Free β-hCG Research Articles

Second Trimester Screening Markers of Fetal Chromosomal Abnormalities Other than Common Trisomies: A Case-Control Study

Background: To enhance the efficacy of maternal serum screening (MSS), we conducted an analysis to examine the correlation between certain factors identified during second-trimester screening (STS) and fetal chromosomal abnormalities, excluding the common trisomies (trisomies 13, 18, and 21). Additionally, specific risk factor ranges were established for each category. Methods: A retrospective 1:3 matched case-control study was conducted. Case data were obtained from 311 STS samples of fetal chromosomal abnormalities other than common trisomies, with testing performed in the Prenatal Diagnosis Center of the Maternal and Child Health Care Hospital of Sichuan Province in China between 6 January 2013 and 12 April 2023. A total of 933 controls were matched accordingly. Univariate and multivariable conditional logistic regression analyses were implemented and sensitivity analysis was performed. Results: Multivariable logistic analyses revealed that the independent risk factors for fetal chromosomal abnormalities other than common trisomies were ultrasonographic structural abnormalities (odds ratio (OR) = 3.038; 95% confidence interval (CI), 1.774–5.202; p < 0.001); free β-human chorionic gonadotropin (free β-hCG) as multiples of the median (MoMs) of ≤0.34 (OR = 3.006; 95% CI, 1.803–5.013; p < 0.001), 2.82–3.53 (OR = 1.884; 95% CI, 1.321–2.688; p < 0.001), 3.54–4.67 (OR = 1.949; 95% CI, 1.300–2.923, p = 0.001), and ≥4.68 (OR = 1.730; 95% CI, 1.045–2.866; p = 0.033); and a trisomy 21 (T21) risk of 1/271–1/1000 (OR = 2.434; 95% CI, 1.706–3.472; p < 0.001), 1/101–1/270 (OR = 3.330; 95% CI, 2.300–4.821; p < 0.001), and ≥1/100 (OR = 3.441; 95% CI, 2.178–5.438; p < 0.001). Conclusions: Ultrasonographic structural abnormalities, free β-hCG MoMs, and T21 risk were identified as independent risk factors for fetal chromosomal abnormalities (with the exception of common trisomies) in STS. Our findings thus provide data to support clinical decision-making.

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

The Association and diagnostic value between Maternal Serum Placental Markers and Placenta Previa

ObjectiveThis study aims to evaluate the correlation and diagnostic value of maternal serum placental markers: pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (free β-hCG), and alpha fetoprotein (AFP) in relation to placenta previa. MethodsA retrospective case-control study was conducted to gather data on 137 pregnant women who were hospitalized for delivery at Hangzhou Obstetrics and Gynecology Hospital. These women participated in the late stage of early and mid-term maternal serum prenatal screening between January 2018 and December 2020. Of the 137 women, 45 were diagnosed with placenta previa, while 92 were selected at random as the control group, in a ratio of 1:2. Independent samples t-test or Mann-Whitney U test were utilized to compare the quantitative data of the two groups, and the Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of maternal serum placental marker levels for placenta previa. ResultsThe levels of first trimester and second trimester free beta subunit of human chorionic gonadotropin (FT-Free β-hCG; ST-Free β-hCG) in the placenta previa group were higher than those in the normal group [1.38 (0.55-6.03) MoM vs.1.08 (0.32-4.00) MoM, 1.38 (0.39-4.10) MoM vs.1.01 (0.29-4.12) MoM], and the differences between the groups were statistically significant (Z = 2.830, Z = 2.846, both P < 0.05). The AFP level was higher than the normal group [1.13 (0.65-2.15) MoM vs. 0.94 (0.51-2.02) MoM], and the difference was statistically significant (Z = 2.551, P < 0.05). There was no significant difference in PAPP-A between the placenta previa group and the normal group (Z = 1.396, P > 0.05). The ROC curve analysis results showed that the AUCs of FT-Free β-hCG and ST-Free β-hCG for placenta previa were 0.649 (95% CI: 0.551-0.747, P=0.005), 0.634 (95% CI: 0.539-0.730, P=0.011), and 0.650 (95% CI: 0.554-0.746, P=0.004). Using PPV, NPV, FPR, FNR, +LR, and -LR as evaluation indicators for the 5 models, the results showed that FT-Free β-hCG was the best performer in terms of PPV, FPR, and +LR, with values of 0.725, 0.600, and 2.632, respectively. The three-indicator combined detection model (AFP + ST-Free β-hCG + FT-Free β-hCG) had the best performance in terms of NPV and -LR, with values of 0.770 and 0.298, respectively. ConclusionThe elevated maternal serum levels of Free β-hCG and AFP may be associated with placenta previa. The combined detection of maternal serum markers in the early and mid-trimesters has better diagnostic value for predicting placenta previa than individual detection.

First trimester maternal serum PAPP-A and free β-hCG levels and risk of SGA or LGA in women with and without GDM

BackgroundMaternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls.MethodsAltogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking.ResultsIn pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5–4.7) and 2.2 (95% CI 1.4–3.5) in the GDM group and 3.8 (95% CI 3.0–4.9) and 2.8 (95% CI 2.3–3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8–3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1–2.5) for LGA.ConclusionAssociation with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies.

An assessment of analytical performance using the six sigma scale in second-trimester maternal prenatal screening practices in China

ObjectivesWe aimed to evaluate the analytical performance of second-trimester maternal serum screening in China, and to compare if there are differences in sigma levels across different methods and months. MethodsA retrospective study was conducted to assess the analytical quality levels of laboratories by calculating the Sigma metrics with prenatal screening biomarkers: AFP, Total β-hCG, free β-hCG, uE3. Data from 591 laboratories were selected. Sigma metrics were computed using the formula: Sigma metrics(σ) = (%TEa - |%Bias|)/%CV. The Friedman test and Mann-Whitney test were used to compare differences across various methods and different months. The Hodges–Lehmann was used for determining 95 % confidence intervals of pseudo-medians. ResultsOnly uE3 showed significant monthly variations in sigma calculations. However, around 8 % of laboratories across all four analytes demonstrated sigma levels both above 6 and below 3 in different months. Laboratories utilizing time-resolved fluorescence methods significantly outperformed those using chemiluminescence in sigma level. For AFP, the pseudo-median difference between these methods lies within a 95 % confidence interval of (−3.22, −1.93), while for uE3, it is at (−2.30, −1.40). Notably, the median sigma levels for all analytes reached the 4-sigma threshold, with free β-hCG even attaining the 6-sigma level. ConclusionWith current standards, China's second-trimester maternal serum screening is of relatively high analytical quality, and variations in sigma levels exist across different months and methods.

Clinical value of prenatal screening markers in early pregnancy combined with perinatal characteristics to predict fetal growth restriction.

Due to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free β-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free β-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin. A retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant. The multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free β-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778. Early screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study

BackgroundA retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15–20+6 weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO).MethodsWe retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups.ResultsThe gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322–3.014; 1.469, 95% CI: 1.130–1.911 and 1.257, 95% CI: 1.029–1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103–2.443 and 1.101, 95% CI: 1.011–1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121–1.307, P < 0.001).ConclusionsAPOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO.

Investigating the Relationship between Serum Levels of PAPP-A and Free β-hCG in the First Trimester of Pregnancy with Placental Thickness and Percentile of Fetal Weight in Third Trimester Ultrasound

Investigating the Relationship between Serum Levels of PAPP-A and Free β-hCG in the First Trimester of Pregnancy with Placental Thickness and Percentile of Fetal Weight in Third Trimester Ultrasound

First-Trimester Screening Tests and Perinatal Outcomes

Aim: Early diagnosis of trisomies occupies an important place in the working life of perinatologists and obstetricians. Early diagnosis of this condition is very important in raising a healthy generation. Early diagnosis informs decisions such as mental and physical preparation after birth or termination of pregnancy. Early detection of this risk is ensured by testing fetal nuchal translucency (NT), free human chorionic gonadotropin-β (free-βhCG) and pregnancy-related plasma protein-A (PAPP-A) levels at appropriate intervals. Also, with the help of these tests, perinatal risks such as chromosomal abnormalities, intrauterine growth retardation (IUGR) and preterm birth can be detected, and precautionary measures can be taken. In this study, we are trying to find out if it is possible to predict IUGR using these tests in the first trimester and evaluating the infants born here. Perhaps retrospective evaluation of these tests can be used to prevent poor pregnancy outcomes or, if necessary, to reduce the incidence of complications by delivering babies in more appropriate centers. Method: One of the hospitals included in this study is a training and research hospital and the other is a state hospital with active birth management, where the number of births is higher than the regional average. This study was conducted using data obtained by pediatrics and obstetrics by scanning the records of patients who had gone to their centers for postnatal care and the babies who were born. The population that served as the control group was reached in the same way. The period for the study was limited to two years. Results: 257 patients who had enrolled in centers for prenatal care over two years were included in the study. While 132 healthy pregnant women participated in the study as a control group, 125 pregnant women diagnosed with IUGR were included in the study. When the screening tests were compared in the first trimester, the mean PAPP-A level was higher in the control group than in the patient group (p=0.006). Free β-hCG was also higher in the control group (p=0.024). The result after performing the necessary statistical adjustments PAPP-A showed the statistical significance of its value in the analysis. However, the same tests did not show the same success in the IUGR group and were not statistically successful in predicting poor neonatal outcomes. Conclusion: In this study, the use of PAPP-A level in the first trimester has been shown to provide successful results in estimating IUGR that may occur later in pregnancy. However, no parameter has shown the same predictive success in predicting poor neonatal outcomes.

Uptake and outcomes of implementing non-invasive prenatal testing (Prenatal Reflex DNA testing) into first-trimester contingent screening protocols for trisomy 21, 18, 13: A study protocol

Chromosomal anomalies (CAs), such as trisomies 21 (T21), 18 (T18), and 13 (T13), are significant contributors to birth defects and genetic conditions worldwide. Cell-free fetal DNA testing (cff-DNA) is the preferred method for detecting these trisomies from maternal blood samples. However, its adoption is hindered by high costs and complexities. To enhance efficiency and reduce financial strain, we propose a practical protocol. This approach involves a contingent test based on biochemical and ultrasound markers commonly used in clinical practice. We aim to leverage cost-effective contingent prenatal DNA screening for trisomies 21, 18, and 13. This is integrated into standard aneuploidy screening during the first trimester at prenatal centers. Screening participants are categorized into four pathways (1T Quad, 1T Combined, 1T Expanded Combined, and 1T Expanded Combined + Ductus Venosus Pulsatility Index) based on biochemical markers (PAPP-A, Free β-hCG, PlGF, AFP) and ultrasound indicators (NT, DV-PI) as per FMF guidelines. Pregnant subjects (Low/High/Moderate Risk) with a high chance of affected pregnancy (1:1000 ≤ Risk < 1:10) undergo the DNA reflex screening test using stored plasma samples.

Navigating Uncertain Waters: First-Trimester Screening's Role in Identifying Neonatal Complications.

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications.

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years

BackgroundEarly morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGβ <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). MethodsThis was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. ResultsAfter exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). ConclusionsSystematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.

The role of second trimester uterine artery Doppler in predicting obstetric and neonatal outcomes in abnormal first trimester maternal serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin values.

This study aims to determine whether second-trimester uterine artery (UtA) Doppler combined with first-trimester abnormal pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-Hcg) levels predicts adverse obstetric and neonatal outcomes. This study of 289 pregnant women included 196 with normal PAPP-A and free β-HCG values (control group) and 93 with abnormal values (study group) in the first-trimester screening test. Second-trimester UtA Doppler sonography was done in these pregnancies. The perinatal prediction and screening potential of UtA Doppler pulsatility index (PI) parameters were examined in the study group. UtA PI >95 percentile increased birth before the 37th week by 4.46 times, birth before the 34th week by 7.44 times, preeclampsia risk by 3.25 times, fetal growth restriction (FGR) risk by 4.89 times, and neonatal intensive care unit (NICU) admission rates by 3.66 times in the study group (p < 0.05 for all). UtA PI >95 percentile had 49.2% sensitivity and 82.1% specificity for birth before 37 weeks. For birth before 34 weeks, sensitivity was 80.0% and specificity 65.0%. FGR has 70.5% sensitivity and 67.1% specificity. Screening for preeclampsia has 66.6% sensitivity and 61.9% specificity. Adding UtA Doppler in the second trimester to pregnancies with abnormal PAPP-A and/or free β-Hcg values in the first trimester may be a useful screening method for adverse outcomes.

Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value.

Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.

Predictive value of first-trimester screening tests (PAPP-A and free βhCG) for placenta previa and placenta accreta spectrum disorders

Predictive value of first-trimester screening tests (PAPP-A and free βhCG) for placenta previa and placenta accreta spectrum disorders

Relationship between first trimester maternal PAPP-A (pregnancy associated plasma protein-A) and free β-hCG (human chorionic gonadotropin) levels with fetal birth weight

Relationship between first trimester maternal PAPP-A (pregnancy associated plasma protein-A) and free β-hCG (human chorionic gonadotropin) levels with fetal birth weight

The impact of fresh versus frozen-thawed embryos on maternal serum analyte levels in IVF singleton and twin pregnancies.

To determine whether embryo cryopreservation is associated with a difference in maternal serum analyte levels in singleton and twin pregnancies conceived via in vitro fertilization (IVF). This was a retrospective cohort study of singleton and twin pregnancies conceived via IVF from a university health system from 01/2014 to 09/2019. Patients with available first and second trimester serum analyte data were included and analyzed separately. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A, alpha-fetoprotein (AFP), Inhibin A, and unconjugated estriol (uE3) were compared between two groups: pregnancies conceived after the transfer of fresh embryos versus pregnancies conceived after the transfer of frozen-thawed embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. For singletons, fresh embryos were associated with a lower median first trimester free β-hCG (1.00 MoM vs. 1.14 MoM; parameter estimate [PE] 0.90, 95% CI 0.82-0.99, p = .03) compared to frozen-thawed embryos. Fresh embryos were also associated with a lower median second trimester uE3 (0.93 MoM vs. 1.05 MoM; PE 0.88, CI 0.83-0.95, p = .0004) and AFP (1.02 MoM vs. 1.19 MoM; PE 0.91, CI 0.84-0.99, p = .02) compared to frozen-thawed embryos in singletons. There were no significant differences between median first and second trimester serum analytes in twin pregnancies compared between the two groups. Singleton pregnancies derived from fresh embryos had lower first (free β-hCG) and second (uE3 and AFP) trimester analytes compared to frozen-thawed embryos. Twin pregnancies demonstrated no difference between the groups.

Maternal and Fetal Factors Affecting Cell-Free Fetal DNA (cffDNA) Fraction: A Systematic Review.

Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application. In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction. A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy. Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.

A new contingent screening strategy increased detection rate of trisomy 21 in the first trimester

BackgroundAlthough the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21.MethodsThis was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care.ResultsWhen cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively.ConclusionsThe new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Adverse pregnancy outcome in low PAPP-A levels: First trimester screening hospital based study

To assess the adverse pregnancy outcome in Low Pregnancy Associated Plasma Protein -A (PAPP-A) levels in serum.This is a prospective cohort study, which included 2150 pregnant women who attended the antenatal clinic of Obstetrics and Gynecology in the Lok Nayak Hospital, New Delhi, India. Blood samples were collected by the venipuncture method for First trimester screening to assess free β-hCG and PAPP-A concentrations were measured by Auto DELFIA (Perkin Elmer, Turku, Finland).In this study a total of 210 women who have the low PAPP-A value less than 0.4 MoM were under the closer surveillance for serious pregnancy outcome. 33(15.6%) women had pre-eclempsia, 27 (12.9%) cases showed intra-utrine growth retardation (IUGR), 6 (3.0%) cases have intra-utrine death. 48 (22.8%) women have pregnancy induced hypertension, and 96(45.6%) cases have other pregnancy related complication. Low PAPP-A levels gives an indication of adverse pregnancy outcome in the early gestation age during the first trimester.