Cardiomyopathies in Pregnancy: Trends and Clinical Outcomes in Delivery Hospitalizations in the United States (2005-2020).

BACKGROUND: Cardiomyopathy (CDM) in pregnancy is associated with maternal morbidity and mortality. OBJECTIVES: To explore trends and clinical outcomes in CDM subtypes during delivery hospitalizations. METHODS: We used the National Inpatient Sample database to identify delivery hospitalizations between 2005-2020 by CDM subtypes: peripartum (PPCM), dilated (DCM), hypertrophic (HCM), and restrictive (RCM). Maternal and fetal outcomes were identified using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes. Baseline characteristics and temporal trends of CDM subtypes were analyzed. Maternal cardiovascular, pregnancy, and fetal outcomes were evaluated by CDM subtype using univariate logistic regression. The primary outcome was in-hospital mortality. RESULTS: During 2005-2020, 37,125 out of 61,811,842 delivery hospitalizations were complicated by CDM. Among CDM-related delivery hospitalizations, the most prevalent were DCM (46%), followed by PPCM (45.6%), HCM (4.6%), and RCM (3.9%). The rates of in-hospital mortality (1.7%), adverse cardiovascular events such as acute heart failure (17%), cardiogenic shock (3.4%), and cardiac arrest (3.1%), and adverse pregnancy outcomes such as preeclampsia (14.2%) and preterm labor (11%), were highest among PPCM (all p < 0.0001). The prevalence of PPCM (49.1% to 38.5%) decreased while the prevalence of HCM (2.7% to 8.8%) and DCM (48% to 52.2%) increased over time. CONCLUSIONS: Over a 15-year period, PPCM had higher rates of in-hospital mortality, cardiovascular events, and adverse pregnancy outcomes compared to other CDM subtypes. While the prevalence of PPCM decreased over time, the prevalence of HCM and DCM increased. Hence, further research on cardiomyopathies during pregnancy and prospective studies on this vulnerable patient cohort are urgently needed.

Association between gestational hypnotic benzodiazepine receptor agonists exposure and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Hypnotic benzodiazepine receptor agonists (HBRA) are frequently prescribed in pregnancy but little is known about their effects on pregnancy outcomes. Herein, we systematically reviewed the evidence on the effects of HBRA exposure during pregnancy and risk of preterm birth (PTB), small for gestational age (SGA), birth defects, and low birth weight (LBW). METHODS: We reviewed the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science from the earliest possible date to 17th May 2024 and included all studies examining adverse pregnancy outcomes with gestational exposure to HBRA. RESULTS: Nine studies were included. Meta-analysis showed that HBRA exposure led to a significant increase in the risk of PTB (OR: 1.28 95% CI: 1.05, 1.56 I2 = 73%), SGA (OR: 1.24 95% CI: 1.18, 1.30 I2 = 0%), and LBW (OR: 1.51 95% CI: 1.27, 1.78 I2 = 26%). We noted no significant association between HBRA exposure in pregnancy and subsequent birth defects (OR: 0.90 95% CI: 0.63, 1.28 I2 = 56%). Subgroup analysis based on exposure time, type of HBRA, method of assessment of exposure, control of psychiatric diagnosis, and psychotropic drugs altered the results of PTB and SGA but not for birth defects. CONCLUSION: HBRA exposure during pregnancy may lead to a small but significant increase in the risk of PTB, SGA, and LBW. HBRA is not associated with an increased risk of birth defects. There are several limitations of current evidence especially with regards to adjustment for psychiatric illness and co-mediations which need to be overcome by future studies.

Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization.

OBJECTIVE: Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes. METHODS: The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. "TwoSampleMR" and "MR-PRESSO" packages were used for data analysis in this study. RESULTS: Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p = 0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p = 0.041), preeclampsia (p = 0.008), premature rupture of membranes (p = 0.030), and preterm (p = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p = 0.012), gestational hypertension (p < 0.001), preeclampsia (p = 0.002), and preterm (p = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (p = 0.010), the number of spontaneous miscarriages (p = 0.024), and placental abruption (p = 0.027). In addition, we found a causal association between nRA and birth weight (p = 0.007), but not between RA and pRA and birth weight. CONCLUSION: The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.

Trend, Pattern, and Prevalence of Adverse Pregnancy Outcomes among Women of Reproductive Age in India, 1992-2021.

Background: Adverse pregnancy outcomes (APOs) are the most important vital statistics used to assess maternal health and child health statistics. They are an indicator of the quality of maternal and child health care services, i.e., antenatal care, intrapartum care, and medical services. Material and Methods: The objective of the study is to analyze the trend, pattern, and prevalence of APOs among women of reproductive age group at the national level over successive NFHS rounds. The current study uses data from the National Family Health Survey (NFHS), conducted during 1992-2021. The study uses geo-spatial mapping techniques through QGIS software and report analysis to arrive at definitive conclusions. Results: The study finds that the incidence of APOs among women of reproductive age (15-49 years) has increased over the years. Twenty states and union territories have APOs that are below the national average. On the other hand, States like Madhya Pradesh, Meghalaya, Sikkim, Goa, Maharashtra, Andhra Pradesh, Karnataka, and Kerala have witnessed their APOs worsening as per NFHS-5 vis-à-vis NFHS-4. The study also finds that apart from the Himalayan belt and the east coast of India, APOs are more prominent in the contiguous regions adjoining these areas. Conclusions: The findings of the study have thrown on very interesting facts. Despite rapid economic development during the intervening period between NFHS-4 and NFHS-5, rising APOs are a testament to the fact that the policymakers in the country need to be more target-oriented and get their acts together.

Clinical Features Between Primary Obstetric Antiphospholipid Syndrome and Non-Criteria Obstetric Antiphospholipid Syndrome and Risk Factors of Adverse Pregnancy Outcomes: A Retrospective Study of 1006 Cases.

PROBLEM: To compare the clinical characteristics and pregnancy outcomes between patients with primary obstetric antiphospholipid syndrome (OAPS) and those with primary non-criteria obstetric antiphospholipid syndrome (NC-OAPS), and to identify the risk factors of adverse pregnancy outcomes in both groups. METHODS: A retrospective single-center study was performed in a university hospital of western China, including 141 patients with OAPS and 865 patients with NC-OAPS. The clinical characteristics, pregnancy complications, and obstetric outcomes of the cohorts were collected from the hospital system and were compared by univariable analysis, and the independent risk factors for adverse pregnancy outcomes (APO) were investigated by logistic regression analysis in these two populations. RESULTS: The OAPS patients had a significantly higher risk for stillbirths compared to the NC-OAPS patients, while the NC-OAPS group had a significantly higher risk for preterm birth and overall APO. Double aPL positivity, triple aPL positivity, and gestational hypertension were the independent risk factors for APO in OAPS patients, whereas two of the double aPL positivity subtypes, triple aPL positivity and placenta previa were independent risk factors for APO in NC-OAPS patients. CONCLUSION: This study identified different rates in different APOs among OAPS and NC-OAPS patients. Additionally, this study revealed different risk factors for the development of APO between the two populations. These findings indicated that OAPS and NC-OAPS are two distinct entities of the same disease, providing new insights into the individualized management for patients with OAPS and NC-OAPS.

COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study.

Background: The extent to which COVID-19 diagnosis and vaccination during pregnancy are associated with risks of common and rare adverse pregnancy outcomes remains uncertain. We compared the incidence of adverse pregnancy outcomes in women with and without COVID-19 diagnosis and vaccination during pregnancy. Methods: We studied population-scale linked electronic health records for women with singleton pregnancies in England and Wales from 1 August 2019 to 31 December 2021. This time period was divided at 8th December 2020 into pre-vaccination and vaccination roll-out eras. We calculated adjusted hazard ratios (HRs) for common and rare pregnancy outcomes according to the time since COVID-19 diagnosis and vaccination and by pregnancy trimester and COVID-19 variant. Findings: Amongst 865,654 pregnant women, we recorded 60,134 (7%) COVID-19 diagnoses and 182,120 (21%) adverse pregnancy outcomes. COVID-19 diagnosis was associated with a higher risk of gestational diabetes (adjusted HR 1.22, 95% CI 1.18-1.26), gestational hypertension (1.16, 1.10-1.22), pre-eclampsia (1.20, 1.12-1.28), preterm birth (1.63, 1.57-1.69, and 1.68, 1.61-1.75 for spontaneous preterm), very preterm birth (2.04, 1.86-2.23), small for gestational age (1.12, 1.07-1.18), thrombotic venous events (1.85, 1.56-2.20) and stillbirth (only within 14-days since COVID-19 diagnosis, 3.39, 2.23-5.15). HRs were more pronounced in the pre-vaccination era, within 14-days since COVID-19 diagnosis, when COVID-19 diagnosis occurred in the 3rd trimester, and in the original variant era. There was no evidence to suggest COVID-19 vaccination during pregnancy was associated with a higher risk of adverse pregnancy outcomes. Instead, dose 1 of COVID-19 vaccine was associated with lower risks of preterm birth (0.90, 0.86-0.95), very preterm birth (0.84, 0.76-0.94), small for gestational age (0.93, 0.88-0.99), and stillbirth (0.67, 0.49-0.92). Interpretation: Pregnant women with a COVID-19 diagnosis have higher risks of adverse pregnancy outcomes. These findings support recommendations towards high-priority vaccination against COVID-19 in pregnant women. Funding: BHF, ESRC, Forte, HDR-UK, MRC, NIHR and VR.

Preterm birth, low birth weight, and their co-occurrence among women with preexisting chronic diseases prior to conception: a cross-sectional analysis of postpartum women in a low-resource setting in Ghana.

BACKGROUND: The incidence of chronic diseases, which are significant contributors to maternal deaths and adverse new-born outcomes, is increasing among women of reproductive age in northern Ghana. This emerging health issue raises serious concerns about the potential exacerbation of adverse birth outcomes in this setting, given that it is one of the regions in the country with a high incidence of such outcomes. We investigated the risks of preterm birth (PTB), low birth weight (LBW), and concurrent PTB and LBW among women with preexisting chronic conditions prior to conception in the Tamale Metropolis of northern Ghana. METHODS: A facility-based cross-sectional study was conducted among 420 postpartum women randomly selected from five public health facilities. Information was collected electronically on participants' self-reported experience of chronic conditions, namely, hypertension, diabetes, asthma, heart disease, and sickle cell disease, prior to their most recent pregnancy. Information on gestational age at delivery and birth weight was also collected. Regression modeling was used to quantify the risk of adverse newborn outcomes among women who reported preexisting chronic conditions prior to pregnancy. RESULTS: Chronic diseases affected 31.2% of our sample. Of these, 28.6% had a single chronic condition, while 2.6% had comorbid chronic conditions. The prevalence of PTB was 24.0% (95% CI: 20.2, 28.4), 27.6% (95% CI: 23.5, 32.1) of the newborns were born LBW, and 17.4% (95% CI: 14.0, 21.3) of the pregnancies resulted in both PTB and LBW. Compared with those without chronic conditions, women with chronic conditions prior to conception had a greater risk of PTB (aOR = 6.78, 95% CI: 3.36, 13.68), LBW (aOR = 5.75, 95% CI: 2.96, 11.18), and the co-occurrence of PTB and LBW (aOR = 7.55, 95% CI: 3.32, 17.18). CONCLUSIONS: We observed significant rates of PTB, LBW, and the co-occurrence of PTB and LBW among women who were already aware that they had preexisting chronic conditions prior to conception. Our findings highlight a potential gap in the quality of prenatal care provided to these women before delivery. Preconception care may offer an opportunity to address preexisting chronic conditions in women before pregnancy and potentially improve maternal and newborn health outcomes.

Impact of isolated fetal congenital heart disease on pregnancy and perinatal outcomes.

OBJECTIVE: The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition. METHODS: In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries. RESULTS: Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35-4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32-45.78; P < 0.001), and pre-eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01-4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11-3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002). CONCLUSION: Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health.

Selective Fetal Reduction of Uncomplicated Dichorionic Twins on Parental Request Versus Ongoing Twins and Pregnancy Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to assess the effect of elective fetal reduction in uncomplicated twin pregnancies on maternal-fetal outcomes, compared to ongoing twin pregnancies. DATA SOURCES: PubMed, Scopus (until December 2023), and references of retrieved articles. STUDY APPRAISAL AND SYNTHESIS METHODS: Quality assessment of observational studies was conducted using the ROBINS-I tool. The overall quality of evidence was evaluated per GRADE. A quantitative analysis was performed for electively reduced dichorionic twins. Primary outcome was preterm birth. Secondary outcomes were gestational age at delivery, stillbirth and neonatal intensive care unit, gestational diabetes mellitus, pre-eclampsia, and pregnancy loss < 24 weeks of gestation. Summary odds ratio (ORs) with 95% confidence intervals (CIs) were calculated, and random-effects models were used for data synthesis. RESULTS: The initial electronic search yielded 745 studies; 175 studies were further identified from reference citations. Five articles included appropriate data and were finally included in the meta-analysis. All studies were evaluated as "moderate risk of bias". Those five studies reported on dichorionic twins. Elective reduction in dichorionic twins reduces the risk for preterm birth <37 weeks (4 studies; n=1577; OR 0.14, 95% CI 0.09-0.22, moderate-quality evidence), <34 weeks (3 studies; n=1335; OR 0.22, 95% CI 0.07-0.69; low-quality evidence), <32 weeks (3 studies; n=1335; OR 0.31, 95% CI, 0.11-0.88; low-quality evidence), gestational diabetes (3 studies; n= 1410; OR 0.57, 95% CI 0.33-0.97, low-quality evidence), pregnancy-associated hypertensive disorders (2 studies; n=581; OR 0.29, 95% CI 0.10-0.83; low-quality evidence), birthweight <10th centile (2 studies; n=1163; OR 0.27, 95% CI 0.17-0.43; moderate-quality evidence), birthweight< 5th centile (2 studies; n=1163; OR 0.31, 95% CI 0.19-0.50; low-quality evidence) and increases gestational age at delivery {four studies; n= 1362; MD 2.93 weeks, 95% CI 2.08-3.77; moderate-quality evidence}. The risk for stillbirth (2 studies; n= 1311; OR 1.63, 95% CI 0.43-6.21; very low-quality evidence) or pregnancy loss< 24 weeks (3 studies; n=1436; OR 1.20, 95% CI 0.55-2.58; very low-quality evidence) were not statistically significant different. CONCLUSIONS: Compared to ongoing dichorionic twin pregnancies, dichorionic pregnancies that undergo elective selective fetal reduction are associated with lower incidences of preterm birth < 37 weeks, <34 weeks, <32 weeks, birthweight <10th centile and <5th centile, gestational diabetes, hypertensive disorders of pregnancy, and later gestational age at delivery by almost 3 weeks. These associations were often based on very low quality of evidence; so these results should be interpreted with caution and further studies should be conducted.

The risk factor for adverse pregnancy outcomes and its impact on clinical effect in IgA nephropathy: A retrospective observational study.

AIM: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear. METHODS: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO. RESULTS: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome. CONCLUSION: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO.

Pregnancy outcomes in Australian patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) affects women, with the onset of disease typically around the childbearing years. AIMS: This study examines the frequency and risk factors for adverse pregnancy outcomes (APOs) in an Australian cohort, and any disease flares during pregnancy and post partum. METHODS: Female patients with SLE enrolled in the Australian Lupus Registry and Biobank (ALRB) between January 2007 and June 2019 were studied. Self-reported pregnancy history, including adverse foetal or maternal outcomes, was collected at the time of enrolment and updated as appropriate. Baseline demographics, clinical parameters, medication exposure and disease activity were collected. Factors associated with APO were examined using univariate and multivariate logistic regression analyses. RESULTS: Pregnancy history was available in 278 patients; 30% were nulliparous. Most pregnancies occurred before the diagnosis of SLE. Patients who had pregnancies after SLE diagnosis had an earlier age of diagnosis, and had fewer pregnancies. The APO rate was 44.3% in the overall cohort, with most presenting as prematurity with or without foetal growth restriction. Women with APO were also diagnosed with SLE at a younger age and had a higher prevalence of anti-cardiolipin antibodies and hypocomplementemia. Early age of SLE diagnosis was a significant independent risk factor for APO. No increase in disease flare was observed in those who experienced APO during the observation period of ALRB. CONCLUSION: This study shows a considerable incidence of APO in patients with SLE, emphasising the need for pre-pregnancy counselling and collaboration between maternal-foetal medicine specialists and rheumatologists, especially for women diagnosed with SLE at a younger age.

Non-criteria and criteria antiphospholipid antibodies and their association with pregnancy outcomes in women with a history of miscarriage: A retrospective study.

INTRODUCTION: The objective of this study was to investigate both antiphospholipid antibodies (aPLs) and non-criteria aPLs (NC-aPLs) in relation with pregnancy outcomes. METHODS: We retrospectively analyzed 1574 pregnant women with experienced at least one miscarriage who were tested for aPLs and NC-aPLs, and compared their clinical characteristics, immune biomarkers, and pregnancy outcomes. The χ2 test or Fisher's exact test compared pregnancy outcomes among patients negative for all aPLs, positive for NC­aPLs subtypes, and positive for criteria aPLs subtypes. RESULTS: Multivariate logistic regression analysis indicated that positive aPLs (OR = 2.216, 95 % CI 1.381-3.558), and positive NC-aPLs (OR = 1.619, 95 % CI 1.245-2.106) are linked to adverse outcomes. For fetal loss, positive aPLs (OR = 2.354, 95 % CI 1.448-3.829), NC-aPLs (OR = 1.443, 95 % CI 1.076-1.936) were significant. Premature delivery was associated with positive NC-aPLs (OR = 2.102, 95 % CI 1.452-3.043). In the NC-aPLs positive group, the rate of adverse outcomes was higher in the multiple-positive subgroup (77.8 %) compared to the double-positive (52.3 %) and single-positive (37.0 %) subgroups. The rates of fetal loss and premature delivery were also higher in the multiple-positive NC-aPLs subgroup compared to the single-positive subgroup (48.1 % vs. 22.6 % for fetal loss and 57.1 % vs. 16.5 % for premature delivery). DISCUSSION: Our findings suggest that both aPLs and NC-aPLs are associated with an increased incidence of adverse pregnancy outcomes, and patients presenting with multiple NC-aPLs positivity were found to have a higher incidence of adverse outcomes compared to their single-positive counterparts.

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.

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.

Incarcerated gravid uterus: a new treatment using the transvaginal ultrasound probe and narrative literature review.

BACKGROUND: 'Incarcerated gravid uterus' is a morbid complication that occurs in 1 in 3000 pregnancies. It is characterized by failure of a retropositioned uterus to become an abdominal organ between 12 to 14 weeks of gestation. If maternal symptoms develop or gestational age surpasses 14 to 16 weeks, replacement of a retropositioned uterus is recommended to reduce adverse outcomes. Previously described techniques for management include passive reduction, digital replacement, or more invasive methods such as laparoscopy, laparotomy, or sigmoidoscopy. These methods are either minimally effective, painful, or risky. OBJECTIVE: The objective of this report is to describe our clinical experience with a new minimally invasive technique that uses the transvaginal ultrasound probe for uterine replacement in cases of incarceration, to conduct a narrative literature review on 'incarcerated gravid uterus,' and to propose an algorithm for management of this condition. STUDY DESIGN: This is a case series of 8 patients with an incarcerated gravid uterus who were managed with the transvaginal ultrasound probe technique at one academic medical institution between March 2020 and July 2023, as well as a narrative review of the literature on 'incarcerated gravid uterus.' PubMed, Google Scholar, and Ovid MEDLINE databases were searched for the terms "incarcerated gravid uterus," "uterine incarceration," "uterine sacculation," and "retroverted uterus" up to April 2024. RESULTS: The transvaginal ultrasound probe technique resulted in successful uterine replacement, with resolution of symptoms, in all 8 patients. All pregnancies resulted in live births with good neonatal outcomes-7 out of 8 patients delivered at term, and 1 delivered in the late preterm period. CONCLUSION: Our proposed technique for treatment of an incarcerated gravid uterus with the transvaginal ultrasound probe is simple, minimally invasive and effective. Based on our experience and the narrative literature review, an algorithm for the management of an incarcerated gravid uterus is proposed.

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.

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.

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.

Predictive Factors for the Common Adverse Maternal and Fetal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus.

Objectives: This study aimed to evaluate the outcomes of pregnancy in patients with systemic lupus erythematosus (SLE). It focused on identifying clinical and laboratory markers that could predict the common adverse pregnancy outcomes (APOs) after 20 weeks of gestation, namely preeclampsia (PE) and preterm birth (PTB) in them. Methods: Pregnant SLE women who delivered at the study center from 2010 to 2023 were retrospectively analyzed. Categorical variables were evaluated using the chi-square test or Fisher's exact test, while continuous variables underwent Mann-Whitney U testing. Stepwise regression was used to assess the predictors of pregnancy outcomes. Results: The study enrolled 445 pregnancies in 408 women diagnosed with SLE. Of these, 202 pregnancies (45.4%) resulted in at least one APO. Disease flare-ups, hypertension, and proteinuria during the first trimester were primary predictors of at least one APO and PTB. The most frequently recorded maternal adverse outcome was PE (14.6%), while PTB accounted for 32.6% of fetal adverse outcomes. Multivariate regression analysis identified hypertension, history of PE, associated antiphospholipid syndrome (APS), proteinuria, and low serum C4 in the first trimester as independent risk factors for PE. Regular follow-ups at our center correlated with lower risks of APOs, PE, and PTB. APS also emerged as a risk factor for PTB, whereas the use of hydroxychloroquine (HCQ) during pregnancy seemed to protect against PTB. Conclusion: For pregnancies complicated by SLE, we recommend early pregnancy screening for proteinuria-even in the absence of lupus nephritis-as well as continued use of HCQ and routine prenatal care throughout pregnancy.