Urinary beta-core hCG: screening for aneuploidies in early pregnancy (11-14 weeks' gestation).

Initial studies at 17-22 weeks' gestation evaluating urinary beta-core human chorionic gonadotrophin (hCG) as a marker for Down's syndrome had suggested that it may have more potential than its serum counterpart. This study measured maternal urinary beta-core-hCG and creatinine at 11-14 weeks' gestation in a series of 26 aneuploidies (nine trisomy 21, five trisomy 18, four 45,X0, and eight others). The normal range for beta-core-hCG and beta-core-hCG/ creatinine was derived from 198 normal singleton pregnancies. Trisomy 18 cases (n = 5) had low maternal urinary beta-core-hCG creatinine levels (median 0.35 MOM, range 0.08-0.82 MOM). Whereas the other aneuploidies had no particular pattern; in particular, the trisomy 21 cases (n = 9) (median 1.16 MOM, range 0.3-4.74 MOM) did not differ significantly from 1 MOM. The findings imply that maternal urinary beta-core-hCG is not as discriminating for Down's syndrome between 11 and 14 weeks as later on in pregnancy.

Pelvic manikins as learning aids.

The use of pelvic trainers in undergraduate teaching was evaluated, using a questionnaire based on examination findings of a series of four pelvic trainers by 20 medical students and 34 gynaecologists. The main outcome measures were the ability to correctly identify pelvic findings in the trainers, and the numbers of false positive findings. There were two adnexal masses in two of the trainers. One was correctly identified by 33 (14 (70%) medical students and 19 (56%) doctors) in one trainer, whereas the other was missed by 52 of 54 examiners. Prolapse was missed by 41 of 54. The normal pelvis was correctly identified by 30 (16 (80%) medical students and 20 (59%) doctors. There were 15 false positive identifications of adnexal masses (6 by medical students and 9 by doctors) and 22 false positive identification of uterine enlargements (5 by medical students and 17 by doctors). The pelvic trainers were of value in demonstrating the process of pelvic and speculum examination. Some of the clinical conditions emulated were missed by most of the gynaecologists, suggesting that they were not suitable for training students in abnormal findings. Although the figures were not statistically significant, there was a trend for qualified doctors rather than medical students to make false positive findings.

Selective miscarriage of Down's syndrome fetuses in women aged 35 years and older.

OBJECTIVE: To estimate the fetal loss of Down's syndrome fetuses between the time of chorionic villus sampling (10 weeks gestation) and the time of amniocentesis (16 weeks gestation) and term in women aged 35 years and older. DESIGN: The age specific prevalence rates in the first trimester of Down's syndrome were estimated using the Danish cytogenetic register in combination with results from four published studies. These were compared with the reported prevalence at the time of amniocentesis and at birth. SUBJECTS: 5927 singleton pregnancies undergoing chorionic villus sampling (71 cases of Down's syndrome and 5856 unaffected cases). This was combined with published data on a further 231 cases of Down's syndrome and 16,620 unaffected cases. MAIN OUTCOME MEASURES: Age specific prevalences at the time of chorionic villus sampling. Proportion of pregnancies lost between the time of chorionic villus sampling and the time of amniocentesis and term. RESULTS: Thirty-two percent of Down's syndrome pregnancies are lost between the time of chorionic villus sampling (10 weeks) and the time of amniocentesis (16 weeks) and 54% are lost by term. CONCLUSIONS: The high fetal loss rates of Down's syndrome between the time of chorionic villus sampling and term introduce problems when evaluating first trimester screening tests with respect to their effective detection rates at term. A recommendation for quoting term risks is made.

Crown-rump length in aneuploid fetuses: implications for first-trimester biochemical screening for aneuploidies.

This study examined the effect of estimation of gestational age from the menstrual history compared with that from crown-rump length (CRL) measurement on the detection rate of screening for aneuploidies in the first trimester. Pregnancy-associated plasma protein A (PAPP-A) was assayed in blood collected prior to chorionic villus sampling in 356 women with unaffected pregnancies and 28 women with an aneuploid pregnancy. There were 14 Down's syndrome (DS) pregnancies. All pregnancies were dated from menstrual history and CRL measurement. The average CRL gestation in the aneuploid population was 2.5 days less than that derived from the LMP (95 per cent confidence interval (CI) for LMP-CRL gestation: using the algorithm based on unaffected pregnancies 0-3.5 days; using the matched case-control approach 1-4.5 days). The average CRL gestation in the DS population was 2 days less but this did not reach statistical significance (95 per cent CI for LMP-CRL gestation: using the algorithm -1 to 4.5 days; using the matched case-control approach 0 to 5.5 days). The detection rate of aneuploidies in the first trimester using maternal serum PAPP-A was reduced by 7 per cent (and by 3 per cent for DS) for a 5 per cent false-positive rate when using CRL rather than LMP to date the pregnancy. This phenomenon is a consequence of an apparent reduction of gestational age when estimated by CRL in the aneuploid population. Further studies are required to evaluate whether CRL is an unbiased estimate of gestation for Down's syndrome pregnancies.

Screening for Down's syndrome.

Down's syndrome (DS) is the commonest cause of severe mental retardation in children. It is the result of trisomy of chromosome 21 which is usually a random event though it is commoner in older mothers. DS can be diagnosed by chorionic villus sampling (CVS) and amniocentesis followed by karyotyping. Because of the risks associated with these invasive procedures, they can only be offered to a high-risk group. At one time the sole basis for identifying this increased risk was maternal age, but within the past ten years a series of biochemical and ultrasound abnormalities have been shown in DS pregnancies. The biochemical abnormalities include changes in the levels of most fetal and placental products in the maternal circulation. The best-known of these changes are the reduced levels of alphafetoprotein (AFP) and oestriol (E3) and increased levels of human chorionic gonadotrophin (hCG). The mechanism underlying these biochemical phenomena is unknown. Screening programmes involving the measurement of hCG and AFP, with or without additional parameters such as E3, at 15-18 weeks of pregnancy can typically identify 60% or more of cases of DS with a screen-positive rate of 5%. The combined risk derived from the various biochemical parameters, together with maternal age, is calculated by one of a number of computer programmes which have been developed for this purpose. There has been considerable discussion as to the exact biochemical tests which should be used for DS screening. This had led to controversy as to whether measurement of E3 has a place, and whether or not measurement of the free beta-subunit of hCG should replace measurement of the intact molecule. A notable recent development is the suggestion that measurement of the urinary beta-core of the hCG could be a highly discriminatory marker. A number of factors can affect the results of biochemical screening for DS. These include maternal weight, gestational age, ethnic origin, smoking, and diabetes. In addition, abnormal levels of the biochemical products may be found in other chromosome abnormalities.

Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A, markers for fetal Down syndrome at 8-14 weeks.

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.

First-trimester maternal serum Schwangerschafts protein 1 (SP1) in pregnancies associated with chromosomal anomalies.

The relationship between first-trimester maternal serum Schwangerschafts protein 1 (SP1) and the karyotype of the pregnancy was examined in 692 women who underwent chorionic villus biopsy at 6-12 weeks. There were 30 pregnancies with abnormal karyotypes, consisting of 14 Down's syndrome (DS), eight trisomy 18, and eight other anomalies, two of which were mosaics. The normal ranges and medians for gestation were defined from the 662 cases in which the karyotype was normal. The median SP1 (0.5 MOM) of the abnormal group was significantly lower than that of the normal group (1.0 MOM). This relationship was maintained for the DS pregnancies (0.4 MOM) and for anomalies other than trisomy 18 (0.43 MOM) but not trisomy 18 (1.1 MOM). It is possible that the use of SP1 as a screening test for chromosome anomalies in the first trimester could have a 43 per cent detection rate for a 5 per cent false-positive rate.

Predicting fetal chromosome anomalies in the first trimester using pregnancy associated plasma protein-A: a comparison of statistical methods.

The analysis of the clinical efficiency of a biochemical parameter in the prediction of chromosome anomalies is described, using a database of 475 cases including 30 abnormalities. A comparison was made of two different approaches to the statistical analysis: the use of Gaussian frequency distributions and likelihood ratios, and logistic regression. Both methods computed that for a 5% false-positive rate approximately 60% of anomalies are detected on the basis of maternal age and serum PAPP-A. The logistic regression analysis is appropriate where the outcome variable (chromosome anomaly) is binary and the detection rates refer to the original data only. The likelihood ratio method is used to predict the outcome in the general population. The latter method depends on the data or some transformation of the data fitting a known frequency distribution (Gaussian in this case). The precision of the predicted detection rates is limited by the small sample of abnormals (30 cases). Varying the means and standard deviations (to the limits of their 95% confidence intervals) of the fitted log Gaussian distributions resulted in a detection rate varying between 42% and 79% for a 5% false-positive rate. Thus, although the likelihood ratio method is potentially the better method in determining the usefulness of a test in the general population, larger numbers of abnormal cases are required to stabilise the means and standard deviations of the fitted log Gaussian distributions.

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype.

OBJECTIVE: To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype. DESIGN: A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling. SETTING: Milan, Italy. SUBJECTS: Five hundred twenty-two women aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18). MAIN OUTCOME MEASURES: Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay. RESULTS: The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P < 0.00001 Mann-Whitney test). CONCLUSIONS: There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.

Incidence of hysterectomy in New Zealand.

The total number of hysterectomies performed in New Zealand from 1978 to 1984 was analysed with respect to age, public or private sector and hospital board area. The crude hysterectomy rate in 1984 was 4.1 per 10(3) female population. In this year 42% of hysterectomies performed were in the private sector. Rates varied between the different hospital board areas from 1.5 to 7.1 per 10(3) female population. Assuming surgical rates remain constant, a New Zealand female has a 39% chance of undergoing hysterectomy by the age of 85. A review of available world literature shows New Zealand to have a high hysterectomy rate second only to North America.

Trends in ectopic pregnancy in New Zealand.

The rate of ectopic pregnancy in New Zealand from 1965 to 1983 was examined and shown to have increased 3-fold from 4.3 per 10(3) total births in 1965 to 13.6 per 10(3) total births in 1983. Over this period the risk was greatest for the older conceiving woman, with a woman aged 35-44 years 2.2 times more likely to experience an ectopic pregnancy than a woman aged 15-24 years.

PIP: Analysis of New Zealand's rate of ectopic pregnancy indicates a 3-fold increase from 1965 to 1983, from 4.3/1000 births to 13.6/1000 births. This trend shows no sign of levelling. The annual number of such pregnancies was 262 in 1965 and 690 in 1983. The risk of conceiving an ectopic pregnancy was greatest among older women. For the peroid 1965-83, the risk was 11.8/1000 in the 35-44-year age group compared with 5.3/1000 in the 15-24-year age group, representing a 2.2-fold increased risk. The increase in the rate of ectopic pregnancies over time has occurred within each age group, however. These findings mirror trends in Europe and North America. It has been suggested that the increased incidence of ectopic pregnancy reflects the spread of sexually transmitted disease and pelvic inflammatory disease. 8 deaths were attributable to ectopic pregnancy in the years 1969-79 in New Zealand. Given the potential mortality and reduced subsequent fertility associated with this condition, the trend toward increased ectopic pregnancy is of serious concern.