Free Human Chorionic Gonadotrophin Research Articles

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.

The relationship between the first trimester maternal serum PAPP-A and β-hCG values and newborn intensive care needs in low-risk pregnancies.

The purpose of the study was to look at the connection between newborn intensive care requirements in low-risk pregnancies and maternal blood pregnancy-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (hCG) levels, which are elements of screening tests within the first trimester. In the delivery unit of our hospital, pregnant women between the years of 18 and 35 had singleton pregnancies who delivered between 37 and 41 weeks of pregnancy between July 2021 and January 2022 were split into 2 groups. One hundred eighty two pregnant women with infants who required neonatal intensive care (NICU) were enrolled in the first group, whereas 890 pregnant women with infants who did not require NICU were enrolled in the second. These two groups' maternal blood PAPP-A and free hCG levels, which are among the first trimester screening procedures, were examined. Additionally, subgroup analysis were performed in terms of cesarean section indications and NICU admission indications. Logistic regression analysis and ROC analysis were performed with related variables for estimating NICU need. The mean serum PAPP-A value was found to be 0.91±0.34 multiples of the median (MoM) in the blood taken from the infant mothers who needed NICU, while the mean serum PAPP-A value in the blood taken from infant mothers who did not need NICU was 1.12±0.59 MoM (p<0.000). The PAPP-A MoM mean of the group with Apgar 5th minute score ≥8 (1.09±0.57) was higher than the PAPP-A mean (0.84±0.27) of the Apgar 5th minute score <7 group (p=0.013). According to the results of our study, in groups with a PAPP-A value below 0.95, the possibility of increased NICU need of newborns is higher. The low serum PAPP-A level, which is used as a screening test among pregnant women, demonstrates that it is successful in predicting perinatal outcomes in the low-risk pregnancy group.

Combination of PLGF and PAPPA as a biochemical markers to the first trimester maternal screening

Screening of fetal chromosomal abnormalities is an essential part of antenatal care. Effective first trimester screening involves PAPP-A (pregnancy associated plasma protein A) and free HCG (human chorionic gonadotropin) levels in the maternal serum along with ultrasound examination. The objective of this study is to investigate whether the measurement of PLGF (Placental Growth Factor) can improve the performance of first trimester combined screening for Trisomy 21, 18 and 13. A total of 350 samples were collected from pregnant women during the first trimester between 10 to 14 weeks of gestation. The ultrasound (US) data were collected from all cases which include US gestational age, NT value, CRL, and fetus number, if any. Blood samples were collected and tested for PAPP-A and free HCG tests. The combined risk of trisomy 21, 18 and 13 were calculated using PRISCA software. The screen positive cases (more than a defined cutoff rate) were stored at -20oC for PLGF testing. A total of 97 cases, including low and high risk patients were analyzed for PLGF. A significant reduction was observed among the risk group p ≤ 0.005 when compared to the negative control group. A positive correlation between PLGF and PAPPA was identified (r=0.69) p ≤0.001. In conclusion the study provide data indicating that inclusion of serum PLGF improve the performance of first trimester combined test for screening of Trisomy 21, 18 and 13 risk

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.

Prediction performance of serum placental growth factor (PLGF) human chorionic gonadotropin β (β-hCG) and PAPP-A levels in early pregnancy for pregnancy outcomes.

Objectives:To investigate the prediction performance of serum placental growth factor (PLGF), free human chorionic gonadotropin β (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels in early pregnancy for pregnancy outcomes.Methods:A total of 4256 pregnant women who underwent obstetric examinations in our hospital from June 2018 to June 2020 and completed their full pregnancy were included in the study. The clinical pregnancy outcomes of pregnant women with different PLGF, PAPP-A and β-hCG levels in early pregnancy were recorded, and the prediction performance of the above indicators for adverse pregnancy outcomes was discussed.Results:Pregnant women with increased or decreased PLGF or increased PAPP-A or β-hCG had significantly higher incidence of adverse pregnancy outcomes than normal pregnant women. Pregnant women with abnormal pregnancy had significantly higher β-hCG and PLGF, and lower PAPP-A than those with normal pregnancy. The sensitivity of serum PLGF, β-hCG and PAPP-A in early pregnancy for predicting adverse pregnancy outcomes was 95.13%, 94.19% and 97.75%, and the specificity was 84.31%, 85.80% and 83.22%, respectively.Conclusions:Serum PLGF, PAPP-A and β-hCG in early pregnancy are more effective in predicting adverse pregnancy outcomes. Clinical monitoring of patients with increased PLGF, decreased PAPP-A, and increased β-hCG should be strengthened, especially the monitoring of antepartum examination and B-ultrasound detection of pregnant women with abnormal indicators in middle and late pregnancy, so as to identify adverse pregnancy outcomes as early as possible and give targeted intervention.

Investigation of Association with First-Trimester Free Human Chorionic Gonadotropin - ß, Pregnancy - Associated Plasma Protein-A, and Adverse Pregnancy Outcomes

OBJECTIVES: This study aimed to investigate the association between first-trimester screening maternal serum markers (free human chorionic gonadotropin-beta (β-hCG), pregnancy-associated plasma protein-A, and adverse pregnancy outcomes (gestational hypertension, preeclampsia, preterm delivery, intrauterine growth restriction, oligohydramnios, intrauterine ex-fetus, abruptio placentae, and gestational diabetes mellitus). STUDY DESIGN: This was a retrospective cohort study including 1516 women who delivered a singleton pregnancy at GATA Haydarpasa Education Hospital from 2006 to 2009. Patients with multiple pregnancies, chromosome aberrations, or fetal anomalies were excluded. Extreme values of corrected- pregnancy-associated plasma protein-A and free β-hCG, and their association with adverse pregnancy outcomes were analyzed. RESULTS: Adverse pregnancy outcomes at the cutoff level of ≤0.25 c-pregnancy-associated plasma protein-A MOM values positive likelihood ratio (+LR) was 7.5 (95%CI 2.426-19.836) and had a significant correlation (r=0.108, p&lt;0.01). It was also a significant correlation with adverse pregnancy outcomes (r=0.189, p&lt;0.01) at the cut-off level of ≤0.50 corrected-pregnancy-associated plasma protein-A MOM values and the +LR was 2.388 (95%CI 1.889-2.991). Association between low corrected-pregnancy-associated plasma protein-A MOM values and adverse pregnancy outcomes were statistically significant and had a poor association (AUC, 0.630 95%CI 0.596-0.663, p&lt;0.01). Preeclampsia was statistically significant, however had a fair association (AUC, 0.74 95% CI 0.690-0.802, p&lt;0.01). Preterm birth was statistically significant but had a poor association (AUC, 0.568 95% CI 0.512-0.624, p&lt;0.05). CONCLUSION: First-trimester maternal serum low pregnancy-associated plasma protein-A values are significantly associated with adverse pregnancy outcomes. It may be a useful tool to predictive not only chromosome anomalies but also adverse pregnancy outcomes.

Impact of preimplantation genetic testing for aneuploidies (PGT-A) on first trimester biochemical markers – PAPP-A (placenta-associated plasma protein) and free β-hCG (human chorionic gonadotropin)

Objective The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers. Methods This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) – 143 patients; group B (ART/no PGT-A/FET) – 100 patients; group C (ART/no PGT-A/fresh ET) – 346 patients, and group D (NC) – 139 patients. Results Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPP-A) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups (p = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/PGT-A/FET group versus ART/no PGT-A/FET group (p = .01) and NC versus ART/no PGT-A/FET (p = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET (p = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (β-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free β-hCG among the compared groups (p = .5789) and when subgroup analysis was performed (p>.05). The normality of the distribution of variables was analyzed by the Kolmogorov–Smirnov test and the median PAPP-A and free βhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA. Conclusions Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A.

A risk prediction model for fetal hypospadias by testing maternal serum AFP and free beta-HCG

ObjectiveWe aimed to determine the correlation between serum alpha-fetoprotein (AFP), the free human chorionic gonadotropin beta subunit (free beta-HCG) in pregnant women during the mid-trimester, and fetal hypospadias, and tried to establish a risk prediction model. MethodsA multi-center case-control study was conducted. We divided the fetuses into two groups (69 with fetal hypospadias and 62 without fetal hypospadias). Time-resolved immunofluorescence was used to determine the serum levels of AFP and free beta-HCG. The best cut -value and area under curve (AUC) were determined based on the Receiver operating characteristics (ROC) curve, and the diagnostic value of AFP and free beta-HCG was evaluated. ResultsThe level of AFP in the study group was 1.14 multiple of Median(MOM), which was higher than in the control group (0.96 MOM); the difference was significant (Z = 2.831, P = .005). Similarly, the free beta-HCG level was 1.30 MOM in the study group, and was also significantly higher than in the control group (0.84 MOM; Z = 3.131, P = .004). We used the AFP and free beta-HCG levels separately to predict fetuses with hypospadias, and the AUCs were 0.644 (95% Confidence interval (CI): 0.5500.737, P = .005) and 0.659 (95% CI: 0.5650.752, P = .002), respectively. According to the ROC curve, the best cut-off values for AFP and free beta-HCG were 0.945 MOM and 1.275 MOM, respectively. When we combined the AFP level with the free beta-HCG level, the AUC was 0.700 (95% CI: 0.610–0.789, P < .001), with a sensitivity of 0.551 and a specificity of 0.855. ConclusionCombined screening for fetal hypospadias with maternal serum AFP and free beta-HCG levels during the early second trimester has high sensitivity and specificity, which can be used as a new marker.

Prenatal Screening Markers for Down Syndrome: Sensitivity, Specificity, Positive and Negative Expected Value Method.

SummaryBackgroundGenetic screening for chromosomopathy is performed in the first trimester of pregnancy by determining fetal nuchal translucency (NT), and the pregnancy associated plasma protein-A (PAPP-A) and free human chorionic gonadotropin (free-beta HCG) biomarkers in maternal serum.MethodsWe tested the sensitivity, specificity, positive and negative expected values of each marker with the aim of setting a model for prenatal screening readings. Statistical data treatment has been performed on a sample of 340 pregnant women with positive results of prenatal screening.ResultsSensitivity of PAPP-A was 0.6250 (probability 62.50%), free beta HCG 0.5893 (58.93%), NT 0.1785 (17.85%). Specificity of PAPP-A was 0.5106 (probability 51.06%), free beta HCG 0.5246 (52.46%), NT 0.9718 (97.18%). Positive expected value of PAPP-A was 0.2011 (probability 20.11%), free beta HCG 0.1964 (19.64%), NT 0.556 (55.56%). Negative expected value of PAPP-A was 0.8735 (probability 87.35%), free beta HCG 0.8662 (86.62%), NT 0.8571 (85.71%). The NT marker has a significantly higher specificity, which means that its normal value will significantly reduce the final risk of trisomy 21. The sensitivity of NT is much lower than that of biochemical markers, which means that a pathological value of NT does not have a significant influence on the final risk, i.e. the significantly higher sensitivity of biochemical markers will reduce the final risk of trisomy 21.ConclusionsThe analyses stress the importance of using a software which has the possibility to separate the level of a biochemical risk by correlating PAPP-A and free beta HCG and, by adding the NT marker, calculate the level of a final risk of Down syndrome.

Is median value of Double Screening Test regional? / İkili Tarama Testi medyan değerleri bölgesel midir?

Abstract Objective: The median values of double test which is commonly used for Down Syndrome screening show diversity between countries. In this study, we aimed to investigate the possible differences in corrected multiplies of median (MoM) values of individiuals between the two cities of the same geographic region. Methods: Blood samples for double test analysis, sent from Corum and Samsun, were studied in the same laboratory. Results of double test analyses were retrospectively evaluated. Mann-Whitney U test was used for comparison of corrected MoM values of free human chorionic gonadotropin (f-β hCG) and pregnancy-specific plasma protein-A (PAPP-A) according to gestational age. Results were given as median (minimum-maximum) values. The p &lt;0.05 was considered significant. Results: The corrected f-β hCG values obtained from Corum and Samsun were as follows: 0.75 (0.24-2.11, n=28), 0.85 (0.21-2.95, n=143) (p=0.378) in 10th gestational week; 0.75 (0.17-4.15, n=349), 0.84 (0.14-4.76, n=672) (p=0.005) in 11th gestational week; 0.81 (0.15-5.15, n=542), 0.86(0.19-5.18, n=946) (p=0.014) in 12th gestational week; 0.77 (0.20-6.32, n=365), 0.87 (0.20-5.54, n=327) (p=0.054) in 13th gestational week, respectively. Corrected PAPP-A values from Corum and Samsun were as follows: in 10th gestational week 0.94 (0.41-5.57), 0.87(0.19-3.53) (p=0.425); in 11th gestational week 0.88 (0.21-3.61), 0.89 (0.19-3.70) (p=0.963); in 12th gestational week 0.89 (0.22-4.24), 0.90 (0.15-4.99) (p=0.704); in 13th gestational week 0.93 (0.19-2.70), 0.90 (0.09-2.80) (p=0.952) respectively. Conclusion: The MoM values of f-β hCG tests, derived from individuals from Corum and Samsun, both located in the Central Black Sea Region, were found to be different. This finding indicates that for double test analysis, different median values may be used for patients from different cities.

Combination of PAPPA, fhCGβ, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia.

OBJECTIVETo evaluate the efficacy of first-trimester markers—pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin β (fhCGβ), alpha-fetoprotein (AFP), placental growth factor (PlGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE).METHODSDuring 2005–2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE.RESULTSPAPPA, fhCGβ, and PlGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR).CONCLUSIONSFirst-trimester maternal serum levels of PAPPA, fhCGβ, AFP, PlGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE.

Role of Pregnancy Associated Plasma Protein (PAPP-A) and Free Human Chorionic Gonadotropin (B-HCG) in Predicting Adverse Pregnancy Outcomes

Role of Pregnancy Associated Plasma Protein (PAPP-A) and Free Human Chorionic Gonadotropin (B-HCG) in Predicting Adverse Pregnancy Outcomes

Estrategias para mejorar el cribado de síndrome de Down: experiencia en el Instituto Dexeus (Barcelona)

ObjectiveTo evaluate the improvement in the effectiveness of trisomy 21 (T21) screening according to the different strategies employed. Material and methodsAn early T21 screening was performed on all single pregnancies from October 2003 to November 2009, combining maternal age, the measurement of nuchal translucency (NT), and the determination of the biochemical markers, pregnancy- associated plasma protein A (PAPP-A) and free human chorionic gonadotropin (β-hCG). Measurement of the ductus venosus pulsatility index (DVPI) has been included in the assessment of the risk index since October 2008. The biochemical parameters were measured using the Kryptor analyser, in a one time (analytical determinations and ultrasound on the same day) or a two time strategy (analytical determinations between 2 and 4 weeks prior to the measurement of NT). The calculation of the combined T21 risk index was performed using the program marketed by SsdwLab5-Software. ResultsA total of 13,132 pregnancies were included, with 61 cases of T21. Distribution curves of the biochemical and ultrasound parameters are described. Different strategies have been introduced since 2003 with the purpose of improving the effectiveness of Down's syndrome (DS) screening. These have led to an improvement in the detection rate (DR) (84.4% to 100%), and a reduction in the false positive rate (FPR) (5.8% to 3.6%). Assuming a DR of 85%, the FPR have significantly decreased from 7.6% to 1.3%. ConclusionsThe effectiveness of SD screening improves when we use our own distribution curves of the biochemical parameters available, we periodically update their values, when we move from one to two-time screening strategy, and incorporate the DVPI as a first line parameter in the assessment of the risk index. We suggest including these strategies in the standard T21 screening policies in experienced centres in order to reduce unnecessary invasive tests.

A New Approach to Calculating the Risk of Chromosomal Abnormalities with First-Trimester Screening Data

First-trimester screening at 11 - 14 weeks has been proven to be very useful in the early detection of chromosomal defects. The aim of this project was to develop a CE-certified new risk calculation program (PRC = Prenatal Risk Calculation) using a nationwide database. The database underlying the new risk calculation procedure was established in Germany from 2003 through 2006. Overall, the database includes measurements from 70,030 pregnant women having given birth to healthy children. Following consideration of all pregnancies associated with a chromosomally abnormal outcome, the sample size was 451. The algorithm used for calculating the risk of a chromosomally abnormal outcome comprises the following variables: maternal age, crown-rump length (CRL) (restricted to a range from 45 - 84 mm or, equivalently, 11 + 1 - 14 + 0 weeks of gestation), nuchal translucency (NT), as well as the maternal serum parameters PAPP-A (pregnancy associated plasma protein A) and free beta-hCG (free human chorionic gonadotropin). In a preliminary cross-validation study, we applied both the new algorithm and the FMF UK program to an independent sample containing n = 40,568 pregnancies with negative outcome, n = 187 cases of trisomy 21, n = 34 trisomies 18 and n = 13 trisomies 13. Using the primary sample of 70,030 pregnancies with a negative outcome, reference bands were constructed for the sonographic parameter fetal nuchal translucency and the biochemical parameters PAPP-A and free beta-HCG. Instead of MoM values we used "degree of extremeness" (DoE) values. This statistical parameter has been proven to give more precise results than the MoM measure because it assesses the deviation of the actual measurement value from the centre of the reference band expressed as a multiple of the width of the respective band section. The result of the risk calculation is visualized by means of a traffic light graph which allows the patient to comprehend her individual risk at first glance. The red color indicates a high risk, green a low risk, and yellow represents a moderate risk. In our preliminary cross-validation study the detection rate obtained for the German algorithm was 86.6 % for trisomy 21, 94.1 % for trisomy 18 and 92.4 for trisomy 13. The corresponding detection rates obtained with the same data by the FMF UK program were 86.1 %, 82.3 % and 69.2 % throughout. The false-positive rate was 5.0 % throughout. The new risk calculation procedure of the FMF Germany (PRC) has been made available as a CE-certified computer program. In screening for trisomy 21 it yields results comparable to those of the program used by the FMF UK. Regarding the diagnosis of trisomy 13 and 18, even higher detection rates are currently achieved with the German algorithm. Program, data base and license key are available free of charge to registered members of the FMF Germany.

First-Trimester Screening for Trisomy 21 by Free Beta-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein-A: Impact of Maternal and Pregnancy Characteristics

In pregnancies complicated by fetal trisomy 21, maternal serum levels of free-human chorionic gonadotropin (free β-hCG) are about twice as high as in pregnancies with a euploid fetus, while levels of pregnancy-associated plasma protein-A (PAPP-A) are reduced by about half. Screening for trisomy 21 using these markers in addition to fetal nuchal translucency thickness has been reported to detect about 90% of affected pregnancies at a false-positive rate of 5%. However, currently the only variables for which adjustments are made are maternal weight and gestational age. To determine if other maternal variables influence screening test results, the present multicenter trial prospectively screened women in the first-trimester of pregnancy for trisomy 21, using multiple regression analysis to learn how maternal factors, particularly ethnic origin, influenced measured levels of β-hCG and PAPP-A. Gaussian distributions were fitted to the distribution of log multiples of the median values in 491 cases of trisomy 21 and 96,803 euploid pregnancies. Compared with Caucasian women who were parous, nonsmokers, and conceived spontaneously, PAPP-A levels were 57% higher in women of Afro-Caribbean origin, 3% higher in South Asians, 9% higher in East Asians, 2% higher in nulliparous women, 17% lower in smokers, and 10% lower in women who conceived by in vitro fertilization (IVF). Maternal serum levels of free β-hCG were 12% higher in women of Afro-Caribbean origin, 9% lower in South Asian women, 8% higher in East Asians, 2% higher in nulliparous women, 4% lower in smokers, and 9% higher in women who conceived by IVF. If no adjustments were made for variables other than maternal age and gestational age, integrated first-trimester screening based on maternal age-related risk and serum PAPP-A and free β-hCG levels resulted in the detection of 51% of all cases of trisomy at a false-positive rate of 1.4% in Afro-Carribean women; after adjustment for race, the detection increased to 68% at a false-positive rate of 4.6%. Similar changes in the detection and false-positive rates occurred after adjustment for smoking, conception by IVF, and parity. In addition, screening was considerably more sensitive when carried out at 11-12 weeks' gestation rather than at 13 weeks. These results indicate that numerous maternal and pregnancy-related factors must be taken into account when screening in the first-trimester of pregnancy for trisomy 21.

Rastreio para anomalias cromossômicas no primeiro trimestre da gestação

Um efetivo rastreio para anomalias cromossômicas pode ser realizado no primeiro trimestre da gestação. A associação entre a transluscência nucal (TN) e as concentrações séricas maternas da fração beta-livre da gonadotrofina coriônica humana e da proteína plasmática-A associada à gestação pode identificar 90% dos fetos com trissomia do cromossomo 21 e outras anomalias cromossômicas, com uma taxa de falso-positivo de 5%. Esses números são superiores aos obtidos pelo rastreio utilizando-se apenas a idade materna (30%) ou o rastreio bioquímico materno, no segundo trimestre da gestação (65%). Um rastreio mais eficaz, no primeiro trimestre, pode ser atingido por meio de uma avaliação ecográfica em dois tempos, dividindo-se as pacientes em grupos de alto, intermediário e baixo risco. No grupo de alto risco, o diagnóstico invasivo estaria indicado, ao contrário do grupo de baixo risco, no qual a presença de uma anomalia seria pouco provável. No grupo de risco intermediário (risco de 1 em 101 a 1 em 1.000), seria oferecida uma segunda avaliação ecográfica, para posicionar a paciente no grupo de alto ou baixo risco (presença/ausência do osso nasal ou presença/ausência da regurgitação tricúspide ou presença/ausência de alteração do fluxo sangüíneo no ducto venoso). A biópsia de vilo corial estaria indicada quando, após a realização da segunda abordagem, o risco ajustado da paciente se tornasse maior ou igual a 1 em 100. Essa segunda abordagem ecográfica deveria ser realizada por pessoal treinado, e os seus resultados deveriam ser constantemente avaliados, como um controle de qualidade. Esse processo foi estabelecido pela Fetal Medicine Foudation e aceito internacionalmente.

1095: Prenatal diagnosis during the first trimester

Ultrasound measurement of nuchal translucency thickness is an effective method of screening for chromosomal abnormalities at 11 to 13 + 6 wk of gestation. It was suggested that, when combined with maternal age, this method can identify about 80% of pregnancies with trisomy 21 at a 5% false-positive rate. It was shown that by the combination of this methodology with the determination of maternal serum free-human chorionic gonadotropin (-hCG) and pregnancy-associated plasma protein-A (PAPP-A), the detection rate of trisomy 21 is about 90%, for a false-positive rate of 5%. Additionally, in chromosomally normal fetuses, increased NT is associated with an increased risk of structural abnormalities, mainly cardiac defects, genetic syndromes and adverse pregnancy outcome. It was also reported that there is an association between chromosomal defects and abnormal ductus venosus blood flow-velocity waveforms (DV-FVWs) at 11 to14 wk of gestation in high-risk pregnancies. More than that, an abnormal DV-FVW is also associated with a high probability of an underlying major cardiac defect, and adverse pregnancy outcome. It was also proposed that a high association between absent fetal nasal bone at the 11 to 13 + 6 gestational wk scan and trisomy so that the addition of this marker could result in a major reduction in the need for invasive testing and a substantial increase in sensitivity. During this lecture, we will review the ultrasound technique for obtaining these different markers correctly according to the Fetal Medicine Foundation criteria. Additionally, we will discuss our experience in two private centers in Argentina during the last 4y. Ultrasound measurement of nuchal translucency thickness is an effective method of screening for chromosomal abnormalities at 11 to 13 + 6 wk of gestation. It was suggested that, when combined with maternal age, this method can identify about 80% of pregnancies with trisomy 21 at a 5% false-positive rate. It was shown that by the combination of this methodology with the determination of maternal serum free-human chorionic gonadotropin (-hCG) and pregnancy-associated plasma protein-A (PAPP-A), the detection rate of trisomy 21 is about 90%, for a false-positive rate of 5%. Additionally, in chromosomally normal fetuses, increased NT is associated with an increased risk of structural abnormalities, mainly cardiac defects, genetic syndromes and adverse pregnancy outcome. It was also reported that there is an association between chromosomal defects and abnormal ductus venosus blood flow-velocity waveforms (DV-FVWs) at 11 to14 wk of gestation in high-risk pregnancies. More than that, an abnormal DV-FVW is also associated with a high probability of an underlying major cardiac defect, and adverse pregnancy outcome. It was also proposed that a high association between absent fetal nasal bone at the 11 to 13 + 6 gestational wk scan and trisomy so that the addition of this marker could result in a major reduction in the need for invasive testing and a substantial increase in sensitivity. During this lecture, we will review the ultrasound technique for obtaining these different markers correctly according to the Fetal Medicine Foundation criteria. Additionally, we will discuss our experience in two private centers in Argentina during the last 4y.

Pregnancy‐associated plasma protein A, free human chorionic gonadotrophin and nuchal translucency as predictors of miscarriage

Pregnancy‐associated plasma protein A, free human chorionic gonadotrophin and nuchal translucency as predictors of miscarriage

Importance of the detection method for intact dimeric human chorionic gonadotropin without interference with the free human chorionic gonadotropin β subunit for pregnancy exclusion before liver transplantation in a woman with cholangiocarcinoma

Assay of human chorionic gonadotropin (hCG) is mainly used for the detection and monitoring of pregnancy, and for the follow-up of trophoblastic tumors. The serum free beta-hCG subunit (hCGbeta) is also a tumor marker in many non-trophoblastic tumors, including gastrointestinal cancers. In this work, we compared the performance of several immunoassays for pregnancy exclusion before liver transplantation and in the follow-up of a woman with cholangiocarcinoma. Serum hCG was detected with the Abbott Testpack plus hCG-Combo and measured with four automated sandwich immunoassays: ADVIA-Centaur, ACS:180, AxSYM and Dimension. hCGbeta was determined by an automated fluorescence sandwich immunoassay (Kryptor-Free beta hCG) and with a specific immunoradiometric assay (ELSA-F beta hCG, Schering). The expression of hCG was also evaluated by immunohistochemistry on sections of intrahepatic cholangiocarcinoma cells and on peritoneal metastases. Before transplantation, discordant results were observed for pregnancy exclusion. Qualitative Testpack and Dimension tests detected no hCG-like immunoreactivity, whereas the ADVIA-Centaur, ACS:180 and AxSYM tests revealed positive levels. The same discrepancy was obtained in follow-up of the patient after liver transplantation. hCGbeta assay and immunohistochemical staining revealed tumor cell secretion of hCGbeta. In conclusion, a specific serum immunoassay for intact dimeric hCG without cross-reaction with hCGbeta should be adopted as routine policy for pregnancy exclusion before liver transplantation.

First Trimester Maternal Serum Free Human Chorionic Gonadotropin as a Predictor of Adverse Pregnancy Outcome

Objective: The purpose of this study was to evaluate whether abnormal levels of first trimester maternal serum free human chorionic gonadotropin (β-hCG) are predictive of adverse pregnancy outcomes. Methods: The study included 1,622 consecutive patients with singleton pregnancies who underwent first trimester Down syndrome screening using nuchal translucency, and maternal serum free β-hCG and pregnancy-associated plasma protein-A. Patients with fetal anomalies or chromosome aberrations were excluded from the study. The incidences of various adverse pregnancy outcomes were evaluated according to maternal serum free β-hCG levels. Outcome variables included spontaneous miscarriage, proteinuric and non-proteinuric pregnancy-induced hypertension, fetal growth restriction, intrauterine fetal demise, spontaneous preterm delivery, oligohydramnios and placental abruption. Results: No significant differences were noted between groups for any of the demographic variables. The only statistically significant result was an increase in the relative risk for spontaneous miscarriage (RR = 6.33) at free β-hCG <0.2 multiples of the medians. No other statistically significant result was noted for the other adverse outcomes or for the overall complication rate. Conclusion: Low free β-hCG is associated with a higher incidence of spontaneous miscarriage but is a poor predictor of other pregnancy complications.