals. Patterns of dispensation suggest room for improvement in the treatment of chronic hypertension after a pregnancy.

Activity restriction and risk of adverse pregnancy outcomes.

BACKGROUND: Activity restriction is a common recommendation given to patients during pregnancy for various indications, despite lack of definitive data showing improvements in pregnancy outcomes. OBJECTIVE: To determine if activity restriction (AR) in pregnancy is associated with decreased odds of adverse pregnancy outcomes (APOs). STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) prospective cohort. Nulliparous singletons were followed at 8 sites from October 2010 - September 2013. Demographic and clinical data were collected at 4 timepoints, and participants were surveyed about AR recommendations at 22w0d-29w6d and delivery. We excluded participants missing data on AR and age. Participants were grouped according to history of AR, and APOs included: gestational hypertension (gHTN), preeclampsia/eclampsia, preterm birth (PTB), and small for gestational age (SGA) neonate. Associations between AR and APOs were examined using uni- and multivariable logistic regression models adjusting for a priori identified APO risk factors. RESULTS: Of 10,038 nuMoM2b participants, 9,312 met inclusion criteria and 1,386 (14.9%) were recommended AR; participants identifying as Black [aOR 0.81 (95% CI 0.68-0.98)] or Hispanic [aOR 0.73 (95% CI 0.61-0.87)] were less likely to be placed on AR when compared to those identifying as White. Overall, 3,197 (34.3%) experienced at least one APO [717 (51.7%) of participants with AR compared to 2,480 (31.3%) participants without AR]. After adjustment for baseline differences, the AR group had increased odds of gHTN [aOR 1.61 (95% CI 1.35-1.92)], preeclampsia/eclampsia [aOR 2.52 (95% CI 2.06-3.09)] and iatrogenic and spontaneous PTB [aOR 2.98 (95% CI 2.41-3.69)], but not delivery of an SGA neonate. CONCLUSION: AR in pregnancy was independently associated with increased odds of hypertensive disorders of pregnancy and PTB, but future prospective work is needed to determine potential causality. Further, participants identifying as Black or Hispanic were significantly less likely to be recommended AR compared to those identifying as White. While AR is not an evidence-based practice, these findings suggest bias may impact which patients receive advice to limit activity in pregnancy.

Prediction of neonatal outcomes using gestational age vs ACOG definitions of maternal disease severity in hypertensive disorders of pregnancy.

PURPOSE: Hypertensive disorders of pregnancy cause significant neonatal complications. Disease severity is often used to predict neonatal outcomes, however gestational age (GA) at delivery may be a better predictor. We aimed to assess whether disease severity or GA was more predictive of adverse neonatal outcomes. METHODS: We included 165 participants with confirmed HELLP syndrome or severe preeclampsia (sPE). Two predictive models were constructed to assess the ability of disease severity compared to GA to predict a composite adverse neonatal outcome. The composite outcome included low birth weight, SGA, IUGR, Apgar score, and neonatal death. RESULTS: Using severity as a predictor of binary neonatal outcome had an AUC of 0.73 (0.65-0.81), with a sensitivity (SE) of 70.3% and a specificity (SP) of 64.4%. For GA, we observed an AUC of 0.82 (0.75-0.89), with a SE of 75.7% and a SP of 76.7%. CONCLUSION: For the composite neonatal outcome, GA was a better predictor than ACOG diagnosis (severity). This observation underscores the need for further research to validate these findings in larger cohorts and to determine their applicability to maternal outcomes.

Elevated maternal serum bile acids level, hypertensive disorders of pregnancy and adverse fetal outcomes: a cohort study of 117,789 pregnant women in China.

BACKGROUND: Elevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive. OBJECTIVE: We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes. METHODS: A large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 µmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB). RESULTS: sTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24-1.59]), SGA (aOR=1.31; [95 % CI: 1.18-1.46]), and PTB (aOR=1.27; [95 % CI: 1.15-1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %-63 %] for LBW, 24 % [95 % CI: 13 %-35 %] for SGA, and 34 % [95 % CI: 19 %-49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %-29 %], 4 % [-6%-14 %], 32 % [15 %-50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis. CONCLUSIONS: The substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level.

Association of Race and Ethnicity and Social Factors With Postpartum Primary Care or Cardiology Follow-Up Visits Among Individuals With Preeclampsia.

BACKGROUND: Preeclampsia is associated with increased cardiovascular morbidity and death. Primary care or cardiology follow-up, in complement to routine postpartum obstetric care, provides an essential opportunity to address cardiovascular risk. Prior studies investigating racial differences in the recommended postpartum follow-up have incompletely assessed the influence of social factors. We hypothesized that racial and ethnic differences in follow-up with a primary care provider or cardiologist would be modified by income and education. METHODS AND RESULTS: We identified adult individuals with preeclampsia (September 2014 to September 2019) in a national administrative database. We compared occurrence of a postpartum visit with a primary care provider or cardiologist within 1 year after delivery by race and ethnicity using multivariable logistic regression models. We examined whether education or income modified the association between race and ethnicity and the likelihood of follow-up. Of 18 050 individuals with preeclampsia (aged 31.8±5.7 years), Black individuals (11.7%) had lower odds of primary care provider or cardiology follow-up within 1 year after delivery compared with White individuals (adjusted odds ratio, 0.77 [95% CI, 0.70-0.85]) as did Hispanic individuals (14.8%; adjusted odds ratio, 0.79 [95% CI, 0.73-0.87]). Black and Hispanic individuals with higher educational attainment were more likely to have follow-up than those with lower educational attainment (P for interaction=0.033) as did those in higher income brackets (P for interaction=0.006). CONCLUSIONS: We identified racial and ethnic differences in primary care or cardiology follow-up in the year postpartum among individuals diagnosed with preeclampsia, a disparity that may be modified by social factors. Enhanced system-level interventions are needed to reduce barriers to follow-up care.

Addressing Racial Disparities in the Hypertensive Disorders in Pregnancy: A Plan for Action from the Preeclampsia Foundation's Racial Disparities Task Force.

Hypertensive disorders of pregnancy (HDP) are among the leading causes of maternal mortality in the United States, with Black women and birthing people disproportionately having higher HDP-related deaths and morbidity. In 2020, the Preeclampsia Foundation formed a national Racial Disparities Task Force (RDTF) to identify key recommendations to address issues of racial disparities related to HDP. Recommendations are centered around the Foundation's three pillars: Community, Healthcare Practice, and Research. Healthcare practices include adequate treatment of chronic hypertension in Black women and birthing people, re-branding low-dose aspirin to prenatal aspirin to facilitate uptake, and innovative models of care that especially focus on postpartum follow-up. A research agenda that examines the influence of social and structural determinants of health (ssDOH) on HDP care, access, and outcomes is essential to addressing disparities. One specific area that requires attention is the development of metrics to evaluate the quality of obstetrical care as it relates to racial disparities in Black women and birthing people with HDP. The recommendations generated by the Preeclampsia Foundation's RDTF highlight the strategic priorities and are a call to action that requires listening to the voices and experiences of Black women and birthing people, engaging their communities, and multi-sectoral collaboration to improve healthcare practices and drive needed research.

A prospective cohort study of pregnancy outcomes following antepartum infection with SARS-CoV-2.

OBJECTIVES: Our study aimed to explore the impact of COVID-19 infection on pregnancy outcomes, accounting for the progression of variants, vaccines, and treatment modalities. STUDY DESIGN: We performed a prospective longitudinal cohort study at two urban tertiary centers enrolling patients with a confirmed intrauterine singleton pregnancy from December 23, 2020 to July 18, 2022. Patients were evaluated for SARS-CoV-2 infection at enrollment and every trimester using serum antibody testing. The primary outcome was preterm birth. Symptom and treatment data were collected from pregnant patients with COVID-19 infections. Variant strain infection status was determined from local wastewater analysis. RESULTS: 448 patients were enrolled, and 390 patients were retained through delivery with 159 unexposed and 231 exposed patients, of whom 56 patients (26.0 %) crossed over after enrollment to the exposed cohorts during pregnancy. There was no difference in rates of preterm birth between exposed and unexposed cohorts (14.6 % vs 11.3 %), in deliveries < 34 weeks (1.5 % vs 2.7 %), PPROM, (0.4 % vs 1.3 %), or gestational age at delivery (38.1 vs 38.2). Exposed patients were significantly more likely to be diagnosed with a hypertensive disorder (aOR 2.3, 95 % CI 1.2-4.1), specifically gestational hypertension (aOR 2.8, 95 % CI 1.3--6.0), but not preeclampsia/eclampsia. There were no differences in individual or composite neonatal outcomes. CONCLUSIONS: Our study contributed to the understanding of the effects of SARS-CoV-2 infection on pregnancy outcomes, with increased risk of hypertensive disorders of pregnancy but overall, no differences in adverse neonatal outcomes. Regular antenatal PCR and antibody screening allowed for higher detection and inclusion of patients with asymptomatic SARS-CoV-2 infection and effects on maternal and neonatal outcomes.

Ambient air pollutants exposure during gestation and incidence risk of hypertensive disorders of pregnancy or preeclampsia in China.

The relationships between the exposure to ambient air pollutants during gestation and the incidence of hypertensive disorders in pregnancy (HDPs) or preeclampsia are contradictory. This prospective cohort study enrolled the participants between January 2020 and December 2021 from the Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology. The exposure to ambient air pollutants and daily temperatures were obtained from the ChinaHighAirPollutants dataset and the Big Earth Data Platform for Three Poles, respectively. Logistic regression models were used as single- and two-pollutant models. Restricted cubic splines were applied to each ambient air pollutant exposure to further evaluate the exposure-response relationships. Quantile G-computation approaches were employed to evaluate the cumulative impact of mixed ambient air pollutants on the incidence risk HDPs and preeclampsia. Among 19,325 participants (median age: 30.2 years), 1669 (8.64%) were diagnosed with HDPs and 180 (0.94%) with preeclampsia. While mostly null risk estimates were observed, exposure to PM1, PM2.5, PM10, and NO2 correlated with a decreased incidence risk for HDPs and preeclampsia during most gestational periods. Additionally, our multi-pollutant model presented that an increase by one quartile in the cumulative effect of ambient air pollutants was associated with a significantly decreased incidence risk for HDPs in the trimester before gestation and in the third trimester during gestation, as well as for preeclampsia in the third trimester during gestation. These findings warrant further investigation into the mechanisms underlying these associations.

Association between changes in glycosylated hemoglobin during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy.

OBJECTIVE: To explore the relationship between changes in glycated hemoglobin (HbA1c) during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy (HIP). RESEARCH DESIGN AND METHODS: A total of 1,057 pregnant women who underwent serum HbA1c and delivered at Women's Hospital, Zhejiang University School of Medicine from May 2022 to March 2023, were included in this study. They were divided into four groups. Associations were evaluated using multivariate logistic regression analysis. RESULTS: In our study, an upward trend in HbA1c levels in the second trimester (HbA1c_S) and third trimester (HbA1c_T) among women without HIP was demonstrated. Multivariate logistics regression analysis showed significant associations: Pregnant women with HbA1c_S<5.5 %, HbA1c_T≥6.1 %, or with HbA1c_S≥5.5 %, HbA1c_T<6.1 % had a significant correlation with hypertensive disorders of pregnancy (HDP) (aOR:2.72, 95 %CI=1.24-5.97；aOR:2.59, 95 %CI=1.15-5.84). Furthermore, for each 1 % increase in the difference value of HbA1c between the second and third trimesters, the risk of HDP increased about 1.96 times, and the risk of delivering a large-for-gestational-age baby increased about 1.30 times. CONCLUSION: Among pregnant women without HIP, elevated HbA1c levels in the second or third trimester are associated with increased risks of adverse pregnancy outcomes.

Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

Autonomic Dysfunction and Cardiac Performance in Pregnant Women with Hypertensive Disorders: A Comparative Study Using Heart Rate Variability and Global Longitudinal Strain.

(1) Background: Pregnancy induces significant physiological adaptations with substantial impacts on the cardiovascular system. Hypertensive disorders of pregnancy (HDPs) are connected to significant risks of maternal and fetal complications, contributing significantly to morbidity and mortality across the globe. This study focuses on evaluating autonomic dysfunction by analyzing heart rate variability (HRV) and assessing cardiac performance through global longitudinal strain (GLS) using speckle tracking echocardiography, as well as examining diastolic function in pregnant women with HDP compared to healthy pregnant controls. (2) Methods: A case-control study was conducted involving pregnant women diagnosed with gestational hypertension (GH), preeclampsia (PE), or severe preeclampsia (SPE) as the case group, and healthy pregnant women as the control group. HRV was measured to evaluate autonomic function, GLS was assessed using speckle tracking echocardiography, and diastolic function was evaluated through standard echocardiographic parameters. Data were analyzed to compare cardiac performance and autonomic regulation between the HDP and control group, as well as among the different HDP subgroups. (3) Results: The HDP group exhibited significantly reduced HRV parameters compared to healthy controls, indicating notable autonomic dysfunction. Speckle tracking echocardiography revealed lower GLS among women with HDP, particularly in those with SPE, compared to the control group. Diastolic dysfunction was also present in the HDP group. (4) Conclusions: HRV and GLS are valuable non-invasive tools for detecting autonomic dysfunction and cardiac performance impairments in pregnant women with hypertensive disorders. These findings suggest that autonomic and cardiac dysfunctions are prevalent in HDP.

Gestational exposure to wildfire PM2.5 and its specific components and the risk of gestational hypertension and eclampsia in the southwestern United States.

In the southwestern United States, the frequency of summer wildfires has elevated ambient PM2.5 concentrations and rates of adverse birth outcomes. Notably, hypertensive disorders in pregnancy (HDP) constitute a significant determinant associated with maternal mortality and adverse birth outcomes. Despite the accumulating body of evidence, scant research has delved into the correlation between chemical components of wildfire PM2.5 and the risk of HDP. Derived from data provided by the National Center for Health Statistics, singleton births from >2.68 million pregnant women were selected across 8 states (Arizona, AZ; California, CA, Idaho, ID, Montana, MT; Nevada, NV; Oregon, OR; Utah, UT, and Wyoming, WY) in the southwestern US from 2001 to 2004. A spatiotemporal model and a Goddard Earth Observing System chemical transport model were employed to forecast daily concentrations of total and wildfire PM2.5-derived exposure. Various modeling techniques including unadjusted analyses, covariate-adjusted models, propensity-score matching, and double robust typical logit models were applied to assess the relationship between wildfire PM2.5 exposure and gestational hypertension and eclampsia. Exposure to fire PM2.5, fire-sourced black carbon (BC) and organic carbon (OC) were associated with an augmented risk of gestational hypertension (ORPM2.5 = 1.125, 95 % CI: 1.109,1.141; ORBC = 1.247, 95 % CI: 1.214,1.281; OROC = 1.153, 95 % CI: 1.132, 1.174) and eclampsia (ORPM2.5 = 1.217, 95 % CI: 1.145,1.293; ORBC = 1.458, 95 % CI: 1.291,1.646; OROC = 1.309, 95 % CI: 1.208,1.418) during the pregnancy exposure window with the strongest effect. The associations were stronger that the observed effects of ambient PM2.5 in which the sources primarily came from urban emissions. Social vulnerability index (SVI), education years, pre-pregnancy diabetes, and hypertension acted as effect modifiers. Gestational exposure to wildfire PM2.5 and specific chemical components (BC and OC) increased gestational hypertension and eclampsia risk in the southwestern United States.