Objective: To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A).Methods: This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free β‐hCG and PAPP‐A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11–13‐week scan.Results: The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50^th, 95^th and 99^th centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free β‐hCG was 1.0 (range, 0.1–29.4) multiples of the median (MoM) and the median PAPP‐A was 1.0 (range, 0.2–3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60–80 kg and > 80 kg, different ethnic origins, cigarette smokers and non‐smokers, natural conception and @ in vitro fertilization. For a false‐positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73–89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56–72%) and by combined screening based on maternal age, fetal NT and maternal serum biochemistry it was 90% (95% CI, 84–96%).Conclusion: This study has validated the new risk algorithm and demonstrated that in combined screening for trisomy 21 based on maternal age, fetal NT and free β‐hCG and PAPP‐A the detection rate is about 90% for a 3% false‐positive rate. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Objectives: To examine the effect of deviations in median nuchal translucency thickness (NT) and the spread in measurements on the performance of screening for trisomy 21 by maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry.Methods: We simulated the NT and multiples of the median values for pregnancy‐associated plasma protein‐A (PAPP‐A) and free β‐human chorionic gonadotropin (β‐hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks of gestation. Detection rates for trisomy 21 and false‐positive rates were calculated without adjustments in NT and by adding or subtracting values ranging from 0.1 to 1.0 mm to each observed measurement. In addition, the effects of variation in the scatter of NT measurements were examined by applying a multiplicative factor ranging from 0.5 to 2 to the SD.Results: The detection rate of trisomy 21 for a fixed false‐positive rate of 3% in screening by maternal age and fetal NT was 72%, and in screening by maternal age, fetal NT and serum free β‐hCG and PAPP‐A it was 86%. A consistent underestimate or overestimate in the measured NT reduced the detection rate of trisomy 21 for a fixed‐false positive rate. At a fixed screen‐positive cut‐off an underestimate in fetal NT reduced the detection rate whereas an overestimate in NT increased the false‐positive rate. A widening in the scatter of measurements had only a small impact on the detection rate but it caused a major increase in the false‐positive rate.Conclusions: High performance of screening necessitates appropriate measurement of fetal NT. This paper demonstrates the effect of deviations in the median and SD of NT from the expected on the performance of screening and can form the basis of audit of results of individual sonographers. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Objective: To describe the contribution of 3-dimensional computed tomography (3D-CT) in the prenatal diagnosis of skeletal dysplasias (SD) in a cohort of patients with inconclusive diagnosis by ultrasound (US). Methods: Between May 2007 and February 2010, six pregnant women with suspected fetal SD on US examination but with no specific diagnosis were studied with 3D-CT. The images were evaluated by a multidisciplinary team who proposed a likely diagnosis. Further postnatal workup included clinical and radiological evaluation in all cases. Prenatal and postnatal diagnoses were compared. Results: The use of 3D-CT provided a precise diagnosis confirmed postnatally in 5/6 patients. These included osteogenesis imperfecta type II (n = 2), osteogenesis imperfecta type III (n = 1), chondrodysplasia punctata (n = 1) and thanatophoric dysplasia type I (n = 1). A precise diagnosis could not be made in 1 case – either pre- or postnatally. Conclusion: Prenatal 3D-CT contributed to the diagnosis of the specific fetal SD in the majority of these cases. 3D-CT may have a complementary role to US where fetal SD is suspected, but no specific diagnosis can be made using US alone. Further studies on clinical performance and risk-benefit analysis are needed.

Objectives: To investigate whether the maternal serum concentration of activin A at 11–13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-α receptor-1 (TNF-R1). Material and Methods: Serum activin A, TNF-R1, PAPP-A and uterine artery PI were determined in a case-control study of 126 cases that developed preeclampsia, 88 that developed gestational hypertension and 214 controls. Results: In preeclampsia, compared to controls, uterine artery PI, serum activin A and serum TNF-R1 were higher and serum PAPP-A was lower. In gestational hypertension, compared to controls, serum activin A was higher but uterine artery PI, serum PAPP-A and serum TNF-R1 were not significantly different. There were no significant associations between serum activin A and either uterine artery PI or serum TNF-R1 in either the hypertensive groups or the controls. Discussion: The data do not support the hypothesis linking activin A with impaired trophoblastic invasion of the maternal spiral arteries, placental hypoxia and the release of cytokines which in turn cause endothelial dysfunction and the development of the clinical symptoms of the disease.