Eighty-seven infants (0.13% of livebirths) developed necrotizing enterocolitis (NEC) during a 15-year period at the Mercy Maternity Hospital, Melbourne. The disease was associated with 23 deaths, representing a mortality rate of 26.4% and comprising 2.6% of all neonatal deaths. The incidence of NEC increased from 0.07% of all livebirths for the years 1971-1974 to 0.25% for the 19-month period from January, 1984 to July, 1985. The mean age at onset was 9.9 days with an inverse relationship between birth-weight and age of onset of the disease. The mothers of the infants who developed NEC belonged to a significantly higher risk obstetric population; gestational diabetes was identified in 3 of 28 mothers (10.6%) having glucose tolerance tested, and 1 other patients was a known diabetic. Subnormal oestriol excretion was detected in 15 of 45 patients tested, treble the overall hospital incidence. Of the 87 infants, 26 (29.9%) were VLBW (birth-weight less than 1,500 g), 5 were term (5.7%) and 9 (10.3%) were small for gestational age. The mean gestational age was 34.7 weeks and mean birth-weight was 1,988 g. Sixty-seven (77%) infants received medical treatment alone and 20 (23%) also received surgical treatment. Sequelae which developed in survivors were colonic strictures (4), fistulas (2) and the short-gut syndrome (1).

OBJECTIVE

To investigate the reason for low maternal serum unconjugated oestriol (uE3) and raised human chorionic gonadotrophin (hCG) levels in Down's syndrome pregnancies.

METHODS

Measurement of uE3, total oestriol (tE3), dehydroepiandrosterone sulphate (DHEAS), a precursor of oestriol, and hCG in 15-20 week amniotic fluid samples from pregnancies with and without Down's syndrome.

METHODS

The retrieval and use of stored amniotic fluid samples collected from women who had had an amniocentesis for antenatal diagnosis.

METHODS

45 women with a Down's syndrome pregnancy and 224 unaffected controls of the same gestational age.

RESULTS

The median level of amniotic fluid in affected pregnancies was low for uE3, tE3 and DHEAS but high for hCG: 0.50, 0.46, 0.35 and 1.58 multiples of the normal median, respectively.

CONCLUSIONS

These results suggest that the abnormal maternal serum levels of uE3 and hCG in affected pregnancies are due mainly to abnormal feto-placental synthesis, rather than feto-maternal transfer.

In 51 patients with antepartum haemorrhage, 24-hour urinary oestriol was measured continuously until delivery. A total of 765 24-hour urinary oestriol measurements was obtained and there were two stillbirths, one neonatal death and three cases of intrauterine growth retardation in this group of patients. It was felt that none of the fetal deaths would have been prevented by obstetrical treatment based on 24-hour urinary oestriol measurements and that these have little practical value in the management of patients with antepartum haemorrhage.

OBJECTIVE

To derive a method for revising the risk of Down's syndrome in maternal serum marker screening when there is vaginal bleeding. The effect on screening performance of routinely allowing for the presence or absence of bleeding in all women is also assessed.

METHODS

Overview of published studies on the rate of reported vaginal bleeding in pregnancies with Down's syndrome, on the rate according to maternal age and on the association of bleeding with alpha-fetoprotein (AFP) level. The publications are supplemented with data on unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG) and AFP levels in a consecutive series of screened women.

METHODS

Routine Down's syndrome screening tests carried out on women having antenatal care at the St James's University Hospital, Leeds.

METHODS

Eight hundred and nine screened women.

RESULTS

In five studies the rate of vaginal bleeding in Down's syndrome pregnancies was 1.7 times that in unaffected pregnancies on average. In three studies, the vaginal bleeding rate increased proportionally by 2.2% on average for each year of maternal age. Three studies and our own data were consistent with a 10% increase in the mean AFP level associated with vaginal bleeding, but it did not appear to materially alter uE3 and hCG levels or the standard deviations and correlation coefficients for any of the three analytes. An individual woman's risk was calculated by multiplying her age-specific odds of Down's syndrome by two likelihood ratios, one relating to the vaginal bleeding itself and one from the marker levels. Routine allowance for the presence or absence of vaginal bleeding was estimated to increase the detection rate by less than 1%.

CONCLUSIONS

Our method is of clinical value in revising the risk when there is concern that vaginal bleeding might be responsible for a negative maternal serum Down's syndrome screening result. A policy of routinely incorporating information on vaginal bleeding in risk estimation for all women would have too small an effect on overall screening performance to recommend it.

This study was conducted to assess endometrial protection in women on a cyclical combined hormone replacement regimen with 1 mg norethisterone BP, and to evaluate the use of the bleeding pattern and serum alpha 2-PEG in monitoring the endometrial response to exogenous hormone therapy. Fifty-one postmenopausal women attending the Menopause Research Unit at Leicester Royal Infirmary, UK, completed the study. All patients were at least 1 year after the menopause, with an average of 26 months since the last menstrual period. All women were prescribed a regimen of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg, and oestradiol 0.6 mg) continuously, with 1 mg of norethisterone added for 12 days out of each 28-day treatment cycle. Menstrual diaries were collected and analysed. The secretory changes were assessed by histology, menstrual bleeding pattern and a biological marker of secretory activity (alpha 2-PEG). Withdrawal bleeding occurred on average on days 11, 12, 11, 12 and 13 on months 2, 3, 6, 9 and 12, respectively. There was a poor degree of consistency in the bleeding pattern. The level of alpha 2-PEG increased from the average baseline measurement of 2.7 ng/ml (S.D., 4.12) to 8.5 ng/ml (S.D., 4.16) after progestogen treatment. This rise, although significant, did not correlate with the uterine bleeding pattern. There was no statistically significant correlation between the level of alpha 2-PEG and endometrial histology. The findings highlight the fact that cycle predictability on HRT, as exemplified in this regimen, is poor. The level of alpha 2-PEG is a poor predictor of the endometrial histology and has a poor correlation with the day of onset of bleeding.

Forty post-menopausal women with urogenital disorders who were inpatients in the same geriatric hospital were treated with oestriol (E3) for 6 weeks. For the first 2 weeks 0.5 mg E3 (Leo AB, Sweden) was administered intravaginally every day. Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose. Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index (KPI), while the degree of maturation of the vaginal epithelium was estimated visually. Urinary bacteria were cultivated. A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment. However, neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3, since the KPI returned to pretreatment values within 4 weeks. The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method. No changes were seen in urinary bacteria. Medroxyprogesterone acetate was given before and after E3 treatment. None of the women suffered from withdrawal bleeding.

53 cases of pregnancy complicated by bleeding between the 7th and 16th week have been studied by repeated estimations of non-conjugated plasma oestradiol and oestriol carried out at the same time as ultrasound morphological measurements were performed. 24 pregnancies went on to term while 29 met with the loss of the fetus. In each case where the outcome was favourable the plasma oestriol and oestradiol levels were comparable to those found in 95 control pregnant women whose pregnancies progressed normally. In 26 cases where the outcome was unfavourable the levels were too low and corresponded to an ultrasound picture that was abnormal or revealed absence of heart beat. In 3 cases the first levels of oestradiol and oestriol seemed to be normal. Later, when failure of growth of the embryo and absence of heart beat were found, a considerable drop in the levels of oestradiol and of oestriol in the blood was also revealed. This study shows a good correlation between hormone levels and ultrasound findings in pregnancies complicated by bleeding. All the same, the prognostic value of hormone measurements as compared with ultrasound measurements has not yet been established, and needs analysis of a far greater number of cases of a similar type.

The perfusion of the intervillous space of the human placenta was investigated with 99Tc-Human Serum Albumin and external counting in 45 pregnant women between the 34th and 38th week of gestation. The pregnancy was normal in 34 women, while there was placental insufficiency in 11. Two variables were calculated from the placenta curve: the placenta flow index (PFI) and the mean transit time (t) for plasma through the intervillous space. From double determinations, the coefficient of variation for PFI was calculated to 1.6%. For t it was 20%. PFI was significantly higher in the controls than in the patients with placental dysfunction (P less than 0.05). There was a significant correlation between PFI and t (rs = - 0.36, P less than 0.05). The plasma oestriol level and the PFI correlated significantly, whereas the correlation between t and the plasma oestriol level was not significant. The placenta flow index can be used to measure the physiological effect of a pharmacological treatment, bedrest or other treatments.

Low implantation of the placenta may protect against the development of pregnancy-induced hypertension (PIH) and is associated with improved values in tests of placental function. PIH occurred in six of 201 (3%) consecutive patients with placenta praevia managed at the City Hospital, Nottingham, from 1 April 1973 to 30 June 1981. None of the six patients developed associated proteinuria. Of the total number of 24,549 patients delivered in the same hospital for the years 1974-1978, 3744 (15%) developed PIH. Of the patients with placenta praevia, 52% had serum levels of human placental lactogen above the 95th centile and 25% had 24-h urinary oestriol levels above the 95th centile. The birthweight distribution was not different from that of the total live births at the City Hospital, Nottingham (based on 1975-1976 deliveries).

Sixty-nine healthy women in the early menopause were assessed in terms of calcium metabolism, coronary risk factors, Kupperman index, and various serum hormones before and during replacement therapy with 17 beta-oestradiol plus oestriol and norethisterone acetate. The patients were followed for 1 year, and the daily doses used were: 17 beta-oestradiol: 2 mg from day 1 to day 22, 1 mg from day 23 to day 28; oestriol: 1 mg from day 1 to day 22, 0.5 mg from day 23 to day 28; and norethisterone acetate: 1 mg from day 13 to day 22. Group A (n = 22) received 17 beta-oestradiol and norethisterone acetate; group B (n = 20) received 17 beta-oestradiol plus oestriol and norethisterone acetate and group C (n = 23) received a placebo. The responses in groups A and B were similar with no significant difference between the two therapy regimens. The results suggest that in the dose given, oestriol does not add significantly to the beneficial effect of combined hormonal prophylaxis against early postmenopausal osteoporosis.

BACKGROUND

The differential diagnosis of vaginal blood loss in childhood is broad, and includes irritation of the mucous membranes, trauma, tumours, foreign bodies and sexual abuse. Physical and additional examination is often initially difficult; however, prompt detection of a rhabdomyosarcoma, a soft-tissue tumour principally diagnosed in childhood, is vitally important.

METHODS

A 3-year-old girl with a history of vaginal blood loss and an introital mass was referred to the gynaecologist. Treatment with oestriol and triamcinolone cream did not lead to healing. Pathological examination of a biopsy taken under general anaesthetic indicated an embryonic rhabdomyosarcoma. Chemotherapy, surgical resection and brachytherapy lead to persistent remission of the tumour.

CONCLUSIONS

Because rhabdomyosarcoma is rare and can present atypically, diagnosis can be delayed. Early recognition is, however, essential and this condition should be placed high in the differential diagnosis by vaginal blood loss or vaginal abnormality in childhood.

Despite great efforts worldwide to evaluate the effects of endocrine-disrupting compounds (EDCs) in fish, there is little information available about the interactions of EDCs with the disruption of the sexual endocrine axis in fish species with matrotrophic viviparity and intraluminal gestation. To understand these interactions, six sampling campaigns were performed within a period of 1 year in two lakes with different degrees of pollution. A battery of biomarkers of the oestrogenic response was assessed in the liver [vitellogenin, CYP 1A1, epoxide hydrolase activity, and metallothioneins (MT)] and MT in the head of Girardinichthys viviparus. Linear correlation analysis and canonical correspondence analysis were performed to explore the relationship between the oestrogenic response with EDCs and with metals. The biomarker responses were assessed using the water content of EDCs (oestrone, 17-β-oestradiol, oestriol, 17-α-ethinyl oestradiol, total phenols, bisphenol A, nonyl phenol, octyl phenol), as well as the PAHs indene[1,2,3-c,d]pyrene, naphthalene, pyrene, benzo[a]anthracene, benzo[k]fluoranthene and benzo[a]pyrene) and metals (Cu, Fe, Mn, Pb and Zn). Greater disruption of the sexual endocrine axis occurred in fish of both sexes inhabiting the polluted lake whose effects were apparently influenced by CYP 1A1 activity and by 17-α-ethinyl oestradiol. In addition, non-estrogenic mechanisms in the hypothalamus and pituitary glands in male fish were observed, elicited by endogenous levels and the water concentration of Pb. In contrast, in females from the less polluted lake, VTG induction was related to exogenous oestrogens. The disruption of the hypothalamic-pituitary-gonadal axis is a complex process influenced by both endogenous and exogenous factors and contributes to male feminisation by exposure to EDCs.

Hypotrophy or intrauterine growth retardation of the foetus associated with placental insufficiency still remains a serious obstetric problem. In the submitted paper the authors compare hypotrophic foetuses treated in 1989 and 1990 at the authors' clinic by conventional methods only (biometry, bed rest, CTG oestriol, glucose and possibly heparin) with a group of hypotrophic foetuses treated in 1991 and 1992 with magnesium and where the therapeutic effect was followed up by Doppler flowmetry. Based on the results, the demand to improve placental insufficiency by pharmacological induction and stimulation of specific placental enzymes is met perfectly by concomitant parenteral and oral magnesium administration to pregnant women.

The effect of oestriol on the rapid oscillation of circulating FSH and LH levels during sleep was investigated by administering oestriol (E3: 2 mg/day) orally for 3 mth to 3 healthy post-menopausal women who experienced frequent hot flushes. Before treatment and at the end of the third mth of treatment, blood samples were drawn the length of sleep, and serum FSH and LH level were measured by radioimmunoassay. Fluctuations of serum FSH and LH levels were recorded and the pulses were defined as a 20% increase of hormone concentration over nadir. The increase of hormone levels of pulses recorded before treatment were compared with those recorded during treatment (the end of the third mth). No significant difference was found in serum FSH levels, yet a difference was found in serum LH levels. The pulses during the treatment nights were lower than those in the pre-treatment nights (P less than or equal to 0.01). The levelling of the pulses of serum LH levels under oestriol treatment is probably an expression of the influence of oestriol on the hypothalamus-anterior-pituitary system.

Plasma values of atrial natriuretic factor (ANF) were evaluated in 31 women with pregnancy-induced hypertension (PIH) and 31 normal pregnant women at the same age of gestation. In 27 women with PIH and 27 normal pregnant women forearm venous tone (FVT) was evaluated by Strain Gauge Plethysmography. Forearm vascular resistance (FVR) was measured as the ratio of mean blood pressure (MBP) to forearm blood flow. In addition Cardiac Index (CI) by means of transthoracic electrical bioimpedance and total peripheral vascular resistance (TPR) (with the Frank Equation) were also measured. In comparison with the normal pregnant women, the women with PIH had similar values of hematocrit (as an index of plasma volume) and significantly higher levels of FVR and TPR, while ANF plasma values did not differ significantly. Subdividing the women with PIH in relation to the presence of proteinuria (greater than or equal to 0.3 g/l), those with proteinuria, in addition to significantly higher levels of FVR and TPR, had significantly higher levels of FVT than normal pregnant women, while ANF plasma values were higher even though the difference was only near the level of significance. Hypertensive women with proteinuria also had higher values of FVT than hypertensive women without proteinuria. By means of multiple regression ANF did not show any significant correlations with hematocrit or sodium excretion. Hypertension with proteinuria seems to represent a more severe form of the disease in which, in addition to the probable influence of other factors such as the renin-angiotensin and prostaglandin systems, a greater increase in peripheral sympathetic tone than in hypertension alone appears to be present, causing a reduction in venous compliance in addition to the elevation in FVR and TPR, with increase in central blood volume and atrial stretch. This may explain the higher ANF plasma levels in these patients in comparison with normal pregnant women, even though the absence of a significant correlation of ANF with hematocrit and the fact that ANF increase was only near the level of significance may suggest a change in the relation between ANF secretion and atrial volume receptors in pregnancy either normal or complicated by hypertension. ANF does not seem to play an important role in water and sodium excretion in PIH probably because of the presence of very high plasma levels of hormones such as aldosterone, progesterone and oestriol which, together with renal prostaglandins, seem to be involved in diuresis and natriuresis in pregnancy.

Levels of beta-core fragment and total oestriol in second-trimester maternal urine samples were measured in 32 Down syndrome pregnancies and 206 control pregnancies. Beta-core fragment and total oestriol values were corrected for the urinary creatinine level and expressed as multiples of the control medians (MOM). In addition, the ratio of the beta-core fragment level to the total oestriol level, without creatinine correction, was calculated, and expressed as MOM values. The median beta-core fragment, total oestriol, and ratio levels in Down syndrome cases were 5.42, 0.64, and 9.32 MOM, respectively. In the Down syndrome pregnancies, 66 per cent of the beta-core fragment levels were above the 95th centile of control levels, while 22 per cent of the total oestriol levels were below the fifth centile of control levels. In combination with maternal age, measurement of beta-core fragment and total oestriol levels in Down syndrome pregnancy resulted in an 80 per cent detection rate at a 5 per cent false-positive rate. Use of the ratio resulted in a univariate detection rate of 72 per cent. In combination with maternal age, the ratio resulted in a detection rate of 81 per cent at a 5 per cent false-positive rate. Based on this unmatched study, the measurement of a ratio of beta-core fragment to total oestriol levels, without the need for creatinine correction, may be useful in screening for fetal Down syndrome in second-trimester urine.