In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we have shown that the median values of four biochemical markers (AFP, total hCG, free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies affected by Down's syndrome on the whole reflect those observed in the maternal serum of affected cases. The median MOM for AFP was lower than average (0.56), as was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and free beta hCG (2.10) were increased on average. The width of the distribution of marker levels in amniotic fluid is similar to that in serum for free beta hCG and total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP. Analysis of data by fetal sex showed a significantly higher median MOM in female control cases compared with male controls for the analytes free beta hCG, total hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome cases, this trend was not statistically significant and we cannot confirm a previous study which reported that elevated levels of amniotic fluid total and free beta hCG were associated only with female fetuses.

Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) were measured in serum samples of 4131 non-smoking and 1018 smoking women during the second trimester of pregnancy. The levels of all three analytes decreased with increasing body weight. The AFP median was significantly increased in smokers in a dose-response association; hCG decreased by 21 per cent and uE3 decreased by 3 per cent in smokers in a non-dose-related fashion. Regression functions for adjustment of serum levels for weight and smoking should be considered in risk estimation for Down syndrome in order to give a woman's individual risk more precisely.

A retrospective evaluation of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) levels in maternal blood in the second trimester was conducted for cases of aneuploid pregnancies identified from a series of women who underwent amniocentesis. Blood samples were collected from 1078 women just before genetic amniocentesis was performed, mainly for individuals of advanced maternal age (greater than 35 years). Twenty-five maternal serum samples from pregnant women with an aneuploid fetus, including 14 with Down's syndrome, were available for analysis of all three parameters. An algorithm to detect Down's syndrome was used for this analysis with a risk of>> or = 1:299 classified as screen-positive, this being found for 20.4 per cent of the cases (220/1078). The actual Down's syndrome detection rate was 85.7 per cent (12/14), whereas the detection rate for all aneuploidies was 72.0 per cent (18/25). Those that were not detected were two cases of trisomy 21, one trisomy 18, two trisomy 13, three sex chromosome abnormalities, and one case of an additional marker chromosome. The data indicate that this tri-analyte test should be provided after thorough genetic counselling and informed decision-making regarding maternal serum screening for women who wish for a prenatal diagnosis.

The risk of developing urogenital disorders increases after menopause due to decline in oestrogen production in postmenopausal women. Symptoms due to atrophy of the squamous epithelium in the vagina, urethra and bladder, recurrent urinary tract infections and abnormal function of lower urinary tract comprise the urogenital oestrogen-deficiency syndrome. The symptoms are directly related to atrophic changes in the urogenital tract. They cause reduced quality of life and persist lifelong if not treated. The present review discusses the incidence, symptoms, pathogenesis and treatment of this syndrome. Substitution therapy with oestriol is effective and has no metabolic effects or serious side effects at the recommended dosage. Oestriol should be used lifelong. The syndrome is underreported and undertreated in Norway. Therefore, an evaluation of the general health condition of elderly women, should include direct questions about these symptoms, and oestriol treatment should be offered liberally. It is effective, safe and cost-effective.

Identification and modification of potential risk factors, early diagnosis, intensive prenatal surveillance, and appropriate, timely intervention is necessary for successful management of the pregnancy complicated by intrauterine growth retardation. Once an antepartum diagnosis of fetal growth retardation has been made, extensive evaluation including a thorough ultrasound examination and amniocentesis (if technically possible) for fetal lung profile studies and karyotype is indicated. Intensive fetal surveillance with nonstressed testing (in the absence of oligohydramnios) or contraction stress testing on a weekly basis (if normal) can usually assure one of fetal well being. A combination of NST/CST testing may increase the effectiveness of predicting perinatal morbidity. Daily increasing serial oestriol urinary values may be of some benefit in assuring fetal well being. Serial sonography to assess amniotic fluid volume and interval fetal growth is important. Use of the biophysical profile may significantly improve the perinatal outcome, but substantiation in a large group of growth retarded infants is lacking. Delay of delivery until 37-38 weeks' gestational age (or, in the hypertensive patient, until fetal lung maturity is documented) currently appears optimal. However, in the face of fetal surveillance testing suggesting a deterioration in fetal status or lack of interval growth, delivery should be undertaken. The mode of delivery will depend rather on the indication for intervention. Caesarean section should be seriously considered in many cases of intrauterine growth retardation. At the time of delivery, the paediatric team should always be present and ready to resuscitate the infant if necessary and to anticipate potential problems associated with the growth retarded fetus.

The endometrial effect of long-term vaginal oestriol (E3) therapy for urogenital atrophy was assessed in 23 post-menopausal women. Hysteroscopic and histological examinations were performed in each patient to assess endometrial atrophy before treatment and after 6 and 12 months of therapy (0.5 mg vaginal E3 for 21 days, then 0.5 mg twice weekly). The primary atrophic picture was confirmed at the end of the 6th month in all but one of the patients. In one case, the histology showed an abnormal stromal reaction with no epithelial alterations. Treatment was continued and after the 12th month complete atrophy was confirmed both hysteroscopically and histologically in all patients. Efficacy as regards vaginal and urogenital complaints was good. Our results demonstrate that in women with endometrial atrophy effective and well-tolerated treatment with vaginal E3 can be safely continued for up to 12 months.

Published studies have shown that some serum markers used in screening for Down syndrome tend to be lower among women with insulin-dependent diabetes mellitus (IDDM). On this basis, many screening programmes adjust the marker levels to take account of this difference. Recent studies suggested that the marker levels were not different, and so adjustment may no longer be needed, possibly because of better diabetic control. Data from a prenatal screening programme for Down syndrome were examined to see whether the median values of second-trimester screening markers were still reduced in pregnant women with IDDM. A total of 366 women with IDDM singleton pregnancies without Down syndrome were identified from the screening programme at Barts from 1989 to 2002. After allowing for maternal weight, the median multiples of the median (MoM) for IDDM-unaffected singleton pregnancies were as follows: 0.88 (95% confidence interval 0.84-0.93) for alphafetoprotein (AFP), 0.95 (0.91-0.99) for unconjugated oestriol (uE3), 0.90 (0.80-1.01) for total human chorionic gonadotrophin (total hCG), 0.98 (0.88-1.08) for free beta-hCG, and 0.99 (0.89-1.10) for inhibin-A. The median levels for AFP and uE3 were statistically significantly lower in pregnant women with IDDM. The other markers were not significantly different in women with and without IDDM. There remains a case for adjusting AFP and uE3 levels in women with IDDM in prenatal screening programmes for Down syndrome.

The leptin to fat ratio early in life could contribute to fixing the set point of leptin feedback at the hypothalamic level. Subjects from Asian and Caucasian ethnicities differ in body composition. We tested the hypothesis that anthropometric markers and their relationship to umbilical cord leptin, cortisol and cortisone, DHEAs and oestriol differed between Caucasians and Asians at birth. Birthweight, length, arm, calf and abdominal circumferences, scapular, triceps, quadriceps and abdominal skinfolds were measured in 180 healthy, full-term newborns of Asian and Caucasian ethnicities. Leptin and steroid hormone concentrations were determined in umbilical cord plasma. There was a significant difference in the slope of the regression between leptin and birthweight (p = 0.03) and calf circumference (p = 0.05) between male Caucasian and Asian neonates. In contrast, in female neonates, there was no significant difference (p = 0.099 and p = 0.07 for birthweight and calf circumference, respectively). In addition, while the slopes of the regression plots were not affected by gender in Asian newborns, there was a significant difference between male and female Caucasian newborns (p = 0.006 and p = 0.002 for birthweight and calf circumference, respectively). There was no significant correlation between cord leptin concentrations or anthropometric markers and steroid hormone concentrations. In conclusion, gender and ethnic differences in the relationship between leptin and anthropometric markers are detectable at birth between Asians and Caucasians, two ethnic groups that have been demonstrated to have different body compositions later in life. This may represent the first clinical evidence of a difference in leptin regulation between these two ethnic groups.

In postmenopausal patients, stress and urge incontinence often occur as a consequence of oestrogen deficiency. We performed a comparative study in a prospectively randomised and placebo controlled group of women with urge incontinence to investigate different dosages of intravaginally applied oestriol. Clinical and urodynamic parameters were also compared. 15 women (Group I) received 1 mg oestriol applied daily intravaginally over 3 weeks; 15 women (Group II) received a daily dosage of 3 mg and 10 women received a placebo. A complete clinical and urodynamic evaluation was carried out twice at a 4-week interval. The women receiving a daily dose of 3 mg oestriol applied intravaginally demonstrated a significant improvement of the parameters strong desire to void, pollakisuria, and nycturia. No improvement was seen in patients with motoric urge incontinence.

A case of malformations of the fetal central nervous system following hypervitaminosis A in early pregnancy is reported. The mother was treated with 150 000 IU vitamin A daily during gestation days 19 to 40. Determination of urinary oestriol carried out in the 42nd week of pregnancy revealed a very low excretion (4.2-6.6) mumol/24 h). Induced delivery resulted in a microcephalic child who died after 18 min. The child had multiple malformations of the central nervous system and very small adrenal glands (1.5 g; normal 11 +/- 4 g). The very low urinary oestriol excretion is well explained by the hypoplastic adrenals, which in turn can be related to insufficient ACTH stimulation, a condition similar to anencephaly. The malformations shown in the present case are considered to be related to the high doses of vitamin A given to the mother, and the authors wish to warn against uncritical use of high doses of vitamin A in whomen of childbearing age.

OBJECTIVE

The aim of this study was to assess the concentration of the first and second trimester maternal serum markers in pregnancies with a vanishing twin.

METHODS

This is a retrospective case-control study of pregnancies screened for Down syndrome in one Ontario center. Singleton pregnancies with ultrasound evidence of a vanishing twin were identified, and each was matched with five normal singleton controls for ethnicity, maternal age, gestational age, and blood sampling date. The median MoM of the first and second trimester serum markers was compared between cases and controls. The differences were assessed using the Mann-Whitney U-test.

RESULTS

The study included 174 pregnancies that had a vanishing twin. Compared with control pregnancies, pregnancy associated plasma protein A increased by 21% (p = 0.0026), alpha-fetoprotein (AFP) increased by 10% (p < 0.0001), and dimeric inhibin A (DIA) increased by 13% (p = 0.0470) in pregnancies with a vanishing twin. Unconjugated oestriol and total human chorionic gonadotrophin were not significantly changed in these pregnancies.

CONCLUSIONS

Pregnancy associated plasma protein A is not an adequate marker for pregnancies with a vanishing twin. The impact of elevated AFP on risk estimation is offset by that of DIA to certain extent. Further studies are needed to establish an adequate adjustment method for AFP and DIA to improve the accuracy of screening results for these pregnancies.

The potential efficacy of screening for trisomy 21 in the first trimester, using maternal serum markers alpha fetoprotein, free beta human chorionic gonadotropin, unconjugated oestriol and pregnancy associated plasma protein A, was studied in an unselected population of women between the seventh and fourteenth week of gestation. Using a combination of alpha fetoprotein and free beta human chorionic gonadotropin, 53% of affected pregnancies could be identified at a false positive rate of 5%. Unconjugated oestriol and pregnancy associated plasma protein A levels were lower in cases of trisomy 21, but their inclusion with other markers did not significantly improve detection rate. Monitoring the same pregnancies also in the second trimester showed that screening in the first trimester identified the same cases as in the second. We conclude that first trimester screening using free beta human chorionic gonadotropin and alpha fetoprotein, is a viable possibility and will lead to detection rates in excess of 50%. Prospective studies are needed to confirm these observations.

Two-hundred and seventy pregnant women (540 ears) were examined for patulous Eustachian tubes. The diagnosis was established by means of a Madsen Zo 70 electroacoustic impedance bridge. Nineteen of the patients were found to have patulous Eustachian tubes in 1 or both ears as evidenced by impedance variations synchronous with the respiration. Only 5 of these women had any subjective symptoms. Nine other women had symptoms, but their Eustachian tubes were closed at the time of examination. The results were related to the duration of the gestation, to oestrogen production and weight gain during pregnancy. A significant correlation was found was found between patulous Eustachian tube and elevated serum oestriol values.

The concentration of secretory immunoglobulin A (IgA) in the vaginal fluid of 20 untreated post-menopausal women (aged 75.4 +/- 1.4 years) was compared with the levels in a group of 20 post-menopausal women (aged 73.2 +/- 1.5 years) treated with oral oestriol (E3) (2 mg/day) and a further group of 20 healthy, non-pregnant, fertile women (aged 28.2 +/- 1.8 years). Secretory IgA was determined using a paper disc modification of the single radial immunodiffusion technique. The vaginal concentration of IgA in the untreated women was 41.5 +/- 5.7 mg/l, which was higher than that recorded in those treated with E3 (20.8 +/- 5.7 mg/l, P less than 0.05) and in the fertile women (16.4 +/- 3.7 mg/l, P less than 0.01). Epithelial cells predominated in the wet smear preparations obtained from the women who received E3 and the fertile women, while a predominance of leucocytes was observed in the untreated women. Lactobacilli were found more frequently in the vaginal flora of the women in the E3 group (P less than 0.001) and the fertile women (P less than 0.001) than the untreated group. Faecal-type bacteria were seen more frequently in the vaginal flora of the untreated women than the E3 group (P less than 0.01) or the fertile women (P less than 0.001). The possible implications of the present findings with regard to the individual variation in the intensity of symptoms experienced by women suffering from the oestrogen deficiency syndrome are discussed.