Free Β-human Chorionic Gonadotropin Research Articles

Atypicality index as an add-on to combined first-trimester screening for chromosomal aberrations.

To compute a set of atypicality indices based on combined first-trimester screening (cFTS) markers and second-trimester estimated fetal weight (EFW), and to demonstrate their potential in identifying pregnancies at reduced or increased risk of chromosomal aberrations following a low-risk cFTS result. The atypicality index quantifies the unusualness of an individual set of measurements relative to a reference distribution and can be computed from any variables or measurements available. A score of 0% on the atypicality index represents the most typical profiles, while a score of 100% indicates the highest level of atypicality. From the Danish Fetal Medicine Database, we retrieved data on all pregnant women seen for cFTS in the Central Denmark Region between January 2008 and December 2018. All pregnancies with a cytogenetic or molecular analysis obtained prenatally, postnatally or following pregnancy loss or termination were identified. A first-trimester atypicality index (AcFTS) was computed based on nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). Furthermore, a second-trimester index (AcFTS + EFW) was computed from cFTS markers and EFW from a routine second-trimester anomaly scan. All pregnancies were stratified into subgroups based on their atypicality levels and their cFTS risk estimates. The risk of chromosomal aberrations in each subgroup was then compared with the overall prevalence, and a graphical presentation of the multivariate measurement profiles was developed. We retrieved data on 145 955 singleton pregnancies, of which 9824 (6.7%) were genetically examined. Overall, 1 in 122 (0.82% (95% CI, 0.77-0.87%)) of all pregnancies seen for cFTS were affected by a fetal chromosomal aberration, and in screen-negative pregnancies (cFTS trisomy 21 risk < 1 in 100 and/or trisomy 18/13 risk < 1 in 50), 0.41% (95% CI, 0.38-0.44%) were affected. In screen-negative pregnancies with a typical first-trimester profile (AcFTS < 80%), the risk of chromosomal aberrations was significantly reduced (0.28%) compared with the overall risk. The risk of chromosomal aberrations increased with higher atypicality index to 0.49% (AcFTS [80-90%)), 1.52% (AcFTS [90-99%)) and 4.44% (AcFTS ≥ 99%) and was significantly increased in the two most atypical subgroups. The same applied for the second-trimester atypicality index, with risks of chromosomal aberrations of 0.76% and 4.16% in the two most atypical subgroups (AcFTS + EFW [90-99%) and AcFTS + EFW ≥ 99%, respectively). As an add-on to cFTS, the atypicality index identifies women with typical measurement profiles, which may provide reassurance, whereas atypical profiles may warrant specialist referral and further investigation. In pregnancies identified as low risk on cFTS but with a highly atypical distribution of NT, PAPP-A and β-hCG, the risk of a chromosomal aberration is substantially increased. The atypicality index optimizes the interpretation of pre-existing prenatal screening profiles and is not limited to cFTS markers or EFW. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Decoding 22q11.2: prenatal profiling and first-trimester risk assessment in Danish nationwide cohort.

To examine the distribution of nuchal translucency thickness (NT), free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in pregnancies with a fetal 22q11.2 aberration. Furthermore, the performance of combined first-trimester screening (cFTS) and a new risk algorithm targeting 22q11.2 deletions in detecting affected pregnancies was evaluated. Finally, prenatal malformations and pregnancy outcome were assessed. This was a nationwide registry-based cohort study of all pregnancies that underwent prenatal screening with a due date between January 2008 and December 2018 in Denmark. All cases with a fetal 22q11.2 deletion or duplication (hg19 chr22:18.9mio-25.0mio) diagnosed pre- or postnatally or following pregnancy loss or termination of pregnancy were retrieved from the Danish Cytogenetic Central Register and linked with pregnancy data from the Danish Fetal Medicine Database. Fetal and maternal characteristics, including cFTS results and pregnancy outcome, of pregnancies with any 22q11.2 deletion or duplication (LCR22-A to -H) and pregnancies with a classic deletion or duplication (LCR22-A to -D) diagnosed by chromosomal microarray were compared with those of a chromosomally normal reference group. A risk algorithm was developed for assessing patient-specific risks for classic 22q11.2 deletions based on NT, PAPP-A and β-hCG. Detection rates and false-positive rates at different risk cut-offs were calculated. We included data on 143 pregnancies with a fetal 22q11.2 aberration, of which 97 were deletions (54 classic) and 46 were duplications (32 classic). NT was significantly increased in fetuses with a classic deletion (mean, 1.89 mm), those with any deletion (mean, 1.78 mm) and those with any duplication (mean, 1.86 mm) compared to the reference group (mean, 1.65 mm). β-hCG multiples of the median (MoM) was decreased in all 22q11.2 subgroups compared with the reference group (mean, 1.02) and reached significance in pregnancies with a classic deletion and those with any deletion (mean, 0.77 and 0.71, respectively). PAPP-A MoM was significantly decreased in pregnancies with a classic duplication and those with any duplication (mean, 0.57 and 0.63, respectively), and was significantly increased in pregnancies with a classic deletion and those with any deletion (mean, 1.34 and 1.16, respectively), compared to reference pregnancies (mean, 1.01). The screen-positive rate by cFTS was significantly increased in pregnancies with a classic deletion (13.7%), any deletion (12.5%), a classic duplication (46.9%) or any duplication (37.8%) compared to the reference group (4.5%). A risk algorithm targeting classic 22q11.2 deletions more than doubled the prenatal detection rate of classic 22q11.2 deletions, but with a substantial increase in the false-positive rate. Structural malformations were detected in 41%, 35%, 17% and 25% of the pregnancies with a classic deletion, any deletion, classic duplication or any duplication, respectively. Pregnancy loss occurred in 40% of pregnancies with a classic deletion and 5% of those with a classic duplication diagnosed prenatally or following pregnancy loss. The distribution of cFTS markers in pregnancies with a classic 22q11.2 duplication resembles that of the common trisomies, with decreased levels of PAPP-A. However, classic 22q11.2 deletions are associated with increased levels of PAPP-A, which likely limits early prenatal detection using the current cFTS risk algorithm. The scope for improving early detection of classic 22q11.2 deletions using targeted risk algorithms based on NT, PAPP-A and β-hCG is limited. This demonstrates the capability, but also the limitations, of cFTS markers in detecting atypical chromosomal anomalies, which is important knowledge when designing new prenatal screening programs. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free β-hCG and PAPP-A

Elevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n1 = 201, n2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free β-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free β-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity.

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Singleton pregnancies recruited at 11-14weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Atypicality index: avoiding false reassurance in prenatal screening.

To demonstrate the application of the atypicality index as an adjunct to first-trimester risk assessment for major trisomies by the combined test. This was a study of 123 998 Danish women with a singleton pregnancy who underwent routine first-trimester screening, including risk assessment for major trisomies. An atypicality index, which is a measure of the degree to which a profile is atypical, was produced for measurements of fetal nuchal translucency thickness and maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A. The incidence of adverse pregnancy outcome, including miscarriage, intrauterine death and termination of pregnancy, was tabulated according to the screening result and atypicality index. In pregnancies with low risk and those with high risk for major trisomies according to the combined screening test, the incidence of adverse pregnancy outcome increased with increasing atypicality index. In pregnancies with a low risk for trisomies and atypicality index of ≥ 99%, the incidence of adverse outcome was 5.1 (95% CI, 3.4-7.6) times higher compared with that in low-risk pregnancies with a typical measurement profile, reflected by an atypicality index of < 80%. Similarly, in high-risk pregnancies, the incidence of adverse outcome was 7.9 (95% CI, 4.4-14.5) times higher in those with an atypicality index of ≥ 99% compared to those with an atypicality index of < 80%. Using individual profile plots, we were able to demonstrate a transparent and intuitive method for visualization of multiple variables, which can help interpret the individual combination of measurements and level of atypicality. In pregnancies undergoing first-trimester combined screening and classified as being at low risk for major trisomies, profiles that are typical of pregnancies with normal outcome provide additional reassurance, whereas those with an atypical profile may warrant further investigation. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive prenatal testing for everybody or contingent screening?

To compare the advantages and disadvantages of two main implementation strategies for non-invasive prenatal testing (NIPT) for the detection of trisomies 21, 13 and 18 in public healthcare settings. These concern NIPT as a first-tier screening test for all pregnant women, or NIPT contingent on an increased risk first-trimester combined test (FCT) result. Comparison based on (un)published data and literature. Despite the lower prevalence of trisomies in the low-risk population, data show that the positive predictive value (PPV) and detection-miscarriage ratio of first-tier NIPT are comparable to NIPT used as contingency test. Advantages of NIPT as a first-tier test compared to FCT with contingent NIPT are that there is no time-window for testing, sensitivity is higher, fewer women need follow-up testing (PPV of NIPT is higher than PPV of FCT), less anxiety for pregnant women and partners. When given the choice, pregnant women prefer first-tier NIPT. Although contingency testing still seems to be the cheaper option, the differences in costs are becoming increasingly smaller and might soon disappear. We argue that NIPT should preferably be offered as a first-tier test for the detection of fetal aneuploidies for all pregnant women, provided that women are supported to make informed decisions. This article is protected by copyright. All rights reserved.

The impact of preimplantation genetic testing on first- and second-trimester maternal serum analyte levels

Objective To determine whether preimplantation genetic testing (PGT) is associated with a change in maternal serum analyte levels in pregnancies conceived via in vitro fertilization (IVF). Methods Retrospective cohort of singleton and twin IVF pregnancies with available first- or second-trimester serum analyte data from 01/2014 to 09/2019. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol, were compared between two groups: pregnancies conceived after transfer of PGT screened euploid embryos vs. those conceived after transfer of untested embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Results Nine hundred and sixty-two singleton and 165 twin IVF pregnancies with serum analyte data available for analysis were included. PGT was associated with a higher median first- and second-trimester AFP compared to no PGT in singletons (1.23 MoM vs. 1.13 MoM; parameter estimate [PE] 1.08, 95% CI 1.00–1.17, p= .04, and 1.21 MoM vs. 1.07 MoM; PE 1.07, 95% CI 1.01–1.13, p= .01, respectively). PGT was also associated with a lower median PAPP-A compared to no PGT in twins (0.75 MoM vs. 1.18 MoM, PE 0.74, 95% CI 0.60–0.92, p= .006). Conclusions Our data suggest that PGT is associated with higher maternal serum levels of second-trimester AFP in singleton and lower levels of first-trimester PAPP-A in twin pregnancies conceived via IVF.

Antenatal Antidepressant Prescription Associated With Reduced Fetal Femur Length but Not Estimated Fetal Weight

Antidepressants are among the most frequently prescribed medications during pregnancy and may affect fetal weight. Associations between antenatal antidepressant use and ultrasonographic measures of fetal development have rarely been examined. We hypothesized that the prescription of an antenatal antidepressant would be associated with lower estimated fetal weight (EFW). A retrospective analysis of routine ultrasonographic data extracted from electronic medical records was performed on a cohort of pregnant women with psychiatric diagnoses and grouped according to the presence of an antenatal antidepressant prescription (n = 32 antidepressant-prescribed and n = 44 antidepressant prescription-free). After stratifying for gestational age, comparisons included 13 ultrasonographic parameters, frequency of oligohydramnios and polyhydramnios and growth deceleration, and maternal serum protein markers assessed per routine care, including α-fetoprotein, free β-human chorionic gonadotropin, and unconjugated estriol levels, using t tests, nonparametric and Fisher tests, and effect sizes (ESs) were computed. No statistically significant EFW differences between groups at any time point were detected (P > 0.05). Antenatal antidepressant prescription was associated with lower femur length at weeks 33 to 40 (P = 0.046, ES = 0.75) and greater left ventricular diameter at weeks 25 to 32 (P = 0.04, ES = 1.18). No differences for frequency of oligohydramnios or polyhydramnios or growth deceleration were observed (P > 0.05). We did not detect group differences for maternal proteins (P > 0.05). Our evidence suggested a lack of association between antenatal antidepressant prescription and lower EFW but indicated an association with lower femur length and greater left ventricular diameter in mid-late gestation. Future research should examine the clinical implications of these findings.

Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. The universal screening for GDM is usually performed between 24-28 weeks' gestation. This often delays the diagnosis and could increase the risk of adverse pregnancy outcomes. Some of the biochemical placental markers - pregnancy associated plasma protein A (PAPP-A) and free-β human chorionic gonadotropin (hCG), probably could provide a diagnostic value for GDM. The aim of our study was to assess if PAPP-A and hCG values were different among pregnant women with and without GDM and respectively, to tested their place in the early GDM screening. We conducted a retrospective, case-control study by reviewing the clinical database records of 662 pregnant women. The analysis includes the data for a two-year period. The patients included in the observation were divided into two groups - GDM group (n = 412) and Euglycemic group (n = 250). Early screening for GDМ between 9-12 weeks' gestation was performed in 173 of the women in the interventional group due to: registered fasting plasma glucose (FPG) above 5.1 mmol/L, obesity, macrosomia in previous pregnancies or family history for diabetes mellitus. The remaining 239 women underwent universal screening at 24-28 weeks' gestation. Mean serum levels of PAPP-A, hCG, FPG, and body mass index (BMI) were measured between 10-13 gestational weeks. Serum levels of PAPP-A and hCG are presented as multiples of the normal median (MoM), adjusted by maternal baseline characteristics and demographics. In patients who developed GDM during pregnancy, compared with the control group, we have found significantly lower MoM values of PAPP-A (p < 0.0001), higher levels of FPG (р < 0.0001) and higher BMI (р < 0.0001). Median hCG MoM was similar in both group of pregnant women. Our findings suggest that low-normal to low reference range values of PAPP-A might be associated with higher risk for GDM. PAAP-A levels can be used as an additional factor to recommend early screening for GDM.

REFERENCE CENTILE CHARTS OF PAPP-AAND FREE β-HCG IN INDIAN PREGNANT WOMEN.

The combined rst-trimester screening (CFTS) for fetal aneuploidy involves a combination of maternal age, fetal nuchal translucency (NT), maternal serum pregnancy-associated plasma protein-A(PAPP-A) and free β-human chorionic gonadotropin (β-hCG) from 11+0 to 13+6 weeks of gestation [1]. International prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the rst trimester are available and used throughout the world. Ethnicity has an effect on the biochemical parameters of rst trimester screening. As there is a lack of reference chart for the women of Indian ethnicity, we aimed to nd out the level of PAPP-Aand free β-hCG for fetal crown rump length (CRL) of 40-84 mm in the rst trimester of pregnancy and construct the centile charts for both the parameters. Asignicant but weak correlation between the individual models of PAPP-A and β-hCG and CRL (P&lt;0.001). In conclusion, the normal range of PAPP-A and free β-hCG depending on the gestation (CRL) was derived in this cohort study. This would act as a reference for our population and would be helpful in calculating the risk of an adverse maternal and fetal outcome.

First trimester screening for aneuploidy: may combined test and fetal DNA work together?

Introduction The purpose of the study was to evaluate the screening performance of combined test (based on the measurement of nuchal translucency, pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, and maternal age) and fetal DNA screening (NIPS) for trisomies 21 (T21), 18 (T18), and 13 (T13). Material and methods Women who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age) and fetal DNA. Results Among 302 women screened (including 4 with affected pregnancies), our study demonstrated that DNA screening for trisomies 21, 18, and 13 achieved a detection rate of 100% with a false-positive rate of 0.02%, overcoming the traditional combined test with 75% of sensitivity and 4.7% of false-positive rate. In particular, fetal DNA may be useful in case of intermediate risk, in order to avoid invasive diagnostic procedures such villocentesis and amniocentesis. Because of fetal DNA costs, it can be used in clinical practice as a second step screening in case of intermediate or high risk at combined test. Conclusion Fetal DNA screening may be successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of screening.

First-trimester Combined Screening for Trisomies 21, 18, and 13 by Three Closed Chemiluminescence Immunoassay Analyzers (an Experiment on Iranian Pregnant Women)

Background: Pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) as valuable biochemical biomarkers are used to screen down syndrome, Edwards syndrome, and Patau syndrome in the first trimester of pregnancy. Closed immunoassay analyzers are regarded as sophisticated platforms to measure biochemical biomarkers. This study compared the performance of three chemiluminescence analyzers when used for combined screening.Methods: The present cross-sectional study was conducted on 371 pregnant women within the age range of 20-47 years during 11+0 to 13+6 weeks of pregnancy referring to Dena laboratory in Tehran, Iran, during July 2018 and August 2018 using random selection. The biochemical biomarkers of PAPP-A and free β-hCG were assayed on Cobas, Immulite, and Maglumi analyzers. Benetech software as a commercial screening software was used to calculate the risks of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). Deming regression, nonparametric spearman analysis, analysis of variance, and Chi-square test were performed to analyze the data.Results: For the screening population, although the three systems well correlated to PAPP-A and free β-hCG, the values of Maglumi were slightly higher than those reported for Cobas and Immulite. The multiples of the median (MoM) of PAPP-A and free β-hCG had a significant correlation on three platforms. There were no significant differences between the calculated risks of T21, T18, and T13 on the three systems. The sensitivity for all systems was reported as 50%. In addition, specificity and negative predictive value (NPV) were higher than 99% and 95%, respectively. Positive predictive value (PPV) was reported as less than 50%.Conclusion: The obtained results of the present study demonstrated that there were significant correlations between three different systems in terms of PAPP-A and free β-hCG values and MoMs. The sensitivity of all systems for all trisomies was 50%; however, the specificity of all systems was almost the same. The best PPV and NPV for T21 were on Cobas, Immulite, and Maglumi, respectively. The PPV and NPV of all systems for T18/13 were almost the same.

Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy

Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free β-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus.

Background—The first trimester combined test (FTCT) is an effective screening tool to estimate the risk of fetal aneuploidy. It is obtained by the combination of maternal age, ultrasound fetal nuchal translucency (NT) measurement, and the maternal serum markers free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A). However, conflicting data have been reported about the association of FTCT, β-hCG, or PAPP-A with the subsequent diagnosis of gestational diabetes mellitus (GDM). Research design and methods—2410 consecutive singleton pregnant women were retrospectively enrolled in Calabria, Southern Italy. All participants underwent examinations for FTCT at 11–13 weeks (plus 6 days) of gestation, and screening for GDM at 16–18 and/or 24–28 weeks of gestation, in accordance with current Italian guidelines and the International Association Diabetes Pregnancy Study Groups (IADPSG) glycemic cut-offs. Data were examined by univariate and logistic regression analyses. Results—1814 (75.3%) pregnant women were normal glucose tolerant, while 596 (24.7%) were diagnosed with GDM. Spearman univariate analysis demonstrated a correlation between FTCT values and subsequent GDM diagnosis (ρ = 0.048, p = 0.018). The logistic regression analysis showed that women with a FTCT <1:10000 had a major GDM risk (p = 0.016), similar to women with a PAPP-A <1 multiple of the expected normal median (MoM, p = 0.014). Conversely, women with β-hCG ≥2.0 MoM had a reduced risk of GDM (p = 0.014). Conclusions—Our findings indicate that GDM susceptibility increases with fetal aneuploidy risk, and that FTCT and its related maternal serum parameters can be used as early predictors of GDM.

The association between antiretroviral therapy and early placental function: a cohort study

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening.Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex).Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067–0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080–0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure.Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP.

The clinical usefulness of biochemical (free β-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy.

The aim of the study was to analyze the correlation of multiples of the normal median of PAPP-A, free β-hCG levels and nuchal translucency values in prenatal, first trimester screening of trisomy 21 in pregnant women. 251 pregnant women underwent antenatal screening at 11-13+6 weeks of pregnancy which was composed of the measurement of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP-A) levels in the maternal serum and an ultrasound assessment of nuchal translucency (NT). The pregnant women with a high risk of trisomy 21 (≥ 1:300) were given amniocentesis to verify fetal defects. There were 217 cases of normal fetal karyotype and 34 cases of trisomy 21. PAPP-A, β-hCGMoM and NT values were analyzed for the predefined ranges. 85% cases of trisomy 21 had elevated free β-hCGMoM (> 1.5) and only 53% of these had a PAPP-AMoM result below 0.5 (p < 0.05). Analysis of NT in selected ranges of β-hCG (> 1.5) and PAPP-AMoM (< 0.05), which are typical for Down Syndrome values, showed that not all fetuses with Down Syndrome presented with an increased NT. Respectively 44.15% and 26.5% of fetuses presented with increased NT. Characteristic for trisomy 21, a correlation with all 1st trimester screening tests' parameters occurred in only 23.5% of cases. In 53% of cases the results were atypical. The PAPP-A and β-hCG values in the selected MoM ranges did not shown a correlation to the NT measurement, therefore they are independent factors in the diagnosis of trisomy 21. Simultaneous biochemical and ultrasound testing is an indispensable condition for prenatal diagnosis of trisomy 21 in the 1st trimester of pregnancy.

First trimester combined screening in patients with systemic lupus erythematosus: impact of pre-analytical variables on risk assessment

BackgroundPrenatal diagnosis of fetal trisomy 21 and other chromosomal abnormalities is based on invasive tests, such as amniocentesis and chorionic villus sampling, which are carried out in women identified through screening as being at high risk for these abnormalities. The most widely used method of screening is the first-trimester combined test which utilizes maternal age, and measurements of fetal nuchal translucency thickness (NT) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (hCG).ObjectivesTo assess the influence of SLE on the levels of NT, PAPP-A, and β-hCG and whether any alterations in such levels may increase the rate of false positives and the subsequent number of invasive tests.MethodThis was a prospective first-trimester screening study for trisomies 21, 18, and 13 by a combination of maternal age, fetal nuchal translucency thickness, and serum PAPP-A and β-hCG at King’s College Hospital, London, between March 2006 and February 2011. The study population included 47 cases with maternal SLE and 45,493 without SLE. The results of biomarkers in the SLE and non-SLE groups were compared.ResultsIn the SLE group, compared to the non-SLE group, there were no significant differences in median maternal age, fetal NT, or serum PAPP-A MoM, but serum free β-hCG MoM was increased (1.402, IQR 0.872–2.290 vs 0.994, IQR 0.676–1.508).ConclusionIn first trimester screening for trisomies, the measured value of free ß-hCG should be adjusted for maternal SLE to avoid false positive results and overuse of invasive tests.

Down's Syndrome Screening in the First Trimester with Additional Serum Markers: Indian Parameters.

To derive a risk calculation algorithm suitable for use in India when screening for Down's syndrome using four first-trimester maternal serum markers either alone or with ultrasound nuchal translucency (NT). Stored maternal serum samples (- 20°C) from 411 singleton unaffected pregnancies were retrieved and measured for pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (hCG), placental growth factor and α-fetoprotein. Samples were taken at 10-13weeks' gestation. Equations were derived to express marker levels in multiples of the gestation-specific normal median, adjusted for maternal weight. Gaussian model parameters were derived and compared with six published non-Indian studies; NT parameters were derived from 27,647 women screened in India. On the basis of the maternal age distribution in 64,473 Indian women screened in 2016-2017, the model was used to predict test performance. The model predicted a detection rate for a serum-only protocol of 80% for a 5% false-positive rate. Using a 1 in 250 at term Down's syndrome risk cut-off, the predicted detection rate was 78% and the false-positive rate was 4.1%. When NT was also included, the rates were 95% for 5% and 90% for 1.4%, respectively. First-trimester screening using four serum markers only can be carried out in India. Performance is expected to be similar to the second-trimester Quad test and will also facilitate early screening for preeclampsia and open spina bifida. A protocol of NT plus the four serum markers enhances the performance compared with NT, PAPP-A and free β-hCG.