Free β-hCG Research Articles

Correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia

The aim of this study was to investigate the correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia (PE). In total, 32 normal pregnant women (the control group) and 58 subjects with PE were randomly selected from eligible case data. The serum levels of miR-146b-5p, pregnancy associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) were then detected. Next, we established predictive models of single or multiple markers for PE. The levels of miR-146b-5p in the mild pre-eclampsia (mPE) and severe pre-eclampsia (sPE) groups were higher than the control group and there were significant differences between the three groups (F = 3.424, P = 0.037). The statistical results of the model before and after 200 times 10-fold cross-validation were as follows: miR-146b-5p (AUC = 0.723 vs AUC = 0.710); miR-146b-5p + BMI + MAP + free β-hCG MoM + PAPP-A MoM (AUC = 0.929 vs AUC = 0.851). We found that expression levels of miR-146b-5p in the first trimester were significantly higher in the serum of pregnant women with PE than in the normal pregnancy group. A prediction model in combination with miR-146b-5p and other markers improved the early predictive value for PE. IMPACT STATEMENT What is already known on this subject? Pre-eclampsia is a complex systemic disease with hypertension as the main clinical manifestation and causes extensive damage to the body. Some existing maternal biochemical markers have limited value in predicting PE, and new biomarkers with high sensitivity and specificity are urgently needed in clinical practice. There are a variety of abnormal expression miRNAs in PE, however, the relationship between miR-146b-5p and PE has yet to be fully elucidated. What do the results of this study add? We first found that expression levels of serum miR-146b-5p in the first trimester were significantly higher in PE than in a normal pregnancy group. A prediction model a combination of miR-146b-5p and other maternal characteristics and biochemical markers can improve the early predictive value for PE. What are the implications of these findings for clinical practice and/or further research? PE progresses rapidly and has become a severe target organ complication when discovered. Therefore, the early prediction of a high risk of PE, along with early intervention and prevention measures, are of great significance. Compared to maternal biochemical markers, combination of miR-146b-5p and maternal characteristics and biochemical markers can improve the early predictive value for PE.

The findings about relationship between autoimmune thyroid disease and first-trimester aneuploidy results

Aim: The aim of this study was to investigate the relationship between thyroid autoantibody and first-trimester aneuploidy results. Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid. Thyroid peroxidase (TPO-Ab) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. The impact of TPO-Ab on first-trimester aneuploidy test results needs to be studied.
 Material and Method: This retrospective case-control study was conducted between December 2019 and May 2022. Patients with thyroid autoantibody positivity (n=112) were included in the study as the case group. The control group was selected from age and body mass index (BMI)-matched patients (n=130). Nuchal translucency (NT), crown rump length (CRL), pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG)) values were compared between the two groups.
 Results: This study included two hundred forty two age-matched (29.86±4.51) and BMI-matched (23.96±2.34) women. There was no statistically significant difference between groups in terms of free thyroxine (FT4), PAPP-A and free β-hCG (p>0.05). NT as a marker for major chromosomal defects and CRL were comparable in case and control groups (p>0.05).
 Conclusion: There is no statistically significant relationship between thyroid autoimmune diseases and the first-trimester aneuploidy results.

Increased risk of low infant birth weight in pregnant women with low PAPP-A values measured in the first trimester

Objectives: Testing pregnant women as early as in the first trimester has multiple advantages. Firstly, the first trimester screening combining ultrasound and serum marker testing (PAPP-A and free β-hCG) offers the highest currently possible — except for expensive tests using cell-free DNA biomarkers from the mother’s blood (ccf DNA) — detectability of aneuploid fetuses. Secondly, nuchal translucency (NT) measurement helps determine the risk of numerous abnormalities other than aneuoploidies. Lastly, nearly complete ultrasound assessment of fetal anatomy can be performed as early as in the first trimester of pregnancy. Material and methods: This study is based on prospective analysis. Study subjects were 236 pregnant women. One hundred thirty-one patients with a single pregnancy were qualified into the study group and had a combined ultrasound and biochemical screening for Down’s syndrome performed between 11 + 0 and 13 + 6 weeks of gestation, with the measured PAPP-A value at ≤ 0.50 MoM (multiples of the median). The control group comprised 105 pregnant women with PAPP-A value at a similar stage of pregnancy at > 0.5 MoM. Results: The average observed value of the PAPP-A in the study group was 0.35 MoM while in the control group 1.29 MoM. Moreover, combined observation of infant birth weights in both groups compared to the PAPP-A MoM values has shown a significant relationship between those characteristics (r = 0.15, p = 0.0184). Conclusions: The results showed that pregnant women with low PAPP-A MoM value measured during the first trimester have a higher risk of giving birth to a low-birth-weight infant (which is the value below 2500 g), than the pregnant women whose PAPP-A MoM value in the first trimester did not meet this criterion.

Prediction of Prevalence Preeclamptic Women by the Screening of First-Trimester Biochemical Indices (PAPP-A andamp; Free B-HCG) and Third-Trimester Uterine Artery Doppler using ARC GIS in Khuzestan Province/Iran

Background & Objective: The objective of this study was to determine the association between the maternal serum concentration of PAPP-A and free B-HCG at 11-13(+6) weeks and the uterine artery pulsatility index (PI) at 30-34 weeks with the prediction of preeclampsia.Materials & Methods: This cohort study was performed on 882 women with singleton pregnancies from March 2018 to November 2020 at the university hospital (referred center) in Ahvaz/Khuzestan. Maternal serum PAPP-A and free B-HCG at 11-13(+6) weeks and uterine artery PI at 30-34 weeks were measured and compared between women with and without PE. MOM PAPP-A<0.4, MOM-free B-HCG>3, and uterine artery pulsatility index >1 (>95%) were considered abnormal. Then The effect of each of the indicators on preeclampsia was determined by overlaying the layers and performing logical calculations in ARC GIS software. The distribution of PE in different cities of Khuzestan province was investigated.Results: The mean MOM PAPP-A was significantly lower (1.05 vs. 1.21 P < /i>=0.03), and uterine artery PI was significantly upper (0.93 vs. 0.88 P < /i><0.01) in preeclamptic women compared to women without PE. No significant differences were observed in the mean MOM-free B-HCG between women with and without PE (1.33 vs. 1.2 P < /i>=0.667). The highest percentage of PE was in two regions of Ahvaz (80%), but concerning women referred from different cities was in Andimeshk (75%). Conclusion: A low level of maternal serum PAPP-A and increased uterine artery PI promoted the chance of developing PE. The highest prevalence of PE was in two regions of the center of Khuzestan province, and the most preferred due to PE in different cities was in Andimeshk.

Analysis of the Effectiveness of First Trimester Nucal Translucence, Free Beta-Human Chorionic Gonadotropin, and Pregnancy-Related Plasma Protein-A in Prediction of Pregnancy Complications

In this study, we aimed to investigate whether there was an association between fetal nuchal translucency (NT) and the serum markers plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) measured by the first-trimester screening test, as well as birth weight and hypertension. 454 pregnant women who had undergone the first-trimester screening test for Down syndrome were included in the study. All measurements and values of NT, PAPP-A and β-hCG levels were performed between gestational weeks 11-14. Values of PAPP-A and β-hCG converted to multiples of the corrected median (MoM) were obtained using the PRISCA software package. Regarding the prediction of SGA infants, when the PAPP-A value &lt; was 0.99MoM as a threshold, and when the free β-hCG value &lt; was 0.69 MoM, SGA cases could be detected with a sensitivity of 83% and a specificity of 71.9%. Regarding the prediction of hypertension, at a threshold PAPP-A value of

Correlations between maternal hepatitis B virus carrier status and Down’s syndrome prenatal screening indicators and their effects on the screening results

The aim of this study was to determine the correlation between maternal hepatitis B virus (HBV) carrier status and pregnancy-associated serum screening indicators, as well as their implications on the prenatal screening results of Down’s syndrome (DS). This retrospective cohort study included two groups, namely the healthy gravidas group (n = 19804) and the maternal HBV carrier group (n = 792). Serum pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG) levels, as well as the foetal nuchal translucency (NT) thickness, were measured. Multivariatebinary logistic regression analysis was used to evaluate the association between the HBV carrier status and prenatal screening biomarkers. The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both P < .05). Multivariate binary logistic regression analysis showed that HBV carrier status was identified as a risk factor for PAPP-A and the intrahepatic cholestasis of pregnancy (ICP), with adjusted odds ratios (aOR) of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. Pregnant women with HBV carrier status had higher influence on serum PAPP-A level and ICP, and the risk calculation algorithm for DS in HBV carriers should be corrected in the first trimester of pregnancy. IMPACT STATEMENT What is already known on this subject? The maternal serum levels of pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG), as well as the foetal nuchal translucency (NT) thickness, have been collectively used in the prenatal screening of Down’s syndrome (DS), Edward’s syndrome (ES), and open neural tube defects (ONTD). However, many factors, including the maternal age; maternal weight; gestational age; race; history of smoking and so on can affect those serum biomarker levels. Our aim is to know whether there is a difference for HBV status to pregnancy-associated serum screening indicators hoes. What the results of this study add? The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both p < .05). Multivariate binary logistic regression analysis showed that the PAPP-A and intrahepatic cholestasis of pregnancy (ICP) were risk factors for HBV carriers, with aORs of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. What the implications are of these findings for clinical practice and/or further research? The PAPP-A MoM in maternal HBV carriers was significantly higher than that in healthy gravidas, and the risk calculation algorithm for DS in maternal HBV carriers should be corrected in the first trimester of pregnancy.

Diagnostic value of maternal alpha-fetoprotein variants in second-trimester biochemical screening for trisomy 21 and 18

To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15–20+6 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer–lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.

What are the predominant parameters for Down syndrome risk estimation in first-trimester screening: a data mining study

Abstract Objectives This study aimed to evaluate the effect size of each parameter used in the first trimester Down syndrome (DS) risk analyses by using multiple regression analysis techniques. Methods This data mining study included data of 44,260 pregnant women screened at the Acibadem Labmed laboratories from 2010 to 2019. In this study, risk was calculated using the PRISCA software on the basis of nuchal translucency (NT), crown-rump length measurement, in vitro fertilization application, diabetes mellitus, Down syndrome story, smoking, maternal age, and the level of maternal serum biochemistry markers including pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (hCGβ). Results Forty-four thousand two hundred sixty risk analysis patients result data were re-investigate, and 851 (1.93%) risk analysis results were found as positive. PAPP-A 747 (CI%, 476–1,170) times, NT value 512 (CI%, 343–764) times, DS story 21 times (CI%, 6.7–63.2) and hCGβ value 7.01 (CI%, 6.31–7.79) times affect the combined first-trimester risk analysis results. Conclusions We have suggested that those accurate PAPP-A levels and NT levels evaluation are the most critical point of combined risk analysis and that the risk of free hCGβ levels after PAPP-A is essential as a biochemical test.

A retrospective cohort study on the effects of Down’s screening markers and maternal characteristics on pregnancy outcomes in preeclampsia

ABSTRACT Background To investigate the effects of down’s screening markers and maternal characteristics on preeclampsia (PE) pregnancy outcome during early and middle pregnancy. Methods A retrospective study of a cohort of 246 PE and 18,709 No-PE pregnant women who participated in Down’s screening during early and middle pregnancy was performed. Clinical data of pregnancy-related were collected. Multivariate binary logistic regression was used to analyze the adjusted odds ratio (aOR) and 95% confidence interval (CI) of Down’s screening markers, maternal characteristics, pregnancy outcome, and other related variables, and to evaluate the influencing factors of each indicator on PE. P < .05 was considered to be statistically significant. Results Compared with the non-PE group, the concentration and median multiple (MoM) of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) in PE group were both lower (P < .001). Multivariate binary logistic regression analysis showed that low birth weight, hydronephrosis, premature delivery, fetal growth retardation, cesarean section, live birth, hyperlipemia, infection, decreased free β-hCG and first trimester maternal weight were risk factors for PE (aOR were: 7.552, 6.684, 4.154, 3.762, 3.612, 2.454, 1.757, 1.562, 1.270, and 1.077, respectively), while uterine scar, premature rupture of membranes and elevated PAPP-A were protective factors of PE (aOR were: 0.222, 0.328 and 0.612, respectively). Conclusion Decreased maternal serum PAPP-A level, increased free β-hCG, hyperlipemia, premature delivery, cesarean section, live birth, hydronephrosis, fetal growth retardation, low birth weight, and infection are risk factors for PE, while uterine scar and premature rupture of membrane are protective factors for PE.

PLACENTA-ASSOCIATED PLASMA PROTEIN AND FREE HUMAN CHORIONIC GONADOTROPIN LEVELS IN DAY 3 VERSUS DAY 5 TRANSFER

Aim: This study was conducted to investigate placenta-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (B-hCG) levels after blastocyst transfer versus cleavage-stage embryo transfer. &#x0D; Materials and method: A total of 449 women were included in this rerospective sudy. The study consisted of two groups: Group 1: pregnant women conceived by intracytoplasmic sperm injection (ICSI) procedures after fresh embryo transfer at the cleavage stage (day 2 or day 3) and had first trimester fetal aneuploidy biochemical markers performed at 11-14th gestational week (n: 275). Group 2: pregnant women conceived by ICSI procedures after fresh embryo transfer at the blastocyst stage (day 5) and had first trimester fetal aneuploidy biochemical markers performed at 11-14th gestational week (n:174). Demographic characteristics, causes of infertility, duration of infertility, stimulation protocol regimens, total gonadotropin doses, number of follicles and oocytes retrieval, endometrial thickness, fundus –embryo distance were recorded and placenta-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (B-hCG) levels were measured. &#x0D; Results: We found no significant differences in PAPP-A and free B-hCG levels, stimulation protocols regimens and endometrial thickness and fundus-embryo distance. Diminished ovarian reserve and total gonadotropin doses were significiantly higher in group 1 (p &lt; 0.05). Number of follicles, number of oocytes retrieval and MII oocytes were significiantly higher in group 2 (p &lt; 0.05). &#x0D; Conclusion: No difference was observed in PAPP-A and free B-hCG levels between the 3rd and the 5th day fresh transfer.

Relationship between extreme values of first trimester maternal pregnancy associated plasma Protein-A, free-β-human chorionic gonadotropin, nuchal translucency and adverse pregnancy outcomes

ObjectiveThe aim of our study was to investigate the relationship between extreme values of first trimester screening markers and adverse obstetric outcomes. Materials and methodsOur study was conducted by examining the prenatal and postnatal perinatal records of 786 singleton gestations between the ages of 18–40, who applied to Prof. Dr. Cemil Taşçıoğlu City Hospital outpatient clinics for first-trimester screening for aneuploidy, between January 1, 2017 and December 31, 2019. ResultsThe presence of small for gestational age (SGA) was found to be statistically significant for the <5 percentile (<0.37) pregnancy-associated plasma protein A (PAPP-A) group (p = 0.016). For <5 percentile β-hCG group, the presence of gestational diabetes mellitus (GDM), premature rupture of membrane (PROM) and preterm premature rupture of membrane (PPROM) was determined as a statistically significant risk (p = 0.015, p = 0.005, p = 0.02 respectively) In the univariate test, fetal death rate was found to be high for ≥90 percentile at nuchal translucency (NT), but the presence of fetal death was found to be statistically insignificant in logistic regression analysis. (p: 0.057). ConclusionFirst trimester screening test can be used in predicting pregnancy complications. In this study we found that serum levels of PAPP-A are associated with developing SGA, while GDM, PROM and PPROM are more common in low serum free β-hCG.

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.

The effect of fetal gender on the biochemical markers of the first-trimester screening.

To determine the effects of fetal gender on the maternal levels of first-trimester screening biochemical markers, such pregnancy-related plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG). In this retrospective study, we assessed 267 cases of singleton pregnancies, who underwent first trimester screening tests and delivered between January 2016 and January 2019 at our hospital. Multiple of median (MoM) levels of PAPP-A and free β-hCG, and the neonatal genders according to the birth records were compared and analyzed. Additionally, patients with small for gestational age (SGA) newborns, preeclampsia, and placental ablation, called ischemic placental diseases, were classified into a separate group and their PAPP-A and free β-hCG MoM values and fetal genders were compared. There was no significant relationship between the mean values of PAPP-A (1.07±0.6) and free β-hCG (1.23±1.14) and the fetal gender (males: 137, 51.3%; females: 130, 48.7%), respectively (p=0.833; p=0.075). In 41 cases (15.4%) with ischemic placental disease, free β-hCG values was significantly higher in the fetal females (19 cases; 46.3%) than males (22 cases; 53.7%), (1.53±1.02 and 0.77±0.53, respectively), (p=0.004). Pregnancy-related plasma protein A and free β-hCG values were not affected by the fetal gender. However, the significant relationship observed between free β-hCG MoM levels and fetal gender in patients with ischemic placental diseases suggests the need for larger studies on this topic.

Predicting Hypertensive Disease in the First Trimester of Pregnancy: Risk Models and Analysis of Serum D-dimer Levels Combined with Plasma Pregnancy-Associated Protein A, Free β-Subunit of Human Chorionic Gonadotropin, and Fetal Nuchal Translucency.

We aimed to investigate the predictive ability of serum levels of D-dimer (DD) in the first trimester for the occurrence of hypertensive disorders of pregnancy (HDP). In this retrospective, case-cohort study, we measured the levels of DD, plasma pregnancy-associated protein A (PAPP-A), and free β-subunit of human chorionic gonadotropin (free β-hCG) and analyzed fetal nuchal translucency (NT) in 150 healthy gravidas, 126 cases of gestational hypertension (GH), 53 cases of preeclampsia (PE), and 41 cases with severe preeclampsia (SPE). Likelihood ratio models and risk models were built using single markers (DD, PAPP-A, free β-hCG, and NT) and combinations of those markers. Analyses showed that the levels of DD multiple of the median (MoM) in the GH, PE, and SPE groups were all significantly higher than those in the control group, with significant differences between groups (χ2 = 70.325, P < 0.001). The area under curve (AUCs) for DD in the GH, PE, and SPE groups was 0.699, 0.784, and 0.893, respectively; the positive likelihood ratio (+LR) was 1.534, 1.804, and 2.941, respectively; and the negative likelihood ratio (-LR) was 0.022, 0.081, and 0, respectively. When the cut-off values of DD for the GH, PE, and SPE groups were 0.725, 0.815, and 0.945 MoM, respectively, the corresponding sensitivities were 0.992, 0.962, and 1.000, respectively. As gestational hypertension progressed, the levels of DD tended to increase gradually. The maternal serum level of DD in the first trimester had correlative and diagnostic value for HDP. The sensitivity and specificity of maternal serum levels of DD level in the first trimester for different types of HDP were significantly different; the best sensitivity and specificity were detected in the SPE group. First trimester DD level, combined with other biochemical markers, may improve our ability to diagnose HDP.

Prediction of Pregnancy Complications With Maternal Biochemical Markers Used in Down Syndrome Screening.

Objective: To determine whether first- and second-trimester maternal serum biomarkers are useful for the prediction of pregnancy complications like preterm birth, intrauterine growth restriction (IUGR), and macrosomia.Methods: We conducted a retrospective analysis of 353 women having first- or second-trimester combined test for Down syndrome screening who delivered at our institution between January 2018 and December 2020. Associations between first- and second-trimester serum markers and adverse pregnancy outcomes among those who underwent prenatal screening for Down syndrome in our clinic were studied. The adverse pregnancy outcomes, serum levels of pregnancy-associated plasma protein-A (PAPP-A), β-human chorionic gonadotropin (β-hCG), and maternal serum alpha-fetoprotein (ms-AFP) were recorded and analyzed. Correlation analyses of PAPP-A, free βhCG, and ms-AFP with pregnancy outcomes were studied. We sought to predict the risks of preterm delivery (PTD, <37 weeks gestational age), low birth weight (LBW, <2500 grams) and macrosomia (>4000 grams).Results: A total of 353 women who had first- and second-trimester screening test for Down syndrome were included. Two hundred fifty (70.08%) of them had first-trimester and 103 (41.2%) had second-trimester test. Mean age of the patients who underwent screening test for Down syndrome was 29.3±5.9, mean maternal weight was 67.3±13.6, mean gestational weeks at birth was 38.6±2.1 weeks and mean birth weight was 3260.9±511.1, preterm birth rate was 40/353 (11.3%), IUGR rate was 21/353 (5.9%), macrosomia rate was 17/353 (4.8%), stillbirth rate was 3/353 (0.8%). When laboratory and clinical parameters affecting birth weight and birth weeks were analysed in correlation analysis, both birth week and birth weight were found to be positively correlated with maternal weight. Of first-trimester markers Papp-A MoM (Multiples of Median) was found to be positively correlated with fetal birth weight (p = 0.044). Of second-trimester biochemical parameters ms-AFP was found to be negatively correlated with fetal birth weight (p = 0.039).Conclusion: The study concluded that there is a relationship between serum markers and adverse pregnancy outcomes. Significant associations were found between the levels of first- and second-trimester serum markers PAPP-A, AFP and IUGR, macromia and additionally significant association was found between maternal weight and both delivery week and fetal weight. These results can highlight the pregnancies at risk and follow-up intervals may be arranged according to risk scala which may help at antenatal follow-up of high-risk patients.

Construction and predictive value of risk models of maternal serum alpha-fetoprotein variants and fetal open neural tube defects.

The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free β-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free β-hCG level was significantly lower in the study group. The triple-index model of free β-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free β-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free β- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free β-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free β-hCG, free β-hCG, AFP-L3, AFP + free β-hCG, and AFP. Indicators of maternal serum free β-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free β-hCG demonstrated better screening efficiency.

External Quality Assessment of Maternal Serum Levels of Alpha-Fetoprotein, Free Beta-Human Chorionic Gonadotropin, and Unconjugated Estriol in Detecting Down Syndrome and Neural Tube Defects in the Second Trimester of 87 Maternal Serum Samples, Based on 105-139 Days.

BackgroundWe aimed to insure the accuracy and reproducibility of alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (free β-hCG), and unconjugated estriol (uE3) concentrations for the screening for trisomy 21 (T21) and neural tube defects (NTD) in the second trimester. We conducted an external quality assessment of 6 laboratories, using maternal serum specimens.Material/MethodsSerum specimens collected from 87 women of singleton pregnancies (4 with T21, 5 with NTD, and 78 with normal fetuses) were divided into 6 equivalent-volume fractions and transported to 6 laboratories (A, B, C, D, E, and F). All laboratories used the time-resolved fluorescence analyzer and supporting reagents to measure concentrations of AFP, free β-hCG, and uE3. The screening efficacies of T21 and NTD were compared with the certified or accredited status of the participants’ quality systems.ResultsConcentrations of AFP measured by laboratory F were low compared with those determined by the other 5 laboratories, and the differences were significant (P<0.01). There was no statistically significant difference in the free β-hCG and uE3 concentrations measured by the 6 laboratories (P>0.05). The correlation coefficients for the 3 multiples of the median values were all >0.900. The McNemar paired chi-squared test showed the differences in the positivity and detection rates were not statistically significant (P=1.000).ConclusionsAFP, freeβ-hCG, and uE3 values measured by the other 5 laboratories were comparable with those of laboratory A, with good linear correlation. When used in the maternal prenatal screening of T21 and NTD, the test results met the clinical requirements.

The Relationship between Screening Markers in the First Trimester of Pregnancy and Chromosome Aberrations

Background:This study was designed and performed to investigate the relationship between fetal chromosome aberrations and screening markers in the first trimester of pregnancy in order to prevent the birth of infants with chromosome aberrations with early prenatal diagnosis.Methods:We conducted an analytic cross-sectional study on result of chromosomal culture of 762 pregnant women with high-risk combined screening test from December 2018 to June 2020 and analyzed by SPSS program.Results:There was a significant relationship between chromosome structural abnormalities with free beta-human chorionic gonadotropin (free β-hCG) values equal to and higher than 1.5 multiples of the median (MoM) (P: 0.05). The highest incidence of disorder in number of chromosomes with abnormal nuchal translucency (NT) percentiles (≥99%) was seen (P < 0.001). It also shows that the cumulative number of chromosome aberrations of 25 (78.12%) occurred in individuals with a NT less than 99th percentile and at the same time a risk of 1/50≤ risk <1/10.Discussion:According to the results, Comparative Genomic Hybridization (CGH) array method is recommended to detect structural abnormalities in chromosomes in samples with NT ≥3.5. In addition, it is noteworthy that chromosomal structural abnormalities occur in free β-hCG ≥1.5 MoM.Conclusion:Due to the frequency of chromosomal structural disorders and its effect on the incidence of fetal abnormalities, the study of chromosomal structural disorders is recommended.

Associations between Nausea and Vomiting in Pregnancy, Disgust Sensitivity, And First-Trimester Maternal Serum Free-β hCG and PAPP-A

Associations between Nausea and Vomiting in Pregnancy, Disgust Sensitivity, And First-Trimester Maternal Serum Free-β hCG and PAPP-A

First Trimester Combined Aneuploidy Screening for Trisomy 21: A Three Years Retrospective Study

Introduction: Prenatal testing also known as maternal screening is primarily performed to screen out most common chromosomal anomalies in the foetus using maternal blood. It provides an accurate and sensitive assessment of a patient’s risk of carrying a foetus with chromosomal anomalies. Aim: To study the first trimester prenatal screening using a Foetal Medicine Foundation (FMF) certified platform to estimate the risk of foetal trisomy 21. Materials and Methods: This retrospective study was conducted at Global Reference Laboratory, Mumbai, Maharashtra, India, from January 2018 to March 2021, samples of 86118 pregnant Asian women with respect to age, the risk cut-off was set at 1:250 for trisomy 21. The study included determination of free β- human Chorionic Gonadotropin (β-hCG) and PregnancyAssociated Plasma Protein-A (PAPP-A) in maternal serum, ultrasound studies of Crown Rump Length (CRL), Nuchal Translucency (NT) and nasal bone and maternal characteristics. Concentration of biochemical parameters was expressed in Multiple of Medians (MoM) respective to gestation age. Risk assessment of trisomy 21 was analysed using lifecycle software cut-off being 1:250 at sampling. Results: The overall positive risk (high risk) for Trisomy 21 obtained was 2.58%, association with advanced maternal age, history of Insulin dependent diabetes mellitus and absent nasal bone status. Biochemically, the MoMs were in accordance with published studies of mean free β-hCG MoM&gt;1.5 and PAPP-A MoM of ≤0.6. Conclusion: This study enabled us to understand the importance of prenatal testing, a non invasive screening of chromosomal disorders like trisomy 21 which gives the advantages of early counseling and of diagnosis quite as early as in the first trimester of pregnancy. It helps in drastically reducing the use of invasive procedures associated with risk of miscarriages. It is suggested that screening for chromosomal abnormalities be offered in all antenatal women irrespective of age and parity.