Free β-hCG Research Articles

First-trimester screening biochemical markers (free beta-subunit human chorionic gonadotropin, pregnancy-associated plasma protein-A) and risk of early fetal loss.

The aim of this work was to assess the risk of early fetal loss (first trimester of pregnancy, 8-13 weeks of gestation) using the results of first-trimester screening (FTS) biochemical markers independently and combined. FTS results of 152 women who suffered early fetal loss were compared to a control group of 150 women with normal pregnancy outcomes. FTS biochemical markers were measured with a Delfia Xpress 6000 analyzer and biochemical risks for Down's and Edward's syndromes were calculated using Prenatal-Lifecycle version 3.0 software. Marker levels were standardized by calculating the gestational-specific multiple of the medians (MoM), further adjusted by maternal age, maternal weight, cigarette consumption and pre-existing type 1 diabetes mellitus. Receiver-operator curves were built to evaluate each marker and its combination. Our results show that values of biochemical risk of t21 of more than 1 in 310 have a poor sensitivity to predict early fetal loss (31.4%) with a positive predictive value (PPV) for fetal loss of 67.7%. Values of pregnancy-associated plasma protein A (PAPP-A) MoM of less than 0.48 show a sensitivity of 62.1% and a PPV of 84.5% for early fetal loss; whereas for free β-human chorionic gonadotropin, values of MoM of less than 0.44 have a sensitivity of 66.4% with a PPV of 85.3%. A novel algorithm, consisting in the multiplication of both markers, shows for values of less than 0.48 a sensitivity of 83.1%, a specificity of 78.7% and a PPV of 77.1%. Combined analysis of PAPP-A and free β-hCG appears to be a potential candidate to predict early fetal loss.

Ten Years of Experience with First-Trimester Screening for Fetal Aneuploidy Employing Biochemistry from Gestational Weeks 6+0 to 13+6

Objectives: To validate the performance of first-trimester screening for fetal aneuploidy employing blood samples drawn in gestational weeks 6-13. Methods: Prospective combined first-trimester screening for fetal aneuploidy in Denmark was validated in two large datasets: (1) a dataset from the Central Denmark Region including 147,768 pregnancies from October 2003 to October 2013, and (2) a national dataset including 220,739 pregnancies from January 2008 to August 2011. Results: For trisomy 21, the weekly median multiple of the median (MoM) increased from 0.37 in week 6 to 0.70 in week 13 (pregnancy-associated plasma protein-A), and from 0.99 in week 6 to 2.68 in week 13 (free βhCG). The overall detection rate (DR) for fetal trisomy 21 was 91.2%. Employing blood samples from gestational week 9, the DR was 97% (p = 0.05). For fetal trisomy 18, trisomy 13 and triploidy, the overall DRs after first-trimester screening were 79.5, 86 and 85%. In the national dataset, the overall DR for trisomy 21 was 86.3% ranging from 89 (weeks 9 and 10) to 80% (weeks 12 and 13). Conclusion: The results from both datasets show that blood sampling in gestational weeks 9-10 is a robust and high-performance strategy, which can be applied for routine first-trimester screening in clinical practice.

Screening for Down syndrome

Screening for Down Syndrome was initially only related to maternal age and has successively developed by introducing biochemical markers and algorithms to estimate the risk for particularly trisomy 21 and 18. We now have a long experience of screening with four biochemical markers, alpha-fetoprotein, total hCG, unconjugated estriol and free β-hCG during the second trimester. Screening is now moving towards screening in the first trimester using a combination of ultrasound (Nuchal Translucency) and the maternal serum biochemical markers free β-hCG and Pregnancy Associated Plasma Protein-A (PAPP-A). This has become known as the combined test. Several maternal and pregnancy factors which can influence the concentrations of biochemical markers are discussed. The possibilities of screening for other aneuploidies in the first trimester and an outline of recent methods to improve overall screening performance are highlighted and the review will suggest some possible options for the future in which Cell Free DNA techniques may become part of an improved overall screening strategy. In conclusion it is emphasized that the time has come to invert the Pyramid of Antenatal Care to focus on the 11–13 week assessment.

Predictive value of combined serum biomarkers for adverse pregnancy outcomes

ObjectiveTo determine if a combination of first and second trimester serum biomarkers (pregnancy-associated plasma protein A (PAPP-A), free βhCG, and maternal serum alpha-fetoprotein (msAFP)) may be utilized to develop a predictive model for adverse pregnancy outcomes. Study designWe conducted a retrospective analysis including all women who delivered at our institution between 2007 and 2010. We estimated the area under the ROC curve (AUC) to compare predictive abilities of PAPP-A, free βhCG, and msAFP singularly, and in combination for adverse pregnancy outcomes. We sought to predict the risks of preeclampsia, preterm delivery (PTD, <37 weeks gestational age) and low birth weight (LBW, <2500g). Using logistic regression analysis, we created models that controlled for maternal age, race, parity, body mass index, and histories of chronic hypertension and tobacco use. ResultsThe final sample included 2199 women. Determining the AUC and optimal cutoff probability values for each of the biomarkers, we found that for PTD and LBW, the combination of all three biomarkers was most predictive, while for preeclampsia the combination of msAFP and PAPP-A was most predictive. The AUC of the three biomarker combination to detect adverse pregnancy outcomes are as follows: LBW 67%, PTD 72%, and preeclampsia 77%. We created race-specific logistic regression models to predict the risk probabilities. To illustrate, the predictive probability for a 33-year-old African American, nullipara with a BMI of 50, chronic hypertension, tobacco use, PAPP-A 0.3, msAFP 2.0 and free βhCG 0.98 MOMs are: PTD 59%, LBW 61% and Preeclampsia 91%. ConclusionThe combination of biomarkers currently utilized in Down syndrome screening may also be used to predict additional adverse pregnancy outcomes. Further studies are needed to determine optimal maternal and fetal surveillance, if and when increased risks are identified.

The Diagnostic Value of β-Human Chorionic Gonadotropin, Progesterone, and Ischemia-Modified Albumin and Their Combined Use in the Prediction of First Trimester Abortions.

Objective. To investigate serum levels of free β-HCG, progesterone, and ischemia-modified albumin (IMA) and their combined use in the prediction of first trimester abortions. Methods. A total of 156 pregnant women between 5 and 13 weeks of gestational age were included in this study. At admission, serum levels of free β-HCG, progesterone, and IMA were noted and all cases were divided into two groups; Group I (n = 77) resulted in abortion including missed abortion, incomplete/complete abortion, and inevitable abortion whereas Group II (n = 79) included normal pregnancies. Results. Compared to Group II, the significantly decreased value of free β-HCG progesterone and significantly increased value of IMA were found in Group I (P < 0.01, P < 0.01, P < 0.01, resp.). When combining all three parameters, sensitivity 75%, specificity 99%, PPV 98%, and NPV 76% were obtained. The multivariate logistic regression analysis revealed the free β-HCG, progesterone, and IMA independent factors in the prediction of abortions. Conclusions. The combined use of free β-HCG, progesterone, and IMA levels can be useful in the prediction of first trimester spontaneous abortions.

The utility of circulating LHCGR as a predictor of Down's syndrome in early pregnancy.

BackgroundPrevious studies showed that soluble LHCGR/hCG-sLHCGR concentrations in serum or plasma combined with PAPP-A and free βhCG significantly increased the sensitivity of Down’s syndrome screen at early pregnancy without altering the false positive rate. The goal of the present study was to further examine the role of sLHCGR forms as combinatorial markers and to investigate whether sLHCGR could serve as an independent biomarker for Down’s syndrome in first trimester pregnancy screens.MethodsThe PAPP-A, free βhCG, and hCG-sLHCGR concentrations together with nuchal translucency (NT) were measured in 40 Down’s and 300 control pregnancies. The sLHCGR concentration was analysed in 40 Down’s and 206 control pregnancies.ResultsThe hCG-LHCGR in combination with PAPP-A and free βhCG increased the detection rate (DR) by 35% without altering the false positive rate (FPR). The sLHCGR: hCG-sLHCGR ratio alone detected 80% of Down’s pregnancies in first trimester screening, with a false positive rate of 0.5%.ConclusionsWhile measurement of sLHCGR forms in combination with PAPP-A and free βhCG significantly increases the detection rate of Down’s syndrome at first trimester, the ratio of sLHCGR: hCG-sLHCGR acts as an independent marker with a detection rate that is significantly higher than the existing biochemical markers individually for prenatal first trimester screening of Down’s syndrome.

PMM.88 Screening for Down’s Syndrome in Women with Renal Disease

IntroductionIn 2001, the UK National Screening Committee advised that all pregnant mothers should be offered a screening test for Down’s syndrome (DS). This is performed at first (biomarkers and ultrasound)...

PPO.45 Low maternal serum PAPP-A in the first trimester and adverse pregnancy outcome: An experience over one year from a University Hospital

IntroductionMaternal serum pregnancy associated plasma protein A (PAPP-A) is derived from the placenta and is a component of combined screening. When combined with maternal age, fetal nuchal translucency and maternal...

Is There an Association Between Placenta Previa and Serum Analytes?

INTRODUCTION: The objective of this study was to evaluate the association between maternal serum analytes and placenta previa. METHODS: Chart review of deliveries from 2004 to 2012 with two comparison groups: placenta previa without accreta and a control group. Patients in the control group were randomly selected from deliveries without placenta previa. Patients with previa were confirmed by third-trimester ultrasonography. Exclusion criteria were placenta previa with pathology-confirmed accreta, multiple gestations, fetal anomalies, or growth restriction. Primary outcomes were maternal serum analytes in the first trimester: pregnancy-associated plasma protein A and free β-human chorionic gonadotropin (β-hCG), and second trimester: α-fetoprotein), free β-hCG, unconjugated estriol, and inhibin. RESULTS: Twenty-six women with previa met inclusion criteria and 43 women in the control group. The groups did not differ with respect to maternal age, gravidity, or parity. Alpha-fetoprotein multiples of the median was significantly higher in women with previa cases than women in the control group (P<.005). Pregnancy-associated plasma protein A multiples of the median was higher (but was not statistically significant) in women with previa than in the women in the control group (P<.064). There were no differences between groups with respect to first-trimester free β-hCG, second-trimester free β-hCG, unconjugated estriol, or inhibin (Table 1). The following analytes were not available on all specimens: second-trimester free β-hCG, unconjugated estriol, and inhibin.CONCLUSIONS: In our women with placenta previa, maternal serum α-fetoprotein was significantly higher than in women in the control group. We also observed higher levels of pregnancy-associated plasma protein A in women with previa but this did not reach statistical significance. Prospective studies are needed to confirm these findings and determine the relationship with pregnancy outcome.

First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation

The first trimester combined screening, which analyzes fetal nuchal translucency and levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum, is routinely used to detect abnormal pregnancies associated with Down syndrome and other trisomy aneuploidies. Based on the hypothesis that major chromosomal translocations could lead to similar biochemical and developmental outcomes during early embryo development, we compared these markers among pregnancies with normal, balanced, or unbalanced fetal karyotypes. Among the parents, 71 (73%) carry balanced reciprocal translocation and 26 (27%) have Robertsonian translocation. Of the 97 pregnancies tested, 39 (40%), 37 (37%), and 22 (23%) fetuses had normal karyotype, balanced chromosomal translocations, and unbalanced chromosomal translocations, respectively. Importantly, we found that pregnancies with an unbalanced translocation had significantly higher free β-hCG multiple of the median (MoM) and larger nuchal translucency thickness than those with normal karyotype or balanced translocations. Analysis showed that the area under a receiver operating characteristic curve (AUC) is 0.716, 0.820, and 0.936 for free β-hCG MoM, PAPP-A MoM, and fetal nuchal translucency, respectively. When these 3 independent factors were combined, the AUC reached 0.976. In addition, logistic regression showed that the most optimal model for predicting an unbalanced chromosomal translocation is a combination of PAPP-A and nuchal translucency with an AUC of 0.980. Therefore, the first trimester combined screening is not only effective in the screening of Down syndrome and other trisomy abnormalities but also has high sensitivity for the detection of unbalanced chromosomal translocations in fetuses.

Incorporating first trimester analytes to predict delivery of a large for gestational infant in women with impaired glucose tolerance.

To investigate first trimester maternal characteristics of women with impaired glucose tolerance that deliver large for gestational age (LGA) infants. Nested analysis from a prospective study of singleton pregnancies enrolled at first trimester. We studied women with an abnormal 1 h glucose challenge test that had normal follow-up oral glucose tolerance testing. Maternal characteristics, ultrasound parameters and serum analytes were stratified by subsequent delivery of an LGA infant. Parameters identified as significant on univariate analysis were used for a derivation of prediction by logistic regression. Odds ratio and prediction performance was determined using receiver operator curve (ROC) statistics. A total of 33/114 (28.9%) women meeting the criteria delivered LGA infants. Maternal height (cm), and first trimester pregnancy-associated protein-A and free β-hCG (MoM) predicted delivery of an LGA infant (ROC area under curve 0.73; 95% CI 0.63-0.83). At a cutoff value of 0.172 the prediction rule achieved 91% sensitivity, 44% specificity, 41% positive predictive and 92% negative predictive value. Maternal height and first trimester high free β-hCG and PAPP-A levels may be used as predictors for delivery of LGA infants in women with impaired glucose tolerance.

Free β-human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin and Maternal Risk of Breast Cancer

We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information.

Elevated Human Chorionic Gonadotropin and Hyperandrogenemia in a Woman With Müllerian Agenesis

Müllerian agenesis is a congenital malformation characterized by absence of the uterus, cervix, and upper vagina. A positive home pregnancy test in a woman with Müllerian agenesis mandated evaluation for malignancy. A woman with Müllerian agenesis presented with elevated levels of human chorionic gonadotropin (hCG), testosterone, and dehydroepiandrosterone sulfate. Pelvic magnetic resonance imaging (MRI), abdominal and pelvic computed tomography scan, chest computed tomography scan, brain MRI, and body positron emission tomography scan did not identify a malignancy. Human chorionic gonadotropin characterization revealed 74% hyperglycosylated and 1.6% free β-hCG, suggesting a trophoblast-containing tumor. Interventional ovarian venous sampling and repeat pelvic MRI suggested a right adnexal source. After laparoscopic removal of a stage 1C right ovarian dysgerminoma, hCG and testosterone returned to normal. A dysgerminoma coincident with Müllerian agenesis expressed hCG before detection by MRI. Human chorionic gonadotropin molecular characterization, ovarian vein sampling, and repeat pelvic MRI led to successful treatment.

Longer time‐to‐pregnancy in spontaneously conceived pregnancies is associated with lower PAPP‐A and free β‐hCG in first trimester screening for Down syndrome

The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β-hCG) and hence the risk estimates in Down syndrome screening. The study included a cohort of 10 469 singleton pregnant women who underwent first trimester combined screening and responded to a questionnaire regarding TTP. PAPP-A and free β-hCG levels were measured between gestational week 8 + 0 and 13 + 6 and were related to TTP. The median PAPP-A and free β-hCG MoMs were significantly lower in women with a TTP ≥24 months compared with the reference group with a TTP <6 months (PAPP-A: 0.96 vs 1.06 MoM, p = 0.003; free β-hCG: 1.04 vs 1.12 MoM, p = 0.03). This led to an increased odds for trisomy 21 risk ≥1 : 300 for TTP ≥24 months compared with TTP <6 months, but when adjusting for potential confounders, the odds ratio (OR) lost significance (OR 1.4, 95% confidence interval; 0.8-2.4). Time-to-pregnancy ≥24 months in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free β-hCG.

First-Trimester Screening for Trisomies 21, 18 and 13 by Ultrasound and Biochemical Testing

Objective: To examine the performance of screening for trisomies 21, 18 and 13 at 11-13 weeks' gestation using specific algorithms for these trisomies based on combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index for veins (DV PIV), and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Methods: Model-based estimates of screening performance were produced for the distribution of maternal ages in England and Wales in 2011, and prospectively collected data on fetal NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP from singleton pregnancies undergoing aneuploidy screening. Results: In screening by NT, FHR, free β-hCG and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy 21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%. Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and 95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. Conclusions: Effective screening for trisomies can be achieved using specific algorithms based on NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP.

Biochemical screening for aneuploidy in patients with donor oocyte pregnancies compared with autologous pregnancies

Objective: The objective was to determine if the rate of abnormal biochemical markers is different in pregnancies conceived by donor oocyte versus those conceived by autologous oocytes.Methods: This is a retrospective cohort study of patients who underwent risk assessment for aneuploidy. Pregnancies conceived by egg donation were matched with control groups who conceived using their own eggs. The primary outcomes were incidence of low PAPP-A or free bHCG in the first trimester or elevated MSAFP, free bHCG or Inhibin A, or low uE3 in the second trimester.Results: 260 singleton gestations were identified who conceived via oocyte donor. There was a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (8% versus 2%, p = 0.028) compared to a control group matched by maternal age. There was also a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (7% versus 2%, p = 0.01) compared to a control group matched by age of the egg donor.Conclusion: Pregnancies conceived by egg donation are more likely to have an unexplained elevation in MSAFP compared to pregnancies not conceived by egg donation regardless of age. Egg donation itself is not associated with other biochemical abnormalities.

First trimester maternal serum alpha-fetoprotein is not raised in pregnancies with open spina bifida

Two recent studies have suggested that maternal serum alpha fetoprotein (AFP) levels are increased in the first trimester of pregnancies in which the fetus has an open spina bifida. This is contrary to previously published studies. This study assesses further whether maternal serum AFP is elevated in the first trimester in cases with open spina bifida. Cases with open spina bifida were identified from our fetal database, and corresponding first trimester screening samples were retrieved and analysed for maternal serum AFP. A control group was selected by taking three samples matched for gestational age (exact day), ethnicity and smoking status and received in the laboratory on the same day. AFP was measured with the Kryptor platform and free β-hCG and pregnancy-associated plasma protein A results were available from the fetal database. Thirty-nine open spina bifida cases were identified with a control group of 126 cases. The median multiple of the median AFP in the cases were not significantly different from the controls (0.92 vs 1.06 p = 0.3511) as was the case for free β-hCG (0.87 vs 0.95 p = 0.7146) and pregnancy-associated plasma protein A (1.04 vs 1.04 p = 0.261). Our results confirm that maternal serum biochemical markers in the first trimester are unable to distinguish cases in which the fetus has open spina bifida.

Screening for Down syndrome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF): a clinical pilot study to confirm the laboratory methods

The corrections necessary to estimate the risk for Down syndrome in twin pregnancies have been pointed out. We performed a nested controlled study to evaluate the validity of these corrections in dichorionic twins conceived by IVF. Detailed clinical data was collected from the medical records. Twins were matched with a contemporaneous cohort of spontaneously conceived singleton pregnancies that serve as reference in a 1 to 4 ratio. All patients had their entire obstetrical care at our Hospital. The Student t-test was used for group comparisons and a p-value <0.05 was considered significant. Nineteen sets of normal twins concordant in size and with appropriate weight for gestational age were matched with 80 normal and mature newborns. Significant differences between groups were found for maternal age, gestational age at delivery and newborn weight (all p < 0.01). No statistical differences were noted for the levels of the biochemical markers expressed as multiples of the median. However, a 15% closer approximation to the laboratory median for PAPP-A and a 10% closer approximation to the laboratory median for free β-hCG was evident in twins when compared to the reference group. These findings support the methods used to estimate the risk for Down syndrome in dichorionic twin pregnancies conceived after IVF. A future study with a larger sample size could confirm if the laboratory corrections done on the combined screening test improve the predictability of Down syndrome in dichorionic twin pregnancy conceived by IVF when compared to singleton pregnancies.

Maternal Thyroid Function at Gestational Weeks 11–13 in Twin Pregnancies

Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyrotropin (TSH) is suppressed because of the increased hormone production induced by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression. The recognition of this phenomenon is important in order to avoid unnecessary concerns and to correctly establish the diagnosis of overt thyroid disease in twin pregnancies. The aim of this study was to establish reference ranges of maternal serum TSH and free thyroxine (FT4) at gestational weeks 11-13 in twin pregnancies. This is a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcomes, and 19 monochorionic pregnancies complicated by severe twin-twin transfusion syndrome. Maternal serum concentrations of TSH, FT4, antithyroperoxidase, and antithyroglobulin antibodies were measured at gestational weeks 11-13. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancies and MoM values in the different groups were compared. In the antibody-negative twin pregnancies with normal outcomes, compared to singletons, serum TSH MoM was lower (median 0.62 [interquartile range [IQR 0.16-1.18] vs. 1.01 [IQR 0.61-1.51]; p < 0.0001), FT4 MoM was not significantly different (median 0.98 [IQR 0.91-1.08] vs. 0.99 [IQR 0.91-1.09]; p = 0.975), and free β-hCG MoM was higher (median 1.91 [IQR 1.33-2.59] vs. 0.98 [IQR 0.66-1.50]; p < 0.0001). In the antibody-positive group (n = 37), compared to the negative group (n = 198), the median TSH was higher, but FT4 and free β-hCG were not significantly different. In the twin-twin transfusion syndrome group, compared to normal twin pregnancies, TSH, FT4, and free β-hCG were not significantly different. In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These reference ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.

The association between gestational diabetes mellitus and first trimester aneuploidy screening markers

To establish whether maternal serum first trimester concentrations of PAPP-A and free hCGβ are altered in pregnancies that subsequently are diagnosed by an oral glucose tolerance test (OGTT) with gestational diabetes mellitus (GDM). Over the period 2009 and 2011, the results for women who had first trimester screening for aneuploidy were matched with those having an oral glucose tolerance test at 22-26 weeks for suspected GDM. Free hCGβ, PAPP-A and NT MoMs were compared amongst the group having an OGTT with confirmed GDM and those in which GDM was not confirmed. A second comparison group consisted of all non-aneuploidy singleton pregnancies in which no OGTT was performed. During the three-year period, 27,660 singleton pregnancies were screened of which 7429 cases had an OGTT of which 870 cases were classed as GDM by WHO criteria. There was a significant 7-9% reduction in both PAPP-A and free hCGβ MoM in the GDM group compared with either the OGTT non-GDM group or the remaining pregnancies with no known risk factors for evidence of GDM. There was no difference in the NT measurements. First trimester concentrations of PAPP-A and free hCGβ are reduced in pregnancies that subsequently are diagnosed with GDM and may be useful in further screening algorithms for this disorder although the sensitivity alone is quite poor.