Correlation of first trimester placental volume and second trimester uterine artery Doppler flow

Uterine artery Doppler examination can identify impaired trophoblast invasion in the second trimester of pregnancy. High resistance and an early diastolic 'notch' show insufficient physiological conversion of the spiral arteries. Uterine artery Doppler is routinely performed between 22-24 weeks which is relatively late for treatment. In this study we wanted to find out whether women with increased uterine blood flow resistance at 22 weeks already have reduced placental volumes in the first trimester measured with 3D sonography.A total of 1060 women with singleton pregnancies had three dimensional (3D) volume measurements of their placentae between 11-13 weeks and uterine Doppler scans between 21-22 weeks. Stepwise logistic and linear regression analyses were used to show a correlation between placental volume (PV) and a CRL dependent placental quotient (PQ) with uterine perfusion parameters.Uterine perfusion at 21-22 weeks depends significantly on PV or PQ at 11-13 weeks (P< 0.0001 for both) and smoking behaviour (P=0.006). The occurrence of a notch also depends significantly on PV and PQ (P< 0.0001 for both) and also on gravidity (P< 0.0001) and age (P=0.0007) as well as on smoking behaviour (P=0.0094). PV and PQ did not show any dependency on age, gravidity, BMI or smoking habits. Placentae of women with high resistance uterine perfusion in the second trimester are already remarkably small in the first trimester. Placental volumetry is probably an efficient method for early and simple identification of impaired trophoblast invasion.     

Pregnancy associated plasma protein-A2: A novel biomarker for down syndrome

IntroductionIn an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21.MethodsTrisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21.ResultsPAPP-A2 (aka PLAC 3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers.DiscussionThis work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein.ConclusionPAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21.     

First trimester pregnancy volumes and subsequent small for gestational age fetuses

Objective

To examine whether in the first trimester, placental, gestational sac and fetal volumes are different in pregnancies that result in small for gestational age (SGA) compared to average for gestational age (AGA) neonates.

Methods

Case–control study comparing first trimester 3D volumes of the placenta, the fetus and the gestational sac between SGA and AGA pregnancies. 3D volumes were acquired for quality assurance and documentation. Pregnancy volumes were calculated by the virtual organ computer-aided analysis technique. Linear regression analysis was used to compute a normal range for the placental, gestational sac and fetal volume based on the crown rump length (CRL) in AGA pregnancies. Multiple regression analysis was used to examine significant influencing covariates. A Student’s t test was used to compare the difference between the SGA and AGA group.

Results

The study population consisted of 19 first trimester pregnancies with subsequent SGA neonates and 105 control pregnancies. In the AGA group, all pregnancy volumes were significantly dependent on the CRL. After controlling the CRL effect, the placental, gestational sac and fetal volumes were not significantly different between the SGA and AGA group.

Conclusion

First trimester 3D pregnancy volume measurements are not different in SGA or AGA pregnancies.     

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 fetal ultrasound parameters associated with PAPP-A and fβ-hCG

Objective: To study the association of fβ-hCG and PAPP-A measured at 11–14 weeks of gestation with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR) and delta nuchal translucency (dNT). To calculate adjusted MoM taking into consideration these associations. Methods: Retrospective cross-sectional study on 5,536 singleton euploid pregnancies participating in a first trimester screening program for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry. Adjusted MoM were calculated for fβ-hCG and PAPP-A and compared to the observed MoM (calculated by the Fetal Medicine Foundation screening algorithm). Results: fβ-hCG correlates positively with dCRL and negatively with dNT, whereas PAPP-A shows a positive correlation with dNT and a negative one with dCRL and dFHR. After adjustment for the ultrasound parameters, the median MoM values for fβ-hCG and PAPP-A changed from 1.02 and 0.92 observed MoM to 0.98 and 0.99 adjusted MoM respectively. The difference between the observed and adjusted MoM was statistically significant (p?<?0.001). Delta CRL increases with gestation and this effect manifests mainly after CRL of 62?mm. Conclusions: Adjustment for dCRL, dFHR and dNT improves the calculation of MoM for fβ-hCG and PAPP-A. CRL measurement overestimates fetal size at the end of the screening period 11–14 weeks.     

Expression of pregnancy-associated plasma protein-A (PAPP-A) during human villous trophoblast differentiation in vitro

Pregnancy-associated placental protein-A (PAPP-A), first isolated from maternal serum, has been identified as a metalloprotease cleaving insulin-like growth factor binding protein-4 (IGFBP-4). The source of PAPP-A during pregnancy is unclear. We therefore investigated PAPP-A expression during in vitro human villous cytotrophoblast cell (CT) differentiation into syncytiotrophoblast (ST). CT were isolated from normal first trimester, second trimester and term placentae (n=10) and cultured to form ST. PAPP-A mRNA was quantified by real-time PCR, and PAPP-A protein expression was studied by immunocytochemistry and TRACE technology with specific monoclonal antibodies. PAPP-A mRNA expression in total placental extracts increased during the course of pregnancy. PAPP-A protein was detected in the cytoplasm of both CT and ST. ST formation in vitro was associated with a 19-fold increase in PAPP-A mRNA expression and an 8-fold increase in PAPP-A secretion into the culture medium. No significant difference in PAPP-A production was observed between cultured cells isolated from early and term placentae. In conclusion, PAPP-A production in vitro, is associated to the differentiation of villous cytotrophoblast cells into syncytiotrophoblast, independently of the age of gestation.     

2D-ultrasound and endocrinologic evaluation of placentation in early pregnancy and its relationship to fetal birthweight in normal pregnancies and pre-eclampsia

Objectives

To study the relationships between 2D ultrasound measurements of placentation and maternal serum (MS) levels of PAPP-A, inhibin A and fβhCG in early pregnancy and subsequent fetal growth in pregnancies with a normal and abnormal outcome.

Study design

Prospective population-based cohort study of 301 pregnancies with a normal outcome, 18 with a pregnancy complicated by pre-term delivery (PTD) and 14 with subsequent pre-eclampsia (PE).

Main outcome measures

Basal placental surface area, placental thickness, ellipsivity and volume; MS PAPP-A and fβhCG at 11–13 + 6 weeks, MS inhibin A at 15–22 weeks and birthweight centile at delivery.

Results

In the normal group, the basal surface area showed a significantly (P < 0.001) positive correlation with placental thickness and placental ellipsivity. With the exception of placental ellipsivity, all other placental ultrasound parameters were significantly related with birthweight centile. Inhibin A showed a significant (P < 0.005) correlation with birthweight centiles. The basal plate surface area and MS PAPP-A were significantly (P < 0.01 and P < 0.001, respectively) lower and MS inhibin A significantly (P < 0.01) higher in PE than in controls. No changes were found in pregnancies complicated by PTD.

Conclusion

The basal plate surface area at 11–14 weeks reflects indirectly normal and abnormal placentation and development of the definitive placenta. Combined with MS PAPP-A and/or inhibin A levels this parameter could be useful in identifying from the end of the first trimester, pregnancies subsequently complicated with PE.     

Between pregnancy biological variability of first trimester markers of Down syndrome: implications for screening in subsequent pregnancies.

In a group of 149 women who had undergone routine first trimester screening using fetal nuchal translucency thickness (NT) and maternal serum free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) in two consecutive pregnancies the within person between pregnancy biological variability of these markers has been assessed. For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r=0.0800). For maternal serum free beta-hCG MoM a significant correlation was observed (r=0.4174) as was also found for PAPP-A MoM (r=0.3270). The implications for such between pregnancy marker association is that women who have an increased risk of Down syndrome in their first pregnancy are 1.5-2 times more likely to repeat this event in their next pregnancy. This observation may be useful in counselling women in the first trimester screening of a subsequent pregnancy.     

Human placental lactogen is a first-trimester maternal serum marker of Down syndrome

BACKGROUND: Human placental lactogen (hPL) is synthesised by the placenta and found in maternal serum. We analysed the potential of hPL as a first-trimester maternal serum-screening marker for fetal Down syndrome (DS). MATERIALS AND METHODS: hPL was quantified by ELISA in 47 DS pregnancies and 136 controls in gestational weeks 8-13. Distributions of log multiples of the median (MoMs) were established. The quantity of hPL in DS screening was estimated using Monte Carlo simulation methods. RESULTS: The mean log10 MoM hPL was - 0.1995 (SD: 0.1993) in affected and 0.0026 (SD: 0.2129) in control pregnancies. This corresponds to a MoM of 0.63 in DS pregnancies. hPL correlated significantly with log10 MoM values of hCGbeta (r = 0.320) and PAPP-A (r = 0.590) in controls, but not with hCGbeta (r = 0.228) or PAPP-A (r = 0.090) in DS pregnancies. The inclusion of hPL in the double test (PAPP-A + hCGbeta) increased the detection rate from 67 to 75% for a false-positive rate of 5%. CONCLUSION: hPL is a DS screening marker that is applicable at weeks 9-13 and could be included in multiple marker first-trimester screening for DS.     

Second- and third-trimester serum levels of placental proteins in preeclampsia and small-for-gestational age pregnancies

BACKGROUND: Poor placentation may perpetuate preeclampsia, but the presence of a major placental pathology has been questioned in cases of preeclampsia where the newborn has an appropriate birthweight for gestational age. On the other hand, poor placentation is also observed in the absence of preeclampsia, in pregnancies with small-for-gestational-age (SGA) fetuses. In late gestation, maternal serum levels of placental protein hormones are changed in both preeclampsia and SGA, but no longitudinal pre-onset studies are available for pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta1-glycoprotein (SP1) or human placental lactogen (HPL). METHODS: In a nested case-control study we compared maternal serum levels of PAPP-A, SP1, HPL and placenta growth factor (PLGF) at 17, 25 and 33 weeks in pregnancies developing preeclampsia without fetal growth restriction (n = 28), or characterized by a growth-retarded fetus (n = 25), with gestation-matched controls (n = 65). The proteins were quantified using microplate enzyme immunometric assays and the serum levels at 17, 25 and 33 weeks compared between the three groups by nonparametric statistical tests. RESULTS: In pregnancies with subsequent preeclampsia PAPP-A, SP1, HPL and PLGF were reduced at 17 weeks of gestation whereas at 25 and 33 weeks only PLGF remained below the controls. In growth-restricted pregnancies PAPP-A, SP1 and HPL were reduced at 17 weeks, and only HPL continued to be strongly affected thereafter. CONCLUSION: The reduced serum levels of the placental proteins PAPP-A, SP1 and HPL in the early second trimester (17 weeks) in pregnancies with subsequent preeclampsia or with fetal growth restriction involve an underlying role for the placenta in either pathology independent from the other.     

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.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta

Objective: The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa.

Study design: A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta.

Results: Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p?=?0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p?=?0.042) values than patients without accreta.

Conclusions: Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta.     

妊娠12～24周胎盘体积的实时三维彩超测量研究

目的:利用实时三维彩色超声测量中孕胎盘体积,初步探讨胎盘体积与孕龄和胎儿生长发育的关系,为进一步研究胎盘体积预测胎儿生长受限(FGR)的可行性提供依据。方法:2009年6月至12月于西安交通大学医学院第一附属医院妇产科B超室就诊的孕妇中,选择孕12周至24周无合并症和并发症的单胎妊娠,总计检查次数516次,孕妇年龄18～41岁,平均孕龄(129.10±23.42)天(12+0周到24+6周)。采用Philip HDI-4000型彩色多普勒超声诊断仪,检查胎儿并测量双顶径、股骨长、顶臀径,观察羊水、胎盘情况,采用实时三维超声VOCAL法测量胎盘体积。结果:(1)妊娠12+0到24+6周胎盘体积中位数范围为55.61～161.40cm3;(2)胎盘体积与孕龄呈线性正相关,回归方程为:胎盘体积=-92.659+1.826×孕龄(d)(r=0.586,P<0.01);(3)胎盘体积与顶臀径、双顶径呈线性正相关,相关系数分别为0.276和0.377(P均<0.01)。结论:妊娠12～24周胎盘体积与孕龄具有相关性,为进一步研究胎盘体积作为FGR的预测指标奠定了基础。     

ADAM12 as a marker of trisomy 18 in the first and second trimester of pregnancy.

BACKGROUND: ADAM12 (a disintegrin and metalloprotease 12) is a placentally derived glycoprotein that appears to be involved in growth and differentiation. The maternal serum concentration of ADAM12 appears to be a very good marker of trisomy 21 in the early first trimester when levels are reduced, and in the second trimester around 16-18 weeks levels are elevated. One small preliminary study of first trimester pregnancies with trisomy 18 found reduced levels in the maternal serum, and we examine herein the potential of ADAM12 as a marker of trisomy 18 in both the first and second trimester of pregnancy. MATERIALS AND METHODS: The concentration of ADAM12 was determined by a time-resolved immunofluorometric assay in 132 first and 12 second trimester cases of trisomy 18, and 389 first and 341 second trimester gestational age-matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and used to determine the population distribution parameters for the trisomy 18 and control groups. Correlation with previously established pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) multiples of the median (MoMs) and nuchal translucency thickness (NT) MoM were determined and used to model the performance of first trimester screening with ADAM12 in combination with other first trimester markers. RESULTS: The maternal serum concentration of ADAM12 in the first trimester was significantly reduced with a median MoM of 0.829 (p < 0.001) and a mean log10 MoM SD of 0.2663 compared to 0.3353 in the controls. In the second trimester small series ADAM12 was significantly increased with a median MoM of 2.09 (p = 0.001) and a mean log10 MoM SD of 0.2607 compared to 0.4318 in controls. There was a significant correlation of ADAM12 MoM with gestational age (r = 0.510) in trisomy 18 cases, and the median MoM increased from 0.51 at 10 weeks to 1.28 at 13 weeks and 2.09 across the 14-18 week window. ADAM12 was correlated with PAPP-A (r = 0.1918) in the first trimester of cases with trisomy 18 but less so with NT (r = 0.1594) and free beta-hCG (r = 0.0938). Modeled detection rates incorporating ADAM12, free beta-hCG, and NT were 92% at 1% false positive rate (88% at 0.5%) A combination of all four markers had a detection rate of 96.5% at a false positive rate of 1% (95% at 0.5%). CONCLUSION: ADAM12 may be a useful addition to early screening for trisomy 18 alongside other chromosomal anomalies, particularly if biochemical screening can occur before 10 weeks.     

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.     

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.     

The best marker combination using the integrated screening test approach for detecting various chromosomal aneuploidies

AIMS: To evaluate the cross-trimester multiple marker correlation and the minimum marker combination needed for detecting various chromosomal aneuploidies. MATERIALS AND METHODS: Parturient women with singleton pregnancies who underwent non-interventional sequential screening test and followed prospectively were recruited. They all underwent first trimester combined nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (f-betahCG), followed by second trimester measurement of unconjugated estriol (uE3), human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). Pearson correlation was applied to compute any cross-trimester marker correlation and logistic regression analysis was used to determine the minimum marker combination for detecting various categories of chromosomal aneuploidies. RESULTS: The current study included 552 normal and 43 chromosomal-affected pregnancies (24 Down's syndrome [DS], 7 Turner's syndrome, 8 Edward's syndrome, 4 Klinefelter syndrome and 5 triploidy) for which the results of both the screening tests and the pregnancy outcome were available. In the normal cases, a significant correlation was found between f-betahCG and hCG (r=0.52), as well as between PAPP-A and uE3 (r=0.174). In DS pregnancies, the NT correlated with both hCG (r=0.45) and uE3 (r=-0.39). In Turner's syndrome, uE3 correlated both with PAPP-A (r=0.97) and f-betahCG (r=0.97). No other significant correlations were found. Furthermore, with the exception of f-betahCG and hCG in the unaffected cases, all other markers correlation appeared very weak. For detecting all the above categories of aneuploidies, the combination of NT, PAPP-A and uE3 and the maternal age background risk were found adequate, with a 74% detection rate (DR) for a 5% false positive rate (FPR). For DS only, the combination of maternal age-related background risk and the combination of NT, PAPP-A, hCG and AFP yielded a 79% DR for a 5% FPR. CONCLUSIONS: The current study agrees with a previous report that, overall, there is no strong correlation between first and second trimester markers. The extension of the integrated test for detecting various categories of common chromosomal aneuploidies using NT, PAPP-A and uE3 deserves further evaluation.     

Weights of placentae from small-for-gestational age infants revisited

The objective of the study was to investigate the association between placental weight and birthweight in appropriate (AGA) and small for gestational age (SGA) infants. Placental weight, birthweight and their ratio in chromosomally normal singleton pregnancies with SGA (n=1569) and AGA (n=15 047) infants were compared, and their determinants were studied by logistic regression. SGA infants had 24 per cent smaller placentae than AGA infants when gestational age was used as a covariate. Placental actual weight was also lower in SGA infants than in AGA infants of the same birthweight (P< 0.001). SGA infants had smaller placentae than the controls, suggesting that fetal growth depends on the actual weight of the placenta. Future studies should evaluate whether growth restriction could be reversed by therapeutic approaches increasing placental weight.     

VCAM-1和PAPP-A在妊娠期高血压疾病患者中的表达及其相关性研究

目的:研究血管细胞黏附分子-1(VCAM-1)和妊娠相关血浆蛋白-A(PAPP-A)在妊娠期高血压疾病患者血清中的变化及在胎盘组织中的表达情况,探讨与妊娠期高血压疾病发病机制的关系。方法:收集2009年3月至2011年6月我院确诊为妊娠期高血压疾病的120例孕妇为实验组,正常孕妇40例为对照组。采用酶联免疫吸附法(ELISA)测定两组孕妇血清中VCAM-1和PAPP-A水平变化并进行比较。采用免疫组织化学染色方法检测VCAM-1和PAPP-A在两组胎盘组织中的表达。结果:①实验组VCAM-1和PAPP-A血清水平明显高于对照组,差异有统计学意义(P<0.05)。②VCAM-1在实验组胎盘组织中阳性表达较对照组减弱,差异有统计学意义(P<0.05)。PAPP-A在实验组胎盘组织中阳性表达较对照组明显增强,差异有统计学意义(P<0.05)。③实验组中血清VCAM-1、PAPP-A表达呈明显正相关(r=0.713,P<0.05),实验组胎盘免疫组化VCAM-1、PAPP-A表达呈负相关(r=-0.513,P<0.05)。结论:VCAM-1和PAPP-A在孕期母血清及胎盘组织中的改变与妊娠期高血压疾病的发病有明确关系。