Maternal Blood Biomarkers Research Articles

Abstract We050: Elevated Cell-Free RNA in Maternal Circulation during Single Ventricle Heart Defect Pregnancies Dysregulate Human Cardiomyocyte Proliferation

Congenital single-ventricle heart defects (SVHDs) are life-threatening conditions in newborns, where one of the heart's ventricular chambers is severely underdeveloped. While medical advancements have improved survival rates, many SVHD patients still suffer lifelong cardiac complications and comorbidities. Clinical diagnosis of fetal SVHD occurs at around 20 weeks of gestation through echocardiogram. In this study, we aimed to identify novel maternal blood biomarkers that could signal SVHD development in fetuses. The study's premise is based on the limited regenerative capacity of adult human cardiomyocytes, like those in pregnant mothers, compared to the extensive proliferation seen in fetal cardiomyocytes that form the functional heart. We hypothesized small signaling molecules secreted by proliferating fetal cardiomyocytes enter the maternal circulatory system and could indicate abnormal ventricular growth in SVHD-affected fetuses. Both clinical and in vitro approaches were employed to identify potential cell-free miRNAs released by the developing fetal heart into maternal circulation. Blood plasma samples from pregnant women carrying healthy and SVHD-affected fetuses were screened for differentially expressed cell-free miRNAs and were compared with those from the supernatants of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) grown from healthy and SVHD donors. This comparative approach led to the identification of an miRNA panel (miR-487b, miR-433, mi-134, and miR-889) that were elevated in pregnant women carrying SVHD-affected fetuses and in proliferating iPSC-CMs from SVHD patients compared to healthy controls (p.adj<0.05). From this panel, forced-expression of miR-487b and mir-134 modulated the proliferation profiles of human cardiomyocytes in vitro . Results from this study establish these circulating cell-free miRNAs in maternal blood as potential non-invasive biomarkers for predicting abnormal fetal cardiac development leading to SVHDs. These findings could potentially revolutionize SVHD screening as an alternative diagnostic tool to echocardiogram.

Bioinformatics identification and validation of maternal blood biomarkers and immune cell infiltration in preeclampsia: An observational study.

Preeclampsia (PE) is a pregnancy complication characterized by placental dysfunction. However, the relationship between maternal blood markers and PE is unclear. It is helpful to improve the diagnosis and treatment of PE using new biomarkers related to PE in the blood. Three PE-related microarray datasets were obtained from the Gene Expression Synthesis database. The limma software package was used to identify differentially expressed genes (DEGs) between PE and control groups. Least absolute shrinkage and selection operator regression, support vector machine, random forest, and multivariate logistic regression analyses were used to determine key diagnostic biomarkers, which were verified using clinical samples. Subsequently, functional enrichment analysis was performed. In addition, the datasets were combined for immune cell infiltration analysis and to determine their relationships with core diagnostic biomarkers. The diagnostic performance of key genes was evaluated using the receiver operating characteristic (ROC) curve, C-index, and GiViTi calibration band. Genes with potential clinical applications were evaluated using decision curve analysis (DCA). Seventeen DEGs were identified, and 6 key genes (FN1, MYADM, CA6, PADI4, SLC4A10, and PPP4R1L) were obtained using 3 types of machine learning methods and logistic regression. High diagnostic performance was found for PE through evaluation of the ROC, C-index, GiViti calibration band, and DCA. The 2 types of immune cells (M0 macrophages and activated mast cells) were significantly different between patients with PE and controls. All of these genes except SLC4A10 showed significant differences in expression levels between the 2 groups using quantitative reverse transcription-polymerase chain reaction. This model used 6 maternal blood markers to predict the occurrence of PE. The findings may stimulate ideas for the treatment and prevention of PE.

Preeclampsia at Term Can Be Classified Into Two Clusters With Different Clinical Characteristics and Outcomes Based on Angiogenic Biomarkers in Maternal Blood

(Am J Obstet Gynecol. 2023;228:569.e1–569.e24) Pre-eclampsia, a complex and multisystemic disorder affecting a significant percentage of pregnancies worldwide, is a leading cause of preterm birth and maternal mortality. This condition is not uniform and can be classified into different subtypes based on gestational age and underlying pathophysiological mechanisms. Understanding these subtypes is crucial for predicting maternal and fetal outcomes and developing targeted therapeutic strategies.

Assessment of the course of the gestational process using survey method and depending on the laboratory confirmed prenatal alcohol use (cross-section study)

Background. Studying the problem of alcohol consumption by pregnant women using modern laboratory research methods has valuable theoretical and practical significance. The aim of the study. To determine the characteristics of the pregnancy course in women consuming alcohol in the prenatal period confirmed by survey and laboratory tests, depending on the phosphatidylethanol levels. Materials and methods. We examined 863 women under observation at the Irkutsk Regional Perinatal Center for the period from 2014 to 2021. To confirm the fact of alcohol consumption in the prenatal period, 545 women were surveyed, 318 women were examined using laboratory analysis. The diagnostic biomarker for alcohol was PEth:16:0/18:1. To assign pregnant women to the control group, a PEth concentration of ≤ 8 ng/ml was taken. If the PEth concentration was > 8 ng/ml, pregnant women were classified as heavy drinkers. Clinical and laboratory indicators of the course of pregnancy and childbirth were carried out in comparative groups. Results. It has been established that every second woman of reproductive age took alcohol before pregnancy. 24.2 % of women did not stop consuming alcohol in the prenatal period. At the same time, the risk of congenital malformations was high, since 20.4 % of women consumed alcohol in the first trimester of pregnancy. Based on the results of the survey, it was revealed that in women who consumed alcohol in the prenatal period, the following pathological conditions are statistically significantly more common: anemia, congenital heart defects in fetuses, prematurity of gestational age, labor anomalies, uterus subinvolution. Based on the results of laboratory confirmation of alcohol consumption, it was established that parity of birth, intrauterine growth retardation, and premature birth were statistically significantly more often in pregnant women who drink. Conclusion. Thus, in order to obtain the most meaningful and high-quality results, it is necessary to conduct larger studies. In addition, maternal blood biomarkers should be used to confirm levels of alcohol consumption throughout all trimesters of pregnancy.

From Molecules to Imaging: Assessment of Placental Hypoxia Biomarkers in Placental Insufficiency Syndromes.

Placental hypoxia poses significant risks to both the developing fetus and the mother during pregnancy, underscoring the importance of early detection and monitoring. Effectively identifying placental hypoxia and evaluating the deterioration in placental function requires reliable biomarkers. Molecular biomarkers in placental tissue can only be determined post-delivery and while maternal blood biomarkers can be measured over time, they can merely serve as proxies for placental function. Therefore, there is an increasing demand for non-invasive imaging techniques capable of directly assessing the placental condition over time. Recent advancements in imaging technologies, including photoacoustic and magnetic resonance imaging, offer promising tools for detecting and monitoring placental hypoxia. Integrating molecular and imaging biomarkers may revolutionize the detection and monitoring of placental hypoxia, improving pregnancy outcomes and reducing long-term health complications. This review describes current research on molecular and imaging biomarkers of placental hypoxia both in human and animal studies and aims to explore the benefits of an integrated approach throughout gestation.

Preeclampsia at term can be classified into 2 clusters with different clinical characteristics and outcomes based on angiogenic biomarkers in maternal blood

An antiangiogenic state has emerged as a mechanism of disease in preeclampsia. Angiogenic biomarkers are used in the risk assessment of this syndrome, particularly of early disease. The role of an antiangiogenic state in late preeclampsia is unclear. This study aimed to determine the prevalence, characteristics, and clinical significance of angiogenic/antiangiogenic factor abnormalities in women with preeclampsia stratified according to gestational age at delivery. Two studies were conducted: (1) a longitudinal nested case-control study comprising women with preeclampsia (n=151) and a control group (n=540); and (2) a case series of patients with preeclampsia (n=452). In patients with preeclampsia, blood was collected at the time of diagnosis. Plasma concentrations of placental growth factor and soluble fms-like tyrosine kinase-1 were determined by enzyme-linked immunosorbent assays. An abnormal angiogenic profile was defined as a plasma ratio of placental growth factor and soluble fms-like tyrosine kinase-1 expressed as a multiple of the median <10th percentile for gestational age based on values derived from the longitudinal study. The proportion of patients diagnosed with preeclampsia who had an abnormal angiogenic profile was determined in the case-series participants and stratified by gestational age at delivery into early (≤34 weeks), intermediate (34.1-36.9 weeks), and term (≥37 weeks) preeclampsia. The demographics, clinical characteristics, and pregnancy outcomes of women with preeclampsia with and without an abnormal angiogenic profile were compared. The prevalence of an abnormal angiogenic profile was higher in preterm than in term preeclampsia (for early, intermediate, and term in the case-control study: 90%, 100%, and 39%; for the case series: 98%, 80%, and 55%, respectively). Women with preeclampsia at term who had an abnormal angiogenic profile were more frequently nulliparous (57% vs 35%), less likely to smoke (14% vs 26%), at greater risk for maternal (14% vs 5%) or neonatal (7% vs 1%) complications, and more often had placental lesions consistent with maternal vascular malperfusion (42% vs 23%; all, P<.05) than those without an abnormal profile. Women with preeclampsia at term who had a normal angiogenic profile had a higher frequency of chronic hypertension (36% vs 21%) and were more likely to have class ≥2 obesity (41% vs 23%) than those with an abnormal profile (both, P<.05). Patients with early preeclampsia had an abnormal angiogenic profile in virtually all cases, whereas only 50% of women with preeclampsia at term had such abnormalities. The profile of angiogenic biomarkers can be used to classify patients with preeclampsia at term, on the basis of mechanisms of disease, into 2 clusters, which have different demographics, clinical characteristics, and risks of adverse maternal and neonatal outcomes. These findings provide a simple approach to classify preeclampsia at term and have implications for future clinical care and research.

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology

The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.

Dynamic changes in maternal immune biomarkers during labor in nulliparous vs multiparous women

Immunomodulation is observed in human parturition. However, data from longitudinal studies for the prelabor phase and the active phase of labor are lacking, and no study had compared the immune responses during labor between nulliparous and multiparous women. This study aimed to investigate the temporal changes of immune biomarkers in maternal blood from the prelabor phase to the latent and active phases of labor and to compare the dynamic changes between nulliparous and multiparous women. A prospective case-control study was conducted on women who had induction of labor at term followed by vaginal delivery. Maternal blood was serially collected at 3 consecutive time points: (1) before the onset of labor, (2) during the latent phase of labor, and (3) during the active phase of labor. Peripheral immune cells were measured by 4-color flow cytometry, and the plasma concentrations of cytokines and chemokines were measured by cytometric bead arrays. A longitudinal comparison was made to assess the dynamic changes in inflammatory parameters over 3 time points in nulliparous and multiparous women, respectively, and a cross-sectional comparison was made between nulliparous and multiparous women. A total of 40 women, including 20 nulliparous and 20 multiparous, were included in the study. Prelabor circulating levels of macrophage inflammatory protein-1β, monokine induced by gamma interferon, and interferon gamma-induced protein-10 were higher in multiparous women than in nulliparous women. In the latent phase of labor, the innate immune system in both groups responded with increases in neutrophils and interleukin 6, and the nulliparous women showed a more pronounced response. During the active phase of labor, such innate immune response continued with both groups, with additional increases in natural killer cells, monocyte chemoattractant protein-1, interleukin 8, and interleukin 10. Conversely, the adaptive immune system in nulliparous women showed a reduction in both cytotoxic and helper T cells, whereas the adaptive immune system in multiparous women only had a reduction in helper T cells, showing a smaller reduction. Innate and adaptive immune responses partake in immunomodulation during human parturition. Nulliparous and multiparous women showed different responses in their blood levels of immune cells and biomarkers during the different phases of labor.

Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? A systematic review.

IntroductionThe ability to predict spontaneous preterm birth (sPTB) prior to labour onset is a challenge, and it is currently unclear which biomarker(s), may be potentially predictive of sPTB, and whether their predictive power has any utility. A systematic review was conducted to identify maternal blood biomarkers of sPTB.MethodsThis study was conducted according to PRISMA protocol for systematic reviews. Four databases (MEDLINE, EMBASE, CINAHL, Scopus) were searched up to September 2021 using search terms: “preterm labor”, “biomarker” and “blood OR serum OR plasma”. Studies assessing blood biomarkers prior to labour onset against the outcome sPTB were eligible for inclusion. Risk of bias was assessed based on the Newcastle Ottawa scale. Increased odds of sPTB associated with maternal blood biomarkers, as reported by odds ratios (OR), or predictive scores were synthesized. This review was not prospectively registered.ResultsSeventy-seven primary research articles met the inclusion criteria, reporting 278 unique markers significantly associated with and/or predictive of sPTB in at least one study. The most frequently investigated biomarkers were those measured during maternal serum screen tests for aneuploidy, or inflammatory cytokines, though no single biomarker was clearly predictive of sPTB based on the synthesized evidence. Immune and signaling pathways were enriched within the set of biomarkers and both at the level of protein and gene expression.ConclusionThere is currently no known predictive biomarker for sPTB. Inflammatory and immune biomarkers show promise, but positive reporting bias limits the utility of results. The biomarkers identified may be more predictive in multi-marker models instead of as single predictors. Omics-style studies provide promising avenues for the identification of novel (and multiple) biomarkers. This will require larger studies with adequate power, with consideration of gestational age and the heterogeneity of sPTB to identify a set of biomarkers predictive of sPTB.

A current view on the alcohol-related teratogenic effects during pregnancy. Potential preventive measures

Aim: to analyze and summarize the available data of studies aimed at obtaining deeper insight in the field of alcohol-related effects on the course of pregnancy and potential consequences thereof; to study the prevalence of alcohol consumption by women in Russia, as well as potential preventive measures.Materials and Methods. The results of the Russian and foreign studies on the alcohol-related effect on the fetus and pregnancy outcome, published in the international databases Scopus, Web of Science, PubMed/MEDLINE, Cochrane Library, have been analyzed. The search for scientific publications was limited to the period from the years 2012 to 2021. We used search queries in Russian and English ("alcohol", "pregnancy", "prevention", "fetus", "fetal alcohol syndrome").Results. The presented data analysis indicates an extremely negative effect of alcohol on the body of pregnant women, as well as on the health of our future generation. This article proves the importance of the problem, the need for further research on the mechanisms of fetal alcohol syndrome (FAS) and the development of effective prevention measures, potential treatment methods, and assistance for FAS. At present, in Russia there is an acute lack of information on the real extent of the problem with maternal alcohol consumption during pregnancy. Still, no precise data on FAS prevalence in Russia are available.Conclusion. Preventing FAS is an urgent and unexplored issue in Russia. Medical doctors able to conduct pregravid preparation of a married couple while they plan to conceive a healthy child are highly demanded. It is necessary to raise awareness and improve the quality of training for obstetricians and gynecologists in order to identify women with high risk factors for alcohol abuse and childbirth with FAS at early stages of pregnancy management. It is also necessary to identify new or use already identified maternal blood biomarkers to verify excessive alcohol consumption during pregnancy.

Oxidative stress biomarkers in fetal growth restriction with and without preeclampsia.

Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics. A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed. Mothers with both severe FGR and PE had significantly reduced FT levels (p<0.001) and PlGF levels (p<0.001), and increased levels of plasma IMA (p<0.05), sFlt (p<0.001), leptin (p<0.05) and sRAGE (p<0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p<0.01) and plasma IMA (p<0.001), leptin (p=0.01) and sRAGE (p<0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only. There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

Course of the sFlt-1/PlGF ratio in fetal growth restriction and correlation with biometric measurements, feto-maternal Doppler parameters and time to delivery

PurposeThe study aimed to assess the course of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in pregnant women with fetal growth restriction (FGR) and to evaluate potential associations between the sFlt-1/PlGF ratio and feto-maternal Doppler parameters, fetal biometric measurements and the time between study inclusion and birth (“time to delivery”).MethodsThis was a retrospective longitudinal single center study including 52 FGR cases. The serum levels of sFlt-1 and PlGF were measured by using the BRAHMS Kryptor Compact PLUS. Fetal biometric and Doppler parameters, as well as the sFlt-1/PlGF ratio, were obtained both upon study inclusion and upon birth.ResultsVarious associations between the levels of the biomarkers in maternal blood upon study inclusion and upon birth and sonographic parameters were observed in FGR cases: umbilical artery (p < 0.01), uterine arteries (p < 0.01), ductus venosus (p < 0.05), cerebroplacental ratio (CPR) (p < 0.01), femur length (p < 0.01) and birth weight (p < 0.01). The higher the sFlt-1/PlGF ratio upon study inclusion, the shorter the “time to delivery” (p < 0.01). The multivariate regression analysis showed that the greater the daily percentage increase of the angiogenic markers, the shorter the “time to delivery” (p < 0.01).ConclusionThe fetal well-being, as measured by feto-maternal Doppler parameters such as CPR and the severity of the placental dysfunction, as measured by the urgency of birth and birth weight, is reflected by the level of the sFlt-1/PlGF ratio in the maternal serum. A rapid daily increase of the sFlt-1/PlGF ratio is significantly associated with the clinical progression of the disease.

Which one affect the other, Recurrent Pregnancy Loss or Serum Level of E?cadherin and c-MycBP

Recurrent pregnancy loss (RPL) is a foremost life event and a common pregnancy complication, whichdefined as losses of two or more pregnancies before 20 weeks of gestation. It affects approximately 1% -2% of couples trying to have children. To evaluate the potential role of cellular myelocytomatosis bindingprotein (c-MycBP) and epithelial cadherin (E-cad) serum level as biomarkers in maternal blood and focuson the similarity between tumour invasion and embryogenesis as phenomena by c-MycBP and E?cadherin.This case control study included 50 women with RPL (25 primary RPL and 25 secondary RPL) from threeinfertility clinics in Iraq. In addition to 50 control women with no history of RPL and at least one childbirth. Both groups are matched in age and BMI. Blood sampling was done for all and protein level ofc-Myc BP and E-cadherin were measured by ELISA Kit and analysis done according to the manufacturerrecommendations. The result presented in this study showed a significant difference in c?MycBP level(p&lt;0.001) and E?cadherin (p&lt;0.001) between patients and control. A significant positive correlation hasbeen found between these two biochemical markers (p &lt;0.001, r=?0.39). The present study showed thatdecreasing both c-MycBP and E-cad serum level signpost possible hypothesis that these proteins participatein one way or another in RPL pathogenesis which affect cell proliferation and invasion. However, thisbinding protein transcription factor is a part of a coordinated network of various set of partners whichneed further studies in future. Taken together, additional studies are required to understand and clarify theimportance of these biomarkers on this multifactorial condition.

Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women With Preterm Premature Rupture of Membranes

We aimed to identify maternal blood biomarkers predictive of histologic chorioamnionitis (HCA) in the plasma of women with preterm premature rupture of membranes (PPROM) and to determine whether the combination of these biomarkers with conventional clinical variables can improve the prediction of HCA. This retrospective cohort study included 82 consecutive women with PPROM (23-34 gestational weeks) who delivered within 96 hours of blood sampling. A membrane-based human antibody microarray was used to analyze the plasma proteome. The validation of 5 candidate biomarkers of interest was performed by enzyme-linked immunosorbent assay (ELISA) in the final cohort (n = 82). Serum C-reactive protein (CRP) levels were measured at sampling. Seventy-nine molecules studied exhibited intergroup differences. Validation by ELISA confirmed higher levels of plasma matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), S100 A8/A9, and insulin-like growth factor-binding protein 1 (IGFBP-1), but not tissue inhibitor of metalloproteinase 1 (TIMP-1), in women with HCA than in women without HCA. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma MMP-9, serum CRP levels, and gestational age (area under the curve [AUC], 0.932). The AUC for this model was significantly greater than that for any single variable included in the predictive model. Protein-antibody microarray technology can be useful in identifying plasma-based predictors for HCA. This study suggests that plasma MMP-9, IL-6, IGFBP-1, and S100 A8/A9 are important noninvasive predictors for HCA in women with PPROM and that the best predictive model, which combined these biomarkers with conventional clinical factors, can significantly improve the predictability for HCA.

The combination of maternal blood and amniotic fluid biomarkers improves the predictive accuracy of histologic chorioamnionitis

IntroductionThis study was performed to determine whether the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of histologic chorioamnionitis (HC). MethodsThis retrospective study included 80 singleton pregnant women who were suspected to have intrauterine infection and underwent measurement of two maternal blood biomarkers [maternal white blood cell count (mWBC) and maternal C-reactive protein level (mCRP)] and three amniotic fluid biomarkers [amniotic white blood cell count (aCell), amniotic glucose level (aGlucose), and amniotic lactate dehydrogenase level (aLDH)]. We divided the patients into two groups based on the presence or absence of HC and assessed the predictors of HC using logistic regression models: Model 1, combination of mWBC and mCRP; Model 2, combination of Model 1 and aGlucose; and Model 3, combination of Model 2, aCell, and aLDH. ResultsThe multivariable analysis showed that aCell was the only significant predictor of HC [odds ratio, 1.24; 95% confidence interval (CI), 1.06–1.68] independent of mWBC, mCRP, aGlucose, and aLDH. The c-statistics were higher in Model 3 (0.803; 95% CI, 0.701–0.905) than Model 1 (0.634; 95% CI, 0.511–0.758) and Model 2 (0.785; 95% CI, 0.684–0.887). DiscussionWe found that the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of HC. Therefore, our data provide relevant information to support counseling with regard to improving the predictive accuracy of HC in patients with suspected intrauterine infection.

Variation of fetuin-A in maternal and fetal serum during human parturition

Backgroundparturition involves multiple signalling pathways and most advances in research underline the importance of fetal development and maturation in the timing of labour, especially the fetal pituitary-adrenal axis. But, there is currently no consensual hypothesis on all the physiological processes responsible for human parturition. Methodssixty low-risk pregnant women were enrolled in a prospective cohort. Maternal blood was sampled regularly during consultations each week in last trimester, at delivery and at postnatal consultation. Cord blood was collected at delivery. We used proteomic analysis to identify maternal blood biomarkers of potential interest, focusing on serum proteins from 39 W G in pregnancies to delivery and postpartum. Resultsamong 56 peaks we identified variation in the N-terminal part of fetuin-A in maternal serum. Fetuin-A is a natural antagonist of TGF-beta and is able to bind calcium. We found a significant decrease in maternal serum fetuin-A in the days preceding delivery, independently of the mode of delivery. Also, there does not appear to be significant influence of the different fetal parameters (sex, Z-score) on maternal serum variations at delivery. Conclusionfetuin-A is described by the literature as a potential biomarker for organ dysfunction and metabolic syndrome disorders. The protein mineral homeostasis would be an interesting pathway to explore during pregnancy and particularly parturition.

Physical activity and epigenetic biomarkers in maternal blood during pregnancy.

Investigate associations of leisure time physical activity (LTPA) with DNA methylation and miRNAs during pregnancy. Patients& methods: LTPA, candidate DNA methylation and circulating miRNAs were measured (average 15 weeks gestation) in pregnant women (n =92). Each additional hour of prepregnancy LTPA duration was associated with hypermethylation in C1orf212 (β=0.137, 95% CI: 0.004-0.270) and higher circulating miR-146b-5p (β=0.084, 95% CI: 0.017-0.151). Each additional metabolic equivalent hour of early-pregnancy LTPA energy expenditure was associated with higher circulating miR-21-3p (β=0.431, 95% CI: 0.089-0.772) in women carrying female offspring, and lower circulating miR-146b-5p (β= -0.285, 95% CI: -0.528 to -0.043) and miR-517-5p (β= -0.406, 95% CI: -0.736 to -0.076) in women carrying male offspring. Our findings suggest that LTPA may influence maternal epigenetic biomarkers, possibly in an offspring sex-specific manner.

Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment

BackgroundTo our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. ObjectiveThe study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. MethodsWe measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin <30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin ≥30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. ResultsOf the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 µg/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 µg/L; P = 0.042). ConclusionHepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy. This trial was registered at www.clinicaltrials.gov as NCT00486863.

498: Placental angiogenic biomarkers in maternal blood improve the prediction of future adverse perinatal outcome in intrauterine growth restriction pregnancies

498: Placental angiogenic biomarkers in maternal blood improve the prediction of future adverse perinatal outcome in intrauterine growth restriction pregnancies

Steroidogenic factor-1 hypermethylation in maternal rat blood could serve as a biomarker for intrauterine growth retardation.

Intrauterine growth retardation (IUGR) is a common obstetric complication lacking an optimal method for prenatal screening. DNA methylation profile in maternal blood holds significant promise for prenatal screening. Here, we aimed to screen out potential IUGR biomarkers in maternal blood from the perspective of DNA methylation. The IUGR rat model was established by prenatal maternal undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation followed by functional clustering analysis for differentially methylated region (DMR)-associated genes demonstrated that genes regulating transcription had the most significantly changed DNA methylation status in maternal blood with IUGR. Genes about apoptosis and placental development were also changed. Besides increased placental apoptosis, IUGR rats demonstrated the same hypermethylated CpG sites of steroidogenic factor-1 (SF-1, a DMR-associated transcription factor about placenta) promoter in maternal blood and placentae. Further, ff1b, the SF-1 ortholog, was knocked out in zebrafish by CRISPR/Cas9 technology. The knock-out zebrafish demonstrated developmental inhibition and increased IUGR rates, which confirmed the role of SF-1 in IUGR development. Finally, hypermethylated SF-1 was observed in human maternal blood of IUGR. This study firstly presented distinct DNA methylation profile in maternal blood of IUGR and showed hypermethylated SF-1 could be a potential IUGR biomarker in maternal rat blood.