We have examined the relationship between foetal levels of E3 and DHEA-SO4 and the birthweight of the child. Levels of these steroids do not relate to birthweight--although the concentration of DHEA-SO4 was marginally but not significantly higher in infants of lower birthweight. These findings suggest that the placental conversion of foetal precursors, and not the level of the precursors themselves, determines the concentration of E3 in the mother. Measurement of E3 as a clinical test reflects the function of both the foetus and the placenta.

The substances in the blood or urine of a pregnant woman which may give an indication of the state of fetal growth are examined. The drawback of measuring such substances is that the values are variable, making it difficult to distinguish between normal and abnormal. Variability arises from technical factors in measurements, from short-term changes of no significance and from the large spread of normal values from one individual to the next. Biochemical parameters of fetal growth can be applied in one of two ways: as screening tests or as control measures by serial assays to guide management. The criteria by which any test should be evaluated--sensitivity, specificity and relative risk--are examined. Particular substances whose measurement may be helpful are considered in terms of the steroids or proteins produced by the fetoplacental unit. The oestrogens, notably oestriol, hold pride of place among the steroids. Dynamic tests of steroid synthesis are also considered. The chief placental proteins of interest are chorionic gonadotrophin, placental lactogen and Schwangerschaftsprotein 1. It is concluded that the method to be recommended is to screen a whole obstetric population with assays of placental lactogen and to follow those with values below the normal limit with serial oestriol assays.

The oestrogen content of two 24 h pools of pregnancy faeces, obtained from 2 normal women in the 33rd-37th week og gestation, was studied. The qualitative analyses were made by gas chromatography - mass spectrometry and the quantitative analyses by mass fragmentography. The presence of the following oestrogens in pregnancy faeces was established: Oestriol, oestrone, oestradiol-17 beta, 16-epioestriol, 17-epioestriol, 16 alpha-hydroxyoestrone, 16-oxo-oestradiol-17 beta, 15 alpha-hydroxyoestrone and 15 alpha-hydroxyoestradiol-17 beta. In addition, mass fragmentographic evidence was obtained for the presence of 16 beta-hydroxyoestrone, 2-methoxyoestrone and oestradiol-17 alpha. The total oestrogen excretion determined in the two pools was 786 and 1300 mug per 24 h. Unconjugated oestrogens accounted for 97.8 and 98.6% of these amounts, respectively. Oestriol, oestradiol-17 beta, 15 alpha-hydroxyoestradiol-17 beta, 16-epioestriol and oestrone, in that order, were quantitatively the most significant of the oestrogens determined. The remarkably high levels of oestradiol-17 beta fround in faeces show, that in pregnancy, this mode of excretion is as important as urine for the elimination of this biologically active steroid. It is suggested that some of the oestradiol may have b-en formed through bacterial enzyme action from other oestrogens or neutral steroids. Only trace amounts of ring D alpha-ketolic oestrogens were found in faeces. This is in marked contrast to the considerable amounts of these steroids found in pregnancy bile and urine.

A simple gas chromatographic technique for the measurement of 16 alpha-hydroxydehydroepiandrosterone sulphate in urine from pregnant women is described. An assessment was made of the effectiveness of the measurement of this oestriol precursor for the antenatal diagnosis of placental steroid sulphatase deficiency. Twenty-two patients whose pregnancies were complicated by subnormal oestrogen excretion for gestation were studied. In nine of these, where placental steroid sulphatase activity was found subsequently in vitro to be normal, the excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate was less than 27 mumol/24 h. In the remaining 13 patients, in whom postnatal in vitro assay demonstrated absence of placental steroid sulphatase activity, urinary excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate was 59-360 mumol/24 h. The excretion of this metabolite was below the limit of detection (20 mumol/24 h) in 30 uncomplicated pregnancies. It is concluded that urinary excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate greater than 50 mumol/day or a ratio of urinary 16 alpha-hydroxydehydroepiandrosterone sulphate to urinary oestrogen greater than 2.0 correctly identifies, before delivery, those pregnancies in which fetus and placenta are deficient in steroid sulphatase activity.

The initial clinical, pathological, and hormonal investigation of a patient with testicular feminization syndrome is described. Incubation of gonadal tissue with various radioactive substrates, together with the isolation and identification of the resulting metabolites, was demonstrated a high capacity to synthesize testosterone. Two biosynthetic pathways were demonstrated, originating from progesterone and pregnenolone. These are essentially similar to those of the normal adult testes. Low levels of activity were found in the phenolic fractions and no measurable production of oestrone, oestradiol, or oestriol was found.

Tissue culture has been used to study the action of different substrates on the secretion of HCG and HCS in human placental explants. The following compounds have been studied: prostaglandins E2 and F2alpha, adrenaline and noradrenaline, oestriol and progesterone, glucose concentration. The investigators first measured the normal secretion of three term placentas and 2 months placentas. The activity of the compounds tested is expressed in per cent of the normal values. The investigators have checked that the cultivated cells were always viable by measuring the oxygen consumption during all the experiments. PG E2 and F2alpha are without action on term placentas. Adrenaline and noradrenaline reduce significantly the secretion HCS by full term placentas and have no action on HCG secretion. Oestriol always stimulates HCS secretion by full term placentas and 2 months old placentas, whereas progesterone stimulates young placentas and inhibits full term placentas. Both steroids have no action on HCG secretion. Glucose is essential for HCS secretion by placentas but high values of glucose in the medium signficantly reduce the HCS secretion by full term placentas.

A case of human placental lactogen (hPL) deficiency together with normal oestriol levels associated with a normal pregnancy in a woman in her second pregnancy is reported. The woman gave birth to a healthy male infant. The placenta was normal. Extremely low hPL levels may be compatible with the delivery of a healthy infant.

Three infants with congenital adrenal hypoplasia are described. The two surviving infants were detected and successfully treated in the neonatal period due to a suggestive family history (Case 1) and antenatal maternal oestriol screening (Case 2). The modes of inheritance, diverse clinical presentation, associated conditions, diagnostic work-up and pathology of congenital adrenal hypoplasia in these three infants is discussed.

Commercial RIA kits for the assay of serum total oestriol using 125I label are used widely in monitoring fetal well-being in pregnancy; they are, however, very expensive for large-scale routine use. An 'in-house' assay using commercially available [125I]oestriol label and antiserum produced by the S.E. and S.W. Thames Regional Antibody Production Unit has been developed. Technical aspects of the method are described. The assay is compared with two commercial kits and correlates very well with one of them. The assay gives good precision and can be used with substantial savings in cost.

Part 1. The present disillusionment with oestriol measurement as a test of fetoplacental function could be explained by the use of poor methodology and inappropriate normal ranges rather than that the test has lost its usefulness. We have updated the Lever method for measuring oestriol in urine, and examined the automatic TDX system supplied by Abbott Laboratories. The precision of the methods and consistency of results between methods have been determined and normal ranges have been established for both methods. The overall accuracy of collection of 24-hour urine specimens in a routine laboratory setting has also been calculated. The normal ranges suggested as a guide for the TDX method by Abbott were based on those derived from the original method of Brown and were found to be too low and therefore unsuitable for clinical use. This study reports appropriate lower limits of normal for both the updated Lever and the TDX methods. Part 2. The results obtained using the updated Lever method since its introduction in 1991 have been compared with those obtained by the original Brown method during the years 1971-1989. The new, user-friendly Lever method of oestriol assay measurement used in 1991-1993 gave results of equivalent clinical value to the Brown method used in 1971-1989, although the perinatal mortality rates in the tested populations fell from 0.95% to 0.37%. During 1971-1989, low oestriol excretion on 1 or more occasions was associated with a 5.6-fold increase in the perinatal mortality rate (0.66% to 3.67%), whereas in 1991-1993, the factor was 4.4 (0.27% to 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14,000 prospectively collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for F beta HCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for intHCG and F beta HCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG 0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free beta human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.