Maternal Serum Biomarkers Research Articles

First-trimester maternal serum biomarkers and the risk of cerebral palsy.

To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy (CP) and to identify CP characteristics associated with abnormal biomarker levels. In this retrospective case-control data linkage study, we matched mothers of 435 singletons with CP from a population register to their cFTS records and selected 10 singleton pregnancy controls per case. We compared mean and abnormal levels (expressed as multiples of the median [MoMs]) of pregnancy-associated plasma protein-A (PAPP-A), beta subunit of human chorionic gonadotrophin (β-hCG), and nuchal translucency between cases and controls and between CP subgroups. Compared with control pregnancies, CP pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01 MoM, p=0.02) and β-hCG (0.93 vs 0.99 MoM, p=0.02). Biomarker levels in CP pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A (p<0.01), 1.4 times for β-hCG (p=0.12), and 2.6 times for low PAPP-A and β-hCG together (p=0.04). In cases with CP, an abnormally low PAPP-A level was associated with moderate preterm birth, low Apgar scores, and Gross Motor Function Classification System level V. Low β-hCG was associated with very low birthweight. Low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to CP. Low first-trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. Causal pathways involving preterm birth, term neonatal encephalopathy, and genetic syndromes may be implicated.

Comprehensive metabolomic analysis of first-trimester serum identifies biomarkers of early-onset hypertensive disorder of pregnancy

Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children’s Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch’s t-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.

Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study

The Fetal Medicine Foundation proposed a competing risks model for early identification of women at a high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders. This study aimed to estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester Fetal Medicine Foundation preterm preeclampsia screening test. We conducted a prospective cohort study of nulliparous women recruited at 11 to 14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers (pregnancy-associated plasma protein-A, placental growth factor, and soluble fms-like tyrosine kinase-1), and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the Fetal Medicine Foundation algorithm. The predicted risks were dichotomized as a positive or negative test according to 2 risk cutoffs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight <10th percentile), fetal death, preterm birth, and a composite outcome, including any of the foregoing. The same analyses were computed for a composite of severe outcomes, including preterm preeclampsia, severe small for gestational age (less than third percentile), and fetal death. We included 4575 participants with complete observations, of whom 494 (10.8%) had an estimated risk of preterm preeclampsia of ≥1 in 70 and 728 (15.9%) had a risk of ≥1 in 100. The test based on a risk cutoff of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cutoff of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia of ≥1 in 70 was 3% for preterm preeclampsia, 32% for the composite outcome, and 9% for the severe composite outcome. Nulliparous women with a first-trimester positive preterm preeclampsia Fetal Medicine Foundation screening test are at a higher risk of both preterm preeclampsia and other severe placenta-mediated pregnancy complications. Approximately 1 woman of 10 identified as high risk by the Fetal Medicine Foundation algorithm developed at least 1 severe placenta-mediated pregnancy complication.

Complement factors and alpha‐fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects

Neural tube defects (NTDs) are serious congenital malformations. In this study, we aimed to identify more specific and sensitive maternal serum biomarkers for noninvasive NTD screenings. We collected serum from 37 pregnant women carrying fetuses with NTDs and 38 pregnant women carrying normal fetuses. Isobaric tags for relative and absolute quantitation were conducted for differential proteomic analysis, and an enzyme-linked immunosorbent assay was used to validate the results. We then used a support vector machine (SVM) classifier to establish a disease prediction model for NTD diagnosis. We identified 113 differentially expressed proteins; of these, 23 were either up- or downregulated 1.5-fold or more, including five complement proteins (C1QA, C1S, C1R, C9, and C3); C3 and C9 were downregulated significantly in NTD groups. The accuracy rate of the SVM model of the complement factors (including C1QA, C1S, and C3) was 62.5%, with 60% sensitivity and 67% specificity, while the accuracy rate of the SVM model of alpha-fetoprotein (AFP, an established biomarker for NTDs) was 62.5%, with 75% sensitivity and 50% specificity. Combination of the complement factor and AFP data resulted in the SVM model accuracy of 75%, and receiver operating characteristic curve analysis showed 75% sensitivity and 75% specificity. These data suggest that a disease prediction model based on combined complement factor and AFP data could serve as a more accurate method of noninvasive prenatal NTD diagnosis.

Evaluation of maternal serum biomarkers in predicting outcome of successful expectant management of tubal ectopic pregnancies

ObjectiveTo assess the value of multiple serum biomarkers for the prediction of successful outcome of expectant management in women with tubal ectopic pregnancy (TEP). Study designWomen with a conclusive ultrasound diagnosis of TEP had a blood test to measure β-human chorionic gonadotropin (β-hCG), progesterone, inhibin A, activin A and high sensitivity C-reactive protein (hsCRP) at the initial visit. Women presenting with pain, serum β-hCG ≥ 1500 IU, evidence of a live ectopic pregnancy or a significant haemoperitoneum were advised to have emergency surgery. Women eligible for expectant management were followed-up prospectively until serum β-hCG declined to non-pregnant level or surgical treatment was required. ResultsA total of 93 women with a TEP were included in the final cohort. Emergency surgery was carried out in 42/93 (45 %) of women whilst 51/93 (55 %) were managed expectantly. Of the latter group, 42/51 (82 %) had successful expectant management and 9/51(18 %) required surgical procedure after a period of follow up. On multi-variable analysis, only higher values of serum β-hCG and progesterone at the initial visit were associated with a lower chance of successful expectant management of TEP. A one-unit increase in either variable on the log-scale was associated with an approximate 20-fold reduction in the odds of a successful outcome. Conclusion(s)Serum β-hCG and progesterone were significantly lower in women who had successful expectant management of TEP. Other biomarkers under consideration were not significantly different in women with successful and failed expectant management.

RETRACTED: Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: A randomized controlled trial from Shanghai, China

ObjectivesTo evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia. Study designThis prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy. Main outcome measures: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered. ResultsLow-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058–1.867; P = 0.019). ConclusionLow-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy.

Immunoassay biomarkers of first and second trimesters: a comparison between pregnant Syrian refugees and Turkish women

Abstract Background It was aimed to investigate maternal serum hormone values used for aneuploidy screening, demographic characteristics and fetal measurements in the population of pregnant Syrian refugees (PSRs) and to compare with data from pregnant Turkish women (PTW). Material and methods The study assessed data from 2697 pregnant who underwent triple and double screening tests, including 1738 Turkish and 959 Syrian women. The maternal serum biomarkers, demographic characteristics and fetal sonography measurements were compared and biases were calculated. By multivariate linear regression analysis, group-specific regression coefficients were estimated. Results Mean total age and weight were found to be significantly different and lower in PSRs in all gestational ages evaluated (p &lt; 0.001; p &lt; 0.001). The first trimester, median biases for fß-hCG were found to be higher by 38% and 24.5% for weeks 11 and 13, respectively. In the second trimester, median values of tß-hCG showed negative biases of 11.8% and 21.2% on weeks 16 and 19 in PSRs, respectively (p &lt; 0.001). It was considered that ethnicity has a stronger effect on first trimester hormone biomarkers than second trimester. The ethnic diversity showed the greatest effect on fß-hCG. Conclusion Race/ethnicity-specific regression coefficients and median values based on validated risk estimations should have to be used for fetal aneuploidy risk reports.

Prospective cohort study of fetal nuchal translucency in first-trimester and pregnancy outcome

Objective: To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome. Methods: A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis. Results: (1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81). Conclusions: A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ)

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Impact of parturition on maternal cardiovascular and neuronal integrity in a high risk cohort \u2013 a prospective cohort study

BackgroundTo better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke.MethodsThe study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data.ResultsPlacental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7–77.8) vs 27.7 (16.7–31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age.ConclusionsParturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.

P02.02: First trimester maternal serum biomarkers in fetuses with major congenital heart defects

P02.02: First trimester maternal serum biomarkers in fetuses with major congenital heart defects

Early Second Trimester Maternal Serum Steroid-Related Biomarkers Associated with Autism Spectrum Disorder.

Epidemiologic studies link increased autism spectrum disorder (ASD) risk to obstetrical conditions associated with inflammation and steroid dysregulation, referred to as prenatal metabolic syndrome (PNMS). This pilot study measured steroid-related biomarkers in early second trimester maternal serum collected during the first and second trimester evaluation of risk study. ASD case and PNMS exposure status of index offspring were determined through linkage with autism registries and birth certificate records. ASD case (N = 53) and control (N = 19) groups were enriched for PNMS exposure. Higher estradiol and lower sex hormone binding globulin (SHBG) were significantly associated with increased ASD risk. Study findings provide preliminary evidence to link greater placental estradiol activity with ASD and support future investigations of the prenatal steroid environment in ASD.

The Urinary Peptidome as a Noninvasive Biomarker Development Strategy for Prenatal Screening of Down's Syndrome.

Prenatal screening for Down's syndrome based on maternal age, ultrasound measures, and maternal serum biomarkers is recommended worldwide, but the false-positive rate and poor diagnostic performance of these screening tests remain problematic. Genetic analysis of cell-free DNA in maternal blood has been developed as a new prenatal screening for Down's syndrome, but it has a number of limitations, including turnaround time and cost. Prenatal screening diagnostic innovation calls for new tests that are noninvasive, accurate, and affordable. We report original observations on potential peptide biomarkers in maternal urine for screening of fetal Down's syndrome. The peptidome of urine samples from 23 pregnant women carrying Down's syndrome fetuses and 30 pregnant women carrying fetuses with normal karyotype was fractionated by weak cation exchange magnetic beads and analyzed by MALDI-TOF mass spectrometry. Levels of six peptides (m/z 1022.1, 1032.1, 1099.5, 1155.9, 1306.6, and 2365.6) were significantly altered between the case and control groups after controlling for maternal and gestational age. A classification model was constructed based on these candidate peptides that could differentiate fetuses with Down's syndrome from controls with a sensitivity of 95.7%, a specificity of 70.0%, and an area under receiver operating characteristic curves of 0.909 (95% confidence interval, 0.835-0.984). Peptide peaks at m/z 1099.5 and 1155.9 were identified as the partial sequences of alpha-1-antitrypsin and heat shock protein beta-1, respectively. These new findings support the new idea that maternal urinary peptidome offers prospects for noninvasive biomarker discovery and development for the prenatal screening of fetal Down's syndrome.

The Efficacy of Serum Biomarkers and Ultrasound Parameters in Prediction of Outcome in Threatened Abortion

Background: miscarriage, also known as a spontaneous loss of pregnancy before the fetus reaches viability. Objectives: the aim of this study is to evaluate the association between ultrasonographic findings and maternal serum biomarkers levels and prediction of pregnancy outcome in threatened miscarriage. Patients and Methods: a prospective observational study was conducted at Al-Zahraa University Hospital through the period from April 2018 to May 2019 involving 76 women in their first trimester threatened abortion. Results: there was a statistically significant difference between group 1 and group 2 regarding cancer antigen (CA) 125, β-hCG, progesterone, yolk sac diameter (YSD), fetal heart rate (FHR) and crown-rump length (CRL). The sensitivity, specificity, PPV and NPV of CA 125 at 37.2 IU/ml were 86.0, 84.3, 84.6 and 85.7, respectively, for β-hCG at 19447 IU/ml were 80.6, 78.0, 78.4 and 79.8, respectively, for progesterone at 12.3 ng/ml were 90.1, 88.0, 88.2 and 89.8, respectively, and for FHR at 122 b pm were 96.1, 94.1 respectively. Conclusion: combining of measurement of serum progesterone at a level of 12.3 ng/ml to FHR at 122 bpm represent noninvasive, early, fast and excellent predictor of pregnancy outcome in women with threatened abortion.

First-trimester ultrasound measurements and maternal serum biomarkers as prognostic factors in monochorionic twins: a cohort study

BackgroundMonochorionic twin pregnancies are at high risk of adverse outcomes, but it is not possible to predict which pregnancies will develop complications. The aim of the study was to evaluate, in monochorionic twin pregnancies, whether first-trimester ultrasound (nuchal translucency [NT], crown-rump length [CRL]), and maternal serum biomarkers (alpha-fetoprotein [AFP], soluble fms-like tyrosine kinase-1 [sFlt-1] and placental growth factor [PlGF]), are prognostic factors for fetal adverse outcome composite, twin-twin transfusion syndrome (TTTS), growth restriction, and intrauterine fetal death (IUFD).MethodsA cohort study of 177 monochorionic diamniotic twin pregnancies. Independent prognostic ability of each factor was assessed by multivariable logistic regression, adjusting for standard prognostic factors. Factors were analysed as continuous data; thus, the reported ORs relate to either 1% change in NT or CRL inter-twin percentage discordance or one unit of measure in each serum biomarker.ResultsThe odds of the fetal adverse outcome composite were significantly associated with increased NT inter-twin percentage discordance (adjusted OR 1.03 [95% CI 1.01, 1.06]) and CRL inter-twin percentage discordance (adjusted OR 1.17 [95% CI 1.07, 1.29]). TTTS was significantly associated with increased NT discordance (adjusted OR 1.06 [95% CI 1.03, 1.10]) and decreased PlGF (adjusted OR 0.42 [95% CI 0.19, 0.93]). Antenatal growth restriction was significantly associated with increased CRL discordance (adjusted OR 1.20 [95% CI 1.08, 1.34]). Single and double IUFD were associated with decreased PlGF (adjusted OR 0.34 [95% CI 0.12, 0.98]) and (adjusted OR 0.18 [95%CI 0.05, 0.58]) respectively.Conclusion(s)This study has identified potential individual prognostic factors in the first trimester (fetal biometric and maternal serum biomarkers) that show promise but require further robust evaluation in a larger, prospective series of MC twin pregnancies, so that their usefulness both individually and in combination can be defined.Trial registrationISRCTN 13114861 (retrospectively registered)

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework. We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical. Odds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior. Our mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.

Maternal serum biomarkers in early diagnosis of preeclampsia

Background: Preeclampsia (PE) is a pregnancy specific disorder, characterized by new onset of hypertension and proteinuria after 20 weeks of gestation. It is one of the leading causes of maternal and perinatal morbidity and mortality. The etiology of the disease process in not known. There is an urgent need for a 1st trimester marker for the prediction of preeclampsia. Recent studies have reported that this disease originate from abnormal placentation and maternal endothelial dysfunction. The intense research in this arena has unveiled some important serum biomarkers which play an important role in placentation. These markers include angiogenic and antiangiogenic molecules. However, these markers when they used alone are not effective for the prediction of preeclampsia, but in combination may help in predicting women who are likely to develop preeclampsia. This review summarizes the various maternal serum biomarkers available and utility in predicting preeclampsia. Keywords: Preeclampsia, Biomarkers, Angiogenic markers, Antiangiogenic markers, Apelin

Diagnostic utility of angiogenic biomarkers in pregnant women with suspected preeclampsia: A health economics review.

Preeclampsia is a major cause of morbidity and mortality, can be difficult to diagnose, and is associated with significant healthcare costs. The prediction, diagnosis and prognosis of preeclampsia have depended on repeated assessment of women with known risk factors, including intensive monitoring and hospitalization. Many of these women may never go on to develop preeclampsia. Recent developments in the pathogenesis of preeclampsia have shown that maternal serum biomarkers can be used to predict preeclampsia. When the ratio of the anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and the pro-angiogenic placental growth factor from the placenta is altered, preeclampsia becomes more likely, providing a diagnostic measurement for risk. The use of angiogenic biomarkers in addition to standard clinical tests can more accurately predict which women are at risk of developing preeclampsia and which are at low or moderate risk, which is likely to streamline the management of pregnant women and target resources in a more efficient way. The studies reviewed here all demonstrate cost savings from use of angiogenic biomarker tests as an addition to standard care.

Maternal biomarkers for fetal heart failure in fetuses with congenital heart defects or arrhythmias

Diagnosis of fetal heart failure depends primarily on fetal ultrasonography assessment. Our recent study demonstrated that plasma natriuretic peptide levels in umbilical cord blood were correlated with the severity of heart failure in fetuses with congenital heart defects or arrhythmias. However, percutaneous umbilical blood sampling is an invasive procedure, and therefore, less or noninvasive biomarkers reflecting fetal heart failure are required. The aim of this study was to investigate the possibility of whether maternal serum biomarkers can diagnose fetal heart failure in fetuses with congenital heart defects or arrhythmias. This exploratory cross-sectional study was conducted at a tertiary pediatric cardiac center. A total of 50 singletons with fetal congenital heart defects or arrhythmias and 50 controls who were registered in the National Cerebral and Cardiovascular Center Biobank from 2013 to 2016 were included. Maternal serum samples obtained during the third trimester were analyzed for 2 hormones and 36 cytokines using the Bio-Plex Pro Human Cancer Biomarker panels 1 and 2. We comprehensively analyzed the association between maternal serum biomarkers and ultrasonography findings or fetal arrhythmia status. Fetal heart failure was defined as a cardiovascular profile score ≤7. Of 37 fetuses with congenital heart defects, heart failure was found in 1 case of tricuspid valve dysplasia with moderate tricuspid regurgitation. Of 13 fetuses with arrhythmias, 5 had heart failure at 28-33 weeks of gestation. Maternal serum cytokine and hormone concentrations were compared between patients with and without fetal heart failure at 28-33 weeks of gestation (n= 6 and n= 61, respectively). Sixty-one fetuses without heart failure consisted of 10 with congenital heart defect, 6 with arrhythmia, and 45 controls. Maternal serum concentrations of tumor necrosis factor-α, interleukin-6, soluble Fas ligand, transforming growth factor-α, and vascular endothelial growth factor-D were significantly higher when fetuses had heart failure than when they did not (P < .05), whereas maternal serum concentrations of heparin-binding epidermal growth factor-like growth factor were significantly lower when fetuses had heart failure than when they did not (P < .05). Multivariate analysis showed that maternal serum concentrations of tumor necrosis factor-α, vascular endothelial growth factor-D, and heparin-binding epidermal growth factor-like growth factor were independently associated with fetal heart failure. The cutoff values were as follows: tumor necrosis factor-α, 68 pg/mL (sensitivity of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6, negative likelihood ratio of 0.5); vascular endothelial growth factor-D, 1156 pg/mL (sensitivity of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6, negative likelihood ratio of 0.5); and heparin-binding epidermal growth factor-like growth factor, 90 pg/mL (sensitivity of 83.3%, specificity of 83.6%, positive likelihood ratio of 5.1, negative likelihood ratio of 0.2). The combination of these 3 cytokines showed sensitivity of 100%, specificity of 80.3%, positive likelihood ratio of 5.1, and negative likelihood ratio of 0. In the absence of fetal heart failure, concentrations of all maternal serum cytokines and hormones were similar in cases of fetal congenital heart defects and controls, while maternal serum soluble CD40 ligand concentrations were increased only in fetal arrhythmias. Maternal serum concentrations of tumor necrosis factor-α, vascular endothelial growth factor-D, and heparin-binding epidermal growth factor-like growth factor were associated with fetal heart failure.

Use of Double Test Biomarkers to Predict Fetal Nuchal Translucency Thickness in the Diagnosis of Trisomy 21: A Compromise between Sensitivity and Specificity

Objectives: The aim of study is to determine the sensitivity and specificity of screening for fetal trisomy 21 in the first trimester of pregnancy using a combination of maternal serum biomarkers and ultrasonography. The objectives of this study were to first duplicate and confirm within the Mongolian population, the results of other similar studies. Our results corroborated closely with those of other studies and further allowed us to draw conclusions and recommendations unique to Mongolia. A second objective was to apply these results to everyday obstetric practices within Mongolia and advance the state of prenatal care for all Mongolian women. Methods: Obstetric History: The obstetric history was recorded, and serum biomarkers were measured in 415 pregnancies.The degree of risk for trisomy 21 and other fetal aneuploidy were calculated using maternal age, the results of maternal serum pregnancy-associated plasma protein-A, free beta human chorionic gonadotropin, and fetal nuchal translucency thickness. Grouping of Test Subjects: Using a cut-off risk estimate of 1 in 300, the women were grouped into positive and negative screening groups. Sensitivity and specificity of the screening method were calculated from the available data. Results: Sensitivity of the screening test for fetal trisomy 21 was 66.6% and for all fetal aneuploidy was 83%. Specificity of the screening test for fetal trisomy 21 was 87.5% and for all fetal aneuploidy was 97.8% and the false positive rate was 2.2%. Our results are consistent with the results obtained in other international studies. Conclusions: Our study is unique in that it is the first such scientific examination of mothers at risk for congenital abnormalities in Mongolia. This study provides empirical evidence that the combination of the double test, maternal age, and fetal nuchal translucency thickness is an effective prenatal screening method for fetal aneuploidy pregnancy outcomes in Mongolia.