Hypertensive states of pregnancyEstados hipertensivos del embarazo / Estados hipertensivos del embarazo

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.(AU)

Los estados hipertensivos del embarazo (EHE) siguen siendo una de las principales causas de morbilidad y mortalidad materna y fetal relacionada con el embarazo en todo el mundo, incluyen la hipertensión crónica, la hipertensión gestacional y la preeclampsia. Las mujeres afectadas y los recién nacidos también tienen un mayor riesgo de sufrir enfermedades cardiovasculares en el futuro, independientemente de los riesgos tradicionales de la enfermedad cardiovascular. A pesar de estos riesgos, las recomendaciones para un diagnóstico y un tratamiento óptimo han cambiado poco en las últimas décadas, probablemente por el miedo a las repercusiones fetales de la disminución de la presión arterial y la posible toxicidad farmacológica. En ese documento revisamos los criterios diagnósticos y la clasificación de los EHE, así como aspectos importantes en cuanto a fisiopatología y la detección temprana que permita la identificación precoz de las mujeres en riesgo, con el objetivo de prevenir tanto las secuelas inmediatas como a largo plazo. También se revisa el tratamiento profiláctico con aspirina de forma precoz y se realiza una aproximación terapéutica que implica una estrecha vigilancia materna y fetal, y si es necesario, el uso de fármacos seguros en cada situación. Esta revisión pretende dar una visión actualizada para la prevención, diagnóstico y tratamiento de los EHE que sea de utilidad en nuestra práctica clínica habitual.(AU)

Pregnancy after kidney transplantation: 40 years single-center experience / Gestação após transplante renal: 40 anos de experiência em centro único

Abstract Background: Kidney transplantation (KT) improves quality of life, including fertility recovery. Objective: to describe outcomes of post-KT pregnancy and long-term patient and graft survival compared to a matched control group of female KT recipients who did not conceive. Methods: retrospective single-center case-control study with female KT recipients from 1977 to 2016, followed-up until 2019. Results: there were 1,253 female KT patients of childbearing age in the study period: 78 (6.2%) pregnant women (cases), with a total of 97 gestations. The median time from KT to conception was 53.0 (21.5 - 91.0) months. Abortion rate was 41% (spontaneous 21.6%, therapeutic 19.6%), preterm delivery, 32%, and at term delivery, 24%. Pre-eclampsia (PE) occurred in 42% of pregnancies that reached at least 20 weeks. The presence of 2 or more risk factors for poor pregnancy outcomes was significantly associated with abortions [OR 3.33 (95%CI 1.43 - 7.75), p = 0.007] and with kidney graft loss in 2 years. The matched control group of 78 female KT patients was comparable on baseline creatinine [1.2 (1.0 - 1.5) mg/dL in both groups, p = 0.95] and urine protein-to-creatinine ratio (UPCR) [0.27 (0.15 - 0.44) vs. 0.24 (0.02 - 0.30), p = 0.06]. Graft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p = 0.012) and 10 years (71.9% vs 55.0%, p = 0.012) of follow-up. Conclusion: pregnancy can be successful after KT, but there are high rates of abortions and preterm deliveries. Pre-conception counseling is necessary, and should include ethical aspects.

Resumo Histórico: Transplante renal (TR) melhora qualidade de vida, incluindo recuperação da fertilidade. Objetivo: descrever desfechos gestacionais pós-TR e sobrevida de longo prazo da paciente e do enxerto renal comparada a um grupo controle pareado de receptoras de TR que não conceberam. Métodos: estudo retrospectivo caso-controle com receptoras de TR de 1977 a 2016, acompanhadas até 2019. Resultados: foram identificadas 1.253 receptoras de TR em idade fértil no período do estudo: 78 (6,2%) gestantes (casos), total de 97 gestações. Tempo mediano entre TR até concepção foi 53,0 (21,5 - 91,0) meses. Taxa de aborto foi 41% (espontâneo 21,6%, terapêutico 19,6%), parto prematuro, 32%, e a termo, 24%. Pré-eclâmpsia (PE) ocorreu em 42% das gestações que alcançaram pelo menos 20 semanas. Presença de 2 ou mais fatores de risco para desfechos gestacionais desfavoráveis foi significativamente associada a abortos [OR 3,33 (IC95% 1,43 - 7,75), p = 0,007] e perda de enxerto renal em 2 anos. O grupo controle de 78 mulheres com TR foi comparável na creatinina basal [1,2 (1,0 - 1,5) mg/dL nos dois grupos, p = 0,95] e na relação proteína/creatinina urinária (RPCU) [0,27 (0,15 - 0,44) vs. 0,24 (0,02 - 0,30), p = 0,06]. Sobrevida do enxerto foi maior nos casos que nos controles em 5 anos (85,6% vs. 71,5%, p = 0,012) e 10 anos (71,9% vs. 55,0%, p = 0,012) de acompanhamento. Conclusão: a gestação pode ser bem-sucedida após TR, mas existem altas taxas de abortos e partos prematuros. Aconselhamento pré-concepção é necessário e deve incluir aspectos éticos.

Diabetic and hypertensive disorders following early pregnancy loss: a systematic review and meta-analysis.

Background: Spontaneous and induced abortions are common outcomes of pregnancy. There is inconsistent evidence of an association between early pregnancy loss and subsequent diabetic and hypertensive disorders in women. This systematic review and meta-analysis evaluated evidence on the risk of the subsequent development of pregnancy and non-pregnancy related diabetic and hypertensive disorders in women who experienced an early pregnancy loss. Methods: Systematic searches were conducted in seven electronic databases (CINAHL Plus, Ovid/EMBASE, Ovid/MEDLINE, ProQuest, PubMed, Scopus, and Web of Science) from inception to 22nd December 2023. Studies were included if they reported an exposure of spontaneous abortion (SAB), induced abortion (IA) or recurrent pregnancy loss (RPL) with an outcome of gestational diabetes mellitus, pre-eclampsia, gestational hypertension, and non-pregnancy related diabetic and hypertensive disorders. Risk of bias was assessed using Risk of Bias Instrument for Non-Randomized Studies of Exposures (ROBINS-E). Random effects meta-analysis was used to pool odds of developing diabetic and hypertensive disorders following an early pregnancy loss. This study is registered with PROSPERO (CRD42022327689). Findings: Of 20,176 records, 60 unique articles were identified for full-text review and 52 met the inclusion criteria, representing a total population of 4,132,895 women from 22 countries. Thirty-five studies were suitable for meta-analysis, resulting in a pooled odds ratio (OR) of 1.44 (95% confidence interval (CI) 1.23-1.68) for gestational diabetes mellitus following a prior SAB and a pooled OR of 1.06 (95% CI 0.90-1.26) for pre-eclampsia following a prior SAB. RPL increased the odds of developing pre-eclampsia (OR 1.37 95% CI 1.05-1.79). There was no association between IA and diabetic and hypertensive disorders. Interpretation: A prior SAB was associated with increased odds of gestational diabetes mellitus, but not pre-eclampsia. However, women who experienced RPL had an increased risk of subsequent pre-eclampsia. Future research is required to establish evidence for an association between early pregnancy loss with non-pregnancy related diabetic and hypertensive disorders. Funding: National Health and Medical Research Council.

Diagnostic performance of lactate dehydrogenase as a potential biomarker in predicting preeclampsia and associated factors.

Background: Preeclampsia (PE), a pregnancy specific syndrome, is defined as new-onset hypertension (≥140/90 mmHg) and proteinuria diagnosed after gestational week 20 or new-onset pre-eclampsia associated signs in the absence of proteinuria, and it may tend to present as late as 4-6 weeks' postpartum period. It is a leading cause of maternal mortality in both developed and developing countries. In order to prevent PE, the disease must be diagnosed at its earliest stage, however, the triads of high blood pressure, edema and albuminuria is neither specific nor sensitive enough for diagnosing the disease. Lactate dehydrogenase (LDH) is useful biochemical marker reflecting the occurrence of complications associated with preeclampsia. Besides, it has been suggested as potential biomarker to predict the severity of preeclampsia and as indicator of multi-organ involvement. The aim of this study was to investigate the diagnostic accuracy of LDH, which is affordable and easy to test, as a potential clinical biomarker to predict onset of preeclampsia. Methods: A hospital based cross-sectional study was conducted as of September 9 to December 24, 2022 at Debre Birhan Comprehensive Specialized Hospital (DBCSH). A total of 132 study subjects (66 preeclamptic and 66 normotensive controls) were enrolled in the study. A receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) and determine diagnostic accuracy of LDH. Youden's index was used to identify an optimal cut-off point for LDH in detecting preeclampsia associated complications. Result: AUC for LDH was found to be 0.963 (95% CI, 0.91, 1.0; p = 0.000) from ROC curve analysis. An optimal cut-off point for LDH was 376.5 U/L having a sensitivity and specificity of 87.5 and 90.8%, respectively. Conclusion: Serum LDH had an AUC of greater than 0.8 and showed good diagnostic accuracy in predicting development of preeclampsia. Disease duration, gestational age, systolic and diastolic blood pressure among enormous number of predictor variables had association with serum level of LDH.

Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses.

BACKGROUND: Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes. OBJECTIVE: To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes. METHODS: Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted. DATA EXTRACTION: Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2). RESULTS: We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization. CONCLUSION: Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.

Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation.

Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.

Relative humidity, temperature, and hypertensive disorders of pregnancy: Findings from the Project Viva cohort.

BACKGROUND: Preeclampsia is a multi-system hypertensive disorder of pregnancy that is a leading cause of maternal and fetal morbidity and mortality. Prior studies disagree on the cause and even the presence of seasonal patterns in its incidence. Using unsuitable time windows for seasonal exposures can bias model results, potentially explaining these inconsistencies. OBJECTIVES: We aimed to investigate humidity and temperature as possible causes for seasonal trends in preeclampsia in Project Viva, a prebirth cohort in Boston, Massachusetts, considering only exposure windows that precede disease onset. METHODS: Using the Parameter-elevation Relationships on Independent Slopes Model (PRISM) Climate Dataset, we estimated daily residential temperature and relative humidity (RH) exposures during pregnancy. Our primary multinomial regression adjusted for person-level covariates and season. Secondary analyses included distributed lag models (DLMs) and adjusted for ambient air pollutants including fine particulates (PM2.5). We used Generalized Additive Mixed Models (GAMMs) for systolic blood pressure (SBP) trajectories across hypertensive disorder statuses to confirm exposure timing. RESULTS: While preeclampsia is typically diagnosed late in pregnancy, GAMM-fitted SBP trajectories for preeclamptic and non-preeclamptic women began to diverge at around 20 weeks' gestation, confirming the need to only consider early exposures. In the primary analysis with 1776 women, RH in the early second trimester, weeks 14-20, was associated with significantly higher odds of preeclampsia (OR per IQR increase: 1.81, 95% CI: 1.10, 2.97). The DLM corroborated this window, finding a positive association from weeks 12-20. There were no other significant associations between RH or temperature and preeclampsia or gestational hypertension in any other time period. DISCUSSION: The association between preeclampsia and RH in the early second trimester was robust to model choice, suggesting that RH may contribute to seasonal trends in preeclampsia incidence. Differences between these results and those of prior studies could be attributable to exposure timing differences.

An Observational Study of Maternal and Perinatal Outcome in Preeclampsia Cases in a Tertiary Care Center.

INTRODUCTION: Preeclampsia, a hypertensive disorder in pregnancy, is a multisystem disease of unknown etiology and is associated with an increased risk of maternal mortality and morbidity. Infants from preeclampsia mothers have significantly higher incidence of prematurity, somatic growth retardation, thrombocytopenia, low birth weight, respiratory distress syndrome, and long duration of admission to neonatal intensive care (NICU). AIMS AND OBJECTIVES: This study was done to study the maternal mortality and morbidity and foetal outcome in pregnant women with severe preeclampsia. METHOD: This observational study was done in the Department of Obstetrics and Gynaecology, of a tertiary care centre, from the period October 2015 to October 2017. Data was collected from all 130 women attending the antenatal clinic of tertiary care hospital and ward admission and all details such as demographic details, obstetrics examination, and all clinical findings were noted and from that made results.  Result: After applying inclusion and exclusion criteria all 130 women were observed in this study. Among 130 women 47 were diagnosed with preeclampsia. Mainly primigravida women were diagnosed with preeclampsia in the 21-25 years group. Among 47 preeclampsia women, 39 women had a BMI of 19-25 kg/m2. Thirty-two of 47 (68.09%) women were diagnosed with preeclampsia around 36-39 weeks. Among all preeclampsia, 28 women out of 47 (59.5%) women delivered babies vaginally, 18 of 47 (38.3%) women delivered through cesarean section, and one of 47 (2.13%) underwent preterm vaginal delivery. In preeclampsia, women's babies were delivered mostly (25/47, 53.19%) ≤2.5 kg weight and only one baby was shifted to NICU because of low birth weight. Preeclampsia increases maternal mortality and morbidity but in this study mortality was not done because our hospital is a tertiary care center with all ICU (intensive care unit) and NICU setup. CONCLUSION: Preterm births and cesarean deliveries were the mild to severe outcomes that were noted. ICU and NICU hospitalizations as a result of severe complications place a heavy demand on medical facilities. There are firm guidelines for the management of pregnancy-induced hypertension and its complications. For appropriate management, there is careful consideration of various factors, and individual case studies are required.

Comparing labour induction outcomes using misoprostol and dinoprostone in term pregnancies: A retrospective study at Kiambu Level 5 Hospital between 2018 and 2020.

BACKGROUND: The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H. METHODS: We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes. RESULTS: We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol. CONCLUSION: While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.

BMI status and weight trajectories across females' reproductive years and risk of adverse pregnancy outcomes: a prospective cohort study.

BACKGROUND: Prepregnancy body mass index (BMI) is a well-established risk factor of adverse pregnancy outcomes (APOs). The associations of long-term and short-term weight trajectories with APOs are less clear. OBJECTIVES: This study aimed to determine the associations of weight trajectories during females' reproductive years, before and between pregnancies, with risk of APOs. METHODS: We followed 16,241 females (25,386 singleton pregnancies) participating in a prospective cohort, the Nurses' Health Study II. Weight at age 18 y, current weight, and height were assessed at baseline (1989), and weight was updated biennially. Pregnancy history was self-reported in 2009. The primary outcome was a composite of hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm birth, and stillbirth. Secondary outcomes were individual APOs. The associations of weight change with APOs were estimated using log-binomial regression, adjusting for demographic, lifestyle, reproductive factors, and baseline BMI (in kg/m2). RESULTS: The mean (standard deviation [SD]) age at first in-study pregnancy was 33.7 (4.1) y. The mean (SD) time from age 18 y to pregnancy, baseline to pregnancy, and between pregnancies was 16.3 (4.0), 6.1 (3.0), and 2.9 (1.6) y, with a corresponding weight change of 6.4 (9.1), 3.1 (5.8), and 2.3 (4.8) kg, respectively. Of the pregnancies, 4628 (18.2%) were complicated by ≥1 APOs. Absolute weight change since age 18 y was most strongly associated with APOs. Compared with females whose weight remained stable (0-2 kg) since age 18, females who gained >2 kg had higher risk of APO (2.1-9.9 kg, relative risk [RR]: 1.12; 95% confidence interval [CI]: 1.02, 1.23; 10.0-14.9 kg, RR: 1.43; 95% CI: 1.29, 1.60; ≥15 kg, RR: 1.87; 95% CI: 1.69, 2.08), primarily driven by HDP and GDM. The associations of per 1 kg weight gain before and between pregnancies with HDP were nearly identical. CONCLUSIONS: Weight trajectories prior to and between pregnancies were associated with the risk of APOs, particularly HDP. Longer periods of weight gain, corresponding to greater absolute weight gain, were most strongly associated with higher risk of APOs.

Serum Hydroxysteroid (17beta) dehydrogenase 1 concentration in pregnant women correlates with pregnancy-associated plasma protein a but does not serve as an independent marker for preeclampsia.

Hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) is a steroid synthetic enzyme expressed in ovarian granulosa cells and placental syncytiotrophoblasts. Here, HSD17B1 serum concentration was measured with a validated immuno assay during pregnancy at three time points (12-14, 18-20 and 26-28 weeks of gestation). The concentration increased 2.5-fold (p < 0.0001) and 1.7-fold (p = 0.0019) during the follow-up period for control women and women who later developed preeclampsia (PE), respectively, and a significant difference was observed at weeks 26-28 (p = 0.0266). HSD17B1 concentration at all the three time points positively correlated with serum PAPPA measured at the first time point (first time point r = 0.38, p = 1.1x10-10; second time point r = 0.27, p = 5.9x10-6 and third timepoint r = 0.26, p = 2.3x10-5). No correlation was observed between HSD17B1 and placental growth factor (PLGF). Serum HSD17B1, furthermore, negatively correlated with the mother's weight and body mass index (BMI), mirroring the pattern observed for PAPPA. The univariable logistic regression identified a weak association between HSD17B1 at 26-28 weeks and later development of PE (P = 0.04). Also, the best multivariable model obtained using penalized logistic regression with stable iterative variable selection at 26-28 weeks included HSD17B1, together with PLGF, PAPPA and the mother's BMI. While the area under the ROC curve of the model was higher than that of the adjusted PLGF, the difference was not statistically significant. In summary, the serum concentration of HSD17B1 correlated with PAPPA, another protein expressed in syncytiotrophoblasts, and with mother's weight and BMI but could not be considered as an independent marker for PE.

Association of sleep traits with risk of hypertensive disorders of pregnancy: a mendelian randomization study.

BACKGROUND: Unhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study. METHODS: Genome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, UK Biobank, and other prominent consortia, with a focus on individuals of European ancestry. The primary analysis utilized an inverse-variance-weighted MR approach supplemented by sensitivity analyses to mitigate potential biases introduced by pleiotropy. Furthermore, a two-step MR framework was employed for mediation analyses. RESULTS: The data analyzed included 200 000-500 000 individuals for each sleep trait, along with approximately 15 000 cases of HDPs. Genetically predicted excessive daytime sleepiness (EDS) exhibited a significant association with an increased risk of HDPs [odds ratio (OR) 2.96, 95% confidence interval (95% CI) 1.40-6.26], and the specific subtype of preeclampsia/eclampsia (OR 2.97, 95% CI 1.06-8.3). Similarly, genetically predicted obstructive sleep apnea (OSA) was associated with a higher risk of HDPs (OR 1.27, 95% CI 1.09-1.47). Sensitivity analysis validated the robustness of these associations. Mediation analysis showed that BMI mediated approximately 25% of the association between EDS and HDPs, while mediating up to approximately 60% of the association between OSA and the outcomes. No statistically significant associations were observed between other genetically predicted sleep traits, such as chronotype, daytime napping, sleep duration, insomnia, snoring, and the risk of HDPs. CONCLUSION: Our findings suggest a causal association between two sleep disorders, EDS and OSA, and the risk of HDPs, with BMI acting as a crucial mediator. EDS and OSA demonstrate promise as potentially preventable risk factors for HDPs, and targeting BMI may represent an alternative treatment strategy to mitigate the adverse impact of sleep disorders.

Clinical Analysis of Postpartum Preeclampsia After an Uncomplicated Pregnancy.

Preeclampsia is a rare complication of pregnancy and can cause maternal death. This case report serves to increase awareness of the range and severity of symptoms in postpartum preeclampsia and highlights a stepwise approach to provide prompt management. The cause of preeclampsia is not fully understood but is correlated with many placental and maternal factors. Preeclampsia typically resolves with delivery, and it is uncommon to have symptoms in the postpartum period. Due to the rarity of the disease, it is not typically at the top of a differential list for postpartum women. A 35-year-old first-time mother presents with shortness of breath, tightness in her chest, and mild pulmonary edema. A series of chest X-rays, computed tomographic angiogram of the chest, and serial labs reveal she has postpartum preeclampsia. Many pre-eclamptic symptoms are common to a variety of conditions leading to an extensive list of differential diagnoses. Used in a stepwise fashion, clinical analysis allows physicians to accurately diagnose postpartum preeclampsia and provide lifesaving treatment for these mothers. This study highlights the need for vigilance in symptom analysis and diagnostic testing.

Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Long-Term Risk of Type 2 Diabetes After Preterm Delivery or Hypertensive Disorders of Pregnancy.

OBJECTIVE: To examine long-term diabetes risk after preterm delivery or hypertensive disorders of pregnancy in a large population-based cohort. METHODS: This retrospective cohort study included all women with a singleton delivery in Sweden during 1973-2015 and no preexisting diabetes mellitus. Participants were followed up for development of type 2 diabetes identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute hazard ratios (HRs) for the association between preterm delivery or hypertensive disorders of pregnancy and type 2 diabetes with adjustment for gestational diabetes and other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic or environmental) factors. RESULTS: Overall, 2,184,417 women were included. Within 10 years after delivery, adjusted HRs for type 2 diabetes associated with specific pregnancy outcomes were as follows: any preterm delivery (before 37 weeks of gestation), 1.96 (95% CI, 1.83-2.09); extremely preterm delivery (22-27 weeks), 2.53 (95% CI, 2.03-3.16); and hypertensive disorders of pregnancy, 1.52 (95% CI, 1.43-1.63). All HRs remained significantly elevated (1.1-1.7-fold) 30-46 years after delivery. These findings were largely unexplained by shared familial factors. CONCLUSION: In this large national cohort, preterm delivery and hypertensive disorders of pregnancy were associated with increased risk for type 2 diabetes up to 46 years later. Women with these pregnancy complications are candidates for early preventive actions and long-term monitoring for type 2 diabetes.

Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy.

ABSTRACT: Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal-fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal-fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk. Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Glycemic control assessed by continuous glucose monitoring during pregnancy in women with type 1 diabetes and its association with preeclampsia, an observational Swedish cohort study.

INTRODUCTION: Women with type 1 diabetes have an increased risk of preeclampsia (PE), but it is not fully understood if degree of glycemic control is associated with this risk. The aim of this study was to assess glycemic control during pregnancy analyzed by continuous glucose monitoring (CGM) in women with and without PE and to investigate if glycemic control is associated with increased risk of PE. MATERIAL AND METHODS: A total of 120 pregnant Swedish women with type 1 diabetes using CGM were included. Background factors and pregnancy outcomes were collected from medical records. CGM data were collected via the internet-based platform Diasend. Mean glucose, standard deviation of mean glucose, percentage of time in target, time below target, and time above target were presented for each trimester in women who did or did not develop PE. Associations between CGM-derived metrics and PE were analyzed with logistic regression and adjusted for confounders. RESULTS: Twenty-two women (18.3%) developed PE. There were no significant differences in maternal characteristics between women with and without PE. Glycemic control improved in each trimester but was suboptimal in both groups. Time in target increased from 59% in the non-PE group and 54% in the PE group in the first trimester to 65% in both groups in the third trimester. There were no significant associations between glycemic control and PE after adjustment for confounders. CONCLUSIONS: Degree of glycemic control during pregnancy assessed by CGM was not associated with development of PE in women with type 1 diabetes. However, more research is needed to understand the role of glycemic control in relation to development of PE.

Phenotypes of maternal vascular malperfusion placental pathology and adverse pregnancy outcomes: A retrospective cohort study.

OBJECTIVE: To identify which components of maternal vascular malperfusion (MVM) pathology are associated with adverse pregnancy outcomes and to investigate the morphological phenotypes of MVM placental pathology and their relationship with distinct clinical presentations of pre-eclampsia and/or fetal growth restriction (FGR). DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Toronto, Canada. POPULATION: Pregnant individuals with low circulating maternal placental growth factor (PlGF) levels (<100 pg/mL) and placental pathology analysis between March 2017 and December 2019. METHODS: Association between each pathological finding and the outcomes of interest were calculated using the chi-square test. Cluster analysis and logistic regression was used to identify phenotypic clusters, and their association with adverse pregnancy outcomes. Cluster analysis was performed using the K-modes unsupervised clustering algorithm. MAIN OUTCOME MEASURES: Preterm delivery <34+0 weeks of gestation, early onset pre-eclampsia with delivery <34+0 weeks of gestation, birthweight <10th percentile (small for gestational age, SGA) and stillbirth. RESULTS: The diagnostic features of MVM most strongly associated with delivery <34+0 weeks of gestation were: infarction, accelerated villous maturation, distal villous hypoplasia and decidual vasculopathy. Two dominant phenotypic clusters of MVM pathology were identified. The largest cluster (n = 104) was characterised by both reduced placental mass and hypoxic ischaemic injury (infarction and accelerated villous maturation), and was associated with combined pre-eclampsia and SGA. The second dominant cluster (n = 59) was characterised by infarction and accelerated villous maturation alone, and was associated with pre-eclampsia and average birthweight for gestational age. CONCLUSIONS: Patients with placental MVM disease are at high risk of pre-eclampsia and FGR, and distinct pathological findings correlate with different clinical phenotypes, suggestive of distinct subtypes of MVM disease.

Oral misoprostol alone, compared with oral misoprostol followed by oxytocin, in women induced for hypertension of pregnancy: A multicentre randomised trial.

OBJECTIVE: To assess whether, in those requiring continuing uterine stimulation after cervical ripening with oral misoprostol and membrane rupture, augmentation with low-dose oral misoprostol is superior to intravenous oxytocin. DESIGN: Open-label, superiority randomised trial. SETTING: Government hospitals in India. POPULATION: Women who were induced for hypertensive disease in pregnancy and had undergone cervical ripening with oral misoprostol, but required continuing stimulation after artificial membrane rupture. METHODS: Participants received misoprostol (25 micrograms, orally, 2-hourly) or titrated oxytocin through an infusion pump. All women had one-to-one care; fetal monitoring was conducted using a mixture of intermittent and continuous electronic fetal monitoring. MAIN OUTCOME MEASURES: Caesarean birth. RESULTS: A total of 520 women were randomised and the baseline characteristics were comparable between the groups. The caesarean section rate was not reduced with the use of misoprostol (misoprostol, 84/260, 32.3%, vs oxytocin, 71/260, 27.3%; aOR 1.23; 95% CI 0.81-1.85; P = 0.33). The interval from randomisation to birth was somewhat longer with misoprostol (225 min, 207-244 min, vs 194 min, 179-210 min; aOR 1.137; 95% CI 1.023-1.264; P = 0.017). There were no cases of hyperstimulation in either arm. The rates of fetal heart rate abnormalities and maternal side effects were similar. Fewer babies in the misoprostol arm were admitted to the special care unit (10 vs 21 in the oxytocin group; aOR 0.463; 95% CI 0.203-1.058; P = 0.068) and there were no neonatal deaths in the misoprostol group, compared with three neonatal deaths in the oxytocin arm. Women's acceptability ratings were high in both study groups. CONCLUSIONS: Following cervical preparation with oral misoprostol and membrane rupture, the use of continuing oral misoprostol for augmentation did not significantly reduce caesarean rates, compared with the use of oxytocin. There were no hyperstimulation or significant adverse events in either arm of the trial.

Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

INTRODUCTION: Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. METHODS: The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. RESULTS: As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381 g to 4762 g, with a mean of 3439.91 g. Twenty-five infants were born at ≥37 weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n = 6 events), ear infection (n = 5 events), neonatal dyspnea (n = 3 events), and respiratory syncytial virus infection (n = 3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. CONCLUSION: A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.