uE3 Levels Research Articles

Correlation between maternal serum biomarkers and the risk of fetal chromosome copy number variants: a single-center retrospective study.

To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs). Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated. Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group. Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.

The early predictive value of maternal serum PAPP-A concentration at 11-14 weeks of pregnancy for preeclampsia.

To determine the expression and clinical significance of maternal serum pregnancy-associated plasma protein A (PAPP-A) in pregnant women with different degrees of preeclampsia at 11-14 weeks of gestation. The clinical data of 65 pregnant women with preeclampsia admitted to our hospital from January 2020 to October 2022 were retrospectively analysed. Another 45 normal pregnant women who came to our hospital for prenatal examination and delivery during the same period were selected as the healthy control group. The serum contents of PAPP-A, a-fetoprotein (AFP) and free estriol (uE3) in each group were compared. The correlation between PAPP-A and AFP as well as uE3 was analysed by Pearson analysis. The clinical value of serological indexes in diagnosing preeclampsia was analysed using ROC curve. The levels of PAPP-A and uE3 in pregnant women in the preeclampsia group were lower, while the contents of AFP were higher than these in the healthy control group ( p < 0.01). The pregnant women with severe preeclampsia had lower levels of PAPP-A and uE3 with higher levels of AFP compared to these with mild preeclampsia ( p < 0.001). Pearson correlation analysis showed that serum PAPP-A was negatively correlated with AFP ( r = -0.246, p < 0.05) and positively correlated with uE3 ( r = 0.398, p < 0.01) in preeclampsia patients. ROC curve analysis demonstrated that the area under the curve (AUC) of PAPP-A, AFP and uE3 to assist in the diagnosis of preeclampsia was 0.740, 0.738 and 0.806, respectively. The AUC of the combination of PAPP-A, AFP and uE3 to assist in the diagnosis was 0.912, with a sensitivity of 90.38% and a specificity of 80.33%. The clinical assisted diagnostic value of combined detection was high. The serum level of PAPP-A in pregnant women with preeclampsia in the early pregnancy was significantly lower and related to the severity of the disease. The combination of routine detection for AFP and uE3 had a good predictive value for preeclampsia, which was helpful to take relevant interventions to reduce the incidence of preeclampsia as early as possible, and had a positive impact on protecting maternal and infant health.

First and second-trimester biochemical serum markers in maternal familial Mediterranean fever: The impact of colchicine use

IntroductionWe aimed to investigate the effects of colchicine use on first and second trimester screening markers in pregnancies complicated with familial Mediterranean fever (FMF) and to evaluate the overall impact of these effects on perinatal outcomes. MethodsA retrospective case-control study was conducted in pregnancies complicated with FMF using colchicine and healthy pregnancies as controls without any defined risk factors and medication use. Biochemical markers for the aneuploidy screening, including free ß-hCG and PAPP-A in the first trimester, and AFP, HCG, and unconjugated estriol (uE3) in the second trimester, were recorded, and MoM levels of these markers were compared between the FMF and control groups. Obstetric history and outcomes were also compared between groups. We used propensity score matching to form a cohort in which patients had similar baseline characteristics. ResultsAmong 93 eligible pregnant women, 31 women in FMF group and 31 in control group had similar propensity scores and were included in the analyses. Levels of serum-free ß-hCG, PAPP-A and AFP were similar between FMF and control groups (p = 0.671, p = 0.387 and p = 0.963, respectively). For the second-trimester markers, maternal serum uE3 MoM level were significantly lower in the FMF group using colchicine than in the controls (p = 0.045). We also compared these markers according to the daily colchicine dose between FMF subgroups. We did not detect significant difference between the different colchicine treatment modalities (0.5–1 mg/day vs. 1.5–2 mg/day, p > 0.05). ConclusionMaternal biochemical serum markers of an aneuploidy screening test in the second trimester may be affected by FMF with colchicine use, leading to misinterpretation of the risk level of tests. For these tests with decreased uE3 levels, FMF and colchicine use should be considered as a causative etiology after ruling out common etiologies and confounding factors before recommending invasive diagnostic testing.

The role of serum markers PAPP-A β-hCG, AFP, and uE3 in predicting the risk of preeclampsia in early, middle, and late pregnancy.

Preeclampsia (PE) has adverse effects on pregnant women, fetuses, and newborns [1], and accounts for 3%-10% of pregnancy-related diseases globally. This study aimed to screen a series of prenatal markers (pregnancy-associated plasma protein [PAPP-A], β-human chorionic gonadotropin [β-hCG], alpha fetoprotein [AFP], and estriol [uE3]) to establish a risk model and evaluate the diagnostic values of the markers for predicting PE. Sixty-five pregnant women were enrolled in this study. They were divided into two groups containing healthy pregnant women (n= 51, the non-PE group) and pregnant women with PE (n= 14, the PE group). According to the stage of pregnancy, the pregnant women in each group were divided into early, middle, and late pregnancy groups for statistical analysis. The levels of PAPPA-A β-hCG, AFP, and uE3 were compared among these groups. Then, a risk model was established, and PE was diagnosed using receiver operating characteristic (ROC) curve results. In the early pregnancy group, the differences in the levels of PAPP-A, AFP, and uE3 between the PE and non-PE groups were statistically significant (P< 0.001, P= 0.029, and P= 0.033, respectively), while the difference in the single remaining marker was not statistically significant. A ROC curve analysis revealed that in early pregnancy, the sensitivity and specificity of PAPP-A were 76.5% and 71.4%, respectively, and the sensitivity and specificity of β-hCG were 82.4% and 57.1%, respectively. The sensitivity and specificity of the combination of the two markers for diagnosing PE were 86.3% and 57.1%, respectively. This study demonstrated that the combination of PAPP-A and β-hCG has diagnostic value for PE in pregnant women. Accordingly, we should formulate innovative PE screening strategies to target the prevention of PE and create important conditions for predictive and preventive personalized medical treatments.

Validation of a monoclonal unconjugated estriol antibody for use in prenatal maternal serum screening.

Unconjugated estriol (uE3) is used as a marker for fetal aneuploidy in maternal serum screening tests. The goal of this study was to examine the validity of a new immunoassay for uE3 that uses a monoclonal antibody (m-uE3) rather than the more commonly used polyclonal antibody (p-uE3). Assays were performed in the Special Chemistry laboratory at Women and Infants Hospital of Rhode Island. Residual fresh (n = 100) and frozen (n = 533) second trimester serum samples from routine clinical care were tested using p-uE3 and/or m-uE3 assays. Assay results were compared between methods using Bland-Altman plots. A median equation was developed for m-uE3 results. Down syndrome risks were compared between the two assays in a case-control sample set (21 cases each matched with five controls for the completed week of gestation, duration of freezer storage and race). Log-transformed serum uE3 levels were highly correlated between the assays (r = 0.93, p < 0.001), with the m-uE3 assay levels yielding, on average, 23% higher (standard deviation of differences in log uE3 concentrations = 0.07) results. Assay and gestation-based median equations were calculated and used to convert m-uE3 concentrations to multiples of the median (MoM). The m-uE3 MoM values fit a log Gaussian distribution well with a log standard deviation of 0.11. Down syndrome risk results were not significantly different between assays. The m-uE3 assay, with results expressed in MoMs, is suitable for screening and as a monoclonal-based assay offers the advantage of a predictable and indefinite supply of antibody to perform the assay.

Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis

Objective: To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE3) levels and XLI. Methods: A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results: Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant (Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions: The decrease levels of uE3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

Geçirilmiş sezaryen öyküsü olan hastalarda ikinci trimester tarama testi biyokimyasal belirteçlerinin kötü gebelik sonuçlarıyla ilişkisi

Aim: The purpose of this study is to investigate the association between maternal serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), unconjugatedestriol (uE3) and poor pregnancy outcomes, determine whether these markers are effective predictors of poor pregnancy outcomes and to compare their levels in women with prior cesarean section and no prior uterine surgery. Material and Methods: Women with cesarean section due to a previous uterine surgery (n= 87) and women with no prior uterine surgery and performed vaginal delivery (n= 105) whose prenatal care was performed in the same clinic were included. Second trimester maternal serum levels of AFP, HCG and uE3, as well as multiples of the median (MoM) of these markers were evaluated. Differences in biochemical marker levels between groups and their relationship to poor maternal-fetal outcomes were assessed. Results: AFP, HCG, and uE3 levels of second trimester screening test markers, no statistically significant difference was found between the groups. When both groups are evaluated together, there is a negative, statistically significant association between neonatal weight and AFP level. When comparing the presence of fetal complications and the biochemical markers of the second trimester screening test HCG and E3, no statistically significant difference was observed. It was found that AFP levels of cases with fetal complications were statistically significantly higher than those of cases without fetal complications (p&lt;0.01). Conclusion: While high AFP-MoM levels may be a warning of fetal complications, second trimester screening test markers were found to be insufficient to predict maternal complications. The levels of these markers was not different between women with prior cesarean section or no prior uterine surgery. Conducting this study with a larger sample could provide further valuable information.

The association of maternal serum biomarkers and birth weight in twin pregnancy: a retrospective cohort study

We retrospectively reviewed the medical records of 524 women with twin pregnancies who underwent antenatal care and gave birth in the past 12 years. Birth weight (BW) data were classified into three groups. We analysed the association between maternal serum biomarkers and BW in twin pregnancies using multiple logistic regression analysis. There were significant differences in the MoM values of pregnancy-associated plasma protein-A (PAPP-A), unconjugated oestriol (uE3) and inhibin A between low BW and healthy newborns. The inhibin A value was significantly higher in women with small-for-gestational-age (SGA) foetuses and the PAPP-A, and uE3 values were lower in the SGA group than in the other groups using the generalised linear mixed model (hierarchical modelling considering cluster effects for twins). Maternal serum biomarkers, including PAPP-A, uE3, and inhibin A, may be associated with SGA in twin pregnancy. Our results might provide useful information for SGA prediction during prenatal period in twin pregnancy. IMPACT STATEMENT What is already known on this subject? The SGA is more frequent in twin pregnancies than in singleton, but there is no clearly identification of the aetiology of SGA. Further, most studies have been conducted in singleton pregnancies. What do the results of this study add? The association of each maternal serum marker with SGA was assessed in the current study, and it is demonstrated that the levels of PAPP-A and uE3 in maternal serum of SGA foetuses were significantly lower than those in the other groups. In contrast, the levels of inhibin A were significantly increased in the SGA. What are the implications of these findings for clinical practice and/or further research? The maternal serum biomarker of inhibin A was a more valuable predictive factor for SGA prediction in twins. The results of this study can be used in counselling prenatal screening. Further prospective research is needed to combine with ultrasound growth parameters, which can be generalised for the prediction of SGA in twins.

Effect of antiepileptic drugs on serum biochemical marker levels of first and second trimester screening tests.

Our aim in this study was to evaluate the effect of antiepileptic drugs on biochemical components of screening tests. This longitudinal case-control study was performed at Ankara City Hospital, Ankara, Turkey, from June 2020 to January 2021. The case group included epileptic singleton pregnant women which were using antiepileptic drugs, between 18 and 44 years of age. The control group included healthy pregnant women between 18 and 44 years old who did not use any drugs. Maternal medical, obstetric, and gynecological history were recorded. The antiepileptic agents that are used in our study were; lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, valproic acid, and clonazepam. For the aneuploidy screening program conducted in our laboratory, the biochemical markers that are analyzed include; free b-hCG and PAPP-A in the first trimester, as well as AFP, HCG, and unconjugated estriol (uE3) in the second trimester. MoM values of these markers were compared between the case and control groups. Fifty-three pregnant women with epilepsy using antiepileptic drugs were compared with 106 healthy pregnant women. The levels of serum-free b-hCG, and PAPP-A were similar between the case and control groups (p=0.653, p=0.351). For the second-trimester screening biochemical markers, the maternal serum uE3 and AFP levels expressed as MoM were significantly higher in the epileptic group than in the control patients (p=0.015 and p=0.001). Serum marker levels of second-trimester screening tests may be affected by antiepileptic drugs, which may lead to misinterpretation of the risk level. Antiepileptic drug usage should be considered when evaluating screening test results.

How to Manage Low Estriol Levels in Pregnancies, One Center Experience.

Objective:Low estriol (uE3) levels in the second-trimester screening for Down syndrome may be the result of fetal demise, congenital abnormalities, or some genetic hormonal disorders of the fetus. Although X-linked ichthyosis, a microdeletion syndrome with mild ichthyosis, which causes steroid sulfatase (STS) deficiency, is the most common genetic cause, second-trimester screening tests calculate the risk for a less common and severe disorder known as the Smith Lemli Opitz syndrome (SLOS). We aimed to investigate the outcomes of pregnancies with low uE3 levels in Down syndrome screening and emphasize the high prevalence of STS deficiency instead of SLOS in such cases.Methods:Fifteen pregnancies with very low uE3 levels and high risk for trisomy and/or SLOS in screening tests were evaluated and tested for STS deficiency and SLOS.Results:Seven of the pregnancies had STS microdeletion syndrome, while additional two cases were supposed to have STS gene mutation according to family and/or postnatal history. Although one fetal death was recorded, no chromosomal abnormality, SLOS, or congenital malformation was recorded in our series.Conclusions:SLOS is a very severe and rare syndrome. The risk estimation for SLOS in screening tests causes stress for pregnant women and healthcare givers. We recommend the addition of risk estimation for STS deficiency when a low uE3 level is detected in the screening test.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to −112.8%] and −23.3% [95%CI −41.9% to −4.7%]. Passing–Bablok indicated significant systematic (−2.78 [95%CI −3.57 to −2.04]) and proportional bias (1.30 [95%CI 1.15 to −1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65–0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and −0.0001 [SD = 0.2078], and −0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81–83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Quad test for fetal aneuploidy screening as a predictor of small-for-gestational age fetuses: a population-based study

BackgroundTo identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for small-for-gestational-age (SGA) fetuses.MethodsWomen who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiples of the median (MoMs) of the four biochemical markers for the SGA group and those of normal fetuses were compared. The models for predicting SGA by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting SGA were determined.ResultsOf 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had SGA and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of SGA. The constructed predictive equations had predictive performance for SGA, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively.ConclusionThe quad test for aneuploidy screening could also be used as a predictor of SGA, without extra-effort and extra-cost.

He assessment of the perinatal outcomes of the patients who underwent quad screening test

Objective The aim of this study is to assess the correlation between the poor perinatal outcomes and the serum biochemical markers such as maternal serum alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3) and inhibin-A (INH-A) checked during the quad screening test. Methods In this retrospective study, the results of 485 pregnant women who underwent quad screening test in the Outpatient Clinic of Gynecology and Obstetrics of Faculty of Medicine at Erciyes University, Kayseri, Turkey between January 2018 and January 2019 and met the inclusion criteria were analyzed. The primary result of the study was established as the development of poor perinatal outcomes. The poor perinatal outcomes were defined as gestational diabetes (GDM), gestational hypertension (GHT), preeclampsia, intrauterine growth restriction (IUGR), preterm labor, premature rupture of membranes (PRM), oligohydramnios, polyhydramnios, HELLP syndrome, and intrahepatic cholestasis of pregnancy (ICP). Results A total of 485 pregnant women, who met the inclusion criteria, were included in the study. A significant correlation was found between AFP MoM≥2 and GHT, PRM, preterm labor, and the development of IUGR (p=0.017, p=0.033, p=0.037, and p=0.038, respectively). It was seen that the risk increased 5.1 times for GHT, 3.2 times for preterm labor, and 3.8 times for the development of IUGR. There was a significant correlation between hCG MoM≥2 and the risk of GHT development (p=0.024); however, the risk of GHT development increased for 3.8 times above this value. A significant correlation was found between INH-A being MoM≥2 and the development of GHT and HELLP syndrome (p=0.009 and p=0.005, respectively). In these pregnant women, the risk increased 31 times for the development of HELLP syndrome, and 9.4 times for GHT. In the cases with uE3 MoM£0.5, there was a significant correlation for the development of preeclampsia and HELLP syndrome (p=0.033 and p=0.049, respectively). On the other hand, there was no significant correlation between GDM, ICP, polyhydramnios, and oligohydramnios and AFP MoM, beta-hCG MoM, uE3 MoM and INH-A MoM values. Conclusion In our study, we found correlation between poor perinatal outcomes and the changes in AFP, hCG, uE3 and INH-A levels.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study

Objective: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. Methods: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. Results: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. Conclusion: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

Alkaline phosphatase ınterference in an unconjugated estriol assay causing a false positive Down syndrome screening result

Abstract Objective Decreased unconjugated estriol (uE3) concentrations increase calculated risk of Down syndrome. Therefore, falsely low uE3, due to assay interference, have the potential to cause false-positive screening results. Here we present a 35 years old woman with a pregnancy of 17+2 weeks. Materials and methods Second-trimester screening test was performed on the UniCelDxI 800 (Beckman Coulter, Brea, CA, USA) analyzer and her uE3 level was 0.21 ng/mL (0.21 MoM). Risk calculated for DS was 1/8. Measurements were repeated on IMMULITE 2000 XPi (Siemens Healthcare Diagnostics Inc., USA). uE3 result was 0.614 ng/mL (0.97 MoM). The risk for DS was negative with this system. There was no sign of fetal anomaly on three-dimensional ultrasound examination and cell-free fetal DNA screening test. We suspected assay interference for uE3. Results Serial dilutions of serum samples revealed nonlinearity. 36.3% increase was observed with heterophile antibody blocking tubes. The post-polyethylene glycol treatment resulted approximately the same uE3 levels as IMMULITE system. Addition of alkaline phosphatase Scavenger to serum increased the result by 90% showing that falsely low E3 result was due to an interferent reacting on assay medium. Conclusion Laboratories should be aware that falsely low uE3 results due to interference may be obtained.

Prenatal diagnosis of chromosomal polymorphisms: most commonly observed polymorphism on Chromosome 9 have associations with low PAPP-A values

Introduction: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters.Materials and methods: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests’ parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated.Results: Fetal chromosomal polymorphism prevalence was 5.3% (n = 101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n = 55); 8.9% (n = 9), and 6.9% (n = 7), respectively]. The most common polymorphic variant was 9qh+ (n = 23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p = .028) and higher unconjugated estriol (uE3) (p = .019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p = .048) or women having fetuses with normal karyotype (p = .007).Conclusions: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.

Maternal serum placental growth factor combined with second trimester aneuploidy screening to predict small-for-gestation neonates without preeclampsia

ObjectiveTo investigate the role of maternal serum placenta growth factor (PlGF) and quadruple test parameters in predicting the risk of small for gestational age (SGA) infants of mothers without preeclampsia. Materials and methodsWe prospectively enrolled 300 pregnant patients who underwent blood sampling at 15–18 weeks gestation and followed them until delivery. Cases with SGA neonate delivery (n = 100) were compared with matched AGA neonate controls (n = 200). The plasma PlGF and quadruple markers were measured by enzyme-linked immunosorbent assay. The results were analyzed with Mann–Whitney U tests, and regression analysis was used to develop a model for the prediction of SGA. ResultsWomen who delivered SGA neonates had decreased levels of PlGF (median 0.71 MoM versus 0.7 MoM; p < 0.01), hCG (median 0.97 MoM versus 1.06 MoM; p = 0.046) and uE3 (median 0.92 MoM versus 1.04 MoM) compared to the AGA group. AFP, hCG and inhibin-A levels did not differ significantly. A PlGF concentration <0.37 MoM had a sensitivity of 28.0% (95% CI: 19.5–37.9) and a specificity of 89.5% (95% CI: 84.4–93.4) for the prediction of SGA neonates without PE. ConclusionSGA neonates in the absence of PE could potentially be identified at 15–18 weeks of pregnancy.

The mid-gestation triple test profile among women diagnosed with vasa previa

Purpose: To assess the mid-trimester triple test biomarkers among women diagnosed with vasa previa (VP).Methods: The study included 43 singleton pregnancies diagnosed with vasa previa between the years 1988 and 2011. The mid-gestation screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation specific normal mean (MoM). Reference MoM values were calculated from the local population. The levels of mid-gestation maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) of patients with VP were compared with control reference group.Results: The mean hCG and αFP levels of women diagnosed with VP was significantly higher compared to control reference group (1.42 versus 0.99 MoM; p < .002 and 1.24 versus1.01 MoM; p < .001, respectively). In contrast, there was no significant difference in uE3 levels between these two groups (0.99 versus 0.98 MoM; p = .71).Conclusions: Our findings suggest that increased mid-gestation hCG and AFP were found among pregnancies complicated with VP. Clinicians should consider targeted scanning of pregnant women with risk factors for VP, including unexplained high maternal levels of hCG and αFP of the triple test, while conducting mid-gestation anomaly scan.

Second trimester maternal serum triple screening marker levels in normal twin and singleton pregnancies.

The aim of the present study was to evaluate the serum levels of α-fetoprotein (AFP), free-β-human chorionic gonadotropin (free-β-hCG) and unconjugated estriol (uE3) in second trimester maternal serum and comparative analysis of serum markers levels in normal twin and singleton pregnancies, and to evaluate the feasible methods for the screening performances of triple markers in twin pregnancy. The levels of maternal serum markers were measured by magnetic microparticle chemiluminescence immunoassay in the second trimester. TCSoft was used for calculating the risk of Down's syndrome (DS). The marker levels were compared between the twin and singleton pregnancies, along with gestational age, and the weight or age of the pregnant women. The concentrations of the maternal serum markers were higher on average in twin compared to in singleton pregnancies in the second trimester of the gestation. The levels of AFP were 2-fold higher in twin compared to those in singleton pregnancies in weeks 16, 17 and total gestational weeks. For free-β-hCG, the levels were higher in 15 and 18 gestational weeks. However, significant differences were found in all the gestational weeks for uE3. There was no correlation between the levels of markers and weight or age in the twin pregnancies. The serum marker levels of AFP, free-β-hCG and uE3 in normal twins were not all 2-fold higher compared to singleton pregnancies. The current singleton gestational age-specific model for DS screening requires further correction so that it is feasible for screening in twin pregnancies.

Association between isolated abnormal levels of maternal serum unconjugated estriol in the second trimester and adverse pregnancy outcomes

Objective: To determine the association between maternal serum unconjugated estriol (uE3) levels in the second trimester and adverse pregnancy outcomes.Patients and methods: The prospective database of our fetal Down screening program was assessed and reviewed for maternal serum uE3 levels. Pregnancies with medical diseases, abnormal levels of beta-human chorionic gonadotropin, alpha-fetoprotein and fetal chromosomal or structural abnormalities were excluded. The recruited women were categorized into three groups: high (>95th percentile), normal (5–95th percentile) and low (<5th percentile) uE3 levels.Results: Of 14 212 screened women, 9183 (high; 455, normal; 8271 and low; 457) levels group, were available for outcome analysis. The rates of most adverse outcomes, including preterm birth, low Apgar scores, fetal death, placental abruption, preeclampsia and gestational diabetes mellitus, of the high and normal groups were comparable. Nevertheless, low uE3 levels increased risk of fetal growth restriction (FGR) (RR: 2.36, 95% CI: 1.79–3.10) and low birth weight (LBW) (RR: 1.87, 95% CI: 1.45–2.39), but not preterm birth. Logistic regression analysis indicated that low uE3 level was an independent risk factor for FGR and LBW.Conclusions: High uE3 levels in the second trimester are not associated with poor outcomes, whereas low levels significantly increase risk of FGR and LBW but not other adverse outcomes.