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BMC Pregnancy and Childbirth Jun 2024To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in...
OBJECTIVE
To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE.
METHODS
Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates.
RESULTS
A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4.
CONCLUSIONS
The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO was completed through Monte Carlo simulation.
Topics: Humans; Female; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Adult; Prospective Studies; China; Young Adult; Dose-Response Relationship, Drug; East Asian People
PubMed: 38872116
DOI: 10.1186/s12884-024-06620-x -
American Journal of Obstetrics and... Jun 2024In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes, type 2 diabetes, gestational diabetes and (most recently) pre-eclampsia. With...
BACKGROUND
In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes, type 2 diabetes, gestational diabetes and (most recently) pre-eclampsia. With its expanded use, however, concerns of unintended harm have been raised.
OBJECTIVE
We developed an experimental primate model and applied triple-quadruple pole LC mass spectrometry (UHPLC-QQQ) for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.
STUDY DESIGN
Within 30 days of confirmed conception (defined as early pregnancy), n=13 time-bred (TMB) Rhesus dams with gestations designated for fetal necropsy were initiated on twice daily human dose-equivalent 10 mg/kg metformin or vehicle control. Pregnant dams were maintained as pairs and fed either a control chow or 36% fat Western-style diet (WSD). Metformin or placebo vehicle control were delivered in a variety of treats while animals were separated via a slide. A Cesarean was performed at G145, and amniotic fluid and blood were collected and the fetus and placenta were delivered. The fetus was immediately necropsied by trained primate center personnel. All fetal organs were dissected, measured, sectioned, and processed per clinical standards. Fluid and tissue metformin levels were assayed using validated UHPLC-QQQ in SRM against standard curves.
RESULTS
Among the n=13 G145 pregnancies with fetal necropsy, n=1 dam and its fetal tissues had detectable metformin levels despite being allocated to the vehicle control group (>1 μM metformin/kg maternal weight or fetal/placental tissue), while a second fetus allocated to the vehicle control group had severe fetal growth restriction (birthweight 248.32 g, <1%) and was suspected of having a fetal congenital condition. After excluding these two fetal gestations from further analyses, 11 fetuses from dams initiated on either vehicle control (n=4, 3 female, 1 male fetuses) or 10 mg/kg metformin (n=7, 5 female, 2 male fetuses) were available for analyses. Among dams initiated on metformin by G30 (regardless of maternal diet), we observed significant bioaccumulation within the fetal kidney (0.78-6.06 μmol/kg, mean 2.48 μmol/kg) , liver (0.16-0.73 μmol/kg, mean 0.38 μmol/kg), fetal gut (0.28-1.22 μmol/kg, mean 0.70 μmol/kg), amniotic fluid (0.43-3.33 μmol/L, mean 1.88 μmol/L), placenta (0.16-1.0 μmol/kg , mean 0.50 μmol/kg) and fetal serum (0 -0.66 μmol/L , mean 0.23 μmol/L ), and fetal urine (4.1-174.1 μmol/L mean 38.5 μmol/L ), with fetal levels near biomolar equivalent to maternal levels (maternal serum 0.18-0.86 μmol/L , mean 0.46 μmol/L; maternal urine 42.6-254.0 μmol/L , mean 149.3 μmol/L). WSD feeding neither accelerated nor reduced metformin bioaccumulations in maternal or fetal serum, urine, amniotic fluid, placenta nor fetal tissues. In these 11 animals, fetal bioaccumulation of metformin was associated with less fetal skeletal muscle (57% lower cross-sectional area of gastrocnemius) and decreased liver, heart, and retroperitoneal fat masses (p<0.05), collectively driving lower delivery weight (p<0.0001) without changing the crown-rump length. Sagittal sections of fetal kidneys demonstrated delayed maturation, with disorganized glomerular generations and increased cortical thickness; this renal dysmorphology was not accompanied by structural nor functional changes indicative of renal insufficiency.
CONCLUSIONS
We demonstrate fetal bioaccumulation of metformin with associated fetal growth restriction and renal dysmorphology following maternal initiation of the drug within 30 days of conception in primates. Given these results and the prevalence of metformin use during pregnancy, additional investigation of any potential immediate and enduring effects of prenatal metformin use is warranted.
PubMed: 38871238
DOI: 10.1016/j.ajog.2024.06.002 -
JAMA Network Open Jun 2024Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders.
IMPORTANCE
Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders.
OBJECTIVE
To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management.
DESIGN, SETTING, AND PARTICIPANTS
This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022.
EXPOSURES
BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed.
MAIN OUTCOME AND MEASURES
Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables.
RESULTS
A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia.
CONCLUSIONS AND RELEVANCE
This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.
Topics: Humans; Female; Adult; Pregnancy; Pre-Eclampsia; Early Diagnosis; Quality Improvement; Patient Readmission; Postpartum Period; Hypertension; Infant, Newborn; Puerperal Disorders
PubMed: 38869897
DOI: 10.1001/jamanetworkopen.2024.16844 -
Revue Medicale de Liege Jun 2024Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It... (Review)
Review
Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.
Topics: Humans; Pregnancy; Pre-Eclampsia; Female; Risk Factors
PubMed: 38869138
DOI: No ID Found -
Frontiers in Immunology 2024
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Inflammation; Fetal Development; Animals; Neurodevelopmental Disorders
PubMed: 38868765
DOI: 10.3389/fimmu.2024.1434260 -
BMC Proceedings Jun 2024The 5th Preeclampsia Scientific Symposium (PSS2023) organized by Action on Preeclampsia (APEC) Ghana was themed: 'Realign, Refocus: Improving outcomes of Hypertensive...
The 5th Preeclampsia Scientific Symposium (PSS2023) organized by Action on Preeclampsia (APEC) Ghana was themed: 'Realign, Refocus: Improving outcomes of Hypertensive Disorders of Pregnancy through Shared Decision Making, Research & Quality of Care'. It took place on the 18th and 19th of May 2023 at the Ghana College of Physicians and Surgeons (GCPS), Accra Ghana. This transdisciplinary symposium brought together a national representation of experts, policy makers, scientists, and healthcare professionals to discuss key priorities, opportunities, approaches, and strategies to improve the maternal and perinatal outcomes of hypertensive disorders of pregnancy (HDP) in Ghana and the sub-region. The symposium centered around three key themes: realigning/refocusing patient-doctor decision making processes to improve outcomes of HDP; realigning/refocusing clinical care to improve outcomes of HDP; and leveraging on research to predict, recognize and manage high-risk women.This report summarizes insights from the diverse presentations and discussions held at the #PSS2023. This will form a roadmap for future research, policy, and interventions to improve outcomes of HDP in Ghana and the sub-region. The symposium provided a wealth of evidence and knowledge from various experts, highlighting the need for women-centered care, equitable re-allocation of resources, multi-sectoral and innovative approaches, capacity strengthening. Other highlights include knowledge base development and increased stakeholder and community engagement with an overall aim of improving outcomes of HDP. The symposium also fostered inclusivity, welcoming survivors of HDP and their families at a scientific platform. They provided invaluable insights into the challenges faced and the lived experiences of those affected by the disease. Trainees and students also benefited from the symposium as it provided networking opportunities with fellow researchers, and a front row to gaining insights into cutting-edge research in Ghana.
PubMed: 38867245
DOI: 10.1186/s12919-024-00295-0 -
Journal of Cardiovascular Computed... Jun 2024Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of...
BACKGROUND
Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women.
METHODS
The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta.
RESULTS
1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p < 0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p = 0.12).
CONCLUSIONS
Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter.
PubMed: 38866633
DOI: 10.1016/j.jcct.2024.06.001 -
PloS One 2024In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
INTRODUCTION
In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance.
OBJECTIVE
To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia.
DESIGN
Randomized Open Label Clinical Trial.
METHODS
The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician's decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15-20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students' t-test.
RESULTS
Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2-2), vs 4(CI: 4-5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm).
TRIAL REGISTRATION
Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).
Topics: Humans; Magnesium Sulfate; Female; Pre-Eclampsia; Pregnancy; Eclampsia; Adult; Standard of Care; Young Adult; Injections, Intramuscular
PubMed: 38865319
DOI: 10.1371/journal.pone.0286361 -
PloS One 2024Preeclampsia is one of the three leading causes of worldwide maternal mortality. Oxidative stress-mediated endothelial damage is expected to be an ultimate common...
Association of catechol-o-methyltransferase gene polymorphism with preeclampsia and biomarkers of oxidative stress: Study protocol for a prospective case-control study in Pakistan.
BACKGROUND
Preeclampsia is one of the three leading causes of worldwide maternal mortality. Oxidative stress-mediated endothelial damage is expected to be an ultimate common mechanism in the pathophysiology of preeclampsia. The role of bioamines is also well-established in the induction of preeclampsia. This project is aimed to understand the factors which may affect the induction, progression, and aggravation of preeclampsia and oxidative stress during pregnancy. This study will explore the methylation pattern of the Catechol-O-methyltransferase gene to determine its role in the pathogenesis of preeclampsia, association of Val158Met polymorphism with a wide range of oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in preeclamptic Pakistani women.
METHODS AND ANALYSIS
In this prospective case-control study, 85 preeclamptic and 85 normotensive pregnant women will be recruited in their third trimesters. DNA will be extracted from peripheral blood and Val158Met polymorphism in the Catechol-O-methyltransferase gene will be examined on PCR amplified product digested with Hin1II (NlaIII) restriction enzyme, further validated by Sanger sequencing. Methylation-sensitive PCR will also be performed. Oxidative stress biomarkers, antioxidant vitamins, bioamines, and catechol-O-methyltransferase levels will be measured by ELISA. The data will be used to correlate maternal and fetal outcomes in both groups.
DISCUSSION
This study will help to identify and understand the multifactorial path and cause-effect relationship of gene polymorphism, oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in the pathogenesis and aggravation of preeclampsia in the Pakistani population. The outcome of this project will be particularly helpful in reducing the incidence of preeclampsia and further improving its management.
Topics: Adult; Female; Humans; Pregnancy; Antioxidants; Biomarkers; Case-Control Studies; Catechol O-Methyltransferase; Genetic Predisposition to Disease; Oxidative Stress; Pakistan; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Pre-Eclampsia; Prospective Studies; Young Adult
PubMed: 38861573
DOI: 10.1371/journal.pone.0304314 -
BMC Pregnancy and Childbirth Jun 2024CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims...
CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.
Topics: Humans; Pre-Eclampsia; Female; MicroRNAs; Pregnancy; RNA, Circular; Trophoblasts; Placenta; Adult; Cell Movement; Cell Proliferation; Case-Control Studies
PubMed: 38849756
DOI: 10.1186/s12884-024-06560-6