The first trimester ‘combined test’ for the detection of Down syndrome pregnancies in 4939 unselected pregnancies

The high detection rate (DR) for Down syndrome (DS) pregnancies which can be achieved by measuring fetal nuchal translucency (NT) early in pregnancy can be improved by combining it with placental hormones [pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (fβ-hCG)] and maternal age (‘combined test’). In this study we wanted to assess the DR using the ‘combined test’ in an unselected population of self-referred pregnant women at a false-positive rate (FPR) of about 5%. NT, PAPP-A, fβ-hCG and maternal age were measured in all women with singleton pregnancies who booked for delivery in our hospital from 1 December 1997 to 31 April 2000 and who were between 10 and 13 completed weeks of gestation [crown–rump length (CRL) 35–70 mm]. The specific DS risk was calculated using the computer program Alpha Version 5aa (Logical Medical Systems, London, UK). A total of 4939 women were tested. Out of 14 DS pregnancies that occurred during this period of time, 12 were detected with the test. A total of 246 women had a false-positive test result in a non-DS pregnancy (FPR 5.0%). This makes the ‘combined test’ by far the best test for the detection of DS pregnancies in a low-risk population. The constant increase in maternal age at the time of delivery can also lead to an improved DR if a simple age-dependant protocol for DS detection is used, but only at the price of a much higher number of amniocenteses and subsequent abortions. The DR for DS can be increased much more markedly using the ‘combined test’ with a FPR that still remains at the level as it was in the early 1970s. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal detection of X-linked ichthyosis by maternal serum screening for down syndrome

Maternal serum unconjugated oestriol (uE3) was measured in 15 375 pregnancies during 2 years of second-trimester risk assessment for Down syndrome using biochemical markers. Very low levels of uE3 (<0·1 MOM) were detected in 22 serum samples (0·14 per cent). Very low uE3 was associated with an adverse outcome in 13 pregnancies including fetal death and miscarriage (N=11), anencephaly (N=1), and Meckel—Gruber syndrome (N=1). Dry scales on the skin appeared in the first year of life in four boys. From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X-linked ichthyosis. Very low uE3 levels in the second trimester are indicative of this disease in pregnancies with normal ultrasound findings.     

上、下悬窗阻风能力对比研究

环境风会改变排烟窗附近的烟气流向和速度,影响建筑内烟气流动,进而导致建筑自然排烟效率受到影响。采用数值模拟方法,对比研究了排烟窗开启角度和环境风对上、下悬窗阻风能力的影响,分析了不同开窗角度下,悬窗进风量和进风区域随开窗角度和风速的变化规律。结果表明:上、下悬窗相对进风量与开窗角度均成指数关系,但上悬窗阻风能力弱于下悬窗,上悬窗开窗角度大于45°后即失去阻风能力,而下悬窗开窗角度大于75°后才逐渐失去阻风能力,且开窗角度小于30°时,下悬窗至少能比上悬窗多减少50%空气进入室内。上悬窗开窗角度小于56°时,主要进风区域为近窗下侧水平区域;下悬窗开窗角度小于30°时,主要进风区域为窗体两侧及远窗下侧竖直区域,随着开窗角度增大,上、下悬窗主要进风区域均过渡到远窗下侧竖直区域。窗体用于日常通风时建议优选上悬窗。若要用于排烟,则应首选下悬窗,开窗角度15°即可满足阻风要求,若选用上悬窗,开窗角度不宜大于45°。     

New estimates of down syndrome risks at chorionic villus sampling,amniocentesis, and livebirth in women of advanced maternal age from a uniquely defined population

Current measures of livebirth prevalence of Down syndrome are derived from data obtained up to 20 years ago, before the introduction of the prenatal diagnostic tests amniocentesis and chorionic villus sampling (CVS). For women aged 36–52 years, but who were not tested prenatally, we proposed to make a direct estimate of current livebirth prevalence of Down syndrome. We could also determine prevalence at the time of CVS and amniocentesis in women of the same age undergoing prenatal testing. Differences in these prevalences allow an estimation of the relative loss of Down syndrome during pregnancy. In Victoria, Australia, we identified 3041 women having CVS, 7504 having amniocentesis, and 13 139 having no test. Smoothed regression estimates of age-specific livebirth prevalence were found to be higher than in the early studies. The estimate of spontaneous loss was 17 per cent between the time of CVS and amniocentesis, and 18 per cent after the time of amniocentesis. The latter figure is lower than previous estimates and may be explained by a greater likelihood of a Down syndrome fetus surviving to be liveborn, given the modern approach to early obstetric intervention. These current risk estimates of livebirth may be useful updates for genetic counselling, but perhaps more importantly, may be used as precise maternal age-related risk figures, necessary in the design and implementation of prenatal screening programmes for Down syndrome.     

Risk for chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration a european collaborative study on prenatal diagnoses 1981

Based on 2890 prenatal diagnoses from 12 European countries the risk for a chromosomally abnormal fetus at amniocentesis after the birth of a child with a chromosome abnormality has been estimated to be 1.3 per cent when the mother's age is 34 years or less at amniocentesis and 1.8 per cent if the mother is older. This risk does not depend on paternal age, and it is independent of the type of the chromosome abnormality of the index child. Some geographical heterogeneities were detected. Therefore, the overall risk has to be considered as a rough estimate. The chromosome constitution of the abnormal fetus differed from that of the index patient in 21 of 41 cases. Several explanations for the higher risk have been discussed. If the index child had trisomy 18, 13 or a sex chromosome abnormality, the fetus tended to be a female. If the index child was a trisomy 21, the fetal sex ratio was normal.     

Macroglossia: Prenatal ultrasonographic diagnosis and proposed management

A case in which macroglossia was the sole unusual prenatal sonographic finding in a fetus affected with trisomy 21 is presented. The differential diagnosis of fetal macroglossia is given, emphasizing its strong relationship to fetal aneuploidy, together with the principles for evaluation and management.     

Serum PAPP-A and free β-hCG are first-trimester screening markers for down syndrome

Serum measurements of pregnancy-associated plasma protein A (PAPP-A) and the free β-human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP-A measurements (0·31 MOM, 95 per cent confidence interval (CI) 0·22–0·65 vs. normal 1·06, 95 per cent CI 0·89–1·20) were lower and free β-hCG subunit measurements (1·13 MOM, 95 per cent CI 0·93–2·63 vs. normal 0·91, 95 per cent CI 0·79–1·03) were higher at statistically significant levels. Receiver operator characteristic (ROC) curves showed that the highest sensitivity for detection, 71·2 per cent (95 per cent CI 54·7–87·6 per cent), was for depressed PAPP-A levels; the combination of low serum PAPP-A levels, maternal age, and elevated free β-hCG levels yielded a detection rate of 78·9 per cent (95 per cent CI 64·9–92·8 per cent) of the affected pregnancies at 8–12 weeks' gestation.     

First-trimester alpha-fetoprotein screening for Down syndrome

Screening for Down syndrome and other chromosomal aneuploidies by biochemical parameters in maternal serum is well established for the second trimester. With screening as late as 16 weeks of gestation, the option of chorionic villus sampling (CVS) unfortunately is lost. In our study population, the maternal serum alpha-fetoprotein (MSAFP) concentration was determined in 2471 women in the first trimester immediately prior to CVS. Although in this sample MSAFP tended to be lower in Down syndrome (DS) pregnancies than in pregnancies with a chromosomally normal fetus, at this early gestational age neither a fixed cut-off level of 0·5 multiples of the normal median (MOM) nor one of 0·6 MOM was suitable for identifying pregnancies at higher risk for DS. This also applied to trisomy 18, although on average MSAFP in trisomy 18 pregnancies was lower than in normal and DS pregnancies.