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Objective: To determine whether assessment of ductus venosus flow at 11-13 weeks' gestation improves the detection rate of cardiac defects achieved by screening with nuchal translucency (NT) thickness., Methods: Prospective first-trimester screening for aneuploidies, including measurement of fetal NT and assessment of ductus venosus flow. The performance of different combinations of increased fetal NT and abnormal blood flow in the ductus venosus in screening for major cardiac defects was examined., Results: The study population of euploid fetuses included 85 cases with major cardiac defects and 40,905 with no cardiac defects. The fetal NT was above the 95th and above the 99th centile in 30 (35.3%) and 18 (21.2%) of the fetuses with cardiac defects, respectively, and in 1,956 (4.8%) and 290 (0.7%) of those without cardiac defects, respectively. Reversed a-wave was observed in 24 (28.2%) of the fetuses with cardiac defects and in 856 (2.1%) of those with no cardiac defects. Specialist fetal echocardiography for cases with NT above the 99th centile and those with reversed a-wave, irrespective of NT, would detect 38.8% of major cardiac defects at an overall false- positive rate of 2.7%., Conclusions: Assessment of ductus venosus flow improves the performance of NT screening for cardiac defects., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To examine the performance of the 11-13 weeks scan in detecting non-chromosomal abnormalities., Methods: Prospective first-trimester screening study for aneuploidies, including basic examination of the fetal anatomy, in 45 191 pregnancies. Findings were compared to those at 20-23 weeks and postnatal examination., Results: Aneuploidies (n = 332) were excluded from the analysis. Fetal abnormalities were observed in 488 (1.1%) of the remaining 44 859 cases; 213 (43.6%) of these were detected at 11-13 weeks. The early scan detected all cases of acrania, alobar holoprosencephaly, exomphalos, gastroschisis, megacystis and body stalk anomaly, 77% of absent hand or foot, 50% of diaphragmatic hernia, 50% of lethal skeletal dysplasias, 60% of polydactyly, 34% of major cardiac defects, 5% of facial clefts and 14% of open spina bifida, but none of agenesis of the corpus callosum, cerebellar or vermian hypoplasia, echogenic lung lesions, bowel obstruction, most renal defects or talipes. Nuchal translucency (NT) was above the 95th percentile in 34% of fetuses with major cardiac defects., Conclusion: At 11-13 weeks some abnormalities are always detectable, some can never be and others are potentially detectable depending on their association with increased NT, the phenotypic expression of the abnormality with gestation and the objectives set for such a scan., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To determine if development of preeclampsia is preceded by altered maternal plasma P-selectin and if the levels are related with uterine artery pulsatility index., Methods: Plasma P-selectin and uterine artery pulsatility index were measured at 11-13 weeks in 121 cases that subsequently developed preeclampsia, 87 cases that developed gestational hypertension and 208 unaffected controls., Results: In the preeclampsia group the median multiple of the median in controls (MoM) P-selectin and uterine artery PI were significantly increased (1.2 MoM and 1.3 MoM). There was no significant association between P-selectin and uterine artery pulsatility index in either the preeclampsia or control group., Conclusion: In pregnancies that develop preeclampsia there is evidence of platelet activation from the first trimester. However, there is no direct link between the degree of impaired placentation and platelet activation.

Objectives: To examine the performance of screening for hypertensive disorders in pregnancy and to compare systolic blood pressure (BP), diastolic BP, and mean arterial pressure (MAP) measured by validated automated devices in a large population of pregnant women at 11-13 weeks., Methods: We recorded maternal variables and measured BP by automated devices in 9149 women with singleton pregnancies. The performance of screening for preeclampsia (PE) and gestational hypertension (GH) by combinations of disease-specific maternal factor-derived a priori risk with systolic BP, diastolic BP, and MAP was determined., Results: There were 8061 cases that were unaffected by PE or GH, 37 that developed PE requiring delivery before 34 weeks (early-PE), 128 with late-PE, and 140 with GH. The systolic BP, diastolic BP, and MAP were significantly higher in early-PE, late-PE, and GH than in the controls (p < 0.0001). The systolic BP was significantly higher in early-PE than in late-PE (p = 0.008) and both systolic BP and MAP were significantly higher in early-PE than in GH (p < 0.01). The best performance in screening was provided by MAP. The detection rate of early-PE at a 10% false-positive rate increased from 47% in screening by maternal factor-derived a priori risk alone to 76% in screening by its combination with MAP. The respective detection rates for late-PE increased from 41 to 52% and for GH increased from 31 to 48%., Conclusion: The measurement of BP can be combined with the maternal factor-derived a priori risk to provide effective first-trimester screening for PE and GH.

Objective: The objective of this study was to investigate the potential value of ADAM12 (A disintegrin and metalloprotease) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities., Study Design: The concentration of ADAM12 was measured at 11-13 weeks in cases of trisomy 21 (n = 49), trisomy 18 (n = 28), trisomy 13 (n = 20), Turner syndrome (n = 29), triploidy (n = 10), and euploid pregnancies (n = 272). The levels of ADAM12, expressed as multiples of median (MoM), were compared in cases and controls and were assessed for association with free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A)., Results: The median ADAM12 value in trisomy 21 (0.961 MoM) was not significantly different from the euploid fetuses (1.013 MoM), but in trisomy 18 (0.697 MoM), trisomy 13 (0.577 MoM), triploidy (0.426 MoM), and Turner syndrome (0.747 MoM), the levels were significantly lower. In both the euploid and aneuploid pregnancies, there was a significant association between ADAM12 and free beta-hCG and PAPP-A., Conclusion: Maternal serum ADAM12 concentration at 11-13 weeks of gestation is unlikely to be useful in first-trimester screening for chromosomal abnormalities because in trisomy 21 the levels are not significantly different from normal, and in the other chromosomal defects, there is a significant association between ADAM12 and the traditional biochemical markers of free beta-hCG and PAPP-A.

Objective: To examine the possible association of maternal serum a disintegrin and metalloprotease (ADAM12) in the first trimester of pregnancy and subsequent development of preeclampsia, delivery of small for gestational age (SGA) neonates, and spontaneous preterm delivery., Methods: The maternal serum concentration of ADAM12 at 11 0/7 to 13 6/7 weeks was measured in 128 cases of preeclampsia, 88 cases of gestational hypertension, 296 cases with SGA neonates, 58 cases of spontaneous preterm delivery, and 570 controls. Regression analysis was used to determine which of the maternal factors and fetal crown rump length were significant predictors of ADAM12 in the control group, and from the regression model the value in each case and control was expressed as a multiple of median (MoM). The levels of ADAM12 MoM were compared in cases and controls., Results: In the control group the concentration of ADAM12 increased with fetal crown rump length, decreased with maternal weight and was higher in African-American than in white women. There was a significant association between ADAM12 and pregnancy-associated plasma protein A (r=0.417, P<.001) and between each metabolite and birth weight percentile (r=0.176, P<.001 and r=0.109, P=.009). In the SGA group, the median ADAM12 concentration (0.848 MoM) was lower (P<.001), but in pregnancies complicated by preeclampsia (0.954 MoM), gestational hypertension (1.013 MoM), and spontaneous preterm delivery (1.048 MoM) the levels were not significantly different from controls (1.011 MoM)., Conclusion: There is a good correlation between the maternal serum ADAM12 and pregnancy-associated plasma protein A concentration. Measurement of ADAM12 does not provide useful prediction of SGA, preeclampsia, or spontaneous preterm delivery., Level of Evidence: II.