First trimester screening for trisomy 21; Do the parameters used detect more pathologies than just Down syndrome?

OBJECTIVE: To assess the value of first trimester maternal serum free beta human chorionic gonadotropin (beta hCG), pregnancy-associated plasma protein (PAPP-A) concentrations and nuchal translucency (NT) as predictors of pregnancy complications. DESIGN: A retrospective collaborative study of beta hCG, PAPP-A and NT between 10 and 14 weeks of pregnancy in patients in whom pregnancy was followed to term. Nuchal translucency, maternal serum PAPP-A and free beta hCG concentrations were measured in 1779 women with singleton pregnancies and without aneuploidies. Individual values were expressed as multiple of medians (MoM). Normal and abnormal pregnancies were compared for these parameters. RESULTS: Irrespective of the presence or absence of pregnancy-associated pathologies; there was no change in the median MoM for NT. The median MoM for free beta hCG was significantly increased in women with threatened abortions whereas the median MoMs for PAPP-A in women with spontaneous abortions or with pre-term deliveries were decreased significantly compared to normal pregnancies. These parameters have however no clinical usefulness as determined by receiver operator characteristics curves. CONCLUSION: Since PAPP-A is a protease that specifically degrades insulin-like growth factor binding proteins we would conclude that the control of the insulin-like growth factor system in the first trimester of pregnancy might play a key role in determining subsequent pregnancy outcome.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome

OBJECTIVE: Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. STUDY DESIGN: The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. RESULTS: Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). CONCLUSIONS: We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome.     

Predicting complications of pregnancy with first-trimester maternal serum free-betahCG, PAPP-A and inhibin-A

OBJECTIVE: To find whether fbetahCG, PAPP-A and inhibin-A levels in maternal serum or fetal nuchal translucency (NT) thickness at the first-trimester screening for trisomy 21 (T21) might detect women at high risk for adverse pregnancy outcomes. METHODS: A retrospective analysis of 1136 women with singleton pregnancy between 10 and 14 weeks. Women with pregnancy complications were allotted to five subgroups: small for gestational age (SGA), large for gestational age (LGA), gestational diabetes (GDM), hypertensive disorders, preterm delivery; women with normal pregnancy represented the control group. NT, maternal serum fbetahCG, PAPP-A and inhibin-A were measured. Mann-Whitney test was used for the comparison of fbetahCG, PAPP-A, inhibin-A and NT between a subgroup of a certain pregnancy complication and the control group. Multivariate logistic regression models were built to explore the relationship among different variables and the occurrence of pregnancy complications. RESULTS: PAPP-A values were significantly lower in women who delivered SGA babies (n=51, 0.76 MoM; p=0.002) and significantly higher in women who delivered LGA babies (n=120, 1.12 MoM; p=0.036). In women with GDM (n=27), fbetahCG, PAPP-A and inhibin-A were insignificantly lower than in controls, whereas in women with hypertensive disorders (n=56) no significant differences between the groups were found. In women with a preterm delivery (<34 weeks) (n=17), inhibin-A levels were significantly higher (1.25 MoM; p=0.015). CONCLUSION: Low PAPP-A level is associated with the delivery of an SGA baby and high PAPP-A with the delivery of an LGA baby. High inhibin-A is associated with preterm delivery before 34 weeks. Feto-placental products in the first trimester do not prove to be useful as a screening tool for predicting pregnancy complications.     

Placental Protein-13 and Pregnancy-Associated Plasma Protein-A as First Trimester Screening Markers for Hypertensive Disorders and Small for Gestational Age Outcomes

Objective. To investigate the role of placenta protein 13 (PP13) and pregnancy-associated plasma protein-A (PAPP-A) in hypertensive disorders and small for gestational age (SGA) during first trimester of pregnancy. Methods. In this case–control study, first trimester serum samples (11⁺⁰ to 13⁺⁶ weeks) were retrieved from frozen storage of which 452 were from normal pregnancies and 47 samples were identified to have pregnancies with at least one of the following adverse outcomes: SGA, preeclampsia (PE), hemolysis, elevated liver enzymes, and low platelets (HELLP), or gestational hypertension (GH). PP13 concentrations were measured by a new AutoDELFIA method. Levels of PAPP-A were measured for a first trimester screening program using Kryptor analyzer. Results. First trimester levels of PAPP-A are significantly lower in cases of SGA, PE, and most subgroups including HELLP. Levels of PP13 were not found to differ between control and affected pregnancies. Conclusion. PP13 needs to be studied further as our results contrast the majority of previous studies.     

First-trimester Down syndrome screening: component analytes and timing for optimal performance

The most effective first-trimester Down syndrome screening protocol in current use employs three independent markers: maternal serum levels of PAPP-A and free beta hCG, and measurement of fetal nuchal translucency (NT). Eleven weeks appears to be the optimum gestational age for performing first trimester DS risk assessment. Although the discrimination of free beta hCG improves with increasing gestational age and is greatest at 13 weeks, PAPP-A and NT perform optimally at 10 and 11 weeks, respectively. In addition to accurate pregnancy dating, first trimester screening performance is improved by using a consistent NT measurement technique, NT cut-offs adjusted for gestational age or crown-rump length, and possibly center- or operator-specific NT medians. Whether or not absence or presence of the nasal bone adds to screening accuracy is a matter of some debate. Finally, because enlarged NT has been associated with cardiac defects and other structural anomalies, even in euploid fetuses, its presence should prompt a targeted second trimester ultrasound examination.     

Screening for Down's syndrome: changes in marker levels and detection rates between first and second trimesters

Objective To monitor changes with gestation in levels of alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (FβhCG) and pregnancy associated plasma protein-A (PAPP-A) in Down's syndrome pregnancies and to compare risks estimated in the first trimester with those obtained by routine screening in the second trimester for the same pregnancies.
Design In each of 47 Down's syndrome pregnancies two maternal serum samples were obtained, one in the first trimester and one in the second trimester. Comparison of marker levels with 10,600 first trimester controls and a smaller sample of second trimester controls allowed case identification criteria based on optimum marker combinations to be developed and compared directly between trimesters.
Setting Biochemical genetics laboratory.
Results FβhCG was an effective marker of Down's syndrome in both the first and second trimesters. PAPP-A levels were significantly reduced in trisomy 21 pregnancies in the first trimester only. Using a population model, these two markers in combination with maternal age gave an overall detection rate of 55% for a 5% false positive rate in the first trimester. For the paired first and second trimester samples, three of six cases classified as low risk by routine second trimester screening were classified as high risk by the first trimester screening protocol of FβhCG/PAPP-A/matemal age. However, fifteen cases identified as high risk by routine second trimester screening were classified as low risk in the first trimester, a net loss in detection of 12 cases by first trimester screening.
Conclusion The data suggest that first trimester detection rates for Down's syndrome using a combination of FβhCG and PAPP-A may vary with gestation and will be lower than those currently obtained by routine second trimester screening with AFP/hCG.     

First trimester screening for Down syndrome in rhesus negative women

OBJECTIVES: To explore the effect of maternal rhesus status on first-trimester screening markers for Down syndrome. METHODS: We accessed a database of singleton pregnancies undergoing first-trimester genetic screen with maternal Rh status documented and pregnancy outcome information available. Excluded were cases of fetal chromosomal or structural abnormalities, or maternal systemic disease. Results of maternal serum pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotrophin (beta-hCG) adjusted for gestational age were compared between Rh-negative and Rh-positive women with p < 0.05 considered significant. RESULTS: Two thousand two hundred and two pregnancies fulfilled the study criteria, and 160 of them (7%) were Rh negative. Only free beta-hCG corrected multiples of the median (MoM) values were statistically increased in Rh-negative women (p < 0.009). Using a cut-off of 1:300, screen-positive rates of maternal serum biochemistry were not significantly different between Rh-negative and Rh-positive women (12.5 vs 10.4%, p = 0.41). CONCLUSION: The present study focused on measurements of beta-hCG and PAPP-A in the sera of women with Rh-negative blood group. Women with Rh-negative blood type have similar first-trimester serum PAPP-A MoM values as Rh-positive women, but significantly higher beta-hCG MoM values. However, there was no significant difference in the screen-positive rate for Down syndrome between the two groups.     

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy

Objective: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. Methods: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. Results: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free β-human chorionic gonadotropin (β-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. Conclusion: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.     

Maternal serum screening for Down syndrome in the first trimester: experience from Belarus.

We have carried out a large retrospective study of alpha-fetoprotein (AFP), free-beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein (PAPP-A) in the first trimester of pregnancy. Unlike other studies all women had routine ultrasound dating, carried out during a nuchal translucency measurement project. A total of 13,477 serum samples were tested for AFP and 11,659 for free beta-hCG. A subset of 1564 samples from unaffected pregnancies were also tested for PAPP-A on a case-control basis. All three markers were also determined in 31 samples from pregnancies with Down syndrome. Equations were derived to express results in multiples of the median using both gestational age and crown rump length and to adjust for maternal weight. Statistical modelling with Gaussian distribution parameters obtained in the study were used to predict the detection rate for a 5 per cent false-positive rate. The predicted rates were: 73.7 per cent for all three markers; 69.1 per cent for PAPP-A and free beta-hCG; 47.4 per cent for PAPP-A and AFP; 57.6 per cent for free beta-hCG and AFP. As these rates are similar to those in the second trimester, health planners may now want to consider a change in policy from second-trimester to first-trimester screening with biochemical markers.     

Combinations of maternal serum markers to predict preeclampsia, small for gestational age, and stillbirth: a systematic review

ObjectiveAbnormal serum screening markers have been associated with adverse pregnancy outcomes. We sought to review the performance of combined abnormal first and/or second trimester maternal serum markers used in prenatal screening for aneuploidy and open neural tube defects for predicting preeclampsia (PET), small for gestational age (SGA), and stillbirth beyond 24 weeks’ gestation.Data Sources and Study SelectionMedline, EMBASE, and Cochrane Library databases were searched for studies from 1970 to May 2010 that analyzed predictive abilities of combined serum markers for defined outcomes.Data Extraction and SynthesisData were extracted independently by two authors, and 15 studies were included. Eight studies of 115 290 pregnancies, 11 studies of 144 853 pregnancies, and seven studies of 80 274 pregnancies examined PET, SGA, and stillbirth respectively. Because of the heterogeneity of marker combinations and thresholds, outcome definitions, and analytic methods, limited meta-analysis was possible for the outcomes of PET and SGA only. Three relatively homogeneous studies on prediction of PET, and two on prediction of SGA were meta-analyzed. Several single studies demonstrated utility in combining markers to predict adverse outcome; however, this effect was not confirmed after metaanalysis. The most common combination of markers evaluated was alpha fetoprotein and human chorionic gonadotrophin for all outcomes. The highest positive likelihood ratios for predicting PET (5.68; 95% CI 0.73 to 43.97) and SGA (6.18; 95% CI 1.84 to 20.85) were seen with combined alpha fetoprotein and human chorionic gonadotrophin (> 2.5 multiples of the median).ConclusionsCurrently, no identifiable combination of serum markers performs well as a screening test for preeclampsia, small for gestational age, and stillbirth beyond 24 weeks. Large cohort studies with standardized screening test parameters and outcomes are needed.     

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.     

The influence of smoking on maternal serum PAPP-A and free beta hCG levels in the first trimester of pregnancy

In an analysis of 3111 singleton pregnancies routinely screened in the first trimester with nuchal translucency, free beta hCG and pregnancy associated plasma protein A (PAPP-A) smoking has been found to occur in 20.8 per cent of pregnant women. When the individual marker levels were assessed in smokers and non-smokers, levels of PAPP-A were reduced in smokers by some 15 per cent. Despite free beta hCG levels being reduced by 10-14 per cent in the second trimester of smoking women, in the first trimester period this is not evident. Simulation studies would suggest that in smokers the detection of trisomy 21 using free beta hCG, PAPP-A and maternal age will be reduced by some 5 to 6 per cent compared with that of the general population.     

Comparison of serum markers in first-trimester down syndrome screening

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: II-2.     

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assesement of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Polish multi-centre research

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assessment of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Poland's multi-centers research. OBJECTIVES: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. Enlarged nuchal translucency (NT) is observed in about 80% of fetuses affected with chromosomal abnormalities and congenital heart defects (CHD). MATERIAL AND METHODS: The aim of this study were to determine value and the medians of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency thickness in the first trimester in a prospective study of a non-selected Polish population. RESULTS: All examinations have been performed according to the Fetal Medicine Foundation (FMF) rules. We have included 800 women between 11 weeks 0 days and 13 weeks 6 days gestation into a biochemical examination. Women booked into the clinic were offered screening, using a combination of maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. The maternal serum were measured using the Kryptor analyzer (Brahms Diagnostica). All pregnant women have been divided into 2 groups younger than (first group) and older than (second group) 35 years of age. CONCLUSIONS: Nomogrames for free beta-hCG and PAPP-A levels in physiological pregnancy between 11(+0) and 13(6) weeks were determined in the examined population. A positive correlation between PAPP-A and CRL levels, as well as a weak negative correlation between free beta-hCG and CRL, were demonstrated.     

Hyperglycosylated-hCG (h-hCG) and Down syndrome screening in the first and second trimesters of pregnancy

OBJECTIVE: To validate Down syndrome screening protocols that include hyperglycosylated-hCG (h-hCG) measurements. METHODS: Measuring h-hCG in 21 641 fresh first- and second-trimester maternal serum samples, but not for clinical interpretation. Nuchal translucency (NT) and pregnancy associated plasma protein-A (PAPP-A) measurements were available in the first trimester; alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG) measurements in the second trimester. RESULTS: Of the 23 first- and 26 second-trimester Down syndrome pregnancies identified, 52 and 65% of h-hCG measurements were above the 95th centile, respectively. At a 3% false positive rate, maternal age, NT, PAPP-A and h-hCG detected 78% of cases (95% CI, 56-93%). Other combinations were consistent with previous modeling utilizing stored samples. A literature summary indicates h-hCG is as strong a marker as free-beta between 10 and 13 weeks' gestation. CONCLUSIONS: Down syndrome screening performance of h-hCG using fresh samples meets published expectations based on stored samples. h-hCG could replace free beta measurements, at gestational ages as early as 10 weeks.     

Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester.     

Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption

Objective

To investigate links between first trimester Down's syndrome screening markers and adverse pregnancy outcomes; preeclampsia (PE), small for gestational age (SGA), preterm delivery (PD) and placental abruption (PA) in spontaneous, chromosomally normal pregnancies.

Study design

Cohort study in a university hospital. Data during pregnancy were routinely collected from a total study population of 2844 pregnant women between 2005 and 2007. Four study groups were pregnancies with PE (N = 175), PA (N = 17), PD (N = 213) and SGA (N = 275) plus a reference group with normal outcome (N = 2164). The median MOMs of maternal serum concentrations of pregnancy associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were compared using two-tailed pooled t-tests, continuous variables were compared using Student's two-way t-tests, and Chi-square tests were used to analyse dichotomous variables. Fisher's exact test was used when there were fewer than five units in any of the classes.

Results

The median MOM of maternal serum PAPP-A was significantly lower in women with PE, PD and SGA (0.79, 0.80 and 0.79 MOM, respectively) than in the reference group (0.99 MOM) (p < 0.01). The median MOM of maternal serum fβ-hCG was also significantly lower in the SGA group (0.90 MOM) and in the PE and PD groups (0.86 and 0.92 MOM) than in the reference group (0.99 MOM, p = 0.02). There was no detectable difference between the biochemical markers in the PA group and the reference group. No statistical difference was found between NT MOMs in the reference and study groups.

Conclusion

The concentrations of first trimester screening (FTS) serum markers were lower in pregnancies where PE, PD and SGA occurred. In the latter two cases, there was an inverse association between incidence and PAPP-A and fβ-hCG values. However, the development of PA during pregnancy could not be predicted from biochemical marker concentrations. The mechanism behind PA is probably less dependent on the placenta than on the decidua.     

Between pregnancy biological variability of first trimester markers of Down syndrome and the implications for screening in subsequent pregnancies: an issue revisited

OBJECTIVES: To assess the level of correlation of first trimester biochemical and biophysical markers of Down syndrome between different pregnancies in the same individual. To assess the impact that between pregnancy biological variability has on the likelihood that women who are at increased risk in a first pregnancy being also at increased risk in a subsequent pregnancy. METHODS: During a three period women attending the OSCAR clinic at Harold Wood Hospital have had the opportunity to have first trimester screening for Down syndrome and other aneuploidies using the maternal serum biochemical markers free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A) in conjunction with fetal nuchal translucency (NT) thickness and maternal age. Of the 111,105 women undergoing such screening, the computer records were examined for women who had more than one pregnancy. The results from 1002 women with two normal singleton pregnancies were available for analysis. Marker correlations (as MoM) were established between the pregnancies and the proportion of women likely to be at increased risk in each pregnancy estimated, as was the likelihood of women being at increased risk in both pregnancies. RESULTS: For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r = 0.0959, p > 0.10). For maternal serum free beta-hCG MoM a significant correlation was found (r = 0.3976, p < 0.001), as was also found for PAPP-A MoM (r = 0.4371, p < 0.001). CONCLUSION: The implication for such between pregnancy marker association is that women who have an increased risk of Down syndrome in one pregnancy are two or three times more likely to repeat this event in their next pregnancy. This information may be useful in counselling women when undergoing first trimester screening in a subsequent pregnancy.     

First-trimester maternal dried blood Down syndrome screening marker levels in early pregnancy loss

OBJECTIVE: To determine the association of free beta hCG and PAPP-A measured during first-trimester Down syndrome risk assessment with early pregnancy loss when blood is drawn prior to scheduled ultrasound. METHODS: Maternal dried blood samples were collected prior to the ultrasound exam for Down syndrome risk assessment. Free beta hCG and PAPP-A levels in 55 patients who experienced loss of pregnancy prior to their scheduled ultrasound appointment were compared to 6464 control pregnancies using logistic regression. RESULTS: Low levels of free beta hCG and PAPP-A were associated with increased risk of early pregnancy loss. The detection rate of early pregnancy loss for a fixed 5% false-positive rate using free beta alone, PAPP-A alone and a combination of the two were 47, 36 and 49%, respectively. CONCLUSION: Free beta hCG and PAPP-A can identify pregnancies at increased risk for early pregnancy loss. More studies are needed to determine whether further evaluation of these pregnancies prior to the scheduled ultrasound is warranted.