Free beta-hCG Levels Research Articles

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening

IntroductionExtreme levels of either PAPP-A or free β-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. MethodsA total number of 8591 patients with singleton pregnancies between 11 + 0–13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free β-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. ResultsValues of PAPP-A ≥ 2,0 MoM and free β-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free β-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free β-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free β-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free β-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DiscussionPregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free β-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free β-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

Association between blastocyst morphology and maternal first trimester serum markers in ongoing pregnancies obtained after single fresh blastocyst transfer

ObjectiveIs there an association between blastocyst morphology and maternal first trimester serum markers in In Vitro Fertilization (IVF) pregnancies obtained after fresh single blastocyst transfer? Study designThis bi-centric retrospective study was conducted between January 2012 and August 2018. We included 122 women aged from 18 to 43 years-old, whose pregnancy progressed at least beyond 13 weeks after a single blastocyst transfer and who participated in the first trimester combined screening test. Day 5 and day 6 blastocysts were evaluated according to Gardner and Schoolcraft classification. Patients were classified into three groups according to blastocysts morphological quality: excellent (≥ 3AA), good (3-6AB, 3-6BA, B2), and medium to poor (3-6BB, 3-6AC, 3-6CA, B1, 3-6CB, 3-6BC). First trimester serum markers were measured in maternal blood between 9 and 11 + 6 gestational weeks. Univariate and multivariate analyses were performed. ResultsFemale body mass index, smoking status, type of infertility, geographical origin, anti-mullerian hormone level, ovarian stimulation characteristics, pregnancy outcomes and obstetrical complications were comparable between the three groups. Patient’s age was not distributed evenly across groups, with women in group “Medium to Poor” appearing to be slightly younger than in other groups. There were no significant differences in mean first trimester serum markers between the three groups (PAPP-A: excellent: 1.23 ± 0.59 MoM; good: 1.45 ± 0.71 MoM; medium to poor: 1.22 ± 0.52 MoM; p = 0,20; free beta-HCG: excellent: 1.66 ± 1.38 MoM; good: 1.19 ± 0.76 MoM; medium to poor: 1.81 ± 1.34 MoM; p = 0,12). No significant difference was found either between mean first trimester serum markers and inner cell mass morphology (PAPP-A: grade A: 1.23 ± 0.58 MoM; grade B: 1.26 ± 0.60 MoM; medium to poor: 1.64 ± 0.87 MoM; p = 0,67 ; free beta-HCG: grade A: 1.66 ± 1.36 MoM; grade B: 1.52 ± 1.10 MoM; medium to poor: 1.57 ± 0.39 MoM p = 0,60), trophectoderm cells morphology (PAPP-A: grade A: 1.25 ± 0.63 MoM; grade B: 1.26 ± 0.51 MoM; medium to poor: not comparable; p = 0,66; free beta-HCG: grade A: 1.60 ± 1.34 MoM; grade B: 1.69 ± 1.14 MoM; medium to poor: not comparable; p = 0,25), or blastocoel expansion (PAPP-A: B1: 1.08 ± 0.51MoM; B2: 1.57 ± 0.70 MoM; B3: 1.26 ± 0.61 MoM; B4: 1.28 ± 0.62 MoM; B5: 1.04 ± 0.38 MoM; p = 0,22; free beta-HCG: B1: 2.01 ± 1.88 MoM; B2: 1.07 ± 0.49 MoM; B3: 1.43 ± 0.87 MoM; B4: 1.68 ± 1.28 MoM ; B5: 1.82 ± 2.03 MoM; p = 0,48).After adjustment on potential confounding factors (female age, type of gonadotropin, parity, number of oocytes retrieved and occurrence of ovarian hyperstimulation syndrome), we did not observe any association between PAPP-A or free beta-HCG levels and blastocyst morphology. ConclusionOur study concluded that first trimester serum markers were not associated with blastocyst morphological characteristics. Although this needs further confirmation, this suggests that blastocyst morphology would not have an impact on placentation. Therefore, these findings are reassuring for couples undergoing IVF and blastocyst transfer.

The effects of progesterone treatment on nuchal translucency in women with threatened miscarriage

This study aims to investigate the effects of progesterone on the possible changes in nuchal translucency (NT) levels for patients diagnosed with threatened miscarriage. The study group was composed of 125 patients diagnosed with threatened miscarriage and taking 400 mg/day micronized orally progesterone at least for two weeks, the control group was composed of 160 healthy pregnant women not taking any progesterone. Crown rump length (CRL) NT thickness, Pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (Beta-HCG) levels of patients were measured for assessment of aneuploidy risk. Both of the groups were divided into four subgroups to determine the relationship between thickness of NT and progesterone use for specific CRL measurements. CRL in the first, second, third and fourth group was 45–55 mm, 55–65 mm, 65–75 mm, 75–84 mm, respectively. The two groups were age and BMI matched. In all groups of CRL there were no significant difference in Mom levels of NT thickness, PAPP-A and free Beta-HCG between the study and control groups. There havent been any relation between NT thickness and progesterone use. IMPACT STATEMENT What is already known about this subject? Recently some studies have claimed that progesterone use might have caused atypical blood flow pattern on foetal circulation, which could possibly increase NT. If the NT thickness is affected by the use of progesterone, then the false positive rate of detecting Down Syndrome screening tests would increase. What the results of this study add? In this study we did not found any relation between NT thickness and progesterone use. What the implications are of these findings for clinical practice and/or further research? Using orally progesterone due to threatened miscarriage do not change NT thickness levels. Further studies have to be done with a large number of participants.

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.

Maternal serum alpha fetoprotein and free β-hCG of second trimester for screening of fetal gastroschisis and omphalocele

To assess the detection of maternal serum alpha fetoprotein (MSAFP) and free beta-HCG levels of second trimester for screening of fetal gastroschisis and omphalocele. Clinical data of 622 639 pregnant women from 5 prenatal screening centers in Hangzhou during October 2007 and September 2016 were analyzed retrospectively. Thirty cases of gastroschisis and 30 cases of omphalocele diagnosed by ultrasonography and postmortem findings were enrolled in the study and 116 cases of pregnant women with normal fetal development during the same period were selected as control group. The cut-off value and area under ROC curve (AUC) of MSAFP and free β-hCG for diagnosis of fetal gastroschisis and omphalocel were analyzed. MSAFP levels of women with fetal gastroschisis and omphalocele were 4.41 (0.88-11.69) MOM and 2.31 (0.72-23.20) MOM, which were significantly higher than that of control group[0.98 (0.41-2.26) MOM, all P<0.01]. Free β-hCG level of women with fetal gastroschisis was 1.25 (0.35-19.94) MOM, which was significantly higher than that of control group[0.86 (0.17-6.11) MOM, P<0.05). But there were no significant difference in free β-hCG between fetal omphalocele group[1.03(0.21-8.95)]and control group (P>0.05). The AUCs of MSAFP for diagnosis of gastroschisis and omphalocele were 0.897 (95% CI:0.822-0.972) and 0.852(95% CI:0.762-0.942), respectively (all P<0.01). Taking 1.655 MOM as the cut-off value of MSAFP for abdominal wall defects (gastroschisis and omphalocele), the sensitivity was 68.30%, specificity was 99.60% and Youden index was 0.649. MSAFP of second trimester is a better biomarker than free β-hCG in screening abdominal wall defects.

Maternal first trimester serum levels of free-beta human chorionic gonadotrophin and male genital anomalies.

Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy. Human chorionic gonadotrophin peaks in first trimester of pregnancy stimulating fetal testosterone production, which is key to normal male genital development. Endocrine-disrupting insults early in pregnancy have been associated with increased risk of common genital anomalies in males such as hypospadias and UDT. One plausible etiological pathway is altered release of hCG. We conducted a record-linkage study of two separate populations of women attending first trimester aneuploidy screening in two Australian states, New South Wales (NSW) and Western Australia (WA), in 2006-2009 and 2001-2003, respectively. Included were women who gave birth to a singleton live born male infant. There were 12 099 boys from NSW and 10 518 from WA included, of whom 90 and 77 had hypospadias; and 107 and 109 UDT, respectively. Serum levels of free-beta hCG were ascertained from laboratory databases and combined with relevant birth outcomes and congenital anomalies via record linkage of laboratory, birth, congenital anomalies and hospital data. Median and quartile levels of gestational age specific free-beta hCG multiple of the median (MoM) were compared between affected and unaffected boys. Logistic regression was used to evaluate the association between levels of free-beta hCG MoM and hypospadias or UDT, stratified by suspected placental dysfunction and co-existing anomalies. Where relevant, pooled analysis was conducted. There was no difference in median hCG levels amongst women with an infant with hypospadias (NSW = 0.88 MoM, P = 0.83; WA = 0.84 MoM, P = 0.76) or UDT (NSW = 0.89 MoM, P = 0.54; WA = 0.95 MoM, P = 0.95), compared with women with an unaffected boy (NSW = 0.92 MoM; WA = 0.88 MoM). Low (<25th centile) or high (>75th centile) hCG levels were not associated with hypospadias or UDT, nor when stratifying by suspected placental dysfunction and co-existing anomalies. However, there was a tendency towards high levels for severe types, although confidence intervals were wide. When combining NSW and WA results, high hCG MoM levels (>75th centile) were associated with increased risk of proximal hypospadias (odds ratio (OR) 4.34; 95% CI: 1.08-17.4) and bilateral UDT (OR 2.86; 95% CI: 1.02-8.03). There were only small numbers of proximal hypospadias and bilateral UDT in both cohorts and although we conducted pooled analyses, results reported on these should be interpreted with caution. Gestational age by ultrasound may have been inaccurately estimated in small and large for gestational age fetuses affecting hCG MoM calculation in those pregnancies. Despite the reliability of our datasets in identifying adverse pregnancy outcomes, we did not have pathology information to confirm tissue lesions in the placenta and therefore our composite outcome should be considered as a proxy for placental dysfunction. This is one of the largest population-based studies examining the association between maternal first trimester serum levels of free-beta hCG and genital anomalies-hypospadias and UDT; and the first to compare specific phenotypes by severity. Overall, our findings does not support the hypothesis that alteration in maternal hCG levels is associated with the development of male genital anomalies; however, high hCG free-beta levels found in severe types suggest different underlying etiology involving higher production and secretion of hCG. These findings require further exploration and replication. This work was funded by the National Health and Medical Research Council (NHMRC) grant APP1047263. N.N. is supported by a NHMRC Career Development Fellowship APP1067066. C.B. was supported by a NHMRC Principal Research Fellowship #634341. The funding agencies had no role in the design, analysis, interpretation or reporting of the findings. There are no competing interests. Not applicable.

Frontomaxillary Facial Angle Measurement in Screening for Trisomy 18 at 11 + 0 to 13 + 6 Weeks of Pregnancy: A Double-Centre Study

Objective. The aim of this study was to evaluate the effectiveness of prenatal screening for trisomy 18 with the use of the frontomaxillary facial angle (FMF angle) measurement. Material and Methods. The study involved 1751 singleton pregnancies at 11–13 + 6 weeks, examined between 2007 and 2011. Serum PAPP-A and free beta-hCG levels were assessed, and crown-rump length, nuchal translucency, and FMF angle were measured in all patients. 1350 fetuses with known follow-up were included in the final analysis. Results. Highly significant (P < 0.01) negative correlation between the CRL and the FMF angle was found. There were 30 fetuses with trisomy 18. FMF angle was highly significantly larger (P < 0.0001) in fetuses with trisomy 18 as compared to chromosomally normal fetuses. Two models of first trimester screening were compared: Model 1 based on maternal age, NT, and first trimester biochemistry test (DR 80–85% and FPR 0.3–0.6%), and Model 2 = Model 1 + FMF angle measurement (DR 87.3–93.3% and FPR 0.8–1.3%). Conclusions. The use of FMF angle measurement increases the effectiveness of the screening for trisomy 18. Introduction of the FMF angle as an independent marker for fetal trisomy 18 risk requires further prospective research in large populations.

First trimester maternal serum PAPP-A levels and macrosomia in nondiabetic mothers

To determine whether or not there is a relationship between first-trimester maternal serum pregnancy-associated placental protein (PAPP-A) levels and fetal macrosomia in nondiabetic mothers. Materials and methods: In this study, 63 consecutive term macrosomic neonates (Group 1) (birth weight >= 4000 g) and 100 consecutive appropriate-for-gestational-age (AGA) term neonates (Group 2) were included. Transabdominal ultrasound examinations were performed to diagnose any major fetal defects and to measure crown-rump length (CRL) and fetal nuchal translucency (NT) thickness. Blood samples were drawn from each woman in order to obtain fasting blood glucose, PAPP-A, and free beta-human chorionic gonadotropin (beta-hCG) levels. Ultrasound measurements of the fetal biparietal diameter, abdominal circumference, and femur length were obtained at 29-34 weeks of gestation. Results: The two groups were similar with respect to maternal age, parity, and gestational age in the first trimester. There were no significant differences between the groups in terms of the mean plasma levels of PAPP-A, free beta-HCG (as MoM values), mean CRL, and NT measurements. First-trimester PAPP-A levels were not correlated with birth weight (r = -0.116, P = 0.146), maternal age (r = 0.137, P = 0.089), maternal body mass index (BMI) in the first trimester (r = -0.037, P = 0.641) or at delivery (r = 0.042, P = 0.620), fasting blood glucose in the first trimester (r = -0.019, P = 0.816), macrosomia (r = -0.092, P = 0.249), or the occurrence of male sex (r = -0.074, P = 0.358) by the Pearson and Spearman correlations. In addition, first-trimester PAPP-A levels were not correlated with ultrasonographic measurements at 29-34 weeks of gestation. Conclusion: Although PAPP-A may promote fetal growth and development through metabolic and differentiation pathways, it seems that there is no relationship between PAPP-A levels and macrosomia.

PAPP‐A and free ß‐hCG stability in first trimester serum using PerkinElmer AutoDELFIA® and DELFIA® Xpress systems

In this study we aim to investigate the stability of free-beta-hCG and PAPP-A over time in serum and whole blood in typical routine temperatures. Serum pools were stored under the following temperatures: 30 degrees C, room temperature, refrigerator temperature and -20 degrees C, for up to 240 days. Stability of the markers in whole blood was examined in a shorter study and compared to serum. Samples were analysed using the AutoDELFIA and DELFIA Xpress analysers. On the AutoDELFIA, considering a 10% change acceptable, PAPP-A levels are stable in serum for 142 days at refrigerator temperature, 37 days at room temperature and 20 days at 30 degrees C. Free-beta hCG is stable in serum for 94 days at refrigerator temperature, 3 days at room temperature and 12 h at 30 degrees C. There was no significant change with either analyte after -20 degrees C storage for up to 240 days or after six repeated freeze-thaw cycles. In whole blood, free-beta hCG levels increased more rapidly compared to serum, especially at 30 degrees C. Normal handling of samples is only likely to minimally effect the risk assessment of chromosomal anomalies. However, careful attention should be paid to minimise the increase of free-beta hCG levels in samples shipped as whole blood.

P11.16: Median levels of free beta-hCG and PAPP-A in the first trimester screening for Down syndrome in a Brazilian population from a private center in Rio de Janeiro

To assess whether there is a need to correct first-trimester biochemical markers (free beta-hCG and PAPP-A) in a Brazilian population from a private center in Rio de Janeiro (Perinatal Group—Laranjeiras) while screening for Down syndrome using the Fetal Medicine Foundation (FMF) algorithm. The data from 546 women undergoing first trimester combined screening for fetal Down syndrome were analyzed to derive our center population-specific medians. The observed medians were compared to those based on the original algorithm of the Fetal Medicine Foundation (FMF) in Caucasians. The median maternal serum levels of free beta-hCG and PAPP-A were similar between the target population and average Caucasians. There was no need to correct the original FMF algorithm for the Brazilian population analyzed in this study. There is no need to adjust the biochemical markers in the Brazilian population from our center in Rio de Janeiro in a first trimester screening program.

Is maternal renal disease a cause of elevated free β‐hCG in first trimester aneuploidy screening?

To asses whether supra elevated levels of maternal serum free beta hCG in the first trimester are associated with impaired renal function. A cohort of 553 women with maternal serum free beta-hCG greater than 5 multiple of median (MoM) with a single euploid fetus was matched with a control of the same maternal age (+/-1 year), ethnic origin and with a free beta-hCG within the range 0.50-1.50 MoM. Screening samples were analysed for serum creatinine and estimated glomerular filtration rate was calculated. Renal function in the two groups was compared. The database was examined to find outcomes registered as known renal disease amongst the high free beta-hCG group. In the group with a supra elevated free beta-hCG MoM there was a significant reduction in estimated glomerular filtration rate (eGFR) (122.85, 95% CI 120.43-124.74 vs 118.80, 95% CI 114.90-121.59; p = 0.009) suggesting a small but increased risk of renal disease. The presence of renal disease should also be considered as one potential cause of supra elevated levels of free beta-hCG in addition to the possibility of paternally derived triploidy and trisomy 21.

Record linkage to obtain birth outcomes for the evaluation of screening biomarkers in pregnancy: a feasibility study

BackgroundLinking population health data to pathology data is a new approach for the evaluation of predictive tests that is potentially more efficient, feasible and efficacious than current methods. Studies evaluating the use of first trimester maternal serum levels as predictors of complications in pregnancy have mostly relied on resource intensive methods such as prospective data collection or retrospective chart review. The aim of this pilot study is to demonstrate that record-linkage between a pathology database and routinely collected population health data sets provides follow-up on patient outcomes that is as effective as more traditional and resource-intensive methods. As a specific example, we evaluate maternal serum levels of PAPP-A and free β-hCG as predictors of adverse pregnancy outcomes, and compare our results with those of prospective studies.MethodsMaternal serum levels of PAPP-A and free β-hCG for 1882 women randomly selected from a pathology database in New South Wales (NSW) were linked to routinely collected birth and hospital databases. Crude relative risks were calculated to investigate the association between low levels (multiples of the median ≤ 5th percentile) of PAPP-A or free β-hCG and the outcomes of preterm delivery (<37 weeks), small for gestational age (<10th percentile), fetal loss and stillbirth.ResultsUsing only full name, sex and date of birth for record linkage, pregnancy outcomes were available for 1681 (89.3%) of women included in the study. Low levels of PAPP-A had a stronger association with adverse pregnancy outcomes than a low level of free β-hCG which is consistent with results in published studies. The relative risk of having a preterm birth with a low maternal serum PAPP-A level was 3.44 (95% CI 1.96–6.10) and a low free β-hCG level was 1.31 (95% CI 0.55–6.16).ConclusionThis study provides data to support the use of record linkage for outcome ascertainment in studies evaluating predictive tests. Linkage proportions are likely to increase if more personal identifiers are available. This method of follow-up is a cost-efficient technique and can now be applied to a larger cohort of women.

P39.05: A study to determine the veracity of the ultrasonographic measurements of the thymus during fetal development

myxo-fibroblastic proliferation. There was focal chorangiosis with intervening normal placental mesenchyme. The fetal chorionic plate vessels were massively dilated, tortuous and congested. There was a 3-vessel umbilical cord with furcated marginal cord insertion. Immunohistochemical studies of the abnormal myxoid villi showed minimal staining for smooth muscle actin and positive p57KIP2 protein staining. This is only the third case of PMD with normal fetus where the p57KIP2 protein staining was used in the diagnosis. The p57KIP2 gene is paternally imprinted and maternally expressed. The presence of this protein indicates a functional maternal allele. This case supports the utility of p57KIP2 protein staining in distinguishing this disorder from molar pregnancy. In our case elevated free beta-hCG level was detected in the first trimester before placental abnormalities were visualized on ultrasound.

Second‐trimester maternal serum free‐β‐human chorionic gonadotropin and α‐fetoprotein levels in normal twin and singleton pregnancies: a report of local Chinese population

The study evaluated the differences between Chinese normal twin and singleton pregnancies in the levels of maternal serum free-beta-human chorionic gonadotropin (free beta-hCG) and alpha-fetoprotein (AFP) used in second-trimester Down syndrome (DS) screening. The concentrations of maternal serum markers of 456 twin pregnancies and 12 067 singleton controls in gestational 15 to 20 weeks were measured by time-resolved fluoroimmunoassay, and the levels of markers were compared between the twins and singletons. Significant differences were found between the levels of free beta-hCG in twins and twice of those in singletons in 16, 17 and 19 gestational weeks (p < 0.05 for all); while considering AFP, significant differences were found in 16 and 19 gestational weeks (p < 0.05 for both). No correlations were found in twins between the levels of markers and maternal weights in most gestational weeks (Free beta-hCG: p > 0.05 for 15 to 18 and 20 gestational weeks; AFP: p > 0.05 for 16 to 20 gestational weeks). The Chinese gestational age-specific levels of maternal serum markers in normal twins are not twice as those in singletons. The current weight-correction model for DS screening may be not feasible for twins.

OP25.05: First trimester combined screening for trisomy 21 in a predominantly Chinese population

To examine the effectiveness of first-trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency (NT), maternal serum free beta-hCG and PAPP-A levels in a predominantly Chinese population in Hong Kong. A prospective study performed in a university fetal medicine unit over a three and a half-year period. Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation were recruited. NT was measured according to the criteria set by the Fetal Medicine Foundation (FMF). Maternal serum biochemistry was measured by Kryptor analyzer. Risk of T21 was calculated using FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above for T21, or 1 : 150 for T13/18. All subjects were followed up for pregnancy and fetal outcome. Among the 9333 women who underwent the screening program, 99% were Chinese and 173 women had a twin pregnancy, with a total of 9506 fetuses. 27.1% of the women were at or above 35 years old. 558 fetuses were screened positive (5.98%) for T21 (with or without increased risk for T13/18). Another 18 cases were positive for T13/18 only, making a total of 576 (6.17%). There were a total of 26 cases of T21, of which two were screened negative (detection rate of 92.3%). There were five cases of T13, 12 cases of T18, 10 cases of monosomy X, and six cases of other chromosomal abnormalities; all were screened positive. The overall positive predictive value for chromosomal abnormality was 1 in 9.9. First-trimester combined screening for fetal T21 is highly effective among Chinese subjects.

The effect of cigarette or sheesha smoking on first‐trimester markers of Down syndrome

To investigate the influence of cigarette or sheesha smoking on first-trimester markers of Down syndrome. A prospective observational study. Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia. Women with a singleton pregnancy who were either nonsmokers (n = 1736) or cigarette smokers (n = 420) or sheesha smokers (n = 181). Fetal nuchal translucency thickness (fetal NT), maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared. Fetal NT, maternal serum free beta-hCG, PAPP-A and cotinine measurements. Compared with nonsmoking women, fetal NT was significantly increased and free beta-hCG and PAPP-A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day. Cigarette and sheesha smoking significantly affect first-trimester markers of Down syndrome (fetal NT, free beta-hCG and PAPP-A). Correction for this effect in women who smoke might improve the effectiveness of first-trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first-trimester markers require further studies.

First‐trimester combined screening for trisomy 21 in a predominantly Chinese population

To examine the effectiveness of first-trimester fetal trisomy 21 screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese population in Hong Kong. This was a prospective study over a 1.5-year period of 2990 women who underwent combined screening for trisomy 21 between 11+0 and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured according to the criteria set by The Fetal Medicine Foundation (FMF), maternal serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21 was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal outcome. Of the 2990 women who underwent the screening program, 99% were Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty-one percent of the women were 35 years old or above. One hundred and eighty-five (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17 cases of other chromosomal abnormalities. The positive predictive value was 16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an unknown fetal outcome. There were no cases in which trisomy 21 was missed and the infant was liveborn. First-trimester combined screening for fetal trisomy 21 is highly effective among Chinese subjects.

Previous aneuploidy does not significantly alter 1st trimester free beta hcg and papp-a in subsequent normal pregnancies

ObjectiveTo investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation.Study designWeight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes.ResultsThe table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant.ConclusionTabled 1Free Beta MoMPAPP-A MoMPrevious AneuploidyNGeom Mean (SD)Geom Mean (SD)None33,2260.99 (0.4972)1.00 (0.5675)Trisomy 211,7831.02 (0.5110)1.03 (0.5771)Trisomy 187961.02 (0.5100)1.05 (0.5694)Trisomy 131601.10 (0.5090)1.08 (0.6185)45, X1121.03 (0.4557)1.10 (0.5356) Open table in a new tab ObjectiveTo investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation. To investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation. Study designWeight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes. Weight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes. ResultsThe table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant. The table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant. ConclusionTabled 1Free Beta MoMPAPP-A MoMPrevious AneuploidyNGeom Mean (SD)Geom Mean (SD)None33,2260.99 (0.4972)1.00 (0.5675)Trisomy 211,7831.02 (0.5110)1.03 (0.5771)Trisomy 187961.02 (0.5100)1.05 (0.5694)Trisomy 131601.10 (0.5090)1.08 (0.6185)45, X1121.03 (0.4557)1.10 (0.5356) Open table in a new tab

Comparison of Serum Markers in First-Trimester Down Syndrome Screening

To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. II-2.

Correlation between first-trimester uterine artery Doppler indices and maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A

To assess the correlation between first-trimester uterine artery Doppler measurements and maternal serum levels of free beta-hCG and pregnancy-associated plasma protein A (PAPP-A). Observational study. Teaching hospital. Four hundred thirty-three women at 10-14 weeks of gestation. Doppler ultrasound of the uterine arteries. Fluorimetric immunoassays for free beta-hCG and PAPP-A. Uterine artery mean resistance index (RI), pulsatility index (PI), and number of early diastolic notches. Maternal serum levels of free beta-hCG and PAPP-A. There were 401 uncomplicated pregnancies. In this group, free beta-hCG and PAPP-A did not significantly correlate with uterine artery RI or PI (r values between -0.089 and 0.029, all nonsignificant). Free beta-hCG and PAPP-A levels did not significantly change with the number of notches. Uterine artery resistance and PAPP-A levels were independently correlated with birth weight. Preliminary evidence suggests that first-trimester uterine artery Doppler measurements do not correlate with maternal serum levels of free beta-hCG and PAPP-A. This may allow their combined use in multivariate screening for pregnancy complications.