Maternal Blood Pressure Research Articles

Calcitriol prevents SARS-CoV spike-induced inflammation in human trophoblasts through downregulating ACE2 and TMPRSS2 expression

SARS-CoV-2, the causative virus of COVID-19, increases the risk of pregnancy complications including hypertensive disorders and placental inflammation. The spike glycoprotein mediates viral cell entry by interacting with the angiotensin-converting enzyme (ACE)2 in conjunction with the transmembrane serine protease 2 (TMPRSS2). ACE1, ACE2 and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. As the placenta expresses all these proteins, it is a target for SARS-CoV-2 and a source of blood pressure modulators. Noteworthy, an ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the most active vitamin D metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby protecting against COVID-19 severity. However, contrasting information exists on the regulatory role of calcitriol upon RAS components and SARS-CoV-2 receptors; while the impact of calcitriol on spike-induced inflammation in placental cells has not been explored. Thus, we studied the effects of calcitriol on these parameters using the trophoblast cell line HTR-8/SVneo and primary syncytiotrophoblasts. By RT-qPCR, ELISA, and immunocytochemistry, we found that the spike enhanced proinflammatory cytokines expression and secretion, while calcitriol significantly downregulated this effect. Calcitriol also diminished ACE1, ACE2, TMPRSS2, and renin gene expression, as well as ACE1/ACE2 mRNA ratio. ConclusionsIn the human placenta, calcitriol reduced the gene expression of main RAS components and TMPRSS2, resulting in the inhibition of spike-induced inflammation. This outcome suggest that vitamin D participates in restricting SARS-CoV-2 placental infection by rendering trophoblasts less permissive to infection while helping to regulate maternal blood pressure and decreasing inflammation.

Mid-late gestation leptin infusion induces placental mitochondrial and endoplasmic reticulum unfolded protein responses in a mouse model of preeclampsia

IntroductionPreeclamptic patients, both lean and obese, present with elevated leptin levels which are associated with the development of maternal endothelial dysfunction and adverse fetal outcomes, such as growth restriction, leading to low birth weight. Recent studies in pregnant mice demonstrate that mid-late gestation leptin infusion induces clinical characteristics of preeclampsia, including elevated maternal blood pressure, maternal endothelial dysfunction and fetal growth restriction. However, whether leptin triggers placental stress responses that contribute to adverse fetal outcomes as in preeclampsia is unknown. MethodsIn the current study we measured the expression of proteins involved in the endoplasmic reticulum (UPRer) and mitochondrial (UPRmt) unfolded protein responses in placentas of wild-type sham normal pregnant and leptin-infused preeclamptic mice. ResultsThe data show that mid-late gestation leptin infusion induced activation of indices of placental UPRer and UPRmt, while reducing placental repair mechanisms to UPRmt in preeclamptic mice. Mid-late gestation infusion with leptin upregulated markers of placental oxidative stress, reduced the placental expression levels of mitochondrial electron transport chain complexes I and II and increased the expression of placental endothelin-1 (ET-1) in preeclamptic mice. The leptin-induced activation of several placental UPRmt markers as well as ET-1 levels correlated with fetal growth restriction and impaired maternal endothelial function in preeclamptic mice. DiscussionCollectively, these data indicate that elevated levels of leptin in mid-late pregnancy in mice promote placental stress responses, akin to those in pregnant women with preeclampsia.

Pattern of Birth Defects, Association And Their Outcomes Among Neonates In A Tertiary Care Hospital In Bangladesh

Introduction: Birth defects are one of the major cause of stillbirths and neonatal mortality in developed and developing countries. The prevalence of birth defects varies in different parts of the world. In many cases, the causes are unknown; however, several factors known to be associated are genetic factors, maternal age, health, dietary factors, maternal infections, geographical factors, drugs, smoking and irradiation. Objectives: To identify the pattern of birth defects, association and their outcomes among neonates Methodology: This observational cross-sectional study was conducted in the department of neonatology, Dhaka Medical College Hospital, Dhaka from 1st July 2019 to 30th June 2021. Sample was collected by purposive sampling technique. Total 407 babies were enrolled. Out of them 207 babies were with birth defects in group-A and 200 babies had no birth defects in group-B. Detail demographic data were collected from the informant and recorded in structured case report form. Clinical examination and relevant investigations were done. Data processing work consist of registration schedules, editing computerization, preparation of dummy table, analyzing and matching of data. Results: In this study the two study groups were almost similar with respect to their demographic characteristics like sex, residence, place of delivery, mode of delivery, gestational age, parity and maternal age. The total number of admission during this period was 3050 and total number of birth defects was 207 (6.78%0). In this study on evaluation of maternal risk factors, group-A maternal high blood pressure were in 25.12% cases( OR=1.62;p=.002), maternal diabetes were in 15.46% cases( OR=1.12;p=.001), poor maternal nutritional status was 14.50%( p=.001), history of taking folic acid was 9.66%(OR=0.10;p=.001), 5.80% of the patient had history of exposure to antenatal radiation(OR=.06;p=.001), 4.43% had history of consanguinity(OR=.05;p=.001), 2.420% of women noticed that exposure to pesticides(OR=.025;p=.001), H/O of taking anticonvulsant was 2.420%(OR=.025;p=.001). Group-B was maternal high blood pressure in 7.25% cases(OR=.078;p=.001), maternal diabetes were in 6.28% cases(OR=.067;p=.001), poor maternal nutritional status was 5.80%(p=.001), history of taking folic acid was 4.83% (OR=.051;p=.001), 1.45% of the patient had history of exposure to antenatal radiation(OR=.015;p=.001) and 0.97% had history of consanguinity(OR=.01;p=.001). In this study pattern of birth defects summarized as the cardiovascular system defects was the most commonly affected(26.57%), followed by defects in the head, neck ear,- and eye(19.32%), Syndromes(14.50%), gastrointestinal defects(12.56%), musculoskeletal system defects(10.14%), central nervous system defects (8.70%) and genitourinary system(4.83%) of total defects. In group-A 78.26% of the patients recovered and 23 patients expired during hospital stay (p=.001). In group-B 85.99% of the patients recovered and 17 patients expired. Conclusion: Congenital cardiac defects were the most prevalent anomaly detected. Maternal high blood pressure and diabetes are the risk factors of birth defects in neonates. Antenatal diagnosis and proper management can improve the outcome of these neonates. J Dhaka Med Coll. 2023; 32(1) : 43-50

Exploration of the optimal programmed intermittent epidural bolus volume with the dural puncture epidural technique for labour analgesia: a biased-coin up-and-down sequential allocation study.

To determine the optimal programmed intermittent epidural bolus (PIEB) volume for providing effective analgesia in 90% of patients (EV90) during the first stage of labour using the dural puncture epidural (DPE) technique to initiate labour analgesia. We conducted a biased-coin up-and-down sequential allocation study. We included 40 nulliparous women requiring epidural labour analgesia. We used a 25G Whitacre spinal needle to puncture the dural mater and then administered a loading dose of 12mL of ropivacaine 0.1% and sufentanil 0.3μg·mL-1. Subsequently, the PIEB pump delivered boluses with an identical solution at a fixed 40-min interval, starting 1hr after epidural initiation. The bolus volume for the first patient was 7mL and was adjusted for subsequent patients according to the study protocol (bolus volume, 7-12mL). The primary endpoint was effective analgesia, indicated by no need for patient-controlled or manual boluses within 6hr after analgesia initiation or until complete cervical dilation, whichever came first. Outcome evaluators assessed the patients' pain ratings, Bromage scores, sensory blockade level, and maternal blood pressure hourly. Using the truncated Dixon and Mood method, the estimated EV90 was 9.2mL (95% confidence interval [CI], 8.5 to 9.9) whereas the isotonic regression method yielded a value of 8.8mL (95% CI, 8.6 to 9.8). None of the patients experienced a motor block. Two patients experienced hypotension without the need for vasopressors. The estimated PIEB EV90 for ropivacaine 0.1% and sufentanil 0.3μg·mL-1 approached 9mL when DPE was combined with a fixed 40-min interval. ChiCTR.org.cn ( ChiCTR2300067281 ); first submitted 3 January 2023.

Correlation and clinical significance of placental tissue selectin (E), angiotensin II and its receptors, and oxidized lipid levels in patients with preeclampsia

Background: The purpose was to analyze the levels of placental tissue selectins (E), angiotensin II (AngII) and its receptors (ATRs), and oxidized lipids (malondialdehyde (MDA), 8-isoprostane 2a) in patients with preeclampsia (PE). (8-iso-PGF2a)) correlation and clinical significance. Methods: Select 30 PE pregnant women who were admitted to our hospital from March 2023 to January 2024 as the case group, and select another 30 normal pregnant women who were registered in our hospital during the same period as the health group .The general information of the two groups and placental tissue selectin (E), plasma AngII, ATRs, placental tissue MDA, 8-iso-PGF2a and blood pressure levels (systolic blood pressure (SBP), diastolic blood pressure (DBP)) were compared. Pearson correlation was used to analyze the correlation between the expression of selectin (E), AngII, ATRs, MDA, 8-iso-PGF2a and the levels of SBP and DBP. Linear regression analysis was used to analyze the correlation between the expression of selectin (E), AngII, ATRs, MDA, 8-iso-PGF2a, SBP, DBP and other indicators and the occurrence of PE. ROC curves were drawn to analyze the value of placental tissue selectin (E), AngII, ATRs, MDA, and 8-iso-PGF2a individually and jointly in predicting the risk of PE. Results The expression of placental tissue selectin (E), AngII, ATRs, MDA, 8-iso-PGF2a and the levels of SBP and DBP in the case group were higher than those in the healthy group (P<0.05). Pearson correlation showed that the expression levels of placental tissue selectin (E), AngII, ATRs, MDA, and 8-iso-PGF2a were positively correlated with SBP and DBP (r>0, P<0.05). Linear regression analysis showed that placental tissue selectin (E), AngII, ATRs, MDA, 8-iso-PGF2a expression and SBP, DBP levels were closely related to the occurrence of PE (P<0.05). The results of drawing the ROC curve showed that the AUCs of placental tissue selectin (E), AngII, ATRs, MDA, and 8-iso-PGF2a expression in predicting the occurrence of PE were 0.854, 0.756, 0.745, 0.885, 0.900, and 0.905 respectively. Conclusion Placenta tissue selectin (E), AngII, ATRs, MDA, and 8-iso-PGF2a are highly expressed in pregnant women with PE. The expression of the above indicators is related to maternal blood pressure levels and the occurrence of PE, and their combination can effectively increase predictive value of the risk of PE.

Optimal Infusion Rate of Norepinephrine for Prevention of Spinal Hypotension for Cesarean Delivery: A Randomized Controlled Trial, Using Up-Down Sequential Allocation.

Norepinephrine has recently been suggested to be as effective as phenylephrine for the prevention of hypotension after spinal anesthesia for cesarean delivery. Moreover, compared to phenylephrine, norepinephrine may be superior in maintaining heart rate (HR) and consequently, cardiac output (CO). A recent study demonstrated that norepinephrine given as a single intravenous bolus is approximately 13 times more potent than phenylephrine. However, it is uncertain whether this finding can be applied when these vasopressors are administered as infusions. Therefore, the optimum infusion rate of norepinephrine remains unknown. We aimed to determine the median effective dose (ED50; defined as the rate of vasopressor infusion required to prevent spinal hypotension in 50% of subjects) of both drugs needed to maintain maternal systolic blood pressure within 20% of the baseline after spinal anesthesia for cesarean delivery and to derive the relative potency ratio. Sixty healthy patients undergoing elective cesarean delivery with standardized spinal anesthesia were randomized into 2 groups. The first patient in group 1 received phenylephrine 1200 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (20 µg.min-1). The first patient in group 2 received norepinephrine 96 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (1.6 µg.min-1). Using up-down sequential allocation technique, the vasopressor dose for every subsequent patient was determined by the response in the previous patient. If effective, the next patient received a dose reduced by 150 µg of phenylephrine (2.5 µg.min-1) or 12 µg (0.2 µg.min-1) of norepinephrine. If ineffective, the dose for the next patient was increased by the same amount. The ED50s were determined according to the Dixon-Massey formula. Stroke volume (SV), HR, and CO were also measured. The ED50 was 12.7 µg.min-1 (95% CI, 10.5-14.9) for phenylephrine and 1.01 µg.min-1 (95% CI, 0.84-1.18) for norepinephrine, giving a potency ratio of 12.6 (95% CI, 9.92-15.9). HR, SV, and CO did not differ between the groups. Norepinephrine is more potent than phenylephrine by a factor of approximately 13 when administered as infusion for equivalent maternal blood pressure control. Based on these findings, we recommend a variable rate prophylactic infusion of norepinephrine to be initiated at 1.9 to 3.8 µg.min-1 for the management of hypotension during cesarean delivery under spinal anesthesia.

Analysis of ICAM-1 rs3093030, VCAM-1 rs3783605, and E-Selectin rs1805193 Polymorphisms in African Women Living with HIV and Preeclampsia.

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.

The intergenerational metabolic-cardiovascular life course: maternal body mass index (BMI), offspring BMI, and blood pressure of adolescents born extremely preterm.

The aim of this study was to evaluate associations between pre-pregnancy maternal obesity and adolescent blood pressures (BPs) among children born extremely preterm. This longitudinal observational cohort study included participants in the multicenter Extremely Low Gestational Age Newborn (ELGAN) study, born before 28weeks of gestation, recruited at birth between 2002 and 2004, and followed prospectively through late adolescence. Between 2015 and 2022, three oscillometric BPs were obtained from participants (mean age 17.8years). We used linear regression modeling to evaluate the association between maternal self-reported pre-pregnancy body mass index (BMI) and offspring adolescent systolic BP (SBP). In secondary analyses, we evaluated the association between maternal pre-pregnancy and offspring preadolescent (10-year-old) BMI and between offspring preadolescent BMI and adolescent SBP. The 100 (24%) participants born to a mother with a history of pre-pregnancy obesity (BMI ≥ 30) had a greater mean SBP of 120.5 (± 14.3) mmHg compared to the 324 (76%) of adolescents born to mothers without pre-pregnancy obesity (SBP 115.6 (± 12.0) mmHg). Pre-pregnancy obesity was associated with higher offspring BMI (aβ 10.8, 95% CI 2.3, 19.2), and higher offspring BMI was associated with higher adolescent SBP (aβ 0.12, 95% CI 0.09,0.16). For ELGANs, higher maternal pre-pregnancy BMI was associated with higher adolescent SBP. Findings from secondary analyses suggest potential mediation through preadolescent BMI. Future research directions include multi-level interventions to reduce maternal pre-pregnancy obesity, followed by offspring obesity prevention interventions as a way of reducing intergenerational cardiovascular disease in high-risk infants born extremely preterm.

Mobil Monitoring Doppler Ultrasound (MoMDUS) study: protocol for a prospective, observational study investigating the use of artificial intelligence and low-cost Doppler ultrasound for the automated quantification of hypertension, pre-eclampsia and fetal growth restriction in rural Guatemala

IntroductionUndetected high-risk conditions in pregnancy are a leading cause of perinatal mortality in low-income and middle-income countries. A key contributor to adverse perinatal outcomes in these settings is limited access...

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Enhancing maternal survival in traumatic cardiovascular collapse during pregnancy: A case series on resuscitative hysterotomy (RH) from a level 1 trauma center

Background: Trauma during pregnancy presents multifaceted risks to both the developing fetus and the expectant mother due to pregnancy-induced physiological adaptations that affect the response to traumatic injuries. The infrequent occurrence of cardiac arrest during pregnancy necessitates interventions such as perimortem cesarean section (PMCS), now termed resuscitative hysterotomy. While early resuscitative hysterotomy focused primarily on fetal survival, more recent literature reports substantial maternal benefits. Resuscitative hysterotomy can lead to the restoration of maternal pulse and blood pressure within minutes and has shown potential to improve maternal outcomes. RH has been demonstrated to aid in fetal and maternal survival in hemodynamic unstable pregnant patients before cardiovascular collapse. The linguistic change from PMCS to resuscitative hysterotomy is a shift towards maternal-centric approaches and survival. ObjectiveIn this series, we evaluate the outcomes of resuscitative hysterotomy performed before or after cardiovascular collapse to maximize maternal survival while concurrently optimizing fetal outcomes. MethodsWe performed a retrospective case series review of 4 consecutive pregnant trauma patients who underwent RH due to hemodynamic instability. In addition, we conducted a descriptive analysis of all pregnant patients from 2013 to May 2024 who presented due to a traumatic injury but did not require a RH. ResultsThe average age of patients undergoing RH was 26.5 ± 6.8 years. All patients were in the third trimester with a mean gestational age of 32.3 ± 0.5 weeks. Fifty percent (50 %) of patients were involved in motor vehicle accidents, one (25 %) pedestrian was hit by a vehicle, and one (25 %) had GSW to the head. The median time to RH was 14.5 min. The mean estimated blood loss (EBL) was 625 mL ±108.9 mL. The maternal survival rate was 50 %, with a fetal survival rate of 100 %. Three patients achieved hemodynamic stability; however, one of the patients progressed to death by neurological criteria. Therefore, we achieved 50 % of maternal survival. A resuscitative hysterotomy was performed due to early signs of maternal hemorrhagic shock and suggestive features of ongoing bleeding (persistent maternal tachycardia despite adequate analgesia and resuscitation, persistent maternal bradycardia, gradual decline of BP, and FHR abnormalities) in three patients. The remaining patient was found to have cardiac arrest at the scene with a brief return of spontaneous circulation and received resuscitative hysterotomy in the ED to restore cardiovascular function. ConclusionRH in pregnant patients with traumatic injury and impending hemorrhagic shock or cardiovascular collapse may provide maternal survival benefits by supporting circulatory function and promoting resuscitation with no additional risks to fetal outcomes. Quick decision-making is crucial to the implementation of this life-saving procedure. Further research with a more significant number of patients is needed to validate the efficacy of RH in maximizing maternal survival. This case series adds to the evolving literature on RH, shedding light on practical aspects and maternal outcomes to inform ongoing discussions and strategies for maternal cardiopulmonary resuscitation.

Abstract P410: Association Between Maternal Magnesium and Offspring Blood Pressure at 4 Years of Age: A Birth Cohort Study

Background: The potential influence of maternal magnesium levels during gestation on offspring's blood pressure remains largely unexplored. Objective： We aim to investigate the association of maternal magnesium concentrations during early pregnancy and child’s blood pressure at four years of age. Methods: Using data from the Shanghai Birth Cohort, this study analyzed the data from 1129 mother-child pairs. Results: Maternal blood magnesium concentrations were inversely associated with blood pressure of offspring at 4 years of age. Each 1mmol/L increment in maternal magnesium was correlation with 3.03 mmHg (95% CI -4.77 to -1.29, P =0.001) decrease of systolic blood pressure and 1.72 mmHg (95% CI -3.22 to -0.23, P =0.024) decrease of diastolic blood pressure in children after adjusting for covariates. Moreover, maternal magnesium concentrations were associated with incident high blood pressure (OR = 0.40, 95% CI, 0.17 to 0.95, P =0.037) of offspring. Exploratory maternal pre-pregnancy body mass index stratified analyses found that the negative regression coefficient (β) of maternal magnesium and child blood pressure was greater in the overweight/obese group than in normal weight group or underweight group ( P for systolic blood pressure difference 0.014, P for diastolic blood pressure difference 0.019). Conclusions: Our data suggest higher maternal magnesium concentrations are associated with lower blood pressure levels and reduced risk of high blood pressure in children. Our findings highlight the importance of maternal Mg levels during pregnancy, especially for the mothers who are overweight or obese.

Protective Assets Reinforced With Integrated Care and Technology (PARITY): Protocol for a Randomized Controlled Trial.

Black women are significantly more likely to experience severe maternal morbidity and are 3 times as likely to die from pregnancy-related causes compared to White women. Using a strengths-based wellness approach within an integrated supportive care program provided by a community doula could offer pragmatic solutions for Black maternal disparities. The Protective Assets Reinforced with Integrated Care and Technology (PARITY) program consists of a wellness technology platform, including informational links to wellness content and reinforcing motivational SMS text messages, as well as community-based doula support delivered both in person and through the technology platform to improve Black maternal wellness. This pilot randomized controlled trial (RCT) and mixed methods evaluation aims to (1) determine the feasibility and acceptability of the PARITY intervention; (2) investigate the preliminary efficacy of the PARITY intervention on clinical outcomes (maternal blood pressure, gestational weight gain, and cesarean birth); and (3) investigate changes to wellness behavioral outcomes (nutrition, physical activity, sleep, and health care adherence) and empowered strengths (self-efficacy, social support, motivation, resilience, problem-solving, and self-regulation) in the intervention group compared to a control group. A 2-arm RCT and mixed methods evaluation will be conducted. Overall, 60 Black pregnant individuals will be randomized in a ratio of 1:1 to either the intervention or informational control group. Participants in the intervention group will receive access to the technology platform over a 12-week period that ends before birth. Intervention participants will be assigned a doula interventionist, who will meet with them 4 times during the intervention. All participants (intervention and control) will receive a referral for a birth doula at no cost, printed materials about having a healthy pregnancy, and community resources. Feasibility and acceptability will be assessed at the end of the program. Measures will be obtained at baseline (20-28 weeks), the 36th week of pregnancy, birth, and 6-12 weeks post partum. Summary statistics and distribution plots will be used to describe measured variables at each time point. A generalized linear mixed model with a shared random component will be used to analyze the effects of PARITY on clinical, wellness behavioral, and empowered strength outcomes, including baseline nutrition, physical activity, and sleep measures as covariates. For significant effects, post hoc contrasts will be adjusted using the Holm method to maintain comparison-wise error at or <.05. Missing data will be addressed using a pattern-mixture model. The National Institute of Nursing Research funded this pilot RCT. Recruitment, enrollment, and data collection are ongoing, and the estimated study completion date is October 2024. The expected results of this study will provide the feasibility and preliminary efficacy of the PARITY intervention, to be used in a larger trial with a 12-month PARITY program intervention. ClinicalTrials.gov NCT05802615; https://clinicaltrials.gov/study/NCT05802615. DERR1-10.2196/58580.

Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among Puerto Rico PROTECT study participants. We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB (95% CI: 0.17, 1.38) and adjusted P-PB (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ; 95% CI: , ). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

First-trimester screening identifies maternal cardiac maladaptation in midgestation.

We have previously established that a logistic regression model, based on maternal demographic characteristics and blood pressure measured at 11-13 weeks' gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the 3 years following pregnancy, at a screen-positive rate of 10%. Furthermore, in midgestation, women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery. In this study, we set out to examine whether use of the first-trimester risk model for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation in midgestation. This was a prospective observational study of 3812 women with singleton pregnancy attending for a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation and again at 19 + 1 to 23 + 3 weeks at King's College Hospital, London, UK, between December 2019 and August 2020. The first-trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. In midgestation, detailed maternal cardiovascular assessment was carried out. The association between risk for development of CH, determined from first-trimester assessment, and cardiovascular indices in midgestation was examined. Women who were at high risk for development of future CH, compared to those at low risk, had a higher incidence of HDP. In addition, high-risk women had reduced systolic and diastolic function in midgestation. Among women with HDP, those who were at high risk for future CH, compared to those at low risk, had worse cardiac function in midgestation. Use of a model for first-trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation in midgestation. Further studies are needed to clarify whether women who screen as high risk for future CH, compared to those at low risk, have reduced cardiac function beyond pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Safety and efficacy of motor imagery-based physical activity in high-risk pregnancy: A randomized controlled study.

This study aimed to investigate the acute effects of motor imagery-based physical activity on maternal well-being, maternal blood pressure, heart rate, oxygen saturation, fetal heart rate, and uterine contractions in women with high-risk pregnancies. This randomized controlled trial was conducted in Izmir Tepecik Education and Research Hospital from August 2023 to January 2024. Seventy-six women with high-risk pregnancies were randomized into two groups: a motor imagery group (n = 38, diaphragmatic-breathing exercise and motor imagery-based physical activity) and a control group (n = 38, diaphragmatic-breathing exercise). Maternal well-being was determined using the Numerical Rating Scale-11. Digital sphygmomanometry was used to measure maternal heart rate and blood pressure, pulse oximetry for oxygen saturation, and cardiotocography for fetal heart rate and uterine contractions. Assessments were performed pre-intervention, mid-intervention, and post-intervention. There were no significant differences in baseline characteristics between groups (P > 0.05). There was a significant main effect of time in terms of maternal well-being and maternal heart rate (P = 0.001 and P = 0.015). In addition, there was a significant main effect of the group on oxygen saturation (P = 0.025). The overall group-by-time interaction was significant for maternal well-beingm with an effect size of 0.05 (P = 0.041). The combination of diaphragmatic-breathing exercises and a motor imagery-based physical activity program in women with high-risk pregnancies was determined to have no adverse effects on the fetus, did not induce uterine contractions, and resulted in a significant improvement in maternal well-being and oxygen saturation. Thus, imagery-based physical activity can be used in high-risk pregnancies where physical activity and exercise are not recommended.

Association between early pregnancy maternal blood pressure and risk of congenital heart disease in offspring

Objective: To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women's and Children's Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD. Results: A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women's and Children's Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (Ptotal<0.001; Pnon-liear=0.315), DBP (Ptotal<0.001; Pnon-liear=0.928) and MAP (Ptotal<0.001; Pnon-liear=0.929) with the risk of CHD in the offspring. Conclusion: Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.

Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure.

The contribution of air pollution-induced cardiopulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continue to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remain sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model. The exposure resulted in acute depression of heart rate and core body temperature as compared to control animals. Ozone-exposed animals also presented with a slight but significant increase in arterial blood pressure which was perpetuated until term. The data presented here illustrates the feasibility of murine models to assess cardiovascular complications caused by inhaled toxicants during the window of pregnancy.

IL-33 Signaling Inhibition Leads to a Preeclampsia-Like Phenotype in Pregnant Rats.

Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal-placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy. In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured. IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels. Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.