Search

BackgroundChildhood 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.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData 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.ResultsOffspring 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.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

During pregnancy, the maternal cardiovascular (CV) system undergoes major haemodynamic alterations ensuring adequate placental perfusion and a healthy pregnancy course. Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations and preeclampsia, a more severe form, in 3–4%. Women with HDP demonstrated impaired myocardial function, biventricular chamber dysfunction and adverse biventricular remodelling. Shortly after delivery, women who experienced HDP express increased risk of classic CV risk factors such as hypertension, renal disease, abnormal lipid profile, and diabetes. Within the first two decades following a HDP, women experience increased rates of heart failure, chronic hypertension, ischaemic heart and cerebral disease. The mechanism underlying the relationship between HDP in younger women and CV disease later in life could be explained by sharing pre‐pregnancy CV risk factors or due to a direct impact of HDP on the maternal CV system conferring a state of increased susceptibility to future metabolic or haemodynamic insults. Racial disparities in CV risk and social determinants of health also play an important role in their remote CV risk. Although there is general agreement that women who suffered from HDP should undertake early CV screening to allow appropriate prevention and timely treatment, a screening and intervention protocol has not been standardized due to limited available evidence. In this review, we discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction and how cardiac remodelling during or after pregnancy may influence its development. [ABSTRACT FROM AUTHOR]

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction. [ABSTRACT FROM AUTHOR]

ABSTRACT Circulating lipids play a crucial role during pregnancy and may impact various pregnancy‐related diseases. This study employed a two‐sample Mendelian randomization (MR) framework to investigate the causal relationship between alterations in multidimensional plasma lipid levels and the risk of preeclampsia or eclampsia, offering deeper insight into this association. The inverse variance weighted (IVW) method was utilized as the main analysis. Summary statistics from plasma lipidomics of 7174 Finnish individuals and summary data on preeclampsia/eclampsia from the FinnGen consortium involving 219 817 European participants were employed. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. The study identified 17 lipid species from a total of 179 lipid species associated with susceptibility to preeclampsia/eclampsia. Notably, ten species, including six triacylglycerols (TAGs) (50:1, 48:1, 56:4, 49:2, 48:2, 54:3), a diacylglycerol (DAG) (16:1_18:1), and three sphingomyelins (SMs) (d36:1, d34:1, d38:1), were found to increase the risk of preeclampsia/eclampsia. Conversely, seven species, including five phosphatidylcholines (PCs) (16:1_20:4, O‐18:1_20:4, 18:1_20:4, 16:0_20:4, 17:0_20:4) and two phosphatidylethanolamines (PEAs) (18:0_20:4, 16:0_20:4), all containing arachidonic acid (ARA) in the sn‐2 position, were associated with a reduced risk of preeclampsia/eclampsia (all p < 0.05). The results of the stratified analysis were consistent with these findings. Furthermore, reverse MR analysis indicated that preeclampsia/eclampsia does not causally affect plasma levels of these lipids. Our findings established a causal relationship between specific plasma lipid species and modulation of preeclampsia/eclampsia risk, providing improved resolution for risk assessment and potential therapeutic targets in the disease. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates. Methods: This was an analytical observational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes. Results: Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01–1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06–0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03–3.05) decreased the likelihood of having low Apgar scores at five minutes. Conclusions: Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5 min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions To investigate serum, placental levels of active‐matrix metalloproteinase‐8 (aMMP‐8), myeloperoxidase (MPO) in preterm‐birth with/without pre‐eclampsia and term counterparts in relation with clinical periodontal parameters.Clinical periodontal measurements were recorded. Serum and placenta samples were collected during 173 full‐term (FT), pre‐term (PT) or pre‐term complicated by pre‐eclampsia (PTPE) deliveries. aMMP‐8 levels were measured by IFMA. MPO levels in the serum and placenta samples were determined by ELISA. Data were tested using non‐parametric tests.PTBE group exhibited higher full‐mouth probing depth and clinical attachment loss values than the other two groups (p < 0.05). Percentages of sites with plaque and bleeding on probing were lower in the PTBE group than in the other groups (p < 0.05). Serum aMMP‐8 and MPO concentrations were higher in PTPE group than in the other groups (p < 0.05). Placenta aMMP‐8 level was higher in the control group than in the PTPE group (p < 0.05). There was no significant difference between the groups in the placenta MPO levels (p > 0.05).Within the limits of this cross‐sectional study, it may be suggested that serum aMMP‐8 and MPO concentrations together with placenta aMMP‐8 levels may be associated with and reflect adverse pregnancy outcomes. Clinical periodontal findings did not reveal significant associations with these proteolytic and oxidative biomarkers. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women. Objective: This study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations. Study design: Multiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity. Results: Helicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06–1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62–2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10–8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29–8.74), p-value 0.03]. Conclusion: Our study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations. [ABSTRACT FROM AUTHOR]

Background: Risk factors for influenza complications in women are poorly understood. We examined the association between pregnancy outcomes and risk of influenza hospitalization up to three decades later. Methods: We analyzed a cohort of 1,421,531 pregnant women who delivered in Quebec, Canada between 1989 and 2021. Patients were followed over time beginning at the first delivery. The main exposure measures included obstetric complications such as preeclampsia, gestational diabetes, and preterm birth. The main outcome was influenza hospitalization up to 32 years later. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between obstetric complications and risk of influenza hospitalization following pregnancy. Results: A total of 4,016 women were hospitalized for influenza during 32 years of follow-up. Influenza hospitalization was more frequent among women with pregnancy complications than women without complications (18.0 vs 14.1 per 100,000 person-years). Compared with no pregnancy complication, women with gestational diabetes (HR 1.48, 95% CI 1.30–1.69), preeclampsia (HR 1.45, 95% CI 1.28–1.65), placental abruption (HR 1.36, 95% CI 1.12–1.66), preterm birth (HR 1.40, 95% CI 1.27–1.55), cesarean section (HR 1.22, 95% CI 1.13–1.31), and severe maternal morbidity (HR 1.43, 95% CI 1.22–1.68) had a greater risk of influenza hospitalization later in life. These pregnancy outcomes were associated with severe influenza infections requiring critical care. Conclusions: Women with pregnancy complications have an elevated risk of severe influenza complications later in life and have potential to benefit from seasonal vaccination to prevent influenza hospitalization. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy affect around 10% of pregnancies and remain a major cause of maternal and foetal morbidity and mortality. Trials have shown that self-monitoring blood pressure during pregnancy is safe, but self-monitoring alone does not improve blood pressure control or pregnancy outcomes. This study aimed to develop and optimise a multicomponent intervention to support blood pressure monitoring, hypertension management and urine testing within current care pathways. Methods: Relevant literature, input from patient and public contributors (PPI) and stakeholder groups, and the researcher's previous experience were used to develop an initial intervention. Think-aloud interviews and focus groups with women from diverse backgrounds with lived experience of hypertension in pregnancy and healthcare professionals provided feedback on the intervention prototype (n = 29). The MRC Framework for Developing Complex Interventions guided the processes to optimise the intervention's acceptability and maximise engagement. A detailed tabulation of participants' views and logic models was produced using the COM-B model of Behaviour Change. Results: The prototype intervention was acceptable and viable to both pregnant women with experience of hypertensive pregnancy and healthcare professionals. Emerging themes centred on how the intervention could be optimised within current National Health Service care pathways and the lives of pregnant women to support behaviour change. Key target behaviours to support the intervention included increasing understanding of blood pressure management, engagement with the intervention, monitoring blood pressure and urine and taking appropriate actions based on those readings. This informed the development of recommendations involving clear action timelines for women and evidence-based guidance to support decision-making by healthcare professionals. The findings were used to produce the multi-component My Pregnancy Care intervention, consisting of a smartphone application and an information leaflet to support blood pressure self-monitoring and proteinuria self-testing, self-management of antihypertensive medication and smartphone application use. Conclusions: This research provided comprehensive insight into the needs of pregnant women with hypertension and their healthcare teams regarding self-monitoring and management of blood pressure. This supported the development of a tailored multi-component digital intervention that addresses barriers to blood pressure self-management by being user-friendly, persuasive and acceptable. It is hoped that the intervention will support the monitoring and management process, collaboration between healthcare professionals and women, clinical action and improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Proper development of the placenta, the transient support organ forms after embryo implantation, is essential for a successful pregnancy. However, the regulation of trophoblast invasion, which is most important during placentation, remains largely unknown. Here, rats, mice, and pigs are used as biomedical models, used scRNA‐seq to comparatively elucidate the regulatory mechanism of placental trophoblast invasion, and verified it using a human preeclampsia disease model combined with scStereo‐seq. A dual‐featured type of immune‐featured trophoblast (iTrophoblast) is unexpectedly discovered. Interestingly, iTrophoblast only exists in invasive placentas and regulates trophoblast invasion during placentation. In a normally developing placenta, iTrophoblast gradually transforms from an immature state into a functional mature state as it develops. Whereas in the developmentally abnormal preeclamptic placenta, disordered iTrophoblast transformation leads to the accumulation of immature iTrophoblasts, thereby disrupting trophoblast invasion and ultimately leading to the progression of preeclampsia. [ABSTRACT FROM AUTHOR]

ABSTRACT The study was conducted to evaluate the effect of butaphosphan and cyanocobalamin (BC) on the metabolic profile, oxidative stress in Kashmiri merino ewes and its effect on the prophylaxis of Ovine pregnancy toxemia (PT). A total of 48 ewes were randomly divided into three groups, each consisting of 16 ewes. High dose BC (HBC): Ewes were given 0.2 mL BC/kg body weight, subcutaneously (SC) weekly from 6 weeks pre‐lambing to lambing. Low dose BC (LBC): Ewes were given 0.1 mL BC/kg body weight, SC weekly from 6 weeks pre‐lambing to lambing. No BC (CON): Ewes were given 0.2 mL normal saline/kg body weight, SC. Weekly from six pre‐lambing to lambing. A significant effect of treatment was observed on non‐esterified fatty acid (NEFA; p = 0.06), beta hydroxybutyric acid (β‐HBA, p = 0.008), fructosamine (p = 0.034) and oxidative stress indices (OSI; p = 0.026) with less NEFA, β‐HBA, OSI and more fructosamine levels in HBC followed by LBC. The BC did not affect glucose, cholesterol, blood urea nitrogen, creatinine, total antioxidant capacity, calcium and phosphorus however a significant difference was observed along the sampling time in all the three groups. Plasma triglyceride, aspartate aminotransferase and total oxidant status levels showed a significant treatment‐time interaction. Taking 0.8 mmol/L β‐HBA as the cutoff limit for subclinical PT, only HBC was able to significantly control PT at 3 weeks pre‐lambing (OR; 5.57; p = 0.035), at 2 weeks pre‐lambing (OR: 9.53; p = 0.007), at 1‐week pre‐lambing (OR: 6.60; p = 0.017) and at lambing (OR: 5.57; p = 0.035). In conclusion, there was a positive effect of BC treatment on the energy metabolism in pregnant ewes and it helped in the amelioration of oxidative stress and hence can be used in the prophylaxis of PT. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) poses significant diagnostic and therapeutic challenges. This study aims to identify novel genes for potential diagnostic and therapeutic targets, illuminating the immune mechanisms involved. Methods: Three GEO datasets were analyzed, merging two for training set, and using the third for external validation. Intersection analysis of differentially expressed genes (DEGs) and WGCNA highlighted candidate genes. These were further refined through LASSO, SVM-RFE, and RF algorithms to identify diagnostic hub genes. Diagnostic efficacy was assessed using ROC curves. A predictive nomogram and fully Connected Neural Network (FCNN) were developed for PE prediction. ssGSEA and correlation analysis were employed to investigate the immune landscape. Further validation was provided by qRT-PCR on human placental samples. Result: Five biomarkers were identified with validation AUCs: CGB5 (0.663, 95% CI: 0.577-0.750), LEP (0.850, 95% CI: 0.792-0.908), LRRC1 (0.797, 95% CI: 0.728-0.867), PAPPA2 (0.839, 95% CI: 0.775-0.902), and SLC20A1 (0.811, 95% CI: 0.742-0.880), all of which are involved in key biological processes. The nomogram showed strong predictive power (C-index 0.873), while FCNN achieved an optimal AUC of 0.911 (95% CI: 0.732-1.000) in five-fold cross-validation. Immune infiltration analysis revealed the importance of T cell subsets, neutrophils, and NK cells in PE, linking these genes to immune mechanisms underlying PE pathogenesis. Conclusion: CGB5 , LEP , LRRC1 , PAPPA2 , and SLC20A1 are validated as key diagnostic biomarkers for PE. Nomogram and FCNN could credibly predict PE. Their association with immune infiltration underscores the crucial role of immune responses in PE pathogenesis. [ABSTRACT FROM AUTHOR]

This study examines cesarean section (C‐section) deliveries in Ghana from 2008 to 2017 in 10 regions, distinguishing between scheduled and emergency procedures. Scheduled C‐sections target specific maternal conditions, such as advanced age, multiparity, and medical history, while emergency C‐sections address acute fetal distress, preeclampsia, bleeding, and other urgent situations. The analysis reveals various regional patterns, with the Brong‐Ahafo Region showing a potential deceleration after 2017 and the Upper West Region indicating a possible acceleration. The high number of C‐sections in Greater Accra and Ashanti may be related to population density and health facilities. The study proposes empirical models, including linear, quadratic, and exponential components, emphasizing quasilinearity. The exponential model suggests transient and permanent phases of cesarean frequency, with the latter dominated by quasilinearity. Optimal parameter values are determined, which highlights the stability of the model. However, caution is advised when projecting too far into the future due to the inevitable slowing of observed trends. The findings offer insights for healthcare planning, resource allocation, and policymaking, emphasizing the need for region‐specific approaches and ongoing monitoring of cesarean dynamics to inform nuanced interventions. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference. [ABSTRACT FROM AUTHOR]

To evaluate whether the presence of proteinuria, although no longer mandatory in the revised diagnostic criteria, results in worse maternal and fetal outcomes in preeclampsia (PE). A retrospective cohort study was conducted, analyzing data from pregnant patients diagnosed with PE between January 2015 and December 2019 at a tertiary care center in Brazil. Ethical approval was obtained, and the patient records were reviewed to assess maternal and perinatal outcomes based on the revised diagnostic criteria by the College of Obstetricians and Gynecologists, focusing on the presence or absence of proteinuria. The study included 816 pregnant patients with PE, of whom 685 (83.9%) were diagnosed based on proteinuria. The revised criteria, which include indicators of organ damage, identified an additional 131 cases (16.4%). Analysis showed no significant differences in maternal outcomes between proteinuria and non‐proteinuria groups, including intensive care unit (ICU) admission, acute pulmonary edema (APE), HELLP syndrome, eclampsia, or C‐section rates. However, babies born to mothers with proteinuria PE experienced worse outcomes, including fetal growth restriction, low birth weight, ICU admission, and higher rates of preterm birth. Relative risk analysis demonstrated a high risk of babies being born with low birth weight, ICU admission, and being born preterm and very preterm in cases where proteinuria was present in mothers with PE. The presence of proteinuria is associated with significantly worse outcomes in babies born to mothers with preeclampsia, while no significant differences were observed in maternal outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Data Sources Study Eligibility Criteria Methods Results Conclusion Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy.The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy.Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024.Studies (prospective, retrospective cohort, cross‐sectional, one arm, survey, follow‐up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post‐pregnancy remission status comparison.The quality of research was checked using the New Castle‐Ottawa risk‐of‐bias tool. A meta‐analysis model with a random effect distribution, coupled with meta‐regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed.Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%–20%). Heterogeneity was low in the present meta‐analysis (I2 = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%–11%) for spontaneous abortion, 4% (95% CI, 1%–11%) for preterm premature rupture of membranes, 10% (95% CI, 3%–28%) for premature rupture of membranes, 6% (95% CI, 3%–11%) for fetal growth restriction, 5% (95% CI, 2%–13%) for intrauterine fetal death, 12% (95% CI, 5%–26%) for post‐partum hemorrhage, 74% (95% CI, 45%–91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%–80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01–0.14), whereas neonatal mortality was 7% (95% CI, 0.03–0.18). The odds of AA complete remission were better in pre‐pregnancy than post‐pregnancy (OR = 0.36; 95% CI = 0.08–1.66), although the results remain insignificant. The leave‐one‐out sensitivity analysis did not change the pooled estimates for the primary outcome.A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of stroke later in life in multiparous women. However, causality of these associations remains unclear. This study employed 2-sample univariate and multivariate Mendelian randomization (MR) to assess the causal connection between HDP and stroke. Methods: Genetic variants for HDP and two subtypes were identified from recent large-scale genome-wide association studies and the FinnGen consortium. Stroke summary data were obtained from the MEGASTROKE consortium. The primary analytical approach for univariate MR was the inverse variance weighting method. Sensitivity analyses incorporated methods such as MR-Egger regression, weighted median, and maximum likelihood to ascertain the robustness of the results. Additionally, multivariable MR analyses were conducted to account for potential associative effects of hypertension and type 2 diabetes. Results: Genetically predicted HDP was associated with a high risk of large artery atherosclerosis (odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.17-1.91, P=1.13×10-3) and small vessel stroke (OR=1.29, 95% CI: 1.20-1.50, P=1.52×10-3). HDP may also correlate with ischemic stroke (OR=1.13, 95% CI: 1.04-1.23, P=4.99×10-3) and stroke (OR=1.11, 95% CI: 1.03-1.20, P=8.85×10-3). An elevated risk of small vessel stroke (OR=1.20, 95% CI: 1.01-1.43, P=3.74×10-2) and large artery atherosclerosis (OR=1.22, 95% CI: 1.01-1.47, P=4.07×10-2) may be related with genetically predicted susceptibility to gestational hypertension. Genetically predicted susceptibility to preeclampsia or eclampsia may be associated with an increased risk of stroke (OR = 1.10, 95% CI: 1.02-1.19, P = 1.16×10-2) and ischemic stroke (OR = 1.10, 95% CI: 1.02-1.20, P = 1.84×10-2). Type 2 diabetes mellitus and hypertension were identified as significant factors contributing to the association between HDP and stroke. Conclusions: This study provides genetic evidence supporting an association between HDP and increased stroke risk bolstering HDP as a cerebrovascular risk factor. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is characterized by de novo hypertension (HTN) and is often associated with intrauterine growth restriction (IUGR). Hallmarks of PE are placental ischemia, decreased nitric oxide (NO) bioavailability, oxidative stress (OS), and organ damage in the kidneys and brain. This study aims to characterize a new model of PE using pregnant IUGR rats from hypertensive placental ischemic dams. It is hypothesized that pregnant IUGR rats from hypertensive placental ischemic dams will have elevated blood pressure (BP), OS, and organ damage. In this study, pregnant rats are divided into two groups: normal pregnant (NP) and hypertensive placental ischemic dams (RUPP). Offspring from NP and RUPP dams were mated at 10 weeks of age to generate pregnant IUGR (IUGR Preg) and pregnant control (CON Preg) rats. BP and other markers of PE were evaluated during late gestation. Pregnant IUGR rats had elevated BP and systemic OS. The maternal body weight of pregnant IUGR rats and their pups' weights were decreased, while the brains were enlarged with elevated OS. In summary, pregnant IUGR rats, born from hypertensive placental ischemic dams, have HTN and increased systemic and brain OS, with larger brain sizes and smaller pups. Furthermore, this study shows that pregnant IUGR rats exhibit a preeclamptic‐like phenotype, suggesting a new epigenetic model of PE. [ABSTRACT FROM AUTHOR]

Unbalanced data can have an impact on the machine learning (ML) algorithms that build predictive models. This manuscript studies the influence of oversampling and undersampling strategies on the learning of the Bayesian classification models that predict the risk of suffering preeclampsia. Given the properties of our dataset, only the oversampling and undersampling methods that operate with numerical and categorical attributes will be taken into consideration. In particular, synthetic minority oversampling techniques for nominal and continuous data (SMOTE-NC), SMOTE—Encoded Nominal and Continuous (SMOTE-ENC), random oversampling examples (ROSE), random undersampling examples (UNDER), and random oversampling techniques (OVER) are considered. According to the results, when balancing the class in the training dataset, the accuracy percentages do not improve. However, in the test dataset, both positive and negative cases of preeclampsia were accurately classified by the models, which were built on a balanced training dataset. In contrast, models built on the imbalanced training dataset were not good at detecting positive cases of preeclampsia. We can conclude that while imbalanced training datasets can be addressed by using oversampling and undersampling techniques before building prediction models, an improvement in model accuracy is not always guaranteed. Despite this, the sensitivity and specificity percentages improve in binary classification problems in most cases, such as the one we are dealing with in this manuscript. [ABSTRACT FROM AUTHOR]

Preeclampsia (preE) is a hypertensive disorder in pregnancies. It is the third leading cause of mortality among pregnant women and fetuses worldwide, and there is much we have yet to learn about its pathophysiology. One complication includes cerebral edema, which causes a breach of the blood–brain barrier (BBB). Urinary marinobufagenin (MBG) is elevated in a preE rat model prior to developing hypertension and proteinuria. We investigated what effect MBG has on the endothelial cell permeability of the BBB. Human brain microvascular endothelial cells (HBMECs) were utilized to examine the permeability caused by MBG. The phosphorylation of ERK1/2, Jnk, p38, and Src was evaluated after the treatment with MBG. Apoptosis was evaluated by examining caspase 3/7. MBG ≥ 1 nM inhibited the proliferation of HBMECs by 46–50%. MBG induced monolayer permeability, causing a decrease in the phosphorylation of ERK1/2 and the activated phosphorylation of Jnk, p38, and Src. MBG increased the caspase 3/7 expression, indicating the activation of apoptosis. Apoptotic signaling or the disruption of endothelia tight junction proteins was not observed when using the p38 inhibitor as a pretreatment in MBG-treated cells. The MBG-induced enhancement of the HBMEC monolayer permeability occurs by the downregulation of ERK1/2, the activation of Jnk, p38, Src, and apoptosis, resulting in the cleavage of tight junction proteins, and are attenuated by p38 inhibition. [ABSTRACT FROM AUTHOR]

The human placenta is a vital organ, encompassing many distinct cell types, that maintains the growth and development of the fetus and is essential for substance exchange, defense, synthesis, and immunity. Abnormalities in placental cells can lead to various pregnancy complications, but the mechanisms remain largely unclear. Single‐cell and spatial transcriptomics technologies have been developed in recent years to demonstrate placental cell heterogeneity and spatial molecular localization. Here, we review and summarize the current literature, demonstrating these technologies and showing the heterogeneity of various placenta cells and cell–cell communication of normal human placenta, as well as placenta‐related diseases, such as preeclampsia, gestational diabetes mellitus, advanced maternal age, recurrent pregnancy loss, and placenta accreta spectrum disorders. Meanwhile, current weaknesses and future direction were discussed. [ABSTRACT FROM AUTHOR]

Introduction: Most pregnancies are low-risk. However, sometimes women develop pre-eclampsia. The incidence varies based on different studies (Havers-Borgersen et al., 2023, 10.1136/jech-2023-220829).Pre-eclampsia is characterized by elevated blood pressure, protein in the urine, and excessive swelling and occurs after 20 weeks of pregnancy though in the case of severe symptoms, all may not be required for diagnosis (Bajpai et al., 2023). Many strategies exist to identify women with pre-eclampsia and to treat it. There are known immediate risks to both the mother and fetus. Some of these risks extend beyond the immediate postpartum period. Much less is known regarding the long-term risks. Therefore, the purpose of our study was to conduct a systematic review of the long-term complications related to pre-eclampsia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to guide this systematic review. PubMed, CINAHL, Medline, Scopus, PschINFO, and Google Scholar were used to identify relevant articles. We focused on articles published within the last 5 years. Search terms were pre-eclampsia and complications, pregnancy-induced hypertension and complications, long-term complications of pre-eclampsia, and long-term follow-up of pre-eclampsia. Results: Two hundred and fifty-eight articles were identified; further analysis identified 91 that seemed relevant. After a thorough review, 19 articles were deemed relevant to identify complications women experience following pre-eclampsia. Discussion: Cardiovascular disease is a major long-term risk. Early-onset pre-eclampsia contributes the greatest risk. Health promotion interventions that target women following a diagnosis of pre-eclampsia are needed. Inadequate knowledge exists to guide efforts to prevent long-term sequelae from pre-eclampsia. Significance: Women who experience pre-eclampsia have significant health risks following the diagnosis. Some risks are immediate (elevated blood pressure) and some risks can take longer to develop (heart disease, diabetes, kidney disease). Because of these risks, it is critical to develop treatment strategies to prevent these risks if possible. There are also risks to the fetus/newborn and these may be amendable to intervention as well. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a common pregnancy disorder characterized by hypertension and proteinuria. Trophoblast behavior severely affect PE progression. Transcription factor Forkhead box protein P2 (FOXP2) was involved in cell migration and invasion, but its role in PE progression remains unknown. Laminin subunit alpha 4 (LAMA4) was predicted as a downstream gene of FOXP2 and related to PE. Thus, we supposed that FOXP2 might regulate PE by regulating LAMA4. We found the decreased FOXP2 expression in patients with PE compared with healthy pregnant women. The rat model of PE was induced by L-NAME oral gavage. FOXP2 overexpression lowered systolic and diastolic blood pressure and restored pathological changes of rats with PE. Trophoblasts under the hypoxia/reoxygenation (H/R) treatment were used to mimic PE in vitro. The results revealed that FOXP2 overexpression inhibited apoptosis but promoted migration, invasion, and angiogenesis of H/R-treated trophoblasts. Dual luciferase and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that FOXP2 transcriptionally upregulated the LAMA4 expression in trophoblasts. LAMA4 knockdown reversed the migration and invasion-promoting role of FOXP2 overexpression in trophoblasts with H/R treatment. Collectively, our findings suggest that the FOXP2/LAMA4 axis regulates PE by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis. Overexpression of FOXP2-mediated LAMA4 expression provides an insight on the preeclampsia treatment by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Glomerular injury may occur during pregnancy as a consequence of systemic disease and pregnancy‐related medical complications. While urinary nephrin has been shown to provide early identification of preeclampsia (PE) in high‐risk pregnancies, the role of urinary nephrin in determining glomerular injury in pregnant women is yet to be explored. This study aimed to investigate the use of urinary nephrin as a predictor for early glomerular injury in a study conducted at the Townville University Hospital. Methods and Materials: A cross‐sectional study was conducted. All pregnant women with a full dataset (n = 273) were classified into three categories according to their urinary albumin‐to‐creatinine ratio (ACR): normoalbuminuria, microalbuminuria and macroalbuminuria. Continuous variables were compared between groups, and the cut‐off value for the urinary nephrin‐to‐creatinine ratio (NCR) was determined to predict albuminuria as an indirect indicator of early glomerular injury. The percentages of pregnant women who had elevated nephrinuria were calculated for each of the ACR categories. Results: Urinary NCR positively correlated with urinary ACR (r = 0.29, p < 0.0001). Urinary NCR increased comparably in women with normoalbuminuria, microalbuminuria and macroalbuminuria. Using a cut‐off value of 14 ng/mg, nephrinuria was detected in 65% of women with normoalbuminuria, 95% with microalbuminuria and 100% with macroalbuminuria. Of the normoalbuminuric women who had an elevated urinary NCR (> 14 ng/mg), 78% were diagnosed with a hypertensive disorder and 63% were diagnosed with diabetes in pregnancy. In women with PE, urinary NCR and ACR were significantly higher when compared to women who did not develop PE. The AUC of the ROC for urinary NCR was 0.74 (95% CI: 0.650–0.824), with a sensitivity of 97% and a specificity of 36% to predict glomerular injury and a sensitivity of 93% and specificity of 42% to predict glomerular injury of PE. Conclusion: The study found that urinary NCR were elevated not only in women with micro‐ and macroalbuminuria but also in pregnant women with normoalbuminuria. Increased urinary NCR without increased urinary albumin may be associated with early glomerular injury. Urinary NCR may be a more sensitive marker than microalbuminuria to detect early glomerular injury in women with systemic disease and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

This Symposium Review examines challenges to surviving birth and infancy at high altitudes. Chronic exposure to the environmental hypoxia of high altitudes increases the incidence of maternal vascular disorders of pregnancy characterized by placental insufficiency, restricted fetal growth and preterm delivery, and impairs pulmonary vascular health during infancy. While each condition independently contributes to excess morbidity and mortality in early life, evidence indicates vascular disorders of pregnancy and infantile pulmonary vascular dysfunction are intertwined. By integrating our recent scientific and clinical observations in Bolivia with existing literature, we propose potential avenues to reduce the infant mortality burden at high altitudes and reduce pulmonary vascular disease in highland neonates, and emphasize the need for further research to address unresolved questions. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to evaluate the safety of discontinuing aspirin treatment at 24–28 weeks in women at high risk after first‐trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24–28 weeks of gestation. Material and Methods: This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high‐risk single pregnancies identified during first‐trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms‐like tyrosine kinase‐1 to PlGF ratio (sFlt‐1/PlGF) ≤38 at 24–28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24–28 weeks were included. As in the StopPRE trial, the non‐inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups. Results: Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high‐risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non‐inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, −5.96; 95% CI, −10.10 to −1.82). Conclusions: Discontinuation of aspirin treatment at 24–28 weeks in women with PlGF levels ≥100 pg/mL was non‐inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial. [ABSTRACT FROM AUTHOR]

Objective The American College of Obstetrics threshold for hypertension (≥140/90 mm Hg) differs from those of the American College of Cardiology (ACC) and the American Heart Association (AHA). It is unknown if ACC/AHA hypertension levels are associated with adverse pregnancy outcomes (APOs) after 20 weeks gestation. The purpose of this study is to analyze APOs in women with blood pressure (BP) in the elevated or stage 1 range after 20 weeks gestation. Study Design This was a secondary analysis of the nuMoM2b prospective cohort study of 10,038 nulliparous, singleton pregnancies between 2010 and 2014. BP was measured at three visits during the pregnancy using a standard protocol. Women without medical comorbidities, with normal BP by ACC/AHA guidelines (systolic BP [SBP] < 120 and diastolic BP [DBP] < 80 mm Hg) up to 22 weeks, were included. Exposure was BP between 22 and 29 weeks gestation: normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP: 120–129 and DBP < 80 mm Hg), and stage 1 (SBP: 130–139 or DBP: 80–89 mm Hg). The primary outcome was hypertensive disorder of pregnancy (HDP) at delivery. Secondary outcomes included fetal growth restriction (FGR), placental abruption, preterm delivery, and cesarean delivery. Multivariable-adjusted odds ratio (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Results Of 4,460 patients that met inclusion criteria, 3,832 (85.9%) had BP in the normal range, 408 (9.1%) in elevated, and 220 (4.9%) in stage 1 range between 22 and 29 weeks. The likelihood of HDP was significantly higher in women with elevated BP (aOR: 1.71, 95%CI: 1.18,2.48), and stage 1 BP (aOR: 2.79, 95%CI: 1.84,4.23) compared to normal BP (p < 0.001). Stage 1 BP had twice odds of FGR (aOR: 2.33, 95%CI: 1.22,4.47) and elevated BP had three times odds of placental abruption (aOR: 3.03; 95%CI: 1.24,7.39). Conclusion Elevated or stage 1 BP >20 weeks of pregnancy are associated with HDP, FGR, and placental abruption. Key Points Elevated and stage 1 BP increases risk for HDP. Elevated BP increases risk for placental abruption. Stage 1 BP increases risk for FGR. [ABSTRACT FROM AUTHOR]

Objective Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. Study Design A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. Results During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. Conclusion The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. Key Points Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine the composite maternal hemorrhagic outcome (CMHO) among individuals with and without hypertensive disorders of pregnancy (HDP), stratified by disease severity. Additionally, we investigated the composite neonatal adverse outcome (CNAO) among individuals with HDP who had postpartum hemorrhage (PPH) versus did not have PPH. Study Design Our retrospective cohort study included all singletons who delivered at a Level IV center over two consecutive years. The primary outcome was the rate of CMHO, defined as blood loss ≥1,000 mL, use of uterotonics, mechanical tamponade, surgical techniques for atony, transfusion, venous thromboembolism, intensive care unit admission, hysterectomy, or maternal death. A subgroup analysis was performed to investigate the primary outcome stratified by (1) chronic hypertension, (2) gestational hypertension and preeclampsia without severe features, and (3) preeclampsia with severe features. A multivariable regression analysis was performed to investigate the association of HDP with and without PPH on a CNAO which included APGAR <7 at 5 minutes, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, neonatal sepsis, meconium aspiration syndrome, ventilation >6 hours, hypoxic–ischemic encephalopathy, or neonatal death. Results Of 8,357 singletons, 2,827 (34%) had HDP. Preterm delivery <37 weeks, induction of labor, prolonged oxytocin use, and magnesium sulfate usage were more common in those with versus without HDP (p < 0.001). CMHO was higher among individuals with HDP than those without HDP (26 vs. 19%; adjusted relative risk [aRR] = 1.11, 95% CI: 1.01–1.22). In the subgroup analysis, only individuals with preeclampsia with severe features were associated with higher CMHO (n = 802; aRR = 1.52, 95% CI: 1.32–1.75). There was a higher likelihood of CNAO in individuals with both HDP and PPH compared to those with HDP without PPH (aRR = 1.49, 95% CI: 1.06–2.09). Conclusion CMHO was higher among those with HDP. After stratification, only those with preeclampsia with severe features had an increased risk of CMHO. Among individuals with HDP, those who also had a PPH had worse neonatal outcomes than those without hemorrhage. Key Points Individuals with HDP had an 11% higher likelihood of CMHO. After stratification, increased CMHO was limited to those with preeclampsia with severe features. There was a higher likelihood of CNAO in those with both HDP and PPH compared to HDP without PPH. [ABSTRACT FROM AUTHOR]

Objective Non-Hispanic Black people (NHBP) have a three-fold higher rate of maternal mortality compared to other racial groups. Racial disparities in maternal morbidity are well-described; however, there are substantial differences in cultural, economic, and social determinants of health among racial groups. We thus sought to study the at-risk, non-Hispanic Black population as its own cohort to identify factors most associated with severe maternal morbidity (SMM). Study Design This is a population-based retrospective case–control study of all live births in the United States between 2017 and 2019 using birth records obtained from the National Center for Health Statistics. The primary outcome for this study was to determine demographic, social, medical, and obstetric factors associated with maternal morbidity among NHBP who did and did not experience an SMM event. Multivariable logistic regression was used to estimate the adjusted odds ratio between each individual factor and the outcome of SMM among NHBP. Results Of the 1,624,744 NHBP who delivered between 2017 and 2019, 1.1% experienced an SMM event defined as a composite of blood product transfusion, eclamptic seizure, intensive care unit admission, unplanned hysterectomy, and uterine rupture. The rates of these individual SMM events per 10,000 deliveries were 50, 40, 20, 5, and 4 among NHBP, respectively. Among NHBP, factors associated in multivariable regression analysis with SMM in order of strength of association included cesarean delivery, earlier gestational age at delivery, preeclampsia, induction of labor, chronic hypertension, prior preterm birth, lower educational attainment, multifetal gestation, advanced maternal age, pregestational diabetes, and cigarette smoking. The population attributable fraction for cesarean delivery, preterm birth, and pregnancy-induced hypertensive disease for the outcome of SMM were 0.46, 0.23, and 0.07, respectively. Conclusion The three factors most associated with SMM among NHBP are potentially avoidable or modifiable by aggressive screening, prevention, and treatment of preeclampsia and preterm birth as well as reducing cesarean rates in this population. Key Points The rate of SMM in NHBP may be modifiable. NHBP have a three-fold higher rate of maternal mortality. Preeclampsia, preterm birth, and cesarean sections are most associated with maternal morbidity. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to evaluate the pregnancy outcomes and identify risk factors for recurrent preeclampsia (PE). Methods: Retrospective analysis of patients discharged with PE between January 1, 2010, and January 1, 2023, from two tertiary referral hospitals. They were classified into recurrent and non-recurrent groups based on the presence of PE in subsequent pregnancies. Results: Among 519 women who had a subsequent pregnancy after a history of PE, 153 developed recurrent PE while 366 did not. The recurrent cases included 81 preterm PE, of which 41 were early-onset PE (EOPE). Recurrent PE correlated significantly with prior EOPE, HELLP syndrome, placental abruption, and stillbirth, as well as with current chronic hypertension (CH) and type 2 diabetes. The recurrent group showed a 5.8-fold higher risk of preterm birth (PTB) compared to the non-recurrent group (50.7% vs. 8.7%). Notably, 58.1% of the PTBs in the non-recurrent group were spontaneous. Logistic regression identified previous EOPE (aOR: 4.22 [95% CI: 2.50–7.13]) and current CH (aOR: 1.86 [95% CI: 1.09–3.18]) as independent contributors for recurrent PE. Furthermore, recurrent preterm PE shared the same risk factors: previous EOPE (aOR: 5.27 [95% CI: 2.82–9.85]) and current CH (aOR: 2.99 [95% CI: 1.57–5.71]). The morbidity of CH in subsequent pregnancy peaked at 31.9% when women with a history of EOPE delivered within three years. Conclusion: Previous EOPE and current CH were sequentially crucial risk factors for the development of PE and preterm PE during the next pregnancy. This may clarify risk stratification in prenatal management for women with a history of PE. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100 ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia–induced hypertension in RUPP rats highlighting its therapeutic potential in PE. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our objective was to investigate the predictive and diagnostic accuracy of the angiogenic proteins sFlt-1 (soluble fms–like tyrosine kinase-1) and PlGF (placental growth factor) for preterm preeclampsia and explore the relationship between renal function and these proteins. METHODS: We completed a blinded, prospective, longitudinal, observational study of patients with chronic kidney disease followed at a tertiary center (2018–2023). Serum samples were obtained at 3 time points along gestation (planned sampling): 12–16, 18–22, and 28–32 weeks. In addition, samples were obtained whenever preeclampsia was suspected (indicated sampling). sFlt-1 and PlGF levels remained concealed until the study ended. The primary outcome was preterm preeclampsia. The planned and indicated samples were used to estimate the predictive and diagnostic accuracy of the angiogenic proteins, respectively. RESULTS: Of the 97 participants, 21 (21.6%) experienced preterm preeclampsia. In asymptomatic patients with chronic kidney disease, the angiogenic proteins were predictive of preterm preeclampsia only when sampled in the third trimester, in which case the sFlt-1/PlGF ratio (false positive rate of 37% for a detection rate of 80%) was more predictive than either sFlt-1 or PlGF in isolation. In patients with suspected preeclampsia, the diagnostic accuracy of the sFlt-1/PlGF ratio (false positive rate of 26% for a detection rate of 80%) was higher than that of sFlt-1 and PlGF in isolation. Diminished renal function was associated with increased levels of PlGF. CONCLUSIONS: sFlt-1 and PlGF can effectively predict and improve the diagnostic accuracy for preterm preeclampsia among patients with chronic kidney disease. The optimal sFlt-1/PlGF ratio cutoff to rule out preeclampsia may need to be lower in patients with impaired renal function. [ABSTRACT FROM AUTHOR]

Objective (s): Circulating angiogenic factors are used for prediction of placenta-related complications, but their associations with first-trimester placental development is unknown. This study investigates associations between maternal angiogenic factors and utero-placental vascular volume (uPVV) and utero-placental vascular skeleton (uPVS) as novel imaging markers of volumetric and morphologic (branching) development of the first-trimester utero-placental vasculature. Methods: In 185 ongoing pregnancies from the VIRTUAL Placenta study, a subcohort of the ongoing prospective Rotterdam Periconception cohort, three-dimensional power Doppler ultrasounds of the placenta were obtained at 7–9–11 weeks gestational age (GA). The uPVV was measured as a parameter of volumetric development and reported the vascular quantity in cm3. The uPVS was generated as a parameter of morphologic (branching) development and reported the number of end-, bifurcation- crossing- or vessel points and total vascular length. At 11 weeks GA, maternal serum biomarkers suggested to reflect placental (vascular) development were assessed: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). sFlt-1/PlGF and sEng/PlGF ratios were calculated. Multivariable linear regression with adjustments was used to estimate associations between serum biomarkers and uPVV and uPVS trajectories. Results: Serum PlGF was positively associated with uPVV and uPVS development (uPVV: β = 0.39, 95% CI = 0.15;0.64; bifurcation points: β = 4.64, 95% CI = 0.04;9.25; crossing points: β = 4.01, 95% CI = 0.65;7.37; total vascular length: β = 13.33, 95% CI = 3.09;23.58, all p-values < 0.05). sEng/PlGF ratio was negatively associated with uPVV and uPVS development. We observed no associations between sFlt-1, sEng or sFlt-1/PlGF ratio and uPVV and uPVS development. Conclusion(s): Higher first-trimester maternal serum PlGF concentration is associated with increased first-trimester utero-placental vascular development as reflected by uPVV and uPVS. Clinical trial registration number Dutch Trial Register NTR6854. [ABSTRACT FROM AUTHOR]

Metabolic diseases are significant diseases that affect the welfare, health, and production of small ruminant flocks raised for dairy and meat purposes. In breeding females, they mainly occur from six to eight weeks before and after parturition, respectively. Pregnancy toxemia and lactational ketosis are manifestations of hyperketonemia, primarily due to energetic deficit. Hypocalcemia and hypomagnesemia are related to the metabolic unavailability of calcium and magnesium, respectively. This review aimed to identify and discuss the current and most relevant aspects related to individual and herd health management of these interrelated metabolic diseases with impact on the sheep and goats' farm sustainability. These diseases are primarily due to nutritional deficits, but homeostatic and homeorhetic disruptions are responsible for clinical signs and forms. Currently, their clinical diagnosis and monitoring are mainly assessed by biochemistry of body fluids and feed bromatological evaluation. Epidemiological studies and measuring risk factors also contribute to their prevention. Nevertheless, research on specific biomarkers and composite indices related to these diseases, in the context of herd health management and precision medicine, are new pathways driven to suitable and efficient animal production. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is associated with intrauterine growth restriction (IUGR), which can lead to impaired postnatal growth and neurodevelopment in preterm infants. Preeclampsia can also occur without IUGR and its impact on postnatal nutrition, growth, and body composition remains not fully investigated to the best of our knowledge. Methods: This study included infants born before 37 weeks of gestation who underwent air displacement plethysmography to measure body composition (fat-free mass [FFM] and fat mass [FM]) at term-equivalent age. We compared infants born to mothers with preeclampsia and IUGR (PE-IUGR group) and preeclampsia without IUGR (PE-non-IUGR group) to those born to mothers without preeclampsia (control group). Results: In total, 291 infants were enrolled (control: n = 227; PE-non-IUGR: n = 43; PE-IUGR: n = 21). FFM was significantly lower in the PE-IUGR (mean differences −231 g (IQR: (−373, −88); p < 0.001)) and PE-non-IUGR groups (mean differences −260 g (IQR: (−372, −149); p < 0.001)) in comparison to the control group. FM was not significantly different between the three groups. Conclusions: This study indicates that infants of preeclamptic mothers, even without IUGR, had significantly lower FFM at term-equivalent age compared to the control group. Further research is necessary to determine if these variations can be modified. [ABSTRACT FROM AUTHOR]

Background: Research on placental oxidative stress is pivotal for comprehending pregnancy-related physiological changes and disease mechanisms. Despite recent advancements, a comprehensive review of current status, hotspots, and trends remains challenging. This bibliometric study systematically analyzes the evolution of placental oxidative stress research, offering a reference for future studies. Objective: To conduct a comprehensive bibliometric analysis of the literature on placental oxidative stress to identify research hotspots, trends, and key contributors, thereby providing guidance for future research. Methods: Relevant data were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, CiteSpace, and the bibliometrix package. An in-depth analysis of 4,796 publications was conducted, focusing on publication year, country/region, institution, author, journal, references, and keywords. Data collection concluded on 29 April 2024. Results: A total of 4,796 papers were retrieved from 1,173 journals, authored by 18,835 researchers from 4,257 institutions across 103 countries/regions. From 1991 to 2023, annual publications on placental oxidative stress increased from 7 to 359. The United States (1,222 publications, 64,158 citations), the University of Cambridge (125 publications, 13,562 citations), and Graham J. Burton (73 publications, 11,182 citations) were the most productive country, institution, and author, respectively. The journal Placenta had the highest number of publications (329) and citations (17,152), followed by the International Journal of Molecular Sciences (122 publications). The most frequent keywords were “oxidative stress,” “expression,” “pregnancy,” “preeclampsia,” and “lipid peroxidation.” Emerging high-frequency keywords included “gestational diabetes mellitus,” “health,” “autophagy,” “pathophysiology,” “infection,” “preterm birth,” “stem cell,” and “inflammation.” Conclusion: Over the past 3 decades, research has concentrated on oxidative stress processes, antioxidant mechanisms, pregnancy-related diseases, and gene expression regulation. Current research frontiers involve exploring pathophysiology and mechanisms, assessing emerging risk factors and environmental impacts, advancing cell biology and stem cell research, and understanding the complex interactions of inflammation and immune regulation. These studies elucidate the mechanisms of placental oxidative stress, offering essential scientific evidence for future intervention strategies, therapeutic approaches, and public health policies. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusion\nKEY POINTSPreeclampsia is a serious pregnancy complication that can lead to life-threatening conditions such as seizures, strokes, and even death. A dysregulated inflammatory response in the placenta plays a crucial role in the development of preeclampsia. Cordycepin, known for its anti-inflammatory and antioxidant properties, was the focus of this study, which aimed to investigate its effects on preeclampsia.A preeclampsia-like rat model was established via tail vein injection of lipopolysaccharides (LPS) at a dose of 1 μg/kg in pregnant rats. These rats were then treated with cordycepin at doses of 5, 25, or 50 mg/kg from embryonic day 6 (E6) today 18 (E18). Systolic blood pressures and urinary protein levels were monitored, and pregnancy outcomes, such as fetal body length and weight, were measured. The expression of target genes or proteins was assessed by qPCR, ELISA, and Western blot.Our findings revealed that cordycepin significantly reduced systolic blood pressure and proteinuria in preeclampsia-like rats. Additionally, cordycepin improved pregnancy outcomes, as shown by increased fetal body length and weight. The treatment also lowered serum sFlt-1 levels, elevated PIGF levels, decreased placental pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, MCP-1, and MIP-2), and raised levels of anti-inflammatory cytokine IL-10 level in preeclampsia-like rats. Furthermore, cordycepin helped restore macrophage population imbalances, increasing M1-type macrophage markers (iNOS, TNF-α, and IL-1β) and reducing M2-type macrophage markers (Arg 1, IL-10, and TGF-β).This study suggests that cordycepin alleviates LPS-induced preeclampsia by reducing placental inflammation and correcting the M1/M2 macrophage imbalance, offering potential therapeutic benefits for managing preeclampsia.1. Cordycepin exerts beneficial effects on lowering systolic blood pressure and proteinuria.2. Cordycepin reduces placental inflammation and corrects the M1/M2 macrophage imbalance.3. Cordycepin alleviates the symptoms of LPS-induced preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions It is well known that both women with polycystic ovary syndrome (PCOS) and women with gestational diabetes mellitus (GDM) have increased risks of adverse pregnancy outcomes, but little is known whether the combination of these two conditions exacerbates the risks. We explored risk estimates for adverse pregnancy outcomes in women with either PCOS or GDM and the combination of both PCOS and GDM.Nationwide register‐based historical cohort study in Sweden including women who gave birth to singleton infants during 1997–2015 (N = 281 806). The risks of adverse pregnancy outcomes were estimated for women exposed for PCOS‐only (n = 40 272), GDM‐only (n = 2236), both PCOS and GDM (n = 1036) using multivariable logistic regression analyses. Risks were expressed as odds ratios with 95% confidence intervals (CIs) and adjusted for maternal characteristics, including maternal BMI. Women with neither PCOS nor GDM served as control group. Maternal outcomes were gestational hypertension, preeclampsia, postpartum hemorrhage, and obstetric anal sphincter injury. Neonatal outcomes were preterm birth, stillbirth, shoulder dystocia, born small or large for gestational age, macrosomia, low Apgar score, infant birth trauma, cerebral impact of the infant, neonatal hypoglycemia, meconium aspiration syndrome and respiratory distress.Based on non‐significant PCOS by GDM interaction analyses, we found no evidence that having PCOS adds any extra risk beyond that of having GDM for maternal and neonatal outcomes. For example, the adjusted odds ratio for preeclampsia in women with PCOS‐only were 1.18 (95% CI 1.11–1.26), for GDM‐only 1.77 (95% CI 1.45–2.15), and for women with PCOS and GDM 1.86 (95% CI 1.46–2.36). Corresponding adjusted odds ratio for preterm birth in women with PCOS‐only were 1.34 (95% CI 1.28–1.41), GDM‐only 1.64 (95% CI 1.39–1.93), and for women with PCOS and GDM 2.08 (95% CI 1.67–2.58). Women with PCOS had an increased risk of stillbirth compared with the control group (aOR 1.52, 95% CI 1.29–1.80), whereas no increased risk was noted in women with GDM (aOR 0.58, 95% CI 0.24–1.39).The combination of PCOS and GDM adds no extra risk beyond that of having GDM alone, for a number of maternal and neonatal outcomes. Nevertheless, PCOS is still an unrecognized risk factor in pregnancy, exemplified by the increased risk of stillbirth. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusions and Clinical Importance Periparturient reproductive complications appear to be common in hospitalized goats. More information is needed about periparturient reproductive complications and survival in goats with these conditions.Identify exposure factors associated with nonsurvival in periparturient does hospitalized ≤1 day or ≥2 days.A total of 198 periparturient does presented to 9 university veterinary hospitals from October 2021 to June 2022.Multicenter, matched case‐control study. Conditional logistic regression was used to identify exposure factors associated with nonsurvival in periparturient does hospitalized ≤1 day or ≥2 days.Overall doe survival was 79% (156/198). Survival in the 1st day of hospitalization was 71% (52/73) and survival in does hospitalized ≥2 days was 83% (104/125). Among goats hospitalized ≤1 day, labor duration before admission (odds ratio [OR] = 4.8; P = .04), uterine tears (OR = 48.2; P < .001), and vaginal/perineal trauma diagnosed during hospitalization (OR = 6.2; P = .03) were associated with nonsurvival. Among goats hospitalized ≥2 days, factors associated with nonsurvival included labor duration before admission (OR = 6.2; P = .004), pregnancy toxemia (OR = 6.07; P = .04), and Cesarean section (OR = 11.35; P = .02).Longer labor duration before admission is an important predictor of nonsurvival in hospitalized does. Clients should be educated that early detection and veterinary care are critical for improving outcome in periparturient does. [ABSTRACT FROM AUTHOR]

To investigate the effect of the combination of uterine artery (UtA) Doppler and vitamin D levels on perinatal outcomes in second trimester pregnants was aimed.UtA Dopplers and vitamin D levels of 226 pregnant women in the second trimester were measured. Patients were followed for adverse pregnancy outcomes. The relationship of this combination with these pregnancy outcomes was evaluated.Sensitivity and specificity values ​​are respectively; Left UtA-S/D ratio for preeclampsia was 85.29 and 81.77 %, left UtA-RI was 90.62 and 43.30 % for preterm birth, and 76.19 and 66.34 % for the development of fetal distress had the best predictive effect. Vitamin D values ​​had no predictive value for any parameter (p>0.005).UtA Doppler has a good predictive value for many adverse pregnancy outcomes. However, in order to correlate these results with second trimester vitamin D levels, more homogeneous and specific groups are needed. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThe objective of this study was to compare the levels of cathepsin B and pentraxin 3 in maternal serum of pregnant women with preeclampsia in the second trimester, to ascertain the impact of these levels on maternal and fetal outcomes, and to present a comprehensive analysis of the combined effects of cathepsin B and pentraxin 3 levels.This prospective case-control study was conducted at Bursa Yuksek Ihtisas Training and Research Hospital between 1 January 2022 and 31 December 2022. The study included 78 pregnant women diagnosed with preeclampsia and 78 healthy pregnant women in the second trimester, between the ages of 18 and 45. Once a diagnosis of preeclampsia was established, maternal serum samples were obtained from the pregnant women prior to the initiation of any therapeutic intervention. Once all samples had been collected, the values for cathepsin B and pentraxin 3 were determined using the ELISA method.The results demonstrated a statistically significant elevation in the levels of pentraxin 3 (p = 0.008) and cathepsin B (p = 0.005) in pregnancies affected by preeclampsia when compared to those deemed healthy. Moreover, pentraxin-3 (p = 0.007) and cathepsin B (p = 0.002) were found to be significantly elevated in severe preeclampsia compared to mild preeclampsia. A comparison of the groups with and without HELLP syndrome revealed no statistically significant difference between the two groups. The ROC analysis revealed that the Cathepsin B 7.04 cut-off value was statistically significantly associated with the prediction of preeclampsia in all cases, with a sensitivity of 78.2% and a specificity of 47.4% (p = 0.005, AUC = 0.631).The levels of CB and PTX3 may be employed as biomarkers to facilitate the early diagnosis of PE during the second trimester. Furthermore, these biomarkers may prove to be promising for the prediction of PE severity. [ABSTRACT FROM AUTHOR]

Background Objectives Search Strategy Selection Criteria Data Collection and Analysis Main results Conclusions Early risk stratification can facilitate timely interventions for adverse pregnancy outcomes, including preeclampsia (PE), small‐for‐gestational‐age neonates (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM).To perform a systematic review and meta‐analysis of first‐trimester prediction models for adverse pregnancy outcomes.The PubMed database was searched until 6 June 2024.First‐trimester prediction models based on maternal characteristics were included. Articles reporting on prediction models that comprised biochemical or ultrasound markers were excluded.Two authors identified articles, extracted data and assessed risk of bias and applicability using PROBAST.A total of 77 articles were included, comprising 30 developed models for PE, 15 for SGA, 11 for sPTB and 35 for GDM. Discriminatory performance in terms of median area under the curve (AUC) of these models was 0.75 [IQR 0.69–0.78] for PE models, 0.62 [0.60–0.71] for SGA models of nulliparous women, 0.74 [0.72–0.74] for SGA models of multiparous women, 0.65 [0.61–0.67] for sPTB models of nulliparous women, 0.71 [0.68–0.74] for sPTB models of multiparous women and 0.71 [0.67–0.76] for GDM models. Internal validation was performed in 40/91 (43.9%) of the models. Model calibration was reported in 21/91 (23.1%) models. External validation was performed a total of 96 times in 45/91 (49.5%) of the models. High risk of bias was observed in 94.5% of the developed models and in 58.3% of the external validations.Multiple first‐trimester prediction models are available, but almost all suffer from high risk of bias, and internal and external validations were often not performed. Hence, methodological quality improvement and assessment of the clinical utility are needed. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Cesarean delivery has been shown to increase the risk of preterm delivery in future pregnancies. The association could be a direct result of the procedure, or because the indications that led to the cesarean delivery also increase the risk of preterm delivery in later pregnancies.298 901 mothers with first and second singleton deliveries from 1999 to 2020 were investigated using data from the Medical Birth Registry of Norway linked with Statistics Norway. The mothers were categorized by mode of cesarean delivery (total, emergency and planned) and vaginal delivery at term in the first pregnancy. We used log‐binomial regression models to estimate relative risks with 95% confidence intervals (CI) of iatrogenic and spontaneous preterm delivery <37 gestational weeks in the second pregnancy. Second, we explored the role of recurrent placental disease in preterm delivery by comparing estimates in mothers with placental disease in neither or both pregnancies.8243 mothers (2.8%) had a preterm delivery in the second pregnancy. The adjusted relative risk (aRR) of preterm delivery was 1.24 (95% CI 1.17–1.32) after cesarean compared with vaginal delivery in the first pregnancy. The association was stronger in previous planned compared with emergency cesarean delivery (aRR 1.52, 95% CI 1.30–1.77 and aRR 1.21, 95% CI 1.14–1.29, respectively). Spontaneous preterm delivery was not associated with the previous mode of delivery; the risk was confined to iatrogenic preterm delivery after both emergency and planned cesarean delivery (aRR 1.69, 95% CI 1.52–1.87 and aRR 2.65, 95% CI 2.12–3.30, respectively). Mothers with placental disease in both pregnancies had a sixfold increased risk of preterm delivery in the second pregnancy compared with mothers with no placental disease, however, the association between mode of delivery and subsequent preterm delivery was similar in mothers with and without placental disease in the pregnancies.Compared with vaginal term delivery in the first pregnancy, cesarean delivery increases the risk of iatrogenic, but not spontaneous preterm delivery in the next pregnancy. Although strongly associated with preterm delivery, placental disease had limited influence on the estimates. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Preeclampsia (PE) is a critical and severe disease in obstetrics, which seriously affects maternal and neonatal life safety and long‐term prognosis. However, the etiology and pathogenesis of PE are complex, and no unified conclusion has been reached. The types and number of exosomes and their transport substances in PE patients changed. The study of exosomes in PE patients helps clarify the etiology, diagnosis, effective treatment, accurate monitoring, and prognosis.The published articles were reviewed.Exosomes may affect endothelial and vascular production and function, participate in maternal‐fetal immune regulation, and transport substances such as miRNAs, lncRNAs, and proteins involved in the development of PE. Detection of the contents of exosomes can help in the early diagnosis of PE, and can help to improve PE by inhibiting the action of exosomes or preventing their binding to target organs.Exosomes may be involved in the development of PE, and exosomes can be used as markers for predicting the onset of PE and tracking the disease process and determining the prognosis, and exosomes have great potential in the treatment of PE. [ABSTRACT FROM AUTHOR]

Background: The objective was to evaluate refractory respiratory distress syndrome (RDS) risk factors among very-low-birth-weight infants (VLBWIs). Method: The data of VLBWIs born between January 2013 and December 2020 registered in the Korean Neonatal Network (KNN) were analyzed. Infants who died within 5 postnatal days or who were not given surfactant were excluded. Infants were divided into a well-responding RDS group, which received surfactant replacement therapy (SRT) only once, and a refractory RDS group, which received SRT twice or more. The associations between perinatal characteristics and refractory RDS were investigated via multivariate logistic regression analysis. Results: Multivariate logistic regression analysis revealed that low gestational age (adjusted odds ratio [aOR] = 1.26, 95% confidence interval (CI) [1.23, 1.26], male sex (aOR = 1.17, 95% CI [1.06, 1.29]), cesarean section (aOR = 1.59, 95% CI [1.38, 1.80]), maternal hypertensive disorder (aOR = 1.54, 95% CI[1.35, 1.75]), and low 5-minute Apgar scores (aOR = 1.24, 95% CI [1.12, 1.37]) were significantly associated with refractory RDS. Antenatal corticosteroid use (aOR = 0.81, 95% CI [0.73, 0.89]) and maternal chorioamnionitis (aOR = 0.79, 95% CI [0.71, 0.88]) were significantly inversely associated with refractory RDS. Compared with well-responding RDS, refractory RDS was significantly associated with increased major neonatal morbidity and mortality risk at 5 postnatal days. Conclusion: Maternal hypertensive disorder is a significant risk factor for refractory RDS. Refractory RDS was associated with unfavorable neonatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a condition in pregnancy characterized by hypertension and proteinuria, thus leading to severe complications for both mother and fetus, including fetal growth restriction (FGR). However, there are still unclear aspects regarding the pathogenesis, prevention, and treatments. This study aimed to elucidate the characteristics of lipid metabolism in maternal and umbilical cord plasma complicated with PE using liquid chromatography-mass spectrometry (LC-MS). Method: The study included singleton pregnant women at Osaka Metropolitan University Hospital from March 2023 to February 2024. PE was diagnosed based on new-onset hypertension after 20 weeks of gestation and other symptoms such as proteinuria and organ dysfunction. FGR was defined by ultrasound measurements below -1.5 standard deviation (SD). Plasma samples were collected from maternal and umbilical cord blood within 24 hours before delivery. Lipid metabolites were comprehensively analyzed using LC-MS, and the lipokine 12,13-diHOME, identified as elevated in the comprehensive analysis, was quantified. Immunohistochemistry was conducted on placental samples to assess soluble epoxide hydrolase (sEH) expression. Results: The study involved 31 participants, with 20 in the control group and 11 in the PE group. A comprehensive analysis of maternal plasma samples identified a significant increase in 12,13-diHOME levels in the PE group compared to the control group. Quantification of 12,13-diHOME showed a significant increase in maternal plasma, umbilical venous plasma, and umbilical arterial plasma in the PE group compared to the control group (p = 0.007, p = 0.008, p = 0.005). PE with FGR showed significantly higher 12,13-diHOME concentrations in the umbilical arterial/venous ratio compared to the PE without FGR group (p = 0.03). Negative correlations were observed between 12,13-diHOME levels and birth weight in the PE group. Immunohistochemistry did not show significant differences in the sEH expression between the groups. Conclusion: This study demonstrated that 12,13-diHOME levels were significantly elevated in maternal and umbilical cord blood in PE patients, particularly in PE with FGR. Elevated 12,13-diHOME may reflect the progression of placental ischemia due to PE pathogenesis. This lipid metabolite could serve as a marker for the severity of preeclampsia, thus providing new insights into perinatal lipidomics and the potential role of 12,13-diHOME in PE. [ABSTRACT FROM AUTHOR]

Dysregulation of macrophage polarization can prevent the invasion of trophoblast cells and further limit spiral artery remodeling in preeclampsia (PE). However, its mechanism is obscure. HTR8-/Svneo cells were cultured under normoxic or hypoxic conditions and extracellular vesicles (EVs) in the culture supernatants were extracted. Next, the cells were incubated with those EVs to investigate their effects on trophoblasts. A co-culture system consisting of HTR8-/Svneo cells and macrophages was used to reveal how the trophoblast-derived EVs affected the macrophage subtype. Finally, a PE mouse model and miR-141-3p knockout mice were used to verify the function of miR-141-3p in PE. Hypoxia induced abnormal increases in the levels of miR-141-3p in HTR8-/Svneo cells and EVs. EVs from hypoxia-treated HTR8-/Svneo cells could downregulate PTEN, a potential target of miR-141-3p, and inhibit trophoblast mitophagy and invasion. However, HTR8-/Svneo cells transfected with an miR-141-3p inhibitor could attenuate the influence of EVs. In an HTR8-/Svneo cell plus macrophage co-culture system, hypoxia-pretreated cells promoted the transformation of macrophages into the M1-phenotye, and HTR8-/Svneo invasion was inhibited by the macrophages. MiR-141 from EVs could target and downregulate dual specificity phosphatase 1 (DUSP1) expression in macrophages, induce formation of the M1 macrophage phenotype in THP-1 cells, downregulate DUSP1 expression, and upregulate TAB2/TAK1 signaling. These results were also demonstrated in normal pregnant mice and PE pregnant mice. A hypoxic environment could upregulate miR-141 expression in the EVs of HTR8-/Svneo cells, and THP-1-derived macrophages could uptake EVs releasing miR-141 to downregulate DUSP1 expression and induce the formation of M1 macrophages, which can lead to the development of PE. [ABSTRACT FROM AUTHOR]

AbstractA low eGFRcystatin C/eGFRcreatinine-ratio is characteristic of a group of serious kidney disorders called ‘Selective Glomerular Hypofiltration Syndromes’. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Skåne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 was found in a subgroup of 32 women diagnosed with ‘preeclampsia with severe features’. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFRcystatin C/eGFRcreatinine-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFRcystatin C/eGFRcreatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications. [ABSTRACT FROM AUTHOR]