Advanced maternal age (AMA) and pregnancy: a feasible but problematic event.

This narrative review aimed to summarize all adverse outcomes of pregnancy in advanced maternal age (AMA) to assess the age of the mother as a potentially crucial risk factor. AMA refers to women older than 35 years. While expectations and the role of women in society have undergone significant changes today, the biology of aging remains unchanged. Various pathologic changes occur in the human body with age, including chronic noncommunicable diseases, as well as notable changes in reproductive organs, that significantly affect fertility. Despite substantial advancements in technology and medicine, pregnancy in AMA remains a formidable challenge. Although there are some advantages to postponing childbirth, they primarily relate to maternal maturity and economic stability. However, regrettably, there are also many adverse aspects of pregnancy at advanced ages. These include complications affecting both the mother and the fetus. Pregnants in AMA were more prone to suffer from gestational diabetes mellitus, preeclampsia, and eclampsia during pregnancy compared to younger women. In addition, miscarriages and ectopic pregnancies were more prevalent. Delivery was more frequently completed via cesarean section, and postpartum complications and maternal mortality were also higher. Unfortunately, there were also complications concerning the fetus, such as chromosomal abnormalities, premature birth, low birth weight, admission to the neonatal intensive care unit, and stillbirth.

Examining the predictive value of fetal fraction on hypertensive disorders of pregnancy.

BACKGROUND: Cell-free fetal DNA (cffDNA) screening is routinely performed in pregnancy. Abnormal fetal fraction has been associated with adverse pregnancy outcomes, including hypertensive disorders of pregnancy, which are associated with severe maternal and neonatal morbidity and mortality. OBJECTIVE: This study examined whether abnormal fetal fraction, defined in this study as fetal fraction either <6 or >15 on the basis of restricted-cubic-spline-plot within our study population, was associated with HDP in a retrospective sample, as well as whether fetal fraction improves the prediction of hypertensive disorders of pregnancy (HDP). We hypothesized that abnormal fetal fraction would be associated with HDP and that adding fetal fraction to a model would significantly improve its strength to predict HDP. STUDY DESIGN: This was a retrospective cohort study of 729 patients delivering singleton, non-anomalous pregnancies with conclusive cffDNA screening. The primary outcome was HDP. Logistic regression models tested associations between fetal fraction and HDP. We evaluated the impact of including fetal fraction on the prediction of hypertensive disorders of pregnancy (HDP) by comparing the area under the receiver operating characteristic (ROC) curve (AUC) between predictive models with and without fetal fraction. RESULTS: Among the study sample, there was an HDP rate of 11.5 %. Abnormal fetal fraction was defined as <6 % percentile and >15 %, HDP incidence was significantly higher in patients with fetal fraction <6 % compared to patients with fetal fraction in normal range (fetal fraction 6-15 %) (19.5 % vs 10.7 %, p = 0.006 on post hoc comparison). Model 1 had one predictor (fetal fraction) with an AUC of 0.59, Model 2 had three predictors (BMI, nulliparity, history of HDP) with an AUC of 0.71, and Model 3 had four predictors (BMI, nulliparity, history of HDP, and fetal fraction) with an AUC of 0.73. Models 2 and 3 were not significantly different (p = 0.18). CONCLUSIONS: More patients who developed HDP had low fetal fraction and fewer patients who developed HDP had high fetal fraction compared to those patients who did not develop HDP. Based on results from multivariable regression models, we cannot conclude that fetal fraction improves HDP prediction. However, developing standardized values for abnormal fetal fraction may be clinically useful.

Effects of Maternal SARS-CoV-2 Infection During Pregnancy on Fetal Development.

BACKGROUND: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development. OBJECTIVE: This study aimed to review the evidence on the impact of SARS-CoV-2 infection during pregnancy on fetal outcomes. METHOD OF STUDY: Literatures since the outbreak of COVID-19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS-CoV-2 infection during pregnancy on fetal development. RESULTS: SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal-fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes. CONCLUSION: SARS-CoV-2 infection during pregnancy activates the maternal-fetal immune interface through vertical transmission, and has short- and long-term effects on fetal development, including the central nervous system. Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.

A comparison of the safety and effectiveness of insulin aspart with other bolus insulins in women with pre-existing Type 1 diabetes during pregnancy: A post hoc analysis of a prospective cohort study.

AIMS: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. METHODS: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. RESULTS: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). CONCLUSIONS: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

Exploring maternal and neonatal outcomes in women with Type-1 Diabetes: A study from Pakistan.

Background & Objective: Pregnancy in women diagnosed with Type-1 diabetes mellitus poses a higher risk of experiencing complications related to the health of the fetus, the mother, and the newborn, along with potential obstetric issues. The objective of this study was to examine the maternal and fetal outcomes, as well as complications faced by pregnant women with type-1 diabetes, and to identify potential preventable factors. Methods: This retrospective cohort study, conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University, Karachi, Pakistan (January 2022 - January 2023), focused on registered pregnancies of women with Type-1 diabetes. A predesigned questionnaire recorded demographic information, diabetes and obstetric history, clinical details, treatment specifics, maternal, perinatal, and neonatal outcomes. Results: This study included 100 women with pre-existing Type-1 diabetes (mean age: 15.11 ± 5.64 years at diabetes diagnosis). Of these, 72% reported unplanned pregnancies, with a mean HbA1C at conception 8.29%. Median gestational age at delivery was 32.15 ± 10.82 weeks. Delivery outcomes included 40% normal vaginal deliveries and 60% C-sections (9% emergency, 51% elective). Stillbirths occurred in 14 cases, while 16 women experienced one miscarriage, seven had two, and 10 had three miscarriages. Glycemic targets (fasting) were achieved in 55 women, and post-meal targets only in 29, whereas, neonatal complications included hypoglycemia in 13 and low birth weight in 12 neonates. Conclusion: The high frequency of unplanned pregnancies and cesarean sections along with poor management of pre-pregnancy care and poor glycemic control results in compromised maternal and perinatal outcomes in this high-risk group.

Impacts of COVID-19 on mothers' and newborns' health outcomes in regional Canada: A cross-sectional analysis.

Background: COVID-19 infection and pandemic-related stressors (e.g., socioeconomic challenges, isolation) resulted in significant concerns for the health of mothers and their newborns during the perinatal period. Therefore, the primary objective of this study was to compare the health outcomes of pregnant mothers and their newborns one year prior to and one year into the pandemic period in Alberta, Canada. Secondary objectives included investigating: 1) predictors of admission to neonatal intensive care units (NICU) and to compare NICU-admitted newborn health outcomes between the two time periods; 2) hospital utilization between the two time periods; and 3) the health outcomes of mothers and their newborns following infection with COVID-19. Methods: This analytical cross-sectional study used a large administrative dataset (n = 32,107) obtained from provincial regional hospitals and homebirths in Alberta, Canada, from April 15, 2019, to April 14, 2021. Descriptive statistics characterized the samples. Chi-squares and two-sample t-tests statistically compared samples. Multivariable logistic regression identified predictor variables. Results: General characteristics, pregnancy and labor complications, and infant outcomes were similar for the two time periods. Preterm birth and low birthweight predicted NICU admission. During the pandemic, prevalence of hospital visits and rehospitalization after discharge decreased for all infants and hospital visits after discharge decreased for NICU-admitted neonates. The odds of hospital revisits and rehospitalization after discharge were higher among newborns with COVID-19 at birth. Conclusions: Most of the findings are contextualized on pandemic-related stressors (rather than COVID-19 infection) and are briefly compared with other countries. Hospitals in Alberta appeared to adapt well to COVID-19 since health conditions were comparable between the two time periods and COVID-19 infection among mothers or newborns resulted in few observable impacts. Further investigation is required to determine causal reasons for changes in hospital utilization during the pandemic and greater birthweight among pandemic-born infants.

Comparison of clinical outcomes and perinatal outcomes between natural cycle and hormone replacement therapy of frozen-thawed embryo transfer in patients with regular menstruation: a propensity score-matched analysis.

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

Incidence of overt diabetes in pregnancy among women with 50-g glucose challenge test ≥ 200 mg/dL.

Objectives: To determine the incidence of overt diabetes in pregnancy (ODIP) among women with 50-g GCT results ≥ 200 mg/dL and compare characteristics and pregnancy outcomes between women with and without gestational diabetes (GDM). Methods: A retrospective cohort study was conducted in 212 pregnant women whose 50-g GCT results ≥ 200 mg/dL. ODIP was diagnosed from 75-g OGTT if fasting plasma glucose ≥ 126 and/or 2-h plasma glucose ≥ 200 mg/dL. Various characteristics and pregnancy outcomes were compared between ODIP and those with and without GDM. Results: Incidence of ODIP was 1.9% of all pregnant women and 23.6% of women with 50-g GCT ≥ 200 mg/dL. Women with ODIP and GDM were more likely to be overweight or obese than those without GDM (52%, 39.6%, and 18.2%, p < 0.001). Women with ODIP had significantly higher 50-g GCT results, lower gestational weight gain, and were less likely to deliver vaginally. Insulin therapy was significantly more common in women with ODIP compared to GDM (70.2% vs. 15.4%, p < 0.001). Rates of LGA, macrosomia, and other neonatal outcomes were comparable. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of any abnormal glucose tolerance [adjusted OR 3.22 (95% CI 1.55-6.70) and 2.28 (95% CI 1.14-4.58)] and ODIP [adjusted OR 9.43 (95% CI 2.15-41.38) and 6.36 (95% CI 2.85-14.18)], respectively. Conclusion: Incidence of ODIP was 23.6% of women with 50-g GCT ≥ 200 mg/dL. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of GDM and ODIP. Neonatal complications were comparable between ODIP and those with and without GDM.

Changes in Maternal Socio-Demographic Characteristics and Pregnancy Outcomes Across Monitoring Regions - Six Provinces, China, 2016-2022.

What is already known about this topic?: In recent years, there has been a significant increase in the proportion of women of advanced maternal age (AMA), accompanied by a rise in adverse pregnancy outcomes in certain regions of China. What is added by this report?: From 2016 to 2022, there was an observed increase in the proportion of AMA, educational levels, and incidences of preterm birth and low birth weight (LBW) in both primiparous and multiparous women. Concurrently, there was a declining trend in the rate of cesarean deliveries and the incidence of macrosomia among multiparous women. What are the implications for public health practice?: In addition to focusing on health management for AMA individuals, proactive steps should be undertaken to enhance the quality of medical services and promote childbirth at optimal ages, thereby reducing the incidence of adverse pregnancy outcomes.

Reproductive Characteristics and Trends of Major Pregnancy Outcomes of Women at Different Parities - Beijing Municipality, China, 2013-2022.

What is already known about this topic?: With socioeconomic development, the increase of older pregnancies and multiparas has brought risks to mothers and infants. What is added by this report?: As parities increased, the proportion of women of advanced maternal age (AMA) and non-local domicile increased, while the proportion of women with higher education levels decreased. Women with ≥3 parities are more likely to have preterm birth (PTB) and macrosomia. What are the implications for public health practice?: A comprehensive analysis of pregnancy traits among women at different parities offers a robust foundation for tailored strategies against adverse pregnancy outcomes.

Associations between antenatal depressive symptoms in different trimesters and perinatal outcomes: A prospective multicenter cohort study in China.

BACKGROUND: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester. METHODS: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses. RESULTS: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted ß=0.026, 95 % CI: 0.003-0.050). CONCLUSION: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester.

First-Trimester Vaginal Bleeding and Adverse Obstetric Outcomes in a Semi-urban Population of India: A Prospective Observational Study.

Background This study aimed to investigate the obstetric outcomes in antenatal women with first-trimester vaginal bleeding. Methodology This single-centered, prospective, observational study was conducted in a tertiary healthcare institution. Antenatal women with first-trimester vaginal bleeding who visited the hospital were screened for eligibility and included in the study. They were followed up until the termination of pregnancy or delivery based on the etiology of vaginal bleeding. Various fetomaternal outcomes such as pregnancy outcomes, obstetric complications, mode of delivery, and neonatal outcomes were analyzed. Results This study included 120 antenatal women who experienced first-trimester vaginal bleeding during the study period. Vaginal bleeding was more prevalent in the age group of 25-34 years and primigravidas. Out of 120 women, 14 (11.6%) either aborted or the pregnancy was terminated as a result of a nonviable gestation, and 106 (88.4%) delivered after the period of viability. Out of 106 women, 56 (52.8%) had full-term pregnancies without any obstetric complications. We analyzed the obstetric complications developed in all the study participants and found that 23 (21.7%) had preterm labor, 12 (11.3%) had placental abruption, 6 (5.7%) had premature rupture of membrane, 4 (3.9%) had anemia, and 2 (1.9%) developed hypertensive disorder of pregnancy. Of all deliveries, 54 (50.9%) delivered vaginally and 52 (49.1%) had cesarean delivery. There were no major adverse neonatal outcomes in terms of birthweight, APGAR score at one minute, and APGAR score at five minutes. Conclusions A large proportion of antenatal women with first-trimester vaginal bleeding can have favorable perinatal outcomes. However, as a few may develop obstetric complications, regular follow-up of such cases is mandated to prevent adverse outcomes.

Evaluation of the Effect of Embryo Transfer Methods on Pregnancy Outcomes: A Retrospective Study and Future Perspectives.

Background: Trans-abdominal ultrasound (TAUS) and transvaginal ultrasound (TVUS) are used for embryo transfer. However, few studies were conducted to compare the methods and assess their effect on pregnancy outcomes. Methods: A retrospective cohort study was conducted at Mahdieh Hospital in Tehran, analyzing 506 ICSI cycles with fresh embryo transfer. The study period was from April 2019 to March 2022. Following the evaluation of patients' profile, they were divided into two groups of TAUS (n=250) and TVUS (n=256). The pregnancy outcomes included positive test of ß-HCG, history of miscarriage, ectopic pregnancy (EP), clinical pregnancy, and the duration of the embryo transfer were compared between two groups. Mann-Whitney U test, Pearson Chi-Square test, Fisher's exact test, and logistic regression were used for data analysis. Results: The rate of chemical and clinical pregnancy in the TAUS group was higher compared to the TVUS group, which was statistically significant (p<0.05). The rate of live term birth and live preterm birth was higher in the TAUS group compared to the TVUS group, though the difference was insignificant. Moreover, EP and abortion rates were higher in TVUS group compared to the TAUS group, but the differences were not statistically significant. The odds ratio of achieving pregnancy was higher with TAUS compared to TVUS, but this was only statistically significant for the age variable. Conclusion: The use of TAUS method appears to be associated with improved pregnancy outcome, including higher rates of chemical and clinical pregnancy, compared to TVUS. Yet, further research is needed to confirm these findings and elucidate underlying mechanisms.

Potential contribution of alpha-fetoprotein level to biomarker of pregnancy outcome in Asian elephants.

Alpha-fetoprotein (AFP) is a structural serum glycoprotein that plays vital roles in reproduction and mammalian development. Analysis of serum prolactin (PRL) is considered one of the useful methods for diagnosing pregnancy in Asian elephants. However, the expression profiles of AFP in pregnant and nonpregnant Asian elephants remain unclear, nor is the relationship with PRL. In this study, serum seven gonadal hormones and AFP in three pregnant and seven nonpregnant Asian elephants were analysed by via radioimmunoassay (RIA) and enzyme-linked immunosorbent (ELISA) assay. We found that the mean (±SD) concentration of prolactin (PRL) in pregnant (136.782 ± 30.987 ng/mL) elephants was significantly higher than that in nonpregnant elephants (52.803 ± 21.070 ng/mL; p ≤ 0.0005). The mean (±SD) concentration of AFP in pregnant elephants (11.598 ± 0.824 ng/mL) was significantly higher than that in nonpregnant elephants (7.200 ± 2.283 ng/mL; p ≤ 0.05). Furthermore, the AFP concentration was positively correlated with the PRL concentration in the 10 Asian elephants studied. In conclusion, our findings suggest that serum AFP concentration is a potential biomarker of pregnancy outcomes in Asian elephants.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.

OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Investigating Menstruation and Adverse Pregnancy Outcomes: Oxymoron or New Frontier? A Narrative Review.

Not discounting the important foetal or placental contribution, the endometrium is a key determinant of pregnancy outcomes. Given the inherently linked processes of menstruation, pregnancy and parturition with the endometrium, further understanding of menstruation will help to elucidate the maternal contribution to pregnancy. Endometrial health can be assessed via menstrual history and menstrual fluid, a cyclically shed, easily and non-invasively accessible biological sample that represents the distinct, heterogeneous composition of the endometrial environment. Menstrual fluid has been applied to the study of endometriosis, unexplained infertility and early pregnancy loss; however, it is yet to be examined regarding adverse pregnancy outcomes. These adverse outcomes, including preeclampsia, foetal growth restriction (FGR), spontaneous preterm birth and perinatal death (stillbirth and neonatal death), lay on a spectrum of severity and are often attributed to placental dysfunction. The source of this placental dysfunction is largely unknown and may be due to underlying endometrial abnormalities or endometrial interactions during placentation. We present existing evidence for the endometrial contribution to adverse pregnancy outcomes and propose that a more comprehensive understanding of menstruation can provide insight into the endometrial environment, offering great potential value as a diagnostic tool to assess pregnancy risk. As yet, this concept has hardly been explored.

Rhekiss-The German Register for Child Wish and Pregnancies in Inflammatory Rheumatic Diseases.

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs.

Association of adverse pregnancy outcomes with cardiovascular risk profiles in later life: Current insights from the Hamburg City Health Study (HCHS).

BACKGROUND AND AIMS: Adverse pregnancy outcomes (APO) have been related to increased cardiovascular (CV) risk and mortality in later life. Underlying pathomechanisms for the development of CV disease in these women are not yet fully understood. In this study, we aimed to investigate the relationship between APO and individual CV risk profiles in later life. METHODS: We used cross-sectional data from 10,000 participants enrolled in the Hamburg City Health Study (HCHS). We analysed self-reported APO, CV risk factors and health status, including biomarkers, electrocardiogram, echocardiography and vascular ultrasound. To examine associations, Wilcoxon rank sum test and Pearson's χ2-test were performed. Multivariable-adjusted regression models were calculated to determine associations. RESULTS: N = 1970 women who reported pregnancies were included. Median age was 63 years, 8.7 % reported gestational hypertension (gHTN), 18 % excessive weight gain and 2.4 % gestational diabetes. Ten percent had delivered newborns with birth weight <2.5 kg, 14 % newborns with birth weight >4 kg. In multivariable-adjusted models, significant associations between APO, CV risk profiles and cardiac remodeling were identified. gHTN correlated with higher body mass index (BMI) (Beta 1.68, CI 95 % 0.86-2.50; p < 0.001), hypertension (OR 4.58, CI 95 % 2.79-7.86; p < 0.001), left ventricular remodeling (e.g. left ventricular mass index (Beta 4.46, CI 95 % 1.05-7.87; p = 0.010)) and myocardial infarction (OR 3.27, CI 95 % 0.94-10.07; p = 0.046). CONCLUSIONS: In this population-based sample, APO were associated with CV risk profiles and cardiac remodeling in later life, suggesting early manifestations of future CV risk during pregnancy. Prospective data is needed for individual risk stratification in women with APO.

hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

Comparison of Characteristics Between Early-Onset and Late-Onset Severe Preeclampsia: A Retrospective Cohort Study from a Tertiary Hospital in China.

This study aimed to explore the different characteristics between early-onset severe preeclampsia (ESPE) and late-onset severe preeclampsia (LSPE) to improve pregnancy outcomes. We performed a retrospective cohort study between January 2016 and December 2021. Eligible hospitalized pregnant women with severe preeclampsia were assigned into the early-onset or late-onset group, depending on the gestational age at the time of severe preeclampsia onset (< or ≥ 34 gestational weeks, respectively). The clinical characteristics, laboratory results, maternal complications, and fetal and neonatal outcomes were recorded and compared between the two groups. A total of 1,238 pregnant women were included, with 525 in the early-onset group and 713 in the late-onset group. The late-onset group had more cases of gestational diabetes, whereas the early-onset group had a higher blood pressure, showed more proteinuria, had more liver and renal damage, exhibited more serious adverse maternal, fetal, and neonatal outcomes, was more likely to be admitted to the intensive care unit, and required longer hospital stays (all P < 0.05). In addition, the early-onset group had fewer prenatal care appointments and was more often transferred from a primary or secondary care hospital. The logistic regression analysis showed that a weekly weight gain of > 100 g was a risk factor for ESPE and that fewer prenatal care appointments were a risk factor for ESPE in pregnant women with female fetuses. Moreover, logistic regression analysis indicated that nulliparity and gestational diabetes during the current pregnancy were risk factors for LSPE. In conclusion, compared with the women with LSPE, those with ESPE usually had worse maternal, fetal, and neonatal outcomes. More frequent prenatal screening and care should be provided for pregnant women with high-risk factors.