A. C. Shalmi

Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia.

Objectives: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. Methods: We developed a semiautomated, time-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78–1248 &mgr;g/L. Serum samples derived from women in the first trimester of a normal pregnancy (n = 324) and from women who later developed preeclampsia during pregnancy (n = 160) were obtained from the First Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. Results: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had a mean log MoM of –0.066, which was significantly lower than the mean log MoM of –0.001 for ADAM12 levels observed in serum samples from women with normal pregnancy (P = .008). The mean log MoM was even lower in serum derived from preeclamptic women whose infants weight at birth was less than 2,500 g (n = 27, mean log MoM of –0.120, P = .053). Conclusion: The maternal serum levels of ADAM12 are significantly lower during the first trimester in women who later develop preeclampsia during pregnancy when compared with levels in women with normal pregnancies. Because the secreted form of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early marker for preeclampsia. Level of Evidence: II-2

Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women

To determine the performance of screening for Down syndrome (DS) and other major chromosomal abnormalities using nuchal translucency (NT), free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) in a prospective study of a non‐selected population.

Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening

The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark.

Free leptin index and PAPP‐A: a first trimester maternal serum screening test for pre‐eclampsia

Prophylaxis with low‐dose aspirin may reduce the risk of pre‐eclampsia (PE) if introduced in first trimester. The performance of first trimester maternal serum screening for PE using free leptin index (fLI) and PAPP‐A, where fLI = leptin/leptin soluble receptor was studied.

Increased nuchal translucency, normal karyotype and infant development

To investigate whether chromosomally normal fetuses with a nuchal translucency (NT) ≥ 99th percentile (3.5 mm) in the first trimester have an increased risk of delayed development at 2 years of age.

First trimester Down syndrome screening : Distribution of markers and comparison of assays for quantification of pregnancy-associated plasma protein-A

Objective. First trimester screening for fetal chromosomal disease is now possible using the maternal serological markers pregnancy‐associated plasma protein‐A (PAPP‐A) and the free β‐form of human chorionic gonadotrophin (βhCG) in combination with the ultrasound marker nuchal translucency (NT) thickness. The availability of well‐defined analytical methods and reference ranges for the involved parameters, and knowledge of the correlation between markers and clinical parameters, e.g. maternal weight, parity and age, are important for the design of efficient screening programs. Material and methods. Women (n = 2702), with singleton pregnancies, participating in the Copenhagen First Trimester Screening Study had PAPP‐A and βhCG values determined and NT measured at a gestational age of 11 to 14 weeks, as determined from crown rump length (CRL). The distribution of gestational age‐independent multiples of the median (MoM) of the parameters was defined and reference intervals established. Three methods for determination of PAPP‐A, one manual in‐house poly‐monoclonal ELISA and two commercial semi‐automatic double‐monoclonal methods, i.e. PAPP‐A for the AutoDelfia platform and PAPP‐A for the Kryptor platform, were compared in 260 women. Results. All markers had log‐normally distributed MoMs. Gestational age independent reference intervals were established. Maternal weight should be included in risk algorithms. The semi‐automated PAPP‐A assays (AutoDelfia and Kryptor) gave similar values, mean difference 10.5 %, whereas the manual assay gave higher values, mean differences 50.4 % and 41.0 %, respectively, Conclusions. This calls for better standardization and a uniform quality control scheme that is focused on discriminatory ability rather than adherence to mean values from a large number of laboratories.

Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

Abstract Background: Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. Methods: PP13 was measured in first trimester (week 10+3–13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation. Results: In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8–85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1–50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4–142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI. Conclusions: PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Maternal Serum Resistin Is Reduced in First Trimester Preeclampsia Pregnancies and Is a Marker of Clinical Severity

Objective: To examine whether resistin levels in first trimester maternal serum are associated with insulin resistance or preeclampsia (PE). Methods: A case-control study of maternal serum resistin concentration conducted using 285 normal pregnancies and 123 PE pregnancies matched for gestational age, parity and maternal age. Samples were taken in gestational weeks 10+0–13+6. Results: There was a negative correlation between resistin and clinical severity of PE, but no correlation with IS, TNF-α, body mass index, birth weight and pregnancy length. Conclusions: Resistin is reduced in first trimester of PE pregnancies, particularly in severe PE. Inflammation and IS cannot explain this phenomenon.

OC057: Combined first and second trimester ultrasonic and serological screening for Down's syndrome—including an evaluation of ProMBP as a marker

To evaluate the possible relationship between ultrasound markers and second trimester maternal serum markers, the current study evaluates seven ultrasound markers in 2183 control pregnancies. We identified 2183 women with apparently normal singleton fetuses who underwent a second trimester ultrasound (14–22 weeks) and maternal serum biochemistry (triple test) screening over a three-year period. Among the 2183 apparently normal fetuses, 304 (14%) had a known normal karyotype and the remaining fetuses were presumed to be normal. A total of seven ultrasound markers were recorded: three were treated as continuous variables and four as categorical variables. The continuous variables were nuchal fold thickness (NF), humerus length (HL), and femur length (FL). These variables are gestational age dependent and as a result were expressed as multiples of the median. Results: The regression equations derived for the continuous variables of nuchal fold thickness (NF), femur length (FL) and humerus length (HL) were NF = − 1.9597 + 1.8888 (BPD) − 0.1727 (BPD) (BPD; FL = − 0.9371 + 0.8595 (BPD; and HL = − 0.6439 + 0.7775 (BPD) respectively. Among the continuous variables, weakly negative but statistically significant correlations were observed between HCG and both femur length (p < 0.01) and humerus length (p < 0.01). A significant correlation was observed between Log HL (MOM) and Log FL (MOM) (p < 0.01). Among the categorical ultrasound markers, no significant correlations at the 1% level (p < 0.01) were found with the biochemical markers. However, at the 5% (p < 0.05) level, the median HCG (MOM) was lower when an EIF was detected. Hyperechoic bowel also tended to be associated with higher median HCG (MOM) and AFP (MOM) levels (p < 0.05). We found that ultrasound and biochemical markers are largely independent in unaffected pregnancies. However, previous data (Souter et al. Benn et al.) has shown that there are some significant correlations between pairs of serum and ultrasound parameters in Down syndrome pregnancies. Correlation coefficients can be viewed as weighting factors in risk estimation with positive correlations diminishing the importance of the two variables in the calculation. For accurate risk estimation, correlation in both affected and unaffected pregnancies need to be considered.

OC01.04: Perinatal outcome after first trimester risk assessment in monochorionic and dichorionic twin pregnancies: a Danish national database study

1.3 to 31.6). We found no differences between late preterm infants and controls in RNFL thickness (96.5 μ vs. 98.7 μ; P = 0.31), macular thickness (279 μ vs. 283.3 μ; P = 0.15) and abnormal Bender test (14.3% vs. 6.4%; P = 0.42). All the late preterm children with abnormal Bender test were born SGA. Conclusions: Although late preterm had worse perinatal outcome, neuronal and cognitive suboptimal development after 6 years are more associated with late onset growth restriction rather than late prematurity.