High AMH levels are associated with gestational hypertension in patients with PCOS who underwent IVF/ICSI-ET.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have a higher risk of obstetric complications. The association between anti-Müllerian hormone (AMH) and gestational hypertension in these patients is poorly understood. OBJECTIVE: To determine the association between serum AMH levels and gestational hypertension in patients with PCOS undergoing fresh embryo transfer. METHODS: This retrospective study included 649 patients with PCOS who had singleton live births after undergoing fresh embryo transfers. The association of AMH with gestational hypertension in these patients was estimated before and after propensity score matching (PSM). RESULTS: Patients with gestational hypertension had higher AMH levels than those without gestational hypertension. In single-factor logistic regression, the odds of gestational hypertension increased by 11.7% and 18.6% for every 1 ng/mL increase in AMH before and after adjusting for confounding factors [OR 1.117, 95% CI(1.025, 1.217), P = 0.012; adjusted OR 1.186, 95% CI(1.061, 1.327), adjusted P = 0.003], respectively. The odds of gestational hypertension increased more than 100% [adjusted OR 2.635, 95% CI(1.132, 6.137), adjusted P = 0.025] in the 75th percentile group (>9.30 ng/ml) and more than thrice [adjusted OR 4.75, 95% CI(1.672, 13.495), adjusted P = 0.003] in the 90th percentile group (>12.31 ng/ml) as compared to the without-gestational hypertension group. AMH level was still associated with gestational hypertension after PSM. The area under the curve of AMH predicting gestational hypertension was 0.654 [95% CI (0.532, 0.776), P = 0.011] with an optimal cutoff value of 11.975 ng/mL. CONCLUSIONS: High serum AMH level pre-pregnancy (especially at levels > 9.30 ng/mL) indicates a high odds of gestational hypertension in patients with PCOS undergoing fresh embryo transfer.

Dynamics of serum levels and reference ranges of copeptin in the 3rd trimester of pregnancy in healthy pregnant women with uncomplicated pregnancy and delivery.

OBJECTIVE: Copeptin is a stable fragment of vasopressin. Copeptin levels have been found to reflect the degree of endothelial stress in various conditions, including acute coronary syndrome. Copeptin may be a bio marker for endothelial stress during pregnancy. However, there is still a lack of understanding of its dynamics and levels throughout pregnancy. This study aims to describe intra-individual and longitudinal changes in copeptin levels at 30th and 36th gestational weeks in healthy pregnant women with uncomplicated pregnancy and delivery and to establish specific reference ranges. METHODS: A total of 125 pregnant women with uncomplicated pregnancy and delivery were included. These women were monitored throughout their pregnancy and gave birth at the Department of Obstetrics and Gynecology Olomouc University Hospital. The blood was taken at ~30 and ~36 gestational weeks. Serum copeptin levels were measured using a Kryptor Compact PLUS analyzer. For statistics, we used R software and the "referenceRanges" package. RESULTS: It was found that serum levels of copeptin were significantly higher in the 36th week group than in the 30th week group (P < 0.05). Cook's distance was used to eliminate outliers. The 30th week median was 3.377 pmol/l, reference range = 1.343-7.829 pmol/l, and the 36 week was median 4.735 pmol/l and reference range = 2.06-13.2 pmol/l. In the 36th week reference range, the median was higher than in healthy, non-pregnant women (P < 0.05). Copeptin values can exceed 10 pmol/l, particularly after the 36th week. In the 3rd trimester, this value may indicate cardiovascular and endothelial overload. CONCLUSION: Copeptin levels were found to vary significantly depending on gestational week. The proposed reference ranges take into account the increased secretion of vasopressin in pregnancy. The existence of specific upper reference limits represents a potential advantage in detecting pregnant women prone to hypertensive disease in the 3rd trimester.

Long-Term Predictors of Gestational Hypertension: Placental Growth Factor, Pregnancy-Associated Plasma Protein-A and Free Beta-Hcg Versus Mean Arterial Pressure and Uterine Artery Doppler Versus a Combination of Both: A Comparative Study.

Background: According to WHO, hypertensive disease is the leading cause of direct maternal mortality accounting for 10-25% in developing countries (James in Heart, 90(12):1499-504). This study compares the combinations of mean arterial pressure (MAP) and uterine artery doppler (UAD) versus serum-free ß HCG, pregnancy-associated plasma protein-A, and placental growth factor (PlGF) versus a combination of all variables at 11 to 13+6 as long-term predictors of pregnancy-induced hypertension (PIH). Materials and Methods: A prospective, observational cohort study recruited 97 primigravidae at 11 to 13+6 weeks gestation at GMCH. Follow-up was done at 32-34 weeks and before delivery. Development of PIH, mode of delivery, birthweight, maternal and fetal adverse outcomes were documented, analyzed and compared among three groups. In Group A-biophysical markers, Group B-biochemical markers and in Group C all variables were used. Results: The mean age, maternal weight, height and BMI of patients developing gestational hypertension were 30 ± 5 years, 64.3 ± 12.5 kg, 155.8 ± 5.5 cm and 26.4 ± 4.1, respectively. Out of the 3, Group C is the best screening test for predicting the overall chance of development of gestational hypertension with a sensitivity of 97.37% and specificity of 38.98% (p < 0.0001). A mild negative correlation is seen between PlGF levels and severity of PIH (p-0.0382). Conclusion: MAP and UAD can be easily incorporated into the infrastructure of most hospitals. If the biochemical test kits are made available at a low cost through available programs such as JSSK, it can bring down the MMR by preventing gestational hypertension.

Effects of magnesium sulfate combined with labetalol on inflammatory stress and pregnancy outcome of patients with gestational hypertension.

Gestational hypertension (GH) is a common disorder during pregnancy that can cause adverse pregnancy outcomes. In the present study, magnesium sulfate (MgSO4) combined with labetalol was used for clinical treatment. Randomized controlled trial was conducted in 100 patients with GH, documented in the Department of Obstetrics and Gynecology (Taicang TCM Hospital) grouped into the experimental (Expt) and control (Ctrl) groups (n=50 cases/group). The Ctrl group was treated with MgSO4, whereas the Expt group was treated with MgSO4 + labetalol. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the Expt group were not significantly different from those in the Ctrl group (P>0.05). By contrast, the SBP and DBP were significantly lower after treatment than those before treatment in both groups (P<0.05). Whole blood viscosity, plasma viscosity and hematocrit were significantly lower in the Expt group compared with those in the Ctrl group after treatment (P<0.05). High mobility group box-1 protein, homocysteine and serum cystatin C levels in the Expt group were also markedly lower than those in the Ctrl group after treatment (P<0.05). In the Expt group, the rate of spontaneous vaginal delivery was much higher, whereas the rates of cesarean section and postpartum hemorrhage were markedly lower than those in the Ctrl group (P<0.05). The occurrence of fetal intrauterine distress, placental abruption, neonatal asphyxia, premature birth and neonatal death were also significantly lower in the Expt group than those in the Ctrl group (P<0.05). In conclusion, MgSO4 + labetalol could improve inflammatory stress and the hemodynamics of patients with GH, and may have a marked antihypertensive effect. Thus, it may improve pregnancy outcome and reduce perinatal complications.

Effects of hypertension and use of antihypertensive drugs in pregnancy on the risks of childhood cancers in Taiwan.

BACKGROUND: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks. OBJECTIVE: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. METHODS: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers. RESULTS: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth. CONCLUSIONS: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Investigation and Comparison of Maternal Pre-Pregnancy Body Mass Index Coupled with Gestational Weight Gain on Maternal-Fetal Complications Based on US and Chinese Guidelines: A Retrospective Study.

Compared to Western populations, Chinese and Asians possess distinct genetics, lifestyles, and dietary habits. They tend to have shorter stature, lower Body Mass Index (BMI), and higher body fat percentages than Western populations. The aim of this study was to compare disparities in maternal-fetal outcomes by combining pre-pregnancy BMI and gestational weight gain (GWG) based on distinct US and Chinese guidelines. A total of 2,271 pregnant women who received perinatal care at Fooyin University Hospital from 2016 to 2021 were included. Logistic regression analysis categorized women into twelve groups based on the two criteria to explore the relationships between BMI and GWG, and maternal-fetal outcomes. Among the subjects, only 23.2% and 21.8% women had a normal weight BMI and adequate GWG, based on US and Chinese criteria, respectively. As BMI and GWG increase, the likelihood of developing complications such as gestational diabetes, gestational hypertension or preeclampsia, Cesarean section, and Large for Gestational Age also rises. Conversely, underweight women with excessive GWG exhibited lower risk of preterm birth either by US or Chinese guidelines. Two criteria exhibited similar odds for investigated outcomes, except for gestational hypertension or preeclampsia. Women had more than double the odds of developing gestational hypertension or preeclampsia when using US criteria compared to Chinese criteria. Therefore, it is essential for Asian, especially Chinese women, to be aware of the differences in adverse outcomes such as gestational hypertension or preeclampsia when using US criteria.

Hypertensive disorders of pregnancy among women with cardiovascular disease in Norway: A historical cohort study.

INTRODUCTION: Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP. MATERIAL AND METHODS: We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre-eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate- and high cardiovascular risk compared to women with low risk. RESULTS: The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%-14.4%) and varied between 8.7% (95% CI: 6.5%-11.3%) in the low-risk group, 15.7% (95% CI: 11.1%-21.4%) in the moderate-risk group, and 22.2% (95% CI: 15.1%-30.8%) in the high-risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%-5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre-eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21-3.44) in the moderate-risk group and 2.99 (95% CI: 1.73-5.18) in the high-risk group. CONCLUSIONS: The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.

Hypertensive disorders of pregnancy and long-term maternal cardiovascular risk: Bridging epidemiological knowledge into personalized postpartum care and follow-up.

Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Salidroside prevents gestational hypertension-induced impairment of offspring learning and memory via Wnt/Skp2 pathway.

BACKGROUND: Salidroside (Sal) has been found to protect against multiple impairments caused by diabetes, and we designed this study to investigate the effect of Sal on gestational hypertension (GHP)-induced impairment of offspring learning and memory. METHODS: We established a GHP rat model by intraperitoneal injection of NG-nitro-L-arginine methyl ester (L-NAME), and treated with Sal by daily gavage. We used Morris Water Maze test to evaluate the learning and memory ability of offspring rats. HE staining was used to measured the pathological changes in hippocampus of offspring. Immunohistochemistry, cellular immunofluorescence and western blot were used to detect the protein expression. RESULTS: The learning and memory abilities of GHP offspring rats were significantly lower than those of normal rat offspring, while Sal treatment could significantly improve the learning and memory abilities of GHP offspring rats. HE staining did not reveal pathological differences in the hippocampus of normal rats, GHP rats and Sal-treated GHP offspring rats. However, Sal treatment can significantly increase the expression of Wnt1 and Skp2 protein, and decrease the expression of P27kiwf and P21waf1 protein in the hippocampus of GHP offspring rats. In vitro, Sal significantly promoted the proliferation and differentiation on neural stem cell, while Wnt1 knockdown could reverse these promotions by Sal. In the hippocampus of GHP offspring rats, Sal treatment significantly increased the expression of Tuj1, SOX2, Ki67 and DCX protein. CONCLUSION: Salidroside significantly improves the learning and memory impairment of offspring caused by GHP, and its mechanism may be related to the fact that Salidroside promotes the proliferation and differentiation of neural stem cells by activating the Wnt1/Skp2 signaling pathway.

Management of hypertensive disorders of pregnancy in two Australian tertiary care maternity hospitals.

Background: Hypertensive disorders of pregnancy (HDP) are common obstetric medical problems. Compliance with clinical guidelines and evidence from major trials has the potential to translate to significantly improve maternal and perinatal outcomes. The aims of this study were to prospectively review management of HDP in an Australian cohort in the context of the Society of Obstetric Medicine of Australian and New Zealand (SOMANZ) guidelines and current evidence in published literature regarding management controversies. Methods: The management of 100 pregnant women with HDP and prescription for antihypertensive medication at two tertiary obstetric centres was prospectively reviewed in 2013. Compliance with SOMANZ guidelines, uptake of findings from the HYPITAT trial and the Control of Hypertension In Pregnancy Study (CHIPS) trial were assessed. Results: Sixty-eight women had chronic hypertension, while 32 had gestational hypertension. Management of HDP was mostly consistent with current SOMANZ guidelines and evidence from CHIPS and HYPITAT. Conclusion: Clinicians were practising according to the current SOMANZ guidelines, indicating vigilance on behalf of the treating team.

Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION.

BACKGROUND: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France. METHODS AND RESULTS: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes. CONCLUSIONS: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

A Second Trimester Prediction Algorithm for Early-Onset Hypertensive Disorders of Pregnancy Occurrence and Severity Based on Soluble fms-like Tyrosine Kinase 1 (sFlt-1)/Placental Growth Factor (PlGF) Ratio and Uterine Doppler Ultrasound in Women at Risk.

Hypertensive disorders of pregnancy (HDPs) represent a significant source of severe maternal and fetal morbidity. Screening strategies relying on traditional medical history and clinical risk factors have traditionally shown relatively modest performance, mainly in the prediction of preeclampsia, displaying a sensitivity of 37% for the early-onset form and 29% for the late-onset form. The development of more accurate predictive and diagnostic models of preeclampsia in the early stages of pregnancy represents a matter of high priority. The aim of the present paper is to create an effective second trimester prediction algorithm of early-onset HDP occurrence and severity, by combining the following two biochemical markers: a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio and uterine artery Doppler ultrasound parameters, namely the pulsatility index (PI) and the resistivity index (RI), in a population of high-risk pregnant women, initially assessed through traditional risk factors. A prospective single-center observational longitudinal study was conducted, in which 100 women with singleton pregnancy and traditional clinical and medical history risk factors for preeclampsia were enrolled at 24 weeks of gestation. Shortly after study enrollment, all women had their sFlt-1 and PlGF levels and mean uterine artery PI and RI determined. All pregnancies were followed up until delivery. Receiver operating characteristic (ROC) analysis established algorithms based on cutoffs for the prediction of the later development of preeclampsia: PI 1.25 (96.15% sensitivity, 86.49% specificity), RI 0.62 (84.6% sensitivity, 89.2% specificity) and sFlt-1/PlGF ratio 59.55 (100% sensitivity, 89.2% specificity). The sFlt-1/PlGF ratio was the best predictor for preeclampsia, as it displayed the highest area under the curve (AUC) of 0.973. The prediction algorithm for the severe form of preeclampsia, complicated by fetal growth restriction leading to preterm birth, antepartum fetal demise or acute fetal distress with a cerebro-placental ratio of

N-terminal prohormone of brain natriuretic peptide in gestational hypertension and preeclampsia - State of the art.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these patients.

Clinical features of preeclampsia and hypertensive disorders in pregnancies after different frozen embryo transfer regimens.

OBJECTIVES: To compare whether the clinical features of preeclampsia (PE) or gestational hypertension (GH) were different in pregnancies after a frozen embryo transfer (FET), depending on the FET regimen used. STUDY DESIGN: A retrospective study including 58 pregnancies with PE and 64 pregnancies with GH, all with singleton live births. Pregnancies were stratified according to the presence or absence of a corpus luteum (CL). MAIN OUTCOME MEASURES: Clinical characteristics of PE and GH, maternal background factors, postpartum hemorrhage (PPH), key perinatal outcomes. RESULTS: Among PE patients, no difference was found in the clinical characteristics and in the maternal background factors, when comparing women with a CL to women without a CL. PE patients in the group without a CL had a hemorrhage of > 500 mL or > 1000 mL significantly more often than patients with a CL. Multivariable analyses confirmed this risk. Perinatal outcomes were similar. Among GH patients, there was no difference in the clinical features and maternal background factors, when comparing CL cycles to cycles without a CL. The amount of PPH was higher among the patients without a CL, but the frequency of a > 500 mL or > 1000 mL hemorrhage was similar between groups. No risk increase was seen in multivariable analyses. CONCLUSIONS: Among FET patients with PE, the risk of PPH wasincreased in pregnancies after cycles without a CL, compared to cycles with a CL. The presence or absence of a CL did noteffectthe severity of PE and GH, the duration of pregnancy or blood pressure levels.

Vitamin D Deficiency and Its Association With Vitamin D Receptor Gene Variants Among Malaysian Women With Hypertensive Disorders in Pregnancy: Protocol for a Nutrigenomics Study.

BACKGROUND: Vitamin D deficiency has been associated with hypertensive disorders in pregnancy (HDP). The risk of developing HDP was reported to be further augmented among individuals with a vitamin D receptor (VDR) genetic variant. However, the reported roles of VDR variants in hypertensive disorders are inconsistent among different populations. Given the relatively higher incidence of vitamin D deficiency among Malaysian pregnant women and the high incidence of HDP in this population, we hypothesize that there may be associations between the risk of vitamin D deficiency and HDP with VDR genetic variants. OBJECTIVE: This paper outlines the protocol for a study to determine the association of vitamin D status and VDR sequence variants among Malaysian pregnant women with HDP. METHODS: This prospective study consists of two phases. The first phase is a cross-sectional study that will entail gathering medical records, a questionnaire survey, and laboratory testing for vitamin D status, with a planned recruitment of 414 pregnant women. The questionnaire will be utilized to assess the risk factors for vitamin D deficiency. The vitamin D status will be obtained from measurement of the vitamin D (25-hydroxyvitamin D3) level in the blood. The second phase is a case-control study involving a Malay ethnic cohort with vitamin D deficiency. Participants will be divided into two groups with and without HDP (n=150 per group). Genomic DNA will be extracted from the peripheral blood monocytes of participants using the Qiagen DNA blood kit, and VDR sequence variants will be determined using polymerase chain reaction-high-resolution melting (PCR-HRM) analysis. Sanger sequencing will then be used to sequence randomly selected samples corresponding to each identified variant to validate our PCR-HRM results. The VDR genotype and mutation frequencies of BsmI, ApaI, TaqI, and FokI will be statistically analyzed to evaluate their relationships with developing HDP. RESULTS: As of December 2023, 340 subjects have been recruited for the phase 1 study, 63% of whom were determined to have vitamin D deficiency. In the phase 2 study, 50 and 22 subjects have been recruited from the control and case groups, respectively. Recruitment is expected to be completed by March 2024 and all analyses should be completed by August 2024. CONCLUSIONS: The outcome of the study will identify the nonmodifiable genetic components contributing to developing vitamin D deficiency leading to HDP. This will in turn enable gaining a better understanding of the contribution of genetic variability to the development of HDP, thus providing more evidence for a need of customized vitamin D supplementation during pregnancy according to the individual variability in the response to vitamin D intake. TRIAL REGISTRATION: ClinicalTrials.gov NCT05659173; https://clinicaltrials.gov/study/NCT05659173. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53722.

Cell­free fetal DNA at 11­13 weeks of gestation is not altered in complicated pregnancies.

Non-invasive maternal cell-free fetal DNA (cffDNA) is a promising biomarker for screening common genetic syndromes. Alterations in the expression levels of cffDNA in the maternal circulation have been demonstrated in abnormal pregnancies. However, the results are conflicting. The present study aimed to investigate whether cffDNA levels are associated with pregnancy complications. The study group comprised pregnant women who presented with pregnancy complications, such as preterm birth, gestational hypertension, intrauterine growth retardation, gestational diabetes, polyhydramnios, oligohydramnios, vaginal bleeding and placental abruption. The control group comprised women who had a normal pregnancy course. Blood samples were obtained from 500 pregnant women between 11-13 weeks of gestation. cffDNA was amplified, sequenced and analyzed using the next-generation aneuploidy test of a Panorama-Natera kit. Nuchal translucency (NT) thickness as well as pregnancy associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were also assessed. Statistical analysis was performed in 494 out of the 500 samples collected with SPSS v.26 using non-parametric methods. The parameters were normalized by the multiples of median (MoM) method. The expression levels of PAPP-A, ß-hCG, and the NT mean MoM values were significantly different between the study and control groups (P=0.005, P<0.001 and P=0.007, respectively). However, the expression levels of cffDNA and the mean MoM values were not significantly different between these two groups (P=0.687). The findings of the present study support the conclusion that cffDNA expression is not altered in a series of pregnancy complications. The prognostic value of cffDNA in predicting adverse pregnancy outcomes requires further investigation.

Caring for Patients with Gestational Hypertensive Disorders: Essential Takeaways.

Hypertensive disorders in pregnancy (HDP) are a group of conditions-including chronic hypertension, gestational hypertension, preeclampsia with and without end-organ damage, and acute complications, which include HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and eclampsia-that could lead to severely adverse outcomes for both mother and fetus. The incidence of HDP has increased, affecting one out of seven delivery hospitalizations. Physicians should be aware of HDP for early identification and proper treatment to improve patient outcomes.

The effects of probiotics administration during pregnancy on preeclampsia and associated maternal, fetal, and newborn outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to synthesize the available evidence on probiotic administration during pregnancy for the prevention of preeclampsia and its effects on related maternal, fetal, and newborn outcomes. DATA SOURCES: Six databases were systematically searched for eligible studies, namely Ovid MEDLINE, Embase, CINAHL, Cochrane, Global Index Medicus, and the Maternity and Infant Care Database, from inception to August 2, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that evaluated the effects of probiotic administration on women during any stage of pregnancy were eligible for inclusion. METHODS: The protocol was registered with the International Prospective Register of Systematic Reviews under identifier CRD42023421613. Evaluating study eligibility, extracting data, assessing risk of bias (ROB-2 tool), and rating certainty (Grading of Recommendations, Assessment, Development and Evaluations) were conducted independently by 2 authors. The primary outcomes were incidence of preeclampsia, eclampsia, and maternal mortality. A meta-analysis was performed, and the results were reported as risk ratios with 95% confidence intervals. RESULTS: A total of 29 trials (7735 pregnant women) met the eligibility criteria. There was heterogeneity across the trials in the population of enrolled women and the type of probiotic tested (20 different strains), although most used oral administration. Probiotics may make no difference to the risk of preeclampsia (risk ratio, 1.14; 95% confidence interval, 0.84-1.53; 11 trials; 2401 women; low certainty evidence), preterm birth at <37 weeks' gestation (risk ratio, 0.93; 95% confidence interval, 0.66-1.30; 18 trials, 4016 women; low certainty evidence), or gestational age at delivery (mean difference, -0.03 weeks [≈0.2 days]; 95% confidence interval, -0.16 to 0.10 weeks [≈ -1.1 to 0.7 days]; 13 trials, 2194 women; low certainty evidence). It is difficult to assess the effects of probiotics on other secondary outcomes because the evidence was of very low certainty, however, no benefits or harms were observed. CONCLUSION: Limited evidence suggests that probiotic supplementation does not affect the risk for preeclampsia. Further high-quality trials are needed to definitively assess the benefits and possible harms of probiotic supplementation during pregnancy. There is also a lack of data from trials that included women who were undernourished or who experienced microbial dysbiosis and for whom probiotic supplementation might be useful.

Ambient air pollution and hypertensive disorders of pregnancy in Rome.

BACKGROUND: Ambient air pollution has been associated with hypertensive disorders of pregnancy (HDP), but few studies rely on assessment of fine-scale variation in air quality, specific subtypes and multi-pollutant exposures. AIM: To study the impact of long-term exposure to individual and mixture of air pollutants on all and specific subtypes of HDP. METHODS: We obtained data from 130,470 liveborn singleton pregnacies in Rome during 2014-2019. Spatiotemporal land-use random-forest models at 1 km spatial resolution assigned to the maternal residential addresses were used to estimate the exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3). RESULTS: For PM2.5, PM10 and NO2, there was suggestive evidence of increased risk of preeclampsia (PE, n = 442), but no evidence of increased risk for all subtypes of HDP (n = 2297) and gestational hypertension (GH, n = 1901). For instance, an interquartile range of 7.0 µg/m3 increase in PM2.5 exposure during the first trimester of pregnancy was associated with an odds ratio (OR) of 1.06 (95% confidence interval: 0.81, 1.39) and 1.04 (0.92, 1.17) after adjustment for NO2 and the corresponding results for a 15.7 µg/m3 increase in NO2 after adjustment for PM2.5 were 1.11 (0.92, 1.34) for PE and 0.83 (0.76, 0.90) for HDP. Increased risks for HDP and GH were suggested for O3 in single-pollutant models and for PM after adjustment for NO2, but all other associations were stable or attenuated in two-pollutant models. CONCLUSIONS: The results of our study suggest that PM2.5, PM10 and NO2 increases the risk of PE and that these effects are robust to adjustment for O3 while the increased risks for GH and HDP suggested for O3 attenuated after adjustment for PM or NO2. Additional studies are needed to evaluate the effects of source-specific component of PM on subtypes as well as all types of HDP which would help to target preventive actions.