PAPP-A MoM Research Articles

First trimester combined screening test in pregnancies derived from blastocyst transfer

ObjectiveTo investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques from blastocyst transfer, with or without cryopreservation. Study designretrospective case-control analysis involving 298 singleton pregnancies with euploid fetuses recruited between 2012 and 2014. Forty-seven women conceived with fresh blastocysts from in vitro fertilization cycles (fresh-blasto), 51 with frozen–thawed blastocysts (frozen-blasto) and 200 were natural conceptions (controls). All cases underwent ultrasound assessment at 11+0–13+6 weeks with measurements of crown rump length, nuchal translucency, free β-hCG and PAPP-A concentrations. The outcome of pregnancy was recorded (gestational age at birth, birth weight, obstetric complications). ResultsBaseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The median delta nuchal translucency was significantly higher both in frozen-blasto group (median: 0.27mm; Interquartile Range [IQR]: 0.02–0.44; p<0.001) and in fresh-blasto group (median: 0.17mm; IQR: 0.04–0.39; p=0.014) as compared to control group (median: 0.06mm; IQR: −0.08 to 0.20), whereas it was not different in the frozen-blasto compared to the fresh-blasto group. The median free β-hCG multiples of the median (MoMs) was significantly higher both in frozen-blasto group (median 1.15; IQR 0.83–2.11; p=0.001) and in fresh-blasto group (median 0.95; IQR 0.52–1.48; p=0.001) as compared to control group (median 0.99; IQR 0.57–1.26), and it was also higher in frozen-blasto group compared to fresh-blasto group (p<0.001). The three groups showed no significant differences in the median PAPP-A MoMs. The median delta crown rump length was also not significantly different among the three groups. Conclusionsin assisted reproduction technique pregnancies from blastocyst transfer, with or without cryopreservation, both the nuchal translucency measurement and free β-hCG concentration are higher as compared to spontaneous conceptions, whereas PAPP-A does not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance.

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

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

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

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

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

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

OP03.07: CRL audit using sonologist‐specific PAPP‐A and β‐hCG median MoMs plots

<scp>OP</scp>03.07: <scp>CRL</scp> audit using sonologist‐specific <scp>PAPP</scp>‐A and β‐<scp>hCG</scp> median <scp>MoMs</scp> plots

First trimester screening: What does biochemistry tell US?

Objective To review clinical information derived from first trimester biochemistry. Methods Study group included: (i) aneuploid: trisomy 21 ( n =128), trisomy 18 ( n = 51), trisomy 13 ( n = 14), triploid ( n = 28), sex chromosome aneuploidies ( n = 24); (ii) failed pregnancies ( n = 374); (iii) fetal structure: anencephaly ( n = 12), fetal growth restriction ( n = 11); and (iv) maternal health: gestational trophoblastic disease (n = 13), sub-chorionic bleeding ( n = 21). PAPP-A, FphCG, AFP and uE3 were quantified (DELFIA DXpress; Perkin Elmer) and marker MoM values calculated by LifeCycle v2.2 (Perkin Elmer), using lot specific derived polynomial regression curves. Results Median PAPP-A MoM values were depressed in failed pregnancies (0.17 ±0.04), pregnancies which failed after testing (0.43 ±0.15), pregnancies carrying an aneuploid fetus (Tri 21 = 0.46 ± 0.24; fetus with lethal aneuploidies = 0.18 ± 0.05 or fetuses with severely restricted growth (0.25 ±0.09). F(βhCG levels were increased in pregnancies carrying trisomy 21 fetus (2.01 ± 0.28), pregnancies with coexistent trophoblastic disease (21.94 ±66.95) or triploid pregnancies with 69XXY karyotype (10.86 ±8.44). AFP levels were increased in pregnancies which experienced transplacental bleeding (4.06 ±2.79) or pregnancies carrying a fetus affected with neural tube defects, such as anencephaly (1.70± 0.41). Conclusions: The above findings confirm: (i) low PAPP-A level is cause for concern requiring assessment of fetoplacental well-being, (ii) elevated FβhCG level warrants examination of fetal and trophoblast development, and (iii) elevated AFP levels may be due leakage of fetal blood into maternal circulation.

Impact of blood collection method on first-trimester dried blood free Beta hCG and PAPP-A.

Background Analysis of dried blood specimens has been an integral part of laboratory medicine dating back to the early 1960s when they were introduced as part of neonatal screening programs. More recently, they have been used in Down syndrome screening programmes. Dried blood spot specimens can be collected either by finger-stick or by traditional venipuncture and spotted onto filter paper. We sought to evaluate whether first-trimester free Beta hCG and PAPP-A multiples of the median (MoMs) were different in dried blood specimens collected via finger-stick compared to specimens collected via venipuncture. Methods A total of 2786 consecutive dried blood specimens were evaluated including 2144 collected using finger-stick and 644 specimens collected using venipuncture and spotted onto filter paper. Linear regression was used to assess the overall impact of collection method on dried blood free Beta hCG and PAPP-A and the impact of collection method on the trend of dried blood free Beta hCG and PAPP-A with transport time. Results For finger-stick and venipuncture, the median for free Beta hCG MoM was 0.99 and 1.04, respectively while the median PAPP-A MoM was 1.00 and 1.01, respectively. The regression formula for free Beta hCG was ln(MoM) = -0.00918 + 0.05112×Venipuncture + 0.00299×Days -0.00983×Days×Venipuncture and for PAPP-A the formula was ln(MoM) = -0.01000 + 0.04779×Venipuncture -0.00051×Days -0.02117×Days×Venipuncture. None of the coefficients were significant. Conclusions Collection method does not impact MoM values. Thus, centres have flexibility in the collection method utilized while being able to use a single reference database for all dried blood specimens.

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.

OC15.04: Operator‐specific PAPP‐A and free beta‐hCG MoM values as a method of individual audit of CRL measurements at the NT scan. National data from 171,469 pregnancies

To evaluate individual PAPP-A and β-hCG median MoM values as a possible audit for the quality of CRL measurement, using data from a national first trimester screening database. Calculation of operator specific PAPP-A and β-hCG MoM values from a national database including all women undergoing first trimester screening and risk calculation in Denmark in the period 2008–2010. All scans were performed by an FMF-certified operator, with a unique ID number. We restricted our analysis to singleton pregnancies where the gestational age at the time of blood sample was between 10 + 0 and 13 + 6 weeks: in 2008, 28664; in 2009, 27230; in 2010, 26230. Data were collected prospectively in the local Astraia database and automatically sent to the national database. Existing models were used to produce MoM values for PAPP-A and β-hCG specific to gestational age, maternal weight, ethnicity, smoking status, mode of conception and laboratory analyzer. For each operator, biases in PAPP-A and β-hCG MoM values were transformed into a bias in CRL measurement. The method was validated using simulated data with known CRL bias. Of those operators performing 10 or more scans, 98% showed CRL bias within ± 5 mm. 70% were within ± 2 mm. These accounted for 99.7% and 77.8%, resp., of all scans. Precision of the CRL measurement appears to increase with increasing number of scans, indicating a learning curve for CRL measurement. However, some very experienced operators showed biases indicating a systematic measurement error. These data indicate that operator-specific median PAPP-A and β-hCG MoM-values are a promising candidate as an audit parameter for CRL measurements in first trimester risk assessment. We have developed a graphical tool that could be incorporated into fetal medicine risk calculation software.

OP23.06: Effects of method of conception and gestational age on first trimester biochemical markers

Objectives: First-trimester levels of PAPP-A and free β-hCG are decreased in pregnancies conceived as a result of assisted reproduction, especially in-vitro fertilization (IVF). The aim of this study was to evaluate if sub-fertility, measured as increased timeto-pregnancy (TTP) in spontaneously conceived pregnancies, affects the levels of PAPP-A and free β-hCG. Methods: We included 13,935 singleton pregnant women, who attended the prenatal screening program between January 2005 and December 2010 and gave birth at Aarhus University Hospital, Denmark. TTP was evaluated through a questionnaire completed by the pregnant women in the first trimester. PAPP-A and free β-hCG were measured between gestational week 8+0 and 13+6. IVF pregnancies (n = 962) were used for comparison, and we excluded unintended pregnancies (n = 2.797) and pregnancies with no information about TTP (n = 460), which left 9,507 spontaneous pregnancies with information about TTP. Results: The median PAPP-A MoM was significantly lower in pregnant women with a TTP ≥24 months compared with the reference group with a TTP < 6 months (0.96 MoM vs. 1.06 MoM, P = 0.003). The levels were not as low as in IVF pregnancies (0.89 MoM). The median level of free β-hCG was also significantly lower in pregnancies with a TTP ≥24 months compared with pregnancies with a TTP < 6 months (1.04 MoM vs. 1.12 MoM, P = 0.03). TTP at 6–11 months and TTP at 12–23 months did not significantly affect levels of PAPP-A or free β-hCG. Conclusions: Increased time-to-pregnancy in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free β-hCG measured in the first trimester, suggesting that some of the well-known decrease in IVF-pregnancies could be related to sub-fertility instead of the infertility treatment per se. OP23.06 Effects of method of conception and gestational age on first trimester biochemical markers

Comparison of Three First Trimester Screening Algorithms for Trisomy 21 with and without Adjustment for Maternal Characteristics

Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics. Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free β-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status. Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg. Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.

OP27.02: Biochemical maternal serum markers alone and in combination predict extremes of Doppler abnormality (AREDV)

Objectives: Maternal serum markers and Doppler velocimetry of the umbilical artery are independent assessments of placental function. Our goal was to evaluate a relationship between maternal serum biochemical markers and extreme Doppler abnormalities of the umbilical artery-absent or reversed end diastolic velocity (AREDV). Methods: A retrospective analysis was performed on 68 patients with AREDV at 18–39 wks who had 1st (1T) and/or 2nd (2T) trimester trisomy screening along with 3700 controls who had 1T and 2T screening. The optimal combination of markers using continuous log MoM values was determined using stepwise logistic regression. Screening performance was evaluated based on modeling of log Gaussian Distributions. Results: Median MoMs in the AREDV group were: free beta hCG (1T)-1.07, PAPP-A-0.52, AFP-1.27, free beta hCG (2T)-1.45, unconjugated estriol (UE3)-0.74 and inhibin-2.15. Except for free beta hCG (FBhCG)-1T, all were significantly different from controls (P 95th percentile. A combination of PAPP-A, inhibin, AFP and UE3 log MoMs significantly predicted risk. Table 1 shows screening performance. Conclusions: Early knowledge of pregnancies that go on to have AREDV may have significant clinical implications. Our data indicate that a combination of maternal serum markers identifies up to 75% of these pregnancies. Such an approach may provide a more precise risk assessment for adverse pregnancy outcomes such as pre-eclampsia, IUGR and stillbirth.

Screening for fetal trisomy 21 in gestational weeks 6 and 7

The objective was to examine the applicability of the two biochemical markers PAPP-A and free beta-hCG for fetal trisomy 21 (T21) in very early pregnancy: gestational weeks (GA) 6 and 7. Medians for the two markers were generated on 36,745 fetal T21 unaffected pregnancies from gestational weeks 6-14. Concentrations were converted to Multiples of the Medians (MoMs). Median MoM from T21 affected pregnancies were compared over three intervals of gestational age; the very early weeks 6 and 7, weeks 8-10 and weeks 11-14. Median MoM from 9 affected pregnancies with a very early blood sample had a PAPP-A median MoM of 0.269, compared to 0.392 in weeks 8-10 and 0.531 in weeks 11-14. On the contrary, free beta-hCG diverged from the median with increasing gestational age. Our data suggest that PAPP-A is a useful marker for very early testing in first trimester screening for fetal T21.

First trimester aneuploidy screening in the presence of a vanishing twin: implications for maternal serum markers

To assess the impact of a vanishing twin on the levels of the biochemical markers used in the first trimester aneuploidy screening. A retrospective analysis of free beta-hCG and PAPP-A levels in 270 women with a normal singleton fetus with ultrasound evidence of a vanishing twin pregnancy. Marker levels (as MoM) were compared in three groups-76 women with a second empty gestational sac, 194 women with a second gestational sac containing a dead fetus with a measurable crown rump length (CRL), and 1360 matched singleton pregnancies. In women with a second empty gestational sac, the median free beta-hCG and PAPP-A MoMs (0.968 and 1.040, respectively) were not significantly different from the 1.0 MoM in singleton pregnancies. In the group with a vanished twin with a measurable-CRL-there was a significantly increased median PAPP-A MoM (1.317) but the median free beta-hCG MoM was not changed (1.024). Modelling this bias in PAPP-A MoM the detection rate for trisomy 21 would fall from 85 to 75%. First trimester screening in the presence of a vanishing twin may lead to errors in risk estimation. In such circumstances it may be advisable to restrict screening to the use of nuchal translucency (NT) alone.

OC28.02: Low levels of PAPP-A in first trimester of pregnancies conceived after ART and the prediction of adverse obstetric outcome

To evaluate the relation between low levels of maternal serum PAPP-A and the risk of adverse obstetric outcome in pregnancies conceived after IVF and ICSI. This is a nationwide prospective cohort study carried out in the period 1 April 2004—31 January 2006 in Denmark. 1000 women with singleton pregnancies following IVF and ICSI had first trimester combined screening performed. Follow up on pregnancy outcome was performed by questionnaire. MoM values of PAPP-A were calculated using either a standard median formula derived from an unselected group of pregnant women, or a median formula corrected for mode of conception established using IVF and ICSI pregnancies. Uncorrected mean MoM value of PAPP-A was 0.76. Excluding pregnancies with preterm delivery (PD = < week 37) and Small for Gestation infants (SGA = < − 2 SD) PAPP-A remained low (0.79). PAPP-A values not corrected for mode of conception were significantly lower in pregnancies with PD 0.60 MoM vs 0.79 MoM (p < 0.001), and in the group with SGA, 0.53 vs 0.77 (p < 0.001). When PAPP-A MoM values were corrected for mode of conception the difference remained significant. In logistic regression analyses uncorrected PAPP-A MoM was an independent significant predictor of SGA (< − 2 SD) with an OR: 0.41 (p = 0.027), and of preterm delivery (< 37 wks) with an OR: 0.61 (p = 0.03). However corrected MoM values could not predict adverse outcome. The higher prevalence of adverse outcome in ART pregnancies cannot explain the low levels of PAPP-A. However, only PAPP-A MoM values not corrected for mode of conception seem to be able to predict adverse outcome.

Early first‐trimester free β‐hCG and PAPP‐A serum distributions in monochorionic and dichorionic twins

In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free beta-hCG and PAPP-A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first-trimester free beta-hCG and PAPP-A between mono- and dichorionic twins. A total of 202 twin pregnant women participated in the study and agreed to donate first-trimester serum for research. The data of 200 twins with normal outcome were used for setting up reference values for free beta-hCG and PAPP-A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight-corrected MoM was 1.99 for free beta-hCG, and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower free beta-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p=0.002) and a significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U, p=0.003) compared to dichorionic. This study strengthened the need to make a distinction between mono- and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins.

The effect of a 'vanishing twin' on biochemical and ultrasound first trimester screening markers for Down's syndrome in pregnancies conceived by assisted reproductive technology

Previous studies have found that 1 in 10 in vitro fertilization (IVF) singletons originates from a twin gestation. First trimester Down's syndrome screening markers are altered in assisted reproductive techniques (ART) pregnancies compared with spontaneously conceived pregnancies. The presence of a perished embryo may further complicate prenatal screening among women pregnant after ART. The aim of this study was to assess the impact of a 'vanishing twin' on first trimester combined biochemical and ultrasound screening in pregnancies conceived after IVF and intracytoplasmatic sperm injection. From a national prospective cohort study concerning first trimester combined screening among women pregnant after ART, 56 cases of pregnancies with a vanishing twin were identified. As control group 897 cases of ART singleton pregnancies were used. All women completed a first trimester combined ultrasound and biochemical screening programme comprising serum PAPP-A and free beta-hCG together with nuchal translucency (NT) measurement. There were no significant differences in geometric mean MoM free beta-hCG and PAPP-A between pregnancies with an early (gestational week <9, EVT) or late vanishing twin (gestational week 9-13, LVT) or singleton pregnancies (0.98, 1.13 and 0.95 for free beta-hCG and 0.84, 0.80 and 0.74 for PAPP-A, respectively). Likewise, no difference was seen for NT measurements. The gestational age at the time of blood sampling and NT scan was similar for the three groups. The proportion of EVT pregnancies with a PAPP-A and free beta-hCG log(10)MoM value below the 5th%iles and above the 95th%iles of the value in the singleton pregnancies were 4.3%, 4.3%, 6.4% and 8.5%, respectively, which did not constitute a significant difference from singletons. The corresponding values for LVT pregnancies were 0%, 22.2%, 0% and 11.1%, respectively; however, these numbers were too small to allow for statistical calculations. First trimester biochemical screening markers in women pregnant after ART, and with a vanished twin diagnosed at early ultrasound, do not differ from those of other ART singleton pregnancies. In cases where the fetal demise was first diagnosed at the time of the NT scan, it is doubtful whether the serum risk assessment is as precise as it is in singleton ART pregnancies. No difference was seen for NT measurements.

Screening for adverse pregnancy outcome by Ductus venosus Doppler at 11–13+6 weeks – Ductus venosus at 11–13+6 weeks

Objective: To examine the contribution of abnormal flow in the ductus venosus(DV)at 11–13+6weeks in the prediction of major fetal abnormalities and fetal death.Methods: In this screening study for trisomy 21 in singleton pregnancies maternal characteristics, serum free ßhCG and PAPP-A,fetal nuchal translucency(NT)as well the a-wave in the DV were assessed. Patients were subdivided into 1.a normal outcome group of live births with no chromosomal abnormalities/fetal defects,2.miscarriage&lt;24 weeks/fetal death at or&gt;24 weeks,3.abnormal karyotype,4.fetal major defect. The significance of the contribution to adverse outcome of reversed a-wave in the DV,maternal characteristics,fetal delta NT,maternal serum log PAPP-A MoM and log free ß was analyzed. Results: Reversed a-wave was observed in 458(4.4%)of the 10,490 fetuses and the prevalence was significantly higher in the groups with miscarriage or fetal death(10.8%),abnormal karyotype(62.1%),fetal cardiac defect(25%)but not non-cardiac defect(4.3%)than in the normal outcome group(3.7%). Logistic regression analysis demonstrated a significant contribution to adverse outcome(3.5%)provided by reversed a-wave,NT,PAPP-A,Black ethnicity and maternal BMI. An adverse outcome was observed in 2.7% of the fetuses with NT at or &lt; the 95thcentile(in 2.6% of those with normal a-wave and in 7% of those with reversed a-wave)and in 19.3% of the fetuses with NT &gt; the 95thcentile(in 8.9% of those with normal a-wave and in 70.9% of those with reversed a-wave). Conclusion: Reversed a-wave in the DV is associated with increased risk for chromosomal abnormalities, cardiac defects and fetal death. However,in about 80% of cases with reversed a-wave the pregnancy outcome is normal

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

To examine the distribution of first-trimester biochemical markers of aneuploidy in twin pregnancies, and to assess whether there are differences in the distributions between monochorionic and dichorionic twins. Maternal serum-free beta-hCG and PAPP-A were measured between 11 + 0 and 13 + 6 weeks as part of a routine first-trimester screening program in conjunction with fetal nuchal translucency (NT) performed at two sites. Data from twin pregnancies were extracted from the fetal databases along with information on the chorionicty. The individual marker concentrations were expressed as weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM using data from singleton pregnancies as the reference. The overall medians were compared to those in singleton pregnancies and between monochorionic and dichorionic twins. Data was available from 1914 sets of twins. Of these, 1214 had information with respect to chorionicity, with 1024 being dichorionic and 190 being monochorionic. The overall median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM amongst twin pregnancies were 2.023 for free beta-hCG (sd log(10) MoM = 0.2611 and 2.121 for PAPP-A (sd log(10) MoM = 0.2255) -- both medians were significantly greater than the medians in singleton pregnancies (1.00 MoM). In the case of monochorionic and dichorionic twins the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected, free beta-hCG MoM's were not significantly different (1.983 v 2.041), however for PAPP-A the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM in monochorionic twins was significantly lower than in dichorionic twins (1.756 v 2.250) whilst the sd log(10) MoM's were not significantly different (0.2185 v 0.2167). Screening in twin pregnancies requires adjustment of the calculated MoM to account for the presence of two fetuses. In general, for free beta-hCG, this should be by dividing the observed corrected MoM by 2.023. For PAPP-A two different factors are required - 2.192 in dichorionic twins and 1.788 in monochorionic twins.

581: First trimester detection of trisomies 13/18 when NT availability is limited

LIMITED MARK EVANS, DAVID KRANTZ, TERRENCE HALLAHAN, JON CARMICHAEL, Comprehensive Genetics, New York, New York, NTD Labs/PerkinElmer, Huntington Station, New York OBJECTIVE: We assess the feasibility of incorporating T13/18 risk assessment within a first trimester Down syndrome screening protocol contingent for NT. STUDY DESIGN: Free Beta hCG and PAPP-A MoMs from 66 cases of T13/18 were used to model screening performance along with published distribution parameters for NT. At stage 1, based on biochemistry only, patients are classified as low risk ( 1 in 500), high risk ( 1 in 50) or intermediate risk (1 in 51 to 1 in 500). High risk patients would be offered CVS while intermediate risk patients would move on to stage 2 and be offered NT. Low risk patients would not be offered further testing. At stage 2, risks would be based on both biochemistry and NT with a cut-off of 1 in 150. RESULTS: The median (SD LOGe) MoM in T13/18 cases was 0.215 (0.7756) and 0.32 (0.7127) for free Beta and PAPP-A, respectively. The correlation between free Beta and PAPP-A was 0.3295. Using the contingent model described above, 2.7% would be offered NT. Overall 0.6% of the population would be offered CVS and 90% of T13/18 cases would be detected.