Centre-specific ultrasound nuchal translucency medians needed for Down syndrome screening.

Nuchal translucency (NT) measurements were compared between 13 centres participating in a multi-marker Down syndrome screening program. Results from 4765 women were analysed, and there were highly statistically significant between-centre differences after allowing for gestation (P < 0.0001). Examination of maternal serum marker levels, expressed in multiples of the median (MoM) for gestation, showed that this was not due to gestational errors. Regression analysis was carried out to derive an equation with a centre-specific component that could be used to express NT in MoMs. Use of this equation reduced the variance of logNT by 15% compared to a published equation. The equation can be readily modified for use in other centres.

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 beta-hCG), alpha-fetoprotein (AFP) and unconjugated estriol (uE(3)). 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.

Descriptive information about Down syndrome: a content analysis of serum screening leaflets.

It is recommended practice that prior to prenatal screening, women receive information about the condition(s) being tested for. The present study critically evaluated information about Down syndrome as contained in 80 leaflets provided to pregnant women in the UK prior to serum screening. First, a content analysis by information type was conducted to give an overall picture of the material provided. Second, the image of the condition as conveyed by the content was analysed and compared with a similar study of cystic fibrosis (CF) screening leaflets. The majority of information (89%) was of a medico-clinical nature, with 11% addressing other issues associated with Down syndrome. The median number of sentences describing the condition was one, with 33% of the leaflets containing no descriptive information. Overall, a negative image of Down syndrome was conveyed by the leaflets, which contrasted with a more neutral image of CF in the comparison study. In order to facilitate informed choices, more attention should be paid to providing women with information about Down syndrome prior to serum screening. Such information needs to be more balanced in its construction, with thought given to the needs of the reader, and to the tone and the content of the message conveyed.

Quality of written information used in Down syndrome screening.

A qualitative assessment was performed on 81 leaflets used in maternal serum Down syndrome screening from National Health Service (NHS) obstetric units and private screening services. Quality was assessed by factual content, presentation and reading ease and this was amalgamated into a single overall score expressed as a percentage of the maximum possible score. Eleven (14%) leaflets included all eight factual items recommended by the Royal College of Obstetricians and Gynaecologists (RCOG); only one included these and a further nine items recognised as important to the consumer. Three (4%) leaflets contained information that was incorrect and 17 (21%) that was misleading or inconsistent. Using published criteria six (7%) leaflets were well presented and ten (12%) were fairly easy to read. The average reading age was 13-14 years. The overall quality score showed that five leaflets had 80% or more of the total possible score. However a substantial number, 15 (19%), were totally unacceptable having scores of 40% or less. In general the quality of leaflets used in the UK is considered poor. A national peer-reviewed leaflet should be prepared which can be modified to suit local policy.

Maternal serum human chorionic gonadotrophin levels in systemic lupus erythematosus and antiphospholipid syndrome.

Maternal serum human chorionic gonadotrophin (hCG) levels were measured during the second and the third trimesters of pregnancy in patients with either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). All results were expressed in multiples of the gestation-specific normal medians (MoM). The median MoM level in 17 samples from SLE patients was 1.48 compared with 0.79 MoM in 99 controls of similar gestation (p < 0.002, Wilcoxon Rank sum test). In contrast the median MoM level in 19 samples from primary APS patients was only 1.14. These preliminary findings should be further studied to evaluate the implications for Down syndrome screening, detection of SLE cases during pregnancy and the prediction of adverse outcome in SLE gestations.

Use of videotapes for viewing at home to inform choice in Down syndrome screening: a randomised controlled trial.

A randomised trial was carried out to assess the effect of a Down syndrome screening video on test uptake, knowledge and psychological stress. A total of 2000 women referred for antenatal care were allocated to two equal groups: one to be sent a video to their home, before their hospital booking visit, and a control group. All women also received screening information in the form of a leaflet before booking and from a midwife at booking. The video had no effect on the screening uptake rate: 638/993 (64.2%) and 652/1007 (64.7%) in the video and control groups, respectively. Women were requested to return the video for reuse in other pregnancies and 612 (62%) did so. A subset of 1200 women were selected to be posted at 17-19 weeks' gestation a self-completed questionnaire to assess the psychological endpoints. Knowledge of screening was increased in the video group with a mean score of 7.3 compared with 6.7 in the controls, a statistically significant difference (t=3.24, p=0.0005). There were no significant differences between the groups in specific worries about abnormalities in the baby, and general anxiety. We conclude that a video can increase knowledge without affecting the uptake of the test, or psychological stress.

Familial Down syndrome: evidence supporting cytoplasmic inheritance.

The frequently observed familial aggregation of Down syndrome (DS) 47,+21 and other aneuploidies and the phenomenon of double aneuploidy involving DS cannot be accounted for by chance alone. To clarify possible aetiological factors, pedigrees from all 7 affected families with repeated marriages referred to two regional genetics centres were examined. In each case the recurrence of aneuploidy was on the mother's side (p<0.01). Such a pattern suggests cytoplasmic inheritance of a risk factor. The hypothesis that mitochondrial DNA mutations have a role in the aetiology of DS is supported by other observations as well as by theoretical considerations.

Current awareness in prenatal diagnosis.

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General Interest; 3 Normal Fetal Development; 4 Gametogenesis and Pre-implantation Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8 Maternal Screening; 9 Screening for Carriers of Genetic Abnormality; 10 Technological Developments; 11 Confined Placental Mosaicism and Uniparental Disomy; 12 Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14 Fetal Therapy; 15 Psychosocial Aspects; 16 Epidemiology and Environmental Factors; 17 Developmental Pathology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

Serum inhibin A levels in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome.

Maternal serum inhibin A levels are increased on average in pregnancies affected by Down syndrome (DS). However, some reports have found increased serum levels in women with pre-eclamptic toxaemia as well. In the current study, maternal serum inhibin A was retrospectively measured in a series of 32 serum samples from pregnant women previously diagnosed as having either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). For comparison, normal medians were calculated from 57 unaffected control pregnancies together with a total of 854 samples tested at 13-19 weeks of gestation as part of the routine antenatal DS screening. All results were expressed in multiples of the gestation specific normal medians (MoM). A cubic regression formula was fitted, weighting for the number of women tested at each gestation. The median MoM value in the 16 cases of SLE and the 16 cases of primary APS is 0.60 (95% confidence interval 0.40-0.91) and 0.88 (95% confidence interval 0.66-1.17), respectively. For primary APS this was not statistically significant, whereas the SLE patients had a highly statistically significant reduction of serum inhibin A (p<0.002, Wilcoxon Rank sum Test, 2 tailed). Six pregnancies in the SLE group had a complicated obstetric outcome, i.e. missed abortion, placental abruption, exacerbation of the underlying disease which necessitated delivery, and severe postpartum haemorrhage. In 85% of this subgroup, serum inhibin A levels were below the normal 10th centile. The current data suggest that serum inhibin A is decreased on average in SLE patients. Those preliminary results might have various obstetric implications such as antenatal DS screening of SLE patients, identification of pregnant women at risk of developing SLE, who have presented for routine DS screening and for monitoring SLE patients throughout their pregnancy.

Maternal urine hyperglycosylated hCG in pregnancies with Down syndrome.

Stored maternal urine samples were used to determine the distribution of hyperglycosylated human chorionic gonadotrophin (H-hCG) levels in pregnancies with Down syndrome. A total of 349 samples from singleton pregnancies, including 45 with Down syndrome, were tested at 10-19 weeks' gestation. Urinary concentration was allowed for by expressing H-hCG in ng per mmol creatinine. The median level in Down syndrome was 3.63 multiples of the gestation-specific median in unaffected pregnancies (p<0.0001, Wilcoxon rank-sum test, two-tail). However, creatinine levels were relatively low in cases and creatinine did not fully correct for concentration. When this bias was allowed for, the median level was 3.34 multiples of the normal median (MoM). The H-hCG elevation in affected pregnancies was more marked at 14 weeks' gestation or later: a median of 4.64 MoM and allowing for creatinine bias 4.46 MoM.

Maternal serum activin A and follistatin levels in pregnancies with Down syndrome.

Inhibin A is now an established second-trimester maternal serum marker of Down syndrome. Since activin A has a common beta-subunit to inhibin A we evaluated this substance and its binding protein, follistatin, as potential markers. We studied 30 affected and 199 unaffected pregnancies at 13-16 weeks' gestation. There was a statistically significant increase in activin A level among the cases with 8 (27 per cent) exceeding the 90th centile in the controls, and 6 (20 per cent) above the 95th centile. However, the extent of overlap was too great to be of value in screening. There was a small decrease in follistatin levels among cases but it did not reach statistical significance.

Calculating correct Down's syndrome risks.

Women having both first trimester nuchal translucency and second trimester serum screening tests are likely to receive two different Down's syndrome risks. Neither will be correct, and we describe how to calculate a valid combined risk. This uses the reported serum-based risk and a likelihood ratio derived from the nuchal translucency report. Tables, figures and examples are provided to aid the calculation of the likelihood ratio from either the nuchal translucency in multiples of the normal median, the nuchal translucency and crown-rump length in millimetres, or the reported prior and nuchal translucency-based risks.

The effect of smoking in pregnancy on maternal serum inhibin A levels.

To assess the effect of smoking on maternal serum, second-trimester inhibin A levels, we studied a database of 1277 women undergoing antenatal serum screening. There were 75 smokers, 1008 non-smokers and 194 women in whom smoking status was undetermined. All groups were matched for age, gestation and parity. The median level of inhibin A in smokers was 1.47 multiples of the normal gestation-specific median (MOM) as compared with 1.01 MOM in non-smokers and 0.95 MOM in the undetermined group. The increase was highly statistically significant (p<0.0001, Wilcoxon rank sum test, two-tail). On the basis of these results we conclude that if inhibin A is used as a marker, adjustment for maternal smoking status may be necessary.