Risk Factor For Pregnancy Loss Research Articles

Correlation of Anti-Phosphatidylserine/Prothrombin and Anti-Phosphatidylserine Antibodies with Pregnancy Outcomes.

The objective of this study was to investigate the clinical relevance of anti-prothrombin antibodies (aPT) and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in relation to pregnancy outcomes and coagulation parameters, as well as immune markers. We retrospectively analyzed 477 pregnant women with experienced at least one spontaneous miscarriage who were tested for aPT and aPS/PT antibodies, and compared their clinical characteristics, coagulation indicators, immune biomarkers, and pregnancy outcomes to assess the diagnostic accuracy of these antibodies. We found that the aPT IgG and the aPS/PT IgM were independently associated with increased risk of pregnancy loss, with odds ratios (ORs) of 1.055 (95% confidence interval [CI]: 1.009-1.103, p=0.017) and 1.041 (95% CI: 1.015-1.067, p=0.002), respectively. Moreover, we found that the aPS/PT IgM had a higher diagnostic performance than the aPT IgG, as indicated by the AUC of 0.663 and 0.593, respectively. The pregnancy loss rate was positively correlated with the level of aPS/PT IgM, while the aPT IgG is not. We also found that in the pregnancy loss group, aPT IgG showed negative correlations with prothrombin time (PT); aPS/PT IgM showed positive correlations with aPS/PT IgG. However, none of aPT IgG, aPT IgM, aPS/PT IgM, or aPS/PT IgG was related to other adverse pregnancy outcomes, such as preterm delivery, fetal growth restriction (FGR), or preeclampsia (PE). Our findings suggest that aPT IgG and aPS/PT IgM are independent risk factors for pregnancy loss, especially aPS/PT IgM, which has a positive linear correlation with pregnancy loss.

A predictive model of pregnancy loss using pre-pregnancy endocrine and immunological parameters in women with abnormal glucose/lipid metabolism and previous pregnancy loss.

To investigate the clinical and endocrine risk factors for pregnancy loss in women with abnormal glucose/lipid metabolism and a history of pregnancy loss, and to develop a predictive model to assess the risk of pregnancy loss in these women's subsequent pregnancies. Patients with a history of pregnancy loss who had abnormal glucose/lipid metabolism were retrospectively included in this study, and their pre-pregnancy baseline and clinical characteristics were collected. A predictive nomogram was constructed based on the results of the multivariable logistic regression model analysis, and its calibration and discriminatory capabilities were evaluated. The internal validation was then performed and the net benefits were assessed by the clinical decision curve. The predictive model was eventually incorporated eight variables, including maternal age, previous pregnancy losses, anticardiolipin antibody (aCL) IgG, aCL IgM, thyroid peroxidase antibody, complement 4, free thyroxine and total cholesterol. The area under the curve (AUC) of the nomogram was 0.709, and Chi-square value and P value of the Hosmer-Lemeshow test were 12.786 and 0.119, respectively, indicating that the nomogram had a satisfactory calibration and discriminatory performance. The validation cohort showed a similar result for the discrimination of the nomogram (AUC = 0.715). The clinical decision curve demonstrated the nomogram had good positive net benefits. This is the first study to predict the risks of subsequent pregnancy loss in women with abnormal glucose/lipid metabolism and history of pregnancy loss using pre-pregnancy clinical and endocrine parameters. This predictive nomogram may provide clinicians assistance to personalize the management of subsequent pregnancies in these patients.

The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss.

Pregnancy loss is the most frequent complication of a pregnancy which is devastating for affected families and poses a significant challenge for the health care system. Genetic factors are known to play an important role in the etiology of pregnancy loss; however, despite advances in diagnostics, the causes remain unexplained in more than 30% of cases. In this review, we aggregated the results of the decade-long studies into the genetic risk factors of pregnancy loss (including miscarriage, termination for fetal abnormality, and recurrent pregnancy loss) in euploid pregnancies, focusing on the spectrum of point mutations associated with these conditions. We reviewed the evolution of molecular genetics methods used for the genetic research into causes of pregnancy loss, and collected information about 270 individual genetic variants in 196 unique genes reported as genetic cause of pregnancy loss. Among these, variants in 18 genes have been reported by multiple studies, and two or more variants were reported as causing pregnancy loss for 57 genes. Further analysis of the properties of all known pregnancy loss genes showed that they correspond to broadly expressed, highly evolutionary conserved genes involved in crucial cell differentiation and developmental processes and related signaling pathways. Given the features of known genes, we made an effort to construct a list of candidate genes, variants in which may be expected to contribute to pregnancy loss. We believe that our results may be useful for prediction of pregnancy loss risk in couples, as well as for further investigation and revealing genetic etiology of pregnancy loss.

The impact of previous conservative treatment of atypical hyperplasia on pregnancy outcomes after IVF/ICSI-embryo transfer: a propensity score-matched retrospective cohort study.

Do women have worse pregnancy and neonatal outcomes of IVF/ICSI-fresh embryo transfer (ET) after conservative treatment of atypical hyperplasia (AH)? AH has no impact on live birth but is associated with increased risks of pregnancy loss and preterm delivery (PTD). AH is a precancerous lesion of endometrial cancer. Several recognized AH risk factors include nulliparity, increased body mass index, ovulation disorders, diabetes mellitus, and others. As such, patients are suggested to attempt conception upon achieving AH regression. Recently, successful pregnancies with IVF/ICSI have been increasingly reported. Forty-two patients with AH regression and 18700 women with no evidence of endometrial abnormality, who underwent their first autologous oocytes' retrieval and fresh ET cycles of IVF/ICSI in the Center for Reproductive Medicine, Shandong University, from May 2008 to July 2021, were retrospectively enrolled. First, 42 AH patients were propensity score matched with control women (n = 168) at a 1:4 ratio. Reproductive outcomes and maternal/neonatal complications were compared between the matched pairs. Binary logistic regression analyses were conducted to assess odds ratios (ORs) of AH for live birth, pregnancy loss, and PTD from AH women and all 18700 eligible controls. Patients with AH achieved a numerically lower live birth rate (LBR) as compared to the matched controls, but without significant difference (26% versus 37%, P = 0.192). However, compared with the matched controls, AH patients showed significantly higher rates of pregnancy loss (52% versus 21%, P = 0.003) and PTD (45% versus 16%, P = 0.041). Further analyses revealed a statistically significantly increased rate of late pregnancy loss (17% versus 3%, P = 0.023), but not early miscarriage (35% versus 18%, P = 0.086), in the AH group. Furthermore, after correcting for potential confounders, the likelihood of a live birth in AH patients narrowly failed to be statistically significantly different from controls (adjusted OR [aOR]: 0.51, 95% CI: 0.25-1.04, P = 0.064). Nonetheless, the logistic regression reconfirmed that AH was an independent risk factor for pregnancy loss (aOR: 3.62, 95% CI: 1.55-8.46, P = 0.003), late pregnancy loss (aOR: 9.33, 95% CI: 3.00-29.02, P < 0.001), and PTD (aOR: 5.70, 95% CI: 1.45-22.38, P = 0.013). Selection bias was an inherent drawback of this study. First, because of the low AH prevalence among women receiving IVF/ICSI treatment, and consequently, limited sample size, the relationship between AH with LBR and adverse complications might be concealed and underestimated. Hence, the results should be interpreted cautiously. Similarly, the impacts of diverse clinical features of AH patients on the pregnancy outcomes need further studies in a larger population. Second, although most data used in this study were obtained by reviewing the medical records, missing data did exist and so did the recall bias. Third, although the propensity score matching and multivariable logistic models were performed collectively in order to minimize potential confounders between AH and controls, the intrinsic disadvantages of the retrospective nature of this study could not be avoided completely, and additional confirmation bias might be induced with reduplication of statistical analyses. Our results highlight the necessity of adequate counseling and intensive pregnancy monitoring for AH individuals and their families. This work was supported by grants from the National Key Research & Developmental Program of China (2022YFC2703800), the Natural Science Foundation of Shandong Province (ZR2022MH009), and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523). There are no conflicts of interest to declare. N/A.

Gene Expression Levels of CSF-1 and CSF-1R Endometrial under The Influence of Prolactin Level in Unexplained Miscarriage: A Case-Control Study.

Hormones such as prolactin, by influencing expression of the endometrial genes, play a pivotal role in embryo implantation and development. The present study aimed to evaluate serum level of prolactin and its effect on altering expression level of colony-stimulating factor-1 (CSF-1) and colony-stimulating factor-1 receptor (CSF-1R) genes in endometrial tissue during in vitro fertilization (IVF) pregnancy in the infertile women and recurrent pregnancy loss (RPL), compared to fertile women, who lost their pregnancies at gestational age <20 weeks. In this case-control study, 40 infertile women, 40 IVF pregnant women with RPL and 40 fertile women who lost their pregnancies at <20 weeks of gestation for unknown reasons were selected. Prolactin serum level was assessed using ELISA technique and expression of CSF-1 and CSF-1R genes was determined in endometrial tissue, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Mean prolactin level of the infertile group was 24.38 ± 1.43 ng/mL and it had statistically significant relationship with the fertile group (P<0.001). Expression level of the CSF-1 and CSF-1R genes were higher in the fertile than infertile groups by 2.88 times (P<0.0001) and 2.64 times (P<0.0001), while it was respectively 2.28 (P<0.0001) and 1.69 (P<0.0001) times higher compared to the RPL group. Risk factors for pregnancy loss, such as aging, increased body mass index (BMI), smoking and diabetes caused decreasing changes in gene expression (CSF-1 and CSF-1R ) and the differences were statistically significant, except in the infertile group. The present study showed a significant relationship of CSF-1 and CSF-1R expression levels with pregnancy loss. Risk factors such as aging, obesity, smoking and diabetes decreased both genes expression levels.

The short-term effect of ozone on pregnancy loss modified by temperature: Findings from a nationwide epidemiological study in the contiguous United States

BackgroundPregnancy loss, a major health issue that affects human sustainability, has been linked to short-term exposure to ground-surface ozone (O3). However, the association is inconsistent, possibly because of the co-occurrence of O3 and heat episodes, as increased temperature is a risk factor for pregnancy loss. To explain this inconsistency, the effect of O3 on pregnancy loss needs to be examined jointly with that of high temperature. MethodsA total of 247,305 pregnancy losses during the warm season were extracted from fetal death certificates from the 386 counties in contiguous United States from 1989 to 2005. We assessed environmental exposure based on the daily maximum 8 h average of O3 from Air Quality System monitors and the 24 h average temperature from the North American Regional Reanalysis product. We conducted a bidirectional, time-stratified case-crossover study of the association between pregnancy loss and exposures to O3 and temperature and their multiplicative interaction. The main time window for the exposure assessment was the day of case occurrence and the preceding 3 days. To estimate the association, we used conditional logistic regression with adjustment for relative humidity, height of the planetary boundary layer, and holidays. Sensitivity analyses were performed on the lagged structure, nonlinearity, and between-subpopulation heterogeneity of the estimated joint effect. ResultsThe joint effect was first estimated by the regression against categorical exposure by tertile. Compared to the low-low exposure group (O3 ≤ 78 μg/m3 and temperature ≤ 18 °C), the odds of pregnancy loss was significantly higher by 6.0 % (95 % confidence interval [CI] 2.4–9.7 %), 9.8 % (6.1–13.8 %), and 7.5 % (4.7–10.3 %) in the high-low (>104 μg/m3 and ≤18 °C), low-high (≤78 μg/m3 and >23 °C), and high-high (>104 μg/m3 and >23 °C) groups. The model of linear exposure and the multiplicative interaction yielded similar results. Each increment of 10 μg/m3 in O3 and 1 °C in temperature was associated with a 3.0 % (2.0 %–4.0 %) and 3.9 % (3.5 %–4.3 %), respectively, increase in the odds of pregnancy loss. A decrease in odds of 0.2 % (0.1 %–0.2 %) was associated with the temperature × O3 interaction. The finding of an antagonistic interaction between temperature and O3 was confirmed by models parametrizing the joint exposure as alternative nonlinear terms (i.e., a two-dimensional spline term or a varying-coefficient term) and was robust to a variety of exposure lags and stratifications. Therefore, the marginal effect of O3 was estimated to vary by climate zone. A significant association between O3 and pregnancy loss was observed in the northern, but not southern, United States. ConclusionJoint exposure to O3 and high temperature can increase the risk for pregnancy loss. The adverse effect of O3 is potentially modified by ambient temperature. In high-latitude cities, controlling for O3 pollution could protect maternal health.

Pregnancy loss in major fetal congenital heart disease: incidence, risk factors and timing.

Fetuses with congenital heart disease (CHD) are at increased risk of pregnancy loss compared with the general population. We aimed to assess the incidence, timing and risk factors of pregnancy loss in cases with major fetal CHD, overall and according to cardiac diagnosis. This was a retrospective, population-level cohort study of fetuses and infants diagnosed with major CHD between 1997 and 2018 identified by the Utah Birth Defect Network (UBDN), excluding cases with termination of pregnancy and minor cardiovascular diagnoses (e.g. isolated aortic/pulmonary pathology and isolated septal defects). The incidence and timing of pregnancy loss were recorded, overall and according to CHD diagnosis, with further stratification based on presence of isolated CHD vs additional fetal diagnosis (genetic diagnosis and/or extracardiac malformation). Adjusted risk of pregnancy loss was calculated and risk factors were assessed using multivariable models for the overall cohort and prenatal diagnosis subgroup. Of 9351 UBDN cases with a cardiovascular code, 3251 cases with major CHD were identified, resulting in a study cohort of 3120 following exclusion of cases with pregnancy termination (n = 131). There were 2956 (94.7%) live births and 164 (5.3%) cases of pregnancy loss, which occurred at a median gestational age of 27.3 weeks. Of study cases, 1848 (59.2%) had isolated CHD and 1272 (40.8%) had an additional fetal diagnosis, including 736 (57.9%) with a genetic diagnosis and 536 (42.1%) with an extracardiac malformation. The observed incidence of pregnancy loss was highest in the presence of mitral stenosis (< 13.5%), hypoplastic left heart syndrome (HLHS) (10.7%), double-outlet right ventricle with normally related great vessels or not otherwise specified (10.5%) and Ebstein's anomaly (9.9%). The adjusted risk of pregnancy loss was 5.3% (95% CI, 3.7-7.6%) in the overall CHD population and 1.4% (95% CI, 0.9-2.3%) in cases with isolated CHD (adjusted risk ratio, 9.0 (95% CI, 6.0-13.0) and 2.0 (95% CI, 1.0-6.0), respectively, based on the general population risk of 0.6%). On multivariable analysis, variables associated with pregnancy loss in the overall CHD population included female fetal sex (adjusted odds ratio (aOR), 1.6 (95% CI, 1.1-2.3)), Hispanic ethnicity (aOR, 1.6 (95% CI, 1.0-2.5)), hydrops (aOR, 6.7 (95% CI, 4.3-10.5)) and additional fetal diagnosis (aOR, 6.3 (95% CI, 4.1-10)). On multivariable analysis of the prenatal diagnosis subgroup, years of maternal education (aOR, 1.2 (95% CI, 1.0-1.4)), presence of an additional fetal diagnosis (aOR, 2.7 (95% CI, 1.4-5.6)), atrioventricular valve regurgitation ≥ moderate (aOR, 3.6 (95% CI, 1.3-8.8)) and ventricular dysfunction (aOR, 3.8 (95% CI, 1.2-11.1)) were associated with pregnancy loss. Diagnostic groups associated with pregnancy loss were HLHS and variants (aOR, 3.0 (95% CI, 1.7-5.3)), other single ventricles (aOR, 2.4 (95% CI, 1.1-4.9)) and other (aOR, 0.1 (95% CI, 0-0.97)). Time-to-pregnancy-loss analysis demonstrated a steeper survival curve for cases with an additional fetal diagnosis, indicating a higher rate of pregnancy loss compared to cases with isolated CHD (P < 0.0001). The risk of pregnancy loss is higher in cases with major fetal CHD compared with the general population and varies according to CHD type and presence of additional fetal diagnoses. Improved understanding of the incidence, risk factors and timing of pregnancy loss in CHD cases should inform patient counseling, antenatal surveillance and delivery planning. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical Risk Factors affecting the Pregnancy Outcome using Pakistan Maternal Mortality Survey (PMMS) 2019

Background: South Asia is the world's most populous region, and it also has the highest rate of pregnancy loss. It is necessary to understand the risk factors for pregnancy loss in South Asian countries like Pakistan for reducing the global burden of pregnancy loss. Aim: To determine the potential clinical factors affecting pregnancy outcomes of Pakistani women aged 15-49 years during 2016-2019. Study design: This study was conducted using Pakistan Maternal Mortality Survey (PMMS 2019) during 2020-2021. All eligible ever-married women (n=7096) aged 15-49 were selected for this study. In this study, the clinical risk factors considered are fever, unconsciousness, high blood pressure, diabetes, vaginal bleeding, problems associated with the placenta, problems associated with the position of the baby, and preeclampsia. The response variable was pregnancy outcome comprising four categories that are live-birth, stillbirth, miscarriage, and abortion. A multinomial logistic regression model was applied to test the relationship between the dependent variable and each of the eight risk factors. Results: Multinomial logistic regression model identified that fever (OR=0.723), vaginal bleeding(OR=1.614), high blood pressure (OR=1.473), and problems associated with the position of the baby (OR=0.396)are significantly associated with a stillbirth at a 10% level of significance. Additionally, unconsciousness (OR=1.019) appears as a potential risk factor for abortion. Practical implication: Understanding the most significant risk factors that contribute to negative pregnancy outcomes, it can prioritize resources to improve maternal health. Also, assistance to healthcare providers and policymakers in making informed decisions regarding maternal health in Pakistan can be provided. Conclusion: Fever, vaginal bleeding, high blood pressure, problems associated with the position of the baby are significant risk factors of stillbirth. However, unconsciousness identified a risk factor of abortion. It is concluded that in Pakistan pregnancy loss can be reduced by controlling the prevalence of diseases during pregnancy. Keywords: Abortion, Clinical risk factors, Miscarriage, Multinomial logistic model, Pregnancy loss, Stillbirth

An Automated System for Early Prediction of Miscarriage in the First Trimester Using Machine Learning

Currently, the risk factors of pregnancy loss are increasing and are considered a major challenge because they vary between cases. The early prediction of miscarriage can help pregnant ladies to take the needed care and avoid any danger. Therefore, an intelligent automated solution must be developed to predict the risk factors for pregnancy loss at an early stage to assist with accurate and effective diagnosis. Machine learning (ML)-based decision support systems are increasingly used in the healthcare sector and have achieved notable performance and objectiveness in disease prediction and prognosis. Thus, we developed a model to help obstetricians predict the probability of miscarriage using ML. And support their decisions and expectations about pregnancy status by providing an easy, automated way to predict miscarriage at early stages using ML tools and techniques. Although many published papers proposed similar models, none of them used Saudi clinical data. Our proposed solution used ML classification algorithms to build a miscarriage prediction model. Four classifiers were used in this study: decision tree (DT), random forest (RF), k-nearest neighbor (KNN), and gradient boosting (GB). Accuracy, Precision, Recall, F1-score, and receiver operating characteristic area under the curve (ROC-AUC) were used to evaluate the proposed model. The results showed that GB overperformed the other classifiers with an accuracy of 93.4% and ROC-AUC of 97%. This proposed model can assist in the early identification of at-risk pregnant women to avoid miscarriage in the first trimester and will improve the healthcare sector in Saudi Arabia.

Pregnancy loss is related to body mass index and prediabetes in early adulthood: Findings from Add Health.

Pregnancy loss, including miscarriage and stillbirth, affects 15-20% of pregnancies in the United States (US) annually. Accumulating evidence suggests that pregnancy loss is associated with a greater cardiovascular disease (CVD) burden later in life. However, few studies have evaluated the impact of pregnancy loss on CVD risk factors in early adulthood (age <35 years). The aim of this study was to examine associations between pregnancy loss and CVD risk factors (body mass index, blood pressure, hyperlipidemia, diabetes status) in early adulthood. We conducted a cross-sectional analysis using the public-use dataset for Wave IV (2007-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Our sample consisted of women, ages 24-32 years, with a previous pregnancy who completed biological data collection (n = 2,968). Pregnancy loss was assessed as any history of miscarriage or stillbirth; and quantified as none, one, or recurrent (≥2) pregnancy loss. Associations between pregnancy loss and each CVD risk factor were tested using linear and logistic regression adjusting for sociodemographic factors, parity, health behaviors during pregnancy, and depression. We tested for interactions with race/ethnicity. A total of 670 women reported a pregnancy loss, of which 28% reported recurrent pregnancy loss. A prior pregnancy loss was related to a 3.79 (kg/mm2) higher BMI in non-Hispanic Black women, but not white women. Women with recurrent pregnancy loss were more likely to have prediabetes (AOR, 1.93; 95% CI, 1.10-3.37, p<0.05) than women with all live births. Findings suggest that pregnancy loss may be associated with a more adverse CVD risk profile in early adulthood, particularly for women who experience recurrent pregnancy loss. This highlights the need for CVD risk assessment in young women with a prior pregnancy loss. Further research is necessary to identify underlying risk factors of pregnancy loss that may predispose women to CVD.

Clinical and laboratory features in pregnant women with body weight deficiency

In recent years, endocrinopathy, in particular, and body weight deficiency have taken an important place in the structure of genital and extragenital pathology. Background somatic diseases are a risk factor for pregnancy loss, but the detailed mechanisms of influence on the course of pregnancy and childbirth in patients with body weight deficiency have not been studied. The objective: to evaluate the clinical and laboratory parameters of pregnant women with body weight deficiency. Materials and methods. A clinical, laboratory and functional examination of 200 pregnant women with body weight deficiency and 30 pregnant women with normal body weight was carried out. Body mass index (BMI) was calculated according to A. Ketle formula. Results. In women with body weight deficiency before pregnancy, the reduction in nutrition (BMI 19.1±0.4 kg/m2) was 50%, hypotrophy of the I degree (BMI 18.0±0.5 kg/m2) – 41% and hypotrophy of the II–III degrees (BMI 16.3±0.9 kg/m2) – 9%. It was established that the total frequency of genital pathology before pregnancy in women with a body weight deficiency was 51.5%, among which menstrual cycle disorders predominated (16.5%). It was found that in pregnant women with a body weight deficiency, the increase in body weight occurs mainly (70–80%) due to lean body mass. During the assessment of clinical and biochemical indicators, no significant differences were found in the levels of hemoglobin, glucose, total protein and blood cholesterol compared to the indicators of women with normal body weight. However, a high frequency of hypocalcemia (71.7–92.8%), which correlates with the degree of hypotrophy, was found in women with body weight deficiency.Conclusions. Pregnant women with body weight deficiency are characterized by a high cumulative frequency of genital pathology before pregnancy, the absence of reliable changes in the levels of hemoglobin, glucose, total protein and blood cholesterol, and the presence of hypocalcemia.

ETIOPATHOGENESIS OF RECURRENT PREGNANCY LOSS DUE TO GENETIC FORMS OF THROMBOPHILIA

The aim of the study was to develop a concept of the etiopathogenesis of miscarriages due to the genetic form of thrombophilia.&#x0D; Materials and methods. In a prospective cohort study, 143 pregnant women were examined, including 109 with pregnancy loss and genetic defects of hemostasis [main (M) group]; the control (K) group consisted of 34 relatively healthy pregnant women with a light history and pregnancy without risk factors for pregnancy loss. Genetic polymorphisms of coagulation factors and fibrinolysis (1691 G→A FVL, 20210 G→A prothrombin, 675 5G/4G PAI-1, 455 G→A fibrinogen β), endothelial dysfunction (677 C→T MTHFR) were studied with the help of allele-specific polymerase chain reaction.&#x0D; Results. A comprehensive clinical, laboratory, instrumental and statistical analysis has determined the main risk factors for pregnancy loss. Pathological polymorphisms of hemostasis and endothelial dysfunction genes play an important role in the development of miscarriage, namely the following pathological genotypes: 1691 GA factor V Leiden - increases the risk by 5.3 times (95% CI 1.5-18.5), 20210 GA prothrombin - 26.47 times (1.6-445.7), 675 4G / 4G PAI-1 - 7.5 times (1.7-33.79), -455AA fibrinogen β - 9.7 times (1.3-74.16), 677 CT MTHFR - 2.6 times (1.0-6.2), 677TT MTHFR - 21.7 times (1.3-368.6). It has been found that multigenic forms of thrombophilia predominate in most patients with pregnancy loss - 76.1% (p &lt;0.001, OR = 12.31, 95% CI 4.8-31.55).&#x0D; Conclusions. The obtained data allowed us to form a concept of the etiopathogenesis of recurrent pregnancy loss due to genetic thrombophilia and justify the need for a personalized approach in each case of pregnancy loss.

Anticardiolipin IgA as a Potential Risk Factor for Pregnancy Morbidity in Patients with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that is characterized by venous or arterial thrombosis and/or obstetric morbidity in the constant presence of persistent antiphospholipid antibodies (aPLs). In patients with APS, the relationship between production of immunoglobulin (Ig)A antiphospholipid antibodies and adverse events in pregnancy is still unclear. As a result of massive trials, the clinical efficiency of IgA-aPLs is used to evaluate pregnancy outcomes in patients with APS. We enrolled 381 female patients with APS and 93 healthy pregnant women. Silica clotting time ratio, dilute Russell viper venom time (dRVVT) ratio, and 6 aPLs, including IgA/IgG/IgM isotypes aβ2GPI and IgA/IgG/IgM isotypes anticardiolipin (aCL), were detected using commercial kits. We found no significant differences in laboratory parameters between patients with APS and the control group. The total prevalence of aCL IgA was 2.9%; the prevalence of aβ2GPI IgA was 3.4%. Only 1.3% of the individuals who tested aCL-positive (5/381) had isolated aCL IgA. Similarly, isolated aβ2GPI IgA was present in only 0.8% (3/381) of the aβ2GPI-positive subjects. Meanwhile, aCL IgA showed the maximum area under the curve (AUC) of 0.666 (95% CI, 0.60-0.73; P < .001), followed by dRVVT ratio (AUC = 0.649; 0.58-0.72; P < .001). Positive aCL IgA and aβ2GPI IgA ratios were extremely low for each isolated isotype of aPLs. For patients with APS who experienced fetal loss, aCL IgA may be utilized as a risk factor for pregnancy loss among patients with APS. Establishing a standardized diagnosis of IgA aPLs is also important for these patients.

Pregnancy Loss After Amniocentesis with Double-Needle Insertions in Twin Pregnancies.

The aim of this study was to determine the pregnancy loss rate of amniocentesis with double-needle insertions in twin pregnancies. This was a retrospective study of twin pregnancies who underwent amniocentesis with double-needle insertion between 2010 and 2019 at a single center. The pregnancy loss rates were recorded as single or double fetal loss before 24 weeks' gestation and within 4 weeks after the procedure. Risk factors for pregnancy loss after amniocentesis were also assessed. A total of 678 twin pregnancies with amniocentesis were finally included. The pregnancy loss rates before 24 weeks' gestation and within 4 weeks after the procedure were 0.9% and 1.9%, respectively. Only one fetal loss was presumed to be a direct result of the procedure. All other cases were complicated by structural or chromosomal anomalies. Twin pregnancies with abnormal ultrasound findings had a significantly higher rate of pregnancy loss with a relative risk of 4.81 (95% CI [1.03, 22.2]). Our study showed a low pregnancy loss rate after amniocentesis in twin pregnancies with double-needle insertions technique of sampling, which can help decision making in prenatal screening and diagnosis for twin pregnancies.

APA scoring system: a novel predictive model based on risk factors of pregnancy loss for recurrent spontaneous abortion patients

The aim of this study was to analyse the risk factors of pregnancy loss of patients with recurrent spontaneous abortion (RSA) and develop a scoring system to predict RSA. Clinical data of 242 cases, with RSA who were treated at Fujian Provincial Maternity and Children’s Hospital, were selected. The factors of pregnancy loss for RSA patients were evaluated by univariate and multivariate analyses. There were 242 RSA patients, of whom 34 (14.0%) developed pregnancy loss. A multivariate analysis showed the following adverse risk factors for RSA: antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies. The pregnancy loss rates of antinuclear antibody spectrum group, protein S deficiency group and antiphospholipid antibodies group were 25.0%, 22.5% and 19.4%, respectively. Each of these factors contributed 1 point to the risk score. The pregnancy loss rates were 6.3%, 24.6%, 50% for the low-, intermediate- and high-risk categories, respectively (p < .001). The area under the receiver operating characteristic curve for the score of RSA was .733. Our findings suggest that this validated and simple scoring system could accurately predict the risk of pregnancy loss of RSA patients. The score might be helpful in the selection of risk-adapted interventions to decrease the incidence. Impact Statement What is already known on this subject? The live birth rate increases to 80%–90% after anticoagulant and/or immunosuppressive treatment in patients with RSA. However, there is still a high rate of re-abortion even after active treatment. What do the results of this study add? Antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies were independent risk factors for pregnancy loss. A novel predictive model based on these factors was then established and validated. What are the implications of these findings for clinical practice and/or further research? The newly developed score might be helpful in the selection of risk-adapted interventions to decrease the incidence. For patients in the intermediate-risk and high-risk groups, we should conduct more targeted studies and formulate corresponding therapies to improve the success rate of treatment.

Association between non-O blood group and spontaneous abortion in women with inherited thrombophilia

Abstract Background Spontaneous abortion is reported to be one of the most frequent pregnancy complications reaching a prevalence up to 15%. The association between congenital thrombophilia and pregnancy loss has been debated in several studies with conflicting results. We aimed to retrospectively evaluate the prevalence of inherited thrombophilia (i.e antithrombin, protein S and C deficiencies, factor V Leiden and prothrombin variant) in a group of women with a personal history of miscarriage. The prevalence non-O blood group, considered the most common thrombophilic condition, was concomitantly considered. Materials and methods A group of n. 566 women with a personal history of spontaneous abortion recruited among caregivers of patients admitted to the Medical Department of our University Hospital between December 2011 and December 2019 were enrolled. Women under 18 yrs, those with a personal history of venous and/or arterial thrombosis and with an acquired thrombophilic condition were excluded. An equally number of healthy women without a personal history of pregnancy loss acted as controls. The Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated as an estimate of pregnancy loss developing. Results Out of n. 566 enrolled women, n. 127 (22.4%) had an inherited thrombophilic condition. The prevalence of congenital thrombophilia was significantly higher in women with miscarriage than controls (OR 2.12; CI 95% 1.51–2.92). Non-O blood type was observed in n. 325 (57.4%) women. The prevalence of non-O blood group was significantly higher in women with pregnancy loss (p 0.01) and the association of thrombophilia and non-O blood type further increased the risk of pregnancy loss (OR 3.28; CI 95% 2.01–5.36). Conclusions Both inherited thrombophilia and non-O blood type should be considered risk factors for pregnancy loss. The knowledge of this information may help the clinician to better manage women with pregnancy loss. Further studies are required to confirm our findings. Funding Acknowledgement Type of funding sources: None.

Association of maternal exposure to ambient particulate pollution with incident spontaneous pregnancy loss

BackgroundMaternal exposure to ambient fine particulate matter (PM2.5) is a potential risk factor for pregnancy loss, but the extant findings are inconsistent. One reason for the inconsistency is the difficulty of distinguishing spontaneous from induced pregnancy losses, particularly in countries with planning policies. ObjectiveTo examine the association between maternal PM2.5 exposure and spontaneous incident pregnancy loss in China. MethodsA total of 18,513 women of reproductive age was recruited from Jiangsu Province, China, in 2007. Among them, 2451 women reported 2613 valid records of incident pregnancies from 2007 to 2010. We used Cox regression to link the outcomes (live birth, spontaneous pregnancy loss, or induced abortion) of those incident pregnancies with maternal PM2.5 exposures, assessed using well-developed estimates of historical concentrations at the county level. ResultsAmong the 2613 incident pregnancies, 69 spontaneous pregnancy losses, 596 induced abortions, and 1948 live births occurred. According to the adjusted model, each 10-μg/m3 increment in the average PM2.5 concentration during pregnancy was associated with a 43.3% (95% confidence interval, 6.6–92.5%) increased probability of spontaneous pregnancy loss. Advanced maternal age, a potential competing risk factor, weakened the association between PM2.5 and spontaneous pregnancy loss. The association was nonsignificant for unintended pregnancies. ConclusionMaternal PM2.5 exposure was associated significantly with incident spontaneous pregnancy loss. Our findings provide insight into the harmful effect of air pollution on human reproduction.

Abstract 14592: Pregnancy Loss and Cardiovascular Disease Risk Factors in Early Adulthood: Preliminary Findings From Add Health

Introduction: Pregnancy loss, including miscarriage and stillbirth, affect 15-20% of pregnancies in the United States annually. Accumulating evidence suggests that pregnancy loss is associated with greater cardiovascular disease (CVD) burden later in life. However, associations between pregnancy loss and CVD risk factors in early adulthood (age&lt;35 years) have not been assessed. Objective: To examine associations between pregnancy loss and CVD risk factors in early adulthood. Methods: We conducted a secondary data analysis using the public-use data set for Wave IV (2007-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Our sample consisted of women, ages 24-32 years, with a previous pregnancy who completed biological data collection (n=2,968). Pregnancy loss was assessed as any history of miscarriage or stillbirth; and as none, one, or recurrent (≥2) pregnancy loss. Dependent variables included physical measures and blood specimens: body mass index (BMI), blood pressure, diabetes status, and dyslipidemia. Associations between pregnancy loss and each CVD risk factor were tested using linear (for BMI) and logistic regression adjusting for sociodemographic factors, parity, pre-pregnancy BMI, smoking during pregnancy, and depression. Results: Six hundred and ninety-three women (23%) reported a pregnancy loss, of which 21% reported recurrent pregnancy loss. Women with all live births were more likely to identify as non-Hispanic White (73%) and report a higher annual income. After adjusting for sociodemographics (age, race/ethnicity, education, income), pregnancy loss was associated with a greater BMI (ß=0.90; SE,0.39). In fully-adjusted models, women with recurrent pregnancy loss were more likely to have hypertension (AOR, 2.50; 95%CI, 1.04-5.96) and prediabetes (AOR, 1.93; 95%CI. 1.11-3.37) than women with all live births; the association was non-significant for women with one pregnancy loss. Conclusions: Pregnancy loss is associated with a more adverse CVD risk factor profile in early adulthood. Findings suggest the need for CVD risk assessment in young women with a prior pregnancy loss. Further research is necessary to identify underlying risk factors of pregnancy loss that may predispose women to CVD.

Stratified risk of pregnancy loss for women with a viable singleton pregnancy in the first trimester

Objective Calculate the risk of miscarriage in women with a viable (defined as presence of fetal heart rate on ultrasound) first trimester singleton pregnancy and to create a model for stratified risk-assessment for pregnancy loss based on significant risk factors. Study Design Retrospective cohort study of unselected women with singleton pregnancies in a large obstetrical practice who presented for prenatal care prior to 14 weeks over a three-year period. All women underwent a formal first-trimester ultrasound, and we only included women with viable pregnancies with fetal heart activity seen on that ultrasound. Our primary outcome was pregnancy loss prior to 20 weeks. Statistical modeling was used to create a risk-assessment tool from adjusted likelihood ratios of pregnancy loss based on risk factors independently associated with this outcome. Results From January 2015-December 2017, 2,446 women met the inclusion criteria for the study and 132 (5.4%) had a pregnancy loss <20 weeks. On regression analysis, the independent risk factors for pregnancy loss were earlier gestational age (aOR 0.72, 95% CI 0.65–0.80) and increasing number of prior miscarriages (aOR 1.56, 95% CI 1.32–1.83). Using these risk factors, we calculated the stratified risk of pregnancy loss, which ranged from 0.8% in women at 13 weeks of gestation with no prior miscarriages to 33.7% in women at six weeks of gestation with three or more prior miscarriages. Conclusion In first trimester singleton pregnancies, the overall risk of pregnancy loss <20 weeks after confirmation of fetal heart activity is 5.4%, but can be stratified for each woman and ranges from 0.8% to 33.7% based on the gestational age and number of prior pregnancy losses.

Clinical features of new-onset systemic lupus erythematosus during pregnancy in Central China: a retrospective study of 68 pregnancies.

The aim of this study is to explore the clinical features and pregnancy outcomes of Chinese patients with new-onset systemic lupus erythematosus (SLE) during pregnancy or puerperium. We retrospectively evaluated the data of all pregnant women with SLE managed at the First Affiliated Hospital of Zhengzhou University between April 2013 and March 2017. Clinical characteristics, laboratory features, medication use, and pregnancy outcomes were compared between pregnant women with new-onset SLE and pregnant women with pre-existing SLE. Risk factors for adverse pregnancy outcomes were determined using binary regression analyses. Overall, 223 pregnancies in 216 patients were included; 148 (69.6%) patients had a history of SLE, and 68 (30.4%) were diagnosed with SLE during pregnancy or puerperium. Most cases of new-onset SLE (72.1%) occurred during the first and second trimesters. Thrombocytopaenia (especially severe thrombocytopaenia) (76.5% vs 54.2%, P = 0.008; 39.7% vs 15.5%, P = 0.001) and anaemia (especially moderate anaemia) (73.5% vs 56.9%, P = 0.007; 52.9% vs 35.2%, P = 0.035) were more common in women with new-onset SLE than in women with pre-existing SLE and active disease during pregnancy. Additionally, patients with new-onset SLE experienced higher rates of moderate-to-severe disease activity than patients with pre-existing SLE (P < 0.01); disease activity occurred mostly during the first and second trimesters (75.4%). Compared with pre-existing SLE patients, disease activity in new-onset SLE patients occurred mostly in the first trimester (33.3% vs 15.3%, P = 0.043) and less in the third trimester (21.1% vs 47.2%, P < 0.001). Pregnancy loss was significantly higher in patients with new-onset SLE than in patients with pre-existing SLE (62.4% vs 27.1%, P < 0.001), with most cases occurring during the first and second trimesters (95.3%). However, there were no significant differences in neonatal outcomes between new-onset and pre-existing SLE patients with active disease. Within the new-onset SLE group, active disease was an independent risk factor for pregnancy loss (odds ratio [OR] = 16.185, confidence interval [CI] = 1.895-138.232, P = 0.011), whereas disease onset at late gestation was a protective factor against pregnancy loss (OR = 0.589, CI = 0.435-0.796, P = 0.013). Patients with new-onset SLE suffered greater haematological involvement (mainly thrombocytopaenia and anaemia) and higher rates of moderate-to-severe disease activity and pregnancy loss than patients with pre-existing SLE. Controlling disease activity and extending gestational age may improve pregnancy outcomes in women with new-onset SLE. Key Points • The clinical features of new-onset SLE during pregnancy and its impact on pregnancy outcomes have rarely been reported, especially in Chinese patients. • New-onset SLE during pregnancy in Chinese women occurred primarily during the first and second trimesters and was characterised by haematological disorders, including thrombocytopaenia and anaemia. • Women with new-onset SLE during pregnancy had significantly higher disease activity scores and pregnancy loss rates than women with pre-existing SLE, especially during the first and second trimesters; controlling disease activity and prolonging gestational age may improve pregnancy outcomes in this setting.