Free β-hCG Research Articles

Macrophage colony-stimulating factor (M-CSF) in first trimester maternal serum: correlation with pathologic pregnancy outcome.

To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies. This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free β-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling. 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270±91 pg/ml (p=0.032), whereas cases of trisomy 13 (183±68 pg/ml) and trisomy 18 (143±40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free β-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M-CSF. M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research.

MATERNAL SERUM PAPP-A LEVELS AT 11+0 TO 13+6 WEEKS OF GESTATION IN THE PREDICTION OF HYPERTENSION DISORDER

Objective: To detect maternal serum PAPP-A levels at 11-13 weeks 6 day of gestation in pregnancies who subsequently develop pre-eclampsia and to evaluating the role of these screening PAPP-A in the prediction of pre-eclampsia. Materials and methods: Prospective screening study for preeclampsia in pregnant attending their first hospital visit at 11-13 weeks 6 of gestation. The performance of screening for PE by serum PAPP-A and free βhCG were determined. Results: Of 2,998 patients with complete outcome data, there were 3.74% of hypertension disorder, and 2.84% cases of pre-eclampsia. free βhCG levels were no different significantly in pregnancy who developed pre-eclampsia compared to the control group. PAPP-A levels were significantly lower in pregnants who developed early pre-eclampsia (0.653 MoM) and late pre-eclampsia (0.744 MoM) compared to the control group (1.039 MoM).In screening for PE by combinematernal factors and PAPP-A,at false positive rate of 5%, the estimateddetection rates were 36.4% and the detection rates were 54.6%, at at false positive rate of 10%. Conclusion: Low PAPP-A levels are associated with the development of preeclampsia; however, it should be combined with other tests to increase effectiveness of hypertension disorder screening at the first trimester. Key words: preeclampsia; gestational hypertension; screening; PAPP-A.

Maternal hCG concentrations in early IVF pregnancies: associations with number of cells in the Day 2 embryo and oocytes retrieved.

Do number of cells in the transferred cleavage stage embryo and number of oocytes retrieved for IVF influence maternal hCG concentrations in early pregnancies? Compared with transfer of a 2-cell embryo, transfer of a 4-cell embryo results in higher hCG concentrations on Day 12 after transfer, and more than 20 oocytes retrieved were associated with low hCG concentrations. Maternal hCG concentration in very early pregnancy varies considerably among women, but is likely to be an indicator of time since implantation of the embryo into the endometrium, in addition to number and function of trophoblast cells. We followed 1047 pregnancies after IVF/ICSI from oocyte retrieval until Day 12 after embryo transfer. Women were recruited in Norway during the years 2005-2013. Successful pregnancies after transfer of one single embryo that had been cultured for 2 days were included. Maternal hCG was quantified on Day 12 after embryo transfer by chemiluminescence immunoassay, which measures intact hCG and the free β-hCG chain. Information on a successful pregnancy, defined as birth after >16 weeks, was obtained by linkage to the Medical Birth Registry of Norway. Transfer of a 4-cell embryo resulted in higher maternal hCG concentrations compared with transfer of a 2-cell embryo (134.8 versus 87.8 IU/l, P < 0.05). A high number of oocytes retrieved (>20) was associated with low hCG concentrations (P < 0.05). The factors studied explain a limited part of the total variation of hCG concentrations in early pregnancy. Although embryo transfer was performed at the same time after fertilization, we do not know the exact time of implantation. A further limitation to our study is that the number of pregnancies after transfer of a 2-cell embryo was small (27 cases). Number of cells in the transferred embryo and number of oocytes retrieved may influence the conditions and timing for embryo implantation in different ways and thereby influence maternal hCG concentrations. Such knowledge may be important for interpretation of hCG concentrations in early pregnancy.

Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

Predictive Value of Free β-hCG Multiple of the Median for Women with Preeclampsia

Background: Preeclampsia (PE) is relatively common and is unpredictable in its onset and progression. Aims: We investigated the clinical value of using the multiple of the median (MoM) of free β-human chorionic gonadotropin (β-hCG) concentrations in women with normal pregnancy and PE. Methods: This study was based on a dataset available from published studies, and the relevant studies were retrieved from multiple electronic databases. Data were extracted from case-control studies; a random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twelve case-control studies (eleven English-based articles and one Chinese-based article) were analyzed in the current meta-analysis and included 702 patients with PE and 8,233 women with normal pregnancies. Results: Statistical analysis revealed a higher MoM of β-hCG serum levels in patients with PE. Ethnicity subgroup analysis showed that the MoM of serum β-hCG levels was significantly higher in women with PE in both Asian and Caucasian populations. Conclusion: The MoM of β-hCG serum levels was significantly increased in women with PE compared to women with normal pregnancies. Screening for serum β-hCG MoM levels will be helpful in the early identification of pregnancies at risk of developing PE.

Prediction of small‐for‐gestational‐age neonates: screening by maternal biochemical markers at 30–34 weeks

To investigate the potential value of serum placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG) and α-fetoprotein (AFP) at 30-34 weeks' gestation in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE). This was a screening study in singleton pregnancies at 30-34 weeks' gestation, including 490 that delivered SGA neonates and 9360 cases that were unaffected by SGA, PE or gestational hypertension (normal outcome). Multivariable logistic regression analysis was used to determine if screening by serum PlGF, sFlt-1, PAPP-A, free β-hCG and AFP, individually or in combination, improved the prediction of SGA neonates provided by screening with maternal characteristics and medical history (maternal factors), and estimated fetal weight (EFW) from fetal head circumference, abdominal circumference and femur length. Compared to the normal group, the mean log10 multiples of the median (MoM) values of PlGF and AFP were significantly lower and the mean log10 MoM values of sFlt-1 and free β-hCG were significantly higher in the SGA group with a birth weight < 5(th) percentile (SGA < 5(th)) delivering < 5 weeks following assessment. The best model for prediction of SGA was provided by a combination of maternal factors, EFW and serum PlGF. Such combined screening, predicted, at a 10% false-positive rate, 85%, 93% and 92% of SGA neonates delivering < 5 weeks following assessment with birth weight < 10(th), < 5(th) and < 3(rd) percentiles, respectively; the respective detection rates of combined screening for SGA neonates delivering ≥ 5 weeks following assessment were 57%, 64% and 71%. Combined screening by maternal factors, EFW and serum PlGF at 30-34 weeks' gestation can identify a high proportion of pregnancies that subsequently deliver SGA neonates.

Does diurnal variation affect the first trimester fetal aneuploidy screening test biochemical parameters of fetuses with normal nuchal translucency?

Objective: The purpose of this study was to investigate the effect of diurnal variation on biochemical results of first trimester aneuploidy screening test.Methods: A total of 2725 singleton pregnant female, who had normal fetal nuchal translucency (NT) thickness, were included in the study during this period. Individuals were divided into two groups according to the sampling time (morning group: 09:00–11:00 am and afternoon group: 02:00–04:00 pm). Hormonal parameters (free-beta human chorionic gonadotropin [free β-hCG] and pregnancy-associated plasma protein-A [PAPP-A] multiples of median [MoM] levels) of first trimester (11+0–13+6 weeks) combined aneuploidy screening test were compared between morning and afternoon groups.Results: PAPP-A MoM levels were significantly lower in the afternoon group when compared to the morning group (p = 0.001), whereas free β-hCG MoM levels were similar in the both groups (p = 0.392). Rate of high risk for Down syndrome (Combine risk >1/300) and amniocentesis ratio were found higher in the afternoon group than morning group, but there were no difference between groups for the number of fetuses with Down syndrome.Conclusion: Receiving the venous blood sample for first trimester aneuploidy screening test in the afternoon causes low PAPP-A MoM levels.

Fetal growth impairment after first-trimester chorionic villus sampling: a case–control study

Objective: The objective of this study is to test if chorionic villus sampling (CVS) is associated with fetal growth impairment, after controlling for maternal and fetal factors.Study design: Case–control study of singleton fetuses whose mothers had undergone CVS (N = 442) and 2969 controls. The primary outcomes were the prevalence of birthweight < 10th centile and birthweight <3rd centile; the prevalence of preeclampsia was the secondary outcome. Tested predictors in logistic regression analysis included CVS, free beta-hCG MoMs, PAPP-A MoMs, first-trimester mean uterine artery pulsatility index (PI) z-scores, maternal height, BMI, age, and smoking.Results: The proportion of newborns with birthweight <10th centile (7.9 versus 6.2%), and <3rd centile (1.6 versus 1.1%) did not differ between the two groups. Maternal age, smoking during pregnancy, PAPP-A MoMs, and mean first-trimester uterine PI z-score were significant predictors for these outcomes. Although the prevalence of preeclampsia was higher in the CVS group (3.2 versus 1.3%, OR 2.62, 95% CI 1.41–4.89), the association was abolished in the regression analysis, in which maternal body mass index, free b-hCG levels, and mean first-trimester uterine PI z-score were the only significant predictors.Conclusions: CVS is not associated with fetal growth impairment, possibly because the resulting mechanical disruption is compensated by the developing placenta, without significantly impairing its function.

Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis.

The meta-analysis was to determine the diagnostic value of the combining tests for Down syndrome and to evaluate their utilities in the Down syndrome screening. Through comprehensive literature search, 24 studies met the inclusion criteria and were included in the databases (PubMed, Wed of knowledge, Chinese National Knowledge Infrastructure (CNKI)). Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of the combination of NT and free β-hCG and PAPP-A for Down syndrome were 0.86(95%CI 0.75-0.92) and 0.96(95%CI 0.95-0.97), respectively. The summary positive likelihood ratio and negative likelihood ratio were 23.3 (95%CI 16.7-32.5) and 0.15(95%CI 0.08-0.26), respectively. The pooled diagnostic odds ratio was 156 (95%CI 75-326). The meta-analysis shows the accumulative evidence for the clinician that the performance of the combined test of MA and NB and NT and PAPP-A and free β-hCG is the most effective test in the four different combined tests, while, the combination of NT and PAPP-A and free β-hCG is a cost-effective screening tool for Down syndrome.

First trimester placental markers in oocyte donation pregnancies

IntroductionThis study investigates the hypothesis that placenta works differently in oocyte donation (OD) compared to spontaneous pregnancies. To verify this hypothesis we examine the first trimester maternal serum levels of free β-hCG and pregnancy-associated plasma protein-A (PAPP-A). Then we evaluated for potential differences of Down syndrome screening between OD pregnancies, in vitro fertilization/intracytoplasmic sperm injection pregnancies with autologous oocytes (IVF/ICSI) and spontaneous pregnancies. MethodsWe analyze 13624 spontaneously conceived pregnancies (Controls), 171 oocyte donation pregnancies (OD IVF/ICSI) and 76 IVF pregnancies with autologous oocytes (Autologous IVF/ICSI). Furthermore, we collect a cohort of 802 spontaneously conceived age-matched pregnancies, in order to evaluate how older uteri contribute to explain the changes in markers concentrations (Age-matched controls We compare the multiples of the median (MoM) of free β-hCG and PAPP-A and nuchal translucency. ResultsFree β-hCG levels are significantly higher both in OD IVF/ICSI pregnancies (1.44 ± 1.06 MoM) and Autologous IVF/ICSI (1.48 ± 1.02 MoM) compared to Controls (1.15 ± 0.84 MoM; p < 0.05) and Age-matched Controls (1.18 ± 0.98 MoM; p < 0.05). PAPP-A levels do not significantly differ among the four groups. Significantly lower nuchal translucency is detected in Controls (1.41 ± 0.36 mm) compared to OD IVF/ICSI (1.46 ± 0.44 mm; p < 0.05), in Autologous IVF/ICSI (1.51 ± 0.34 mm; p < 0.05) and Age-matched Controls (1.44 ± 0.42 mm; p < 0.05). DiscussionOocyte donation pregnancies (OD IVF/ICSI) are significantly related to altered maternal serum placenta marker levels. These alterations might be due to the IVF technique.

Serum free β-human chorionic gonadotropin in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum free β-human chorionic gonadotropin (β-hCG) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum free β-hCG was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of free β-hCG were determined from a linear mixed-effects multiple regression. Serum free β-hCG was measured in 94 985 cases in the first trimester, 7879 in the second trimester and 8424 in the third trimester. Significant independent contributions to serum free β-hCG were provided by gestational age, maternal weight, age and racial origin, cigarette smoking, method of conception, diabetes mellitus and family history of pre-eclampsia (PE) in the mother of the patient. The effects of some variables were similar and those for others differed in each trimester. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum free β-hCG and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication. A model was fitted to express measured serum free β-hCG across the three trimesters of pregnancy as MoMs after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Relation of conspicuous biochemical results in first trimester screening and pregnancy complications

Background: Early detection of high risk pregnancies is an important matter in modern obstetrics in order to avoid severe pregnancy complications. Aim of the posed study is to analyze the relevance of conspicuous biochemical results in first trimester screening concerning the pregnancy outcome. We assume that differed levels of biomarkers PAPP-A, free βHCG and PlGF can provide information about the risk of developing hypertensive complications (gestational hypertension, preeclampsia, eclampsia, HELLP-syndrome), intrauterine growth restriction, intrauterine fetal death, abruption of the placenta, gestational diabetes or preterm delivery. Routinely, these biomarkers are determined during first trimester screening. They mark disorders in trophoblastic/placental growth and development. Methods: We evaluated data of patients who delivered between the years 2010 and 2012 at the delivery department of the Medical University of Graz, Austria. We defined two patient-groups. The first consisting of patients with conspicuous biochemical results during first trimester screening and the second with normal biochemical results. The course and outcome of pregnancy was observed and pregnancy complications were noted. Results: 18,1% of pregnant women showed conspicuous biochemical results in first trimester screening. 23,5% of these women developed severe complications during pregnancy. 84,3% had normal biochemical markers and 15,7% of them developed severe pregnancy complications. Conclusion: A conspicuous biochemical result in first trimester screening implies higher risks of developing hypertensive complications during pregnancy, but also further severe complications like abruption of placenta, gestational diabetes or preterm delivery.

Comparing outcomes and costs between contingent and combined first-trimester screening strategies for Down's syndrome

ObjectiveTo compare a contingent strategy with a combined strategy for prenatal detection of Down's syndrome (DS) in terms of cost, outcomes and safety. Study designThe contingent strategy was based on a simulation, removing measurement of the free beta subunit of human chorionic gonadotropin (free βhCG) and calculating the DS risk retrospectively in 32,371 pregnant women who had been screened with the combined strategy in the first trimester. In the contingent strategy, a risk between 1:31 and 1:1000 in the first trimester indicated further testing in the second trimester (alpha-fetoprotein, inhibin A, unconjugated oestriol and free βhCG). The cut-off risk values for the contingent and combined strategies in the first trimester were 1:30 and 1:250, respectively, and the cut-off risk value for integrated screening in the second trimester was 1:250. Costs were compared in terms of avoided DS births, and the ratio of loss of healthy fetuses following invasive procedures per avoided DS birth was calculated. ResultsThe combined strategy had sensitivity of 40/44 (90.9%) and a false-positive rate of 2.8%. Corresponding values for the contingent strategy were 39/44 (88.6%) and 1.3%, respectively. Only 11% of pregnant women required tests in the second trimester, and the approximate cost reduction for each avoided DS birth was 5000€. The ratio of lost healthy fetuses following invasive procedures per avoided DS birth improved by up to 0.65. ConclusionThe contingent strategy has similar effectiveness to the combined strategy, but has lower costs and fewer invasive procedures.

First trimester maternal serum biochemical markers of aneuploidy in pregnancies with abnormally invasive placentation

To examine whether differences exist in routine first trimester maternal serum screening analyte measurements between normal pregnancies, placenta praevia and abnormally invasive placentation (AIP). Multidisciplinary audit. Associated university teaching hospital with 9000 annual deliveries. Five hundred and sixteen pregnancies in total, including 344 normal controls, 17 with AIP and 155 placenta praevia cases. Comparison of maternal serum free βhCG and PAPP-A MoMs distribution in pregnancies with abnormally invasive placentation, placenta praevia and normal controls, after correcting for known confounding factors between October 2005 and September 2013. Data from a previously published first trimester AIP and biochemistry study were combined with our study data and compared in the above way to complete the analysis. Differences in first trimester maternal serum PAPP-A and free βhCG in AIP, placenta praevia, and normal pregnancies. Median free βhCG MoM in the control group was 1.04, and 1.08 (P = 0.859) in the placenta praevia group compared with 0.81 in the AIP group (P = 0.06). Median PAPP-A MoM was 1.01 in the control group and 1.05 (P = 0.83) in praevia, compared with 1.22 in AIP cases (0.16). The combined AIP dataset gave an overall PAPP-A median MoM of 1.40, and free βhCG of 0.85. Both markers showed a significantly different distribution from controls (PAPP-A P = 0.002 and free βhCG P = 0.031). There may be differences between first trimester maternal serum biochemical markers between normal pregnancies and those complicated by abnormally invasive placentation. If upheld, this may provide useful information for the early identification of abnormally invasive placentation. More studies are required.

Prediction of Preeclampsia by First Trimester Combined Test and Simple Complete Blood Count Parameters.

Preeclampsia is a serious disease which may result in maternal and neonatal mortality and morbidity. Improving the outcome for preeclampsia necessitates early prediction of the disease to identify women at high risk. Measuring blood cell subtype ratios, such as the neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios, might provide prognostic and diagnostic clues to diseases. To investigate hematological changes in early pregnancy, using simple complete blood count (CBC) and blood concentrations of beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) to determine whether these measures are of any value in the prediction and early diagnosis of preeclampsia. Six hundred fourteen consecutive pregnant women with preeclampsia (288 with mild disease and 326 with severe disease) and 320 uncomplicated pregnant women were included in the study. Blood samples for routine CBC and first trimester screen, which combines PAPP-A and free β-hCG blood concentrations, were analyzed. The NLR values were significantly higher in the severe preeclampsia group compared with the control group (p<0.001). We also confirmed that levels of PAPP-A were lower in patients who developed preeclampsia. Because measuring CBC parameters, particularly NLR, is fast and easily applicable, they may be used to predict preeclampsia.

Cell-free fetal DNA screening in the USA: a cost analysis of screening strategies.

To determine whether implementation of primary cell-free fetal DNA (cffDNA) screening would be cost-effective in the USA and to evaluate potential lower-cost alternatives. Three strategies to screen for trisomy 21 were evaluated using decision tree analysis: 1) a primary strategy in which cffDNA screening was offered to all patients, 2) a contingent strategy in which cffDNA screening was offered only to patients who were high risk on traditional first-trimester screening and 3) a hybrid strategy in which cffDNA screening was offered to all patients ≥ 35 years of age and only to patients < 35 years who were high risk after first-trimester screening. Four traditional screening protocols were evaluated, each assessing nuchal translucency (NT) and pregnancy-associated plasma protein-A (PAPP-A) along with either free or total beta-human chorionic gonadotropin (β-hCG), with or without nasal bone (NB) assessment. Utilizing a primary cffDNA screening strategy, the cost per patient was 1017 US$. With a traditional screening protocol using free β-hCG, PAPP-A and NT assessment as part of a hybrid screening strategy, a contingent strategy with a 1/300 cut-off and a contingent strategy with a 1/1000 cut-off, the cost per patient was 474, 430 and 409 US$, respectively. Findings were similar using the other traditional screening protocols. Marginal cost per viable case detected for the primary screening strategy as compared to the other strategies was 3-16 times greater than the cost of care for a missed case. Primary cffDNA screening is not currently a cost-effective strategy. The contingent strategy was the lowest-cost alternative, especially with a risk cut-off of 1/1000. The hybrid strategy, although less costly than primary cffDNA screening, was more costly than the contingent strategy.

Prediction of small for gestational age neonates in twin pregnancies by first trimester maternal serum PAPP-A and free β-hCG

Prediction of small for gestational age neonates in twin pregnancies by first trimester maternal serum PAPP-A and free β-hCG

İkiz gebeliklerde ilk trimester maternal serum PAPP-A ve serbest b-hCG ile SGA ilişkisi

İkiz gebeliklerde ilk trimester maternal serum PAPP-A ve serbest b-hCG ile SGA ilişkisi

Maternal serum alpha-fetoprotein and free beta-human chorionic gonadotropin in the second trimester: implication for high risk of down’s syndrome in the ghanaian population

Maternal serum screening during pregnancy for adverse changes in levels of alpha-fetoprotein (AFP) and free beta- Human Chorionic Gonadotropin (free β-HCG) in the second trimester to assess risk of Down’s syndrome (DS) is a rare obstetric practice in Ghana. The aim of this study was to determine changes in the levels of these markers, and assess for risk of DS and adverse pregnancy outcomes in the Ghanaian population. Levels of AFP and free β-HCG were determined in maternal serum samples from eighty one women with singleton pregnancy collected at recruitment (12-13 gestational weeks), and in the second trimester (16 gestational weeks). AFP and free β-HCG markers were expressed in multiples of the normal median (MoM) for gestation. Delivery outcomes and features of the new born at delivery were also noted. The mean age of subjects at recruitment was 33.9±3.2 years. AFP levels at recruitment and in the second trimester were 18.8 ± 7.5 ng/ml (mean ± SD) and 30.9 ± 9.8 ng/ml (mean ± SD) respectively. Similarly, free β-HCG at recruitment and in the second trimester were 47.2 ± 12.2 ng/ml (mean ± SD) and 29.8 ± 11.3 ng/ml (mean ± SD) respectively. The differences in the serum levels of AFP and free β-HCG between the first and second trimesters were significant (p<0.0001: 95% CI -14.9-(-9.3) and p<0.0001: 95% CI 13.6-21.2). Whilst the AFP level did not correlate with weight, free β-HCG weakly correlated with maternal weight (p=0.29 and r 2 =0.017; p=0.08 and r 2 =0.055 respectively), but not age in the second trimester. There were no cases of DS observed in the study population. The mean concentrations of free β-HCG in adverse pregnancies were higher than in normal pregnancies (38.4 ± 6.6; 29.3 ± 10.6) but not for AFP (p=0.059, and p=0.477 respectively). Although no DS was seen for comparison, free b-HCG appears to be a useful marker for risk assessments of poor pregnancy outcomes in the population.

Predictive value of abnormal second-trimester maternal serum triple screening markers for adverse pregnancy outcomes

To investigate the predictive value of abnormal multiples of the median (MoM) of second trimester maternal serum triple screening (STMSTS) markers for adverse pregnancy outcomes. 16 000 singleton pregnancies at 15⁺⁰ to 20⁺⁵ weeks' gestation who underwent STMSTS between July 2010 and January 2013 in the First Hospital of Jilin University were recruited. Maternal serum AFP, free β-hCG (F-β-hCG) and unconjugated estriol (uE3) levels were measured using time- resolved fluoroimmunoassay, and then converted to MoM. LifeCycle 3.2 software was used to calculate risk, and a risk value greater than 1 in 270 or 1 in 350 was considered as high risk for trisomy 21 syndrome (Down syndrome, DS) and trisomy 18 syndrome (Edwards syndrome, ES), respectively. MoM of AFP more than 2.5 was considered high risk for open neural tube defect (ONTD). Amniocentesis and karyotyping, ultrasound screening were advised for high risk women. AFP, F-β-hCG higher than 2.0 MoM or uE3 lower than 0.5 MoM was considered as abnormal, respectively. The MoM of STMSTS marker between women with adverse pregnancy outcome and with normal outcome was compared. (1) The median MoM of AFP, F-β-hCG and uE3 was 0.91 MoM, 0.94 MoM and 1.05 MoM, respectively. Of the 16 000 pregnant women, there was no statistical difference in the median MoM of triple screening marker at different weeks of gestation (P > 0.05). The positive rate of DS, ES and ONTD in women ≤35 years old (n = 14 972) was 4.03% (603/14 972), 0.36% (54/14 972) and 0.29% (44/14 972) respectively. And in women>35 years old (n = 1 028), the positive rate was 24.51% (252/1 028), 1.95% (20/1 028) and 0.78% (8/1 028), respectively. There was a statistically significant difference of positive rate between the two groups (P < 0.05). (2) 9 cases of DS, 1 case of ES and 1 case of ONTD were found in the high risk group, and 2 cases of DS in the low risk group. The detection rate of DS, ES and ONTD was 9/11, 1/1 and 1/1 respectively; and the positive predictive value was 1.05% (9/855), 1.35% (1/74) and 1.92% (1/52), respectively. (3)The incidence of adverse outcome (group 1) was 1.49 % ( 239/16 000). 7 760 pregnant women in this study were healthy during pregnancy, so were their fetuses (group 2). There were significant differences in the age at delivery, body weight and markers' MoM of STMSTS between the two groups (P < 0.01). (4) In group 1, the rate of abnormal MoM of AFP or F-β-hCG was 7.95% (19/239) and 23.85% (57/239), and the abnormal rate of MoM of uE3 was 4.18% (10/239). The rate of two abnormal MoM of markers was 5.02% (12/239); the rate that all three MoM were abnormal was 0.84% (2/239). However, in group 2, the rate of two abnormal MoM of markers was 0.14 % ( 11/7 760); and the rate that all three MoM were abnormal was 0. There was a significant difference of abnormal MoM of maternal serum marker between the two groups (P < 0.01). There is a relationship between abnormal marker of STMSTS and adverse outcomes. STMSTS show a high value in the detection of DS, ES and ONTD.