Temporal changes in the utilization of amniocentesis for prenatal diagnosis by women of advanced maternal age, 1976–1983

Utilization of amniocentesis for prenatal diagnosis because of the indication of advanced maternal age (≥ 35 years at delivery) was examined in the population of B.C. over an 8-year period (1976–1983). As of 1983, approximately one out of three eligible women (≥ 35 years at delivery) is having the test. In the older group (≥ 38 years at delivery) approximately one out of two eligible women is having the test. The data do not indicate that the proportion of eligible women having amniocentesis has reached a plateau; utilization is continuing to increase. It appears that prenatal diagnosis is an ethically acceptable alternative for a large proportion of the population.     

Down syndrome maternal serum marker screening after 18 weeks' gestation

Women having access to prenatal care late in pregnancy may still wish to benefit from maternal serum screening for Down syndrome. Therefore, we established reference values for α-feto protein (AFP) and free β-human chorionic gonadotrophin (β-hCG), and assessed the diagnostic value of maternal serum marker screening at 18–35 weeks' gestation based upon a series of 4072 sera from unaffected pregnancies and 118 sera from pregnant women with fetuses affected by Down syndrome. Using a 1/250 risk cut-off, a detection rate of 72.9% (95% CI = 71.5–74.3%) was achieved with a false-positive rate of 7.51% (95% CI = 6.71–8.3%). This was not significantly different from the percentages observed in our 14–17 weeks routine screening (50 596 patients): 71.9% (95% CI = 71.5–72.3%) and 6.48% (95% CI = 6.28–6.68%), respectively. Detection and screen-positive rates were, respectively, 51.3% (95% CI = 35.6–67.0%) and 5.95% (95% CI = 5.12–6.68%) in women aunder 35 years of age, and 84.8% (95% CI = 76.9–92.7%) and 24% (95% CI = 20.7–27.3%) in women aged 35 years and over. In conclusion, maternal serum marker screening is feasible at 18 weeks' gestation and later, which may be of interest in selected cases. Copyright © 2002 John Wiley & Sons, Ltd.     

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.     

Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages

Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women ≥35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women ≥35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (β-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35–45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2×2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57–71% detection rates were achieved at 35 years with 12–18% false-positive rates. At 45 years, 61–100% detection rates were achieved with 66–95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35–45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed. Copyright © 2002 John Wiley & Sons, Ltd.     

Compromise ultrasound dating policy in maternal serum screening for Down syndrome

Routine ultrasound biometry is the method of choice for gestational dating when screening for Down syndrome. However, it is costly and an alternative policy is to restrict ultrasound to women most likely to have menstrual dating errors. This was evaluated by statistical modelling with parameters from 14 274 women screened between January 1997 and July 2001 using free beta-human chorionic gonadotrophin (free β-hCG), α-fetoprotein (AFP) and unconjugated estriol (uE₃). A total of 12 711 (89%) women had both ultrasound and menstrual gestations, but in 4101 (29%) women either the last menstrual period (LMP) was uncertain or a pill-withdrawal period, or there were irregular or abnormal length cycles. The LMP was not entered in the test request form for a further 1404 (9.8%) women. Routine ultrasound dating yielded a predicted detection rate higher than for menstrual dating by 3.9–7.1%, depending on the marker combination and cut-off. The false-positive rate was reduced by 0.2–1.1%. Selectively scanning the 39% with unreliable dates increased detection by 2.6–4.6%, and reduced the false-positive rate by 0.04–0.6%. Some centres only use the ultrasound estimate of gestation when it differs from the menstrual estimate by more than 7 days. Such a rule reduces the gain in detection rate to 2.5–4.6% for routine ultrasound and 1.7–3.1% with the compromise policy; the false-positive rate reductions are 0.06–0.6% and 0.0–0.3%, respectively. We conclude that if routine ultrasound is not financially and practically feasible, the compromise policy yields a clinically important improvement in screening performance compared to menstrual dating. Copyright © 2002 John Wiley & Sons, Ltd.     

Early amniocentesis and fetal nuchal translucency in women requesting karyotyping for advanced maternal age

Fetal nuchal translucency was measured at 11–14 weeks' gestation in 97 pregnancies referred for early amniocentesis for advanced maternal age. The nuchal translucency was abnormal in 11 fetuses and the fetal karyotype was abnormal in five of these 11 cases. The karyotype was normal in 86 cases with normal nuchal translucency. The culture failure and miscarriage rates associated with early amniocentesis were 3·3 per cent and 2·2 per cent respectively. Amniotic fluid leakage occurred in 6 per cent of cases. In women requesting fetal karyotyping for advanced maternal age without additional biochemical screening, fetal nuchal translucency should be measured at 11–14 weeks. If the nuchal thickness is ≥ 3 mm, a first-trimester diagnostic procedure is indicated; however, if it is <3 mm, amniocentesis should be delayed until 16 weeks' gestation.     

Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening

Of the 65 328 pregnancies of South Australian mothers screened by the South Australian Maternal Serum Antenatal Screening (SAMSAS) Programme between 1 January 1991 and 31 December 1997, 3431 (5.25%) were declared at increased risk of fetal Down syndrome. Fetal or neonatal karyotype was determined in 2737/3431 (79.8%) of these pregnancies, including 16 with early fetal loss. Interrogation of the database of the South Australian Neonatal Screening Service showed 643 live-born infants whose phenotype was not subsequently questioned among the 694 pregnancies whose karyotype was not determined. Of the remaining 51/3431 pregnancies, 19 ended in early fetal loss without karyotyping and no newborn screening or other records could be found for 32 cases. The 129 instances of abnormal karyotype found were Down syndrome (84), trisomy 18 (four), trisomy 13 (three), triploidy (two), female sex chromosome aneuploidy (six) and male sex chromosome aneuploidy (five), inherited balanced rearrangements (19), mosaic or de novo balanced abnormalities (four) and unbalanced karyotypes (two). In the pregnancies declared at increased risk of fetal Down syndrome, only the karyotype for Down syndrome occurred with a frequency greater than that expected for the general, pregnant population. Copyright © 2001 John Wiley & Sons, Ltd.