Effect of Ampicillin Administration of Plasma Levels of Oestradiol-17β, Oestriol and Placental Lactogen

Summary: Ampicillin was given to 21 noninfected patients in the last trimester of pregnancy. There was no significant alteration in plasma unconjugated oestradiol-17β and placental lactogen levels during treatment. Total plasma oestriol, on the other hand, showed a significant reduction of 30% to 40% during and after treatment.     

Value of Total Serum Oestriol and Human Placental Lactogen in the Assessment of Fetal-Placental Function

Serum levels of total oestriol and human placental lactogen (HPL) were measured in 360 pregnancies; in 182 there were abnormalities likely to be associated with increased fetal risk. A total of 217 estimations of oestriol and HPL were performed in 163 normal pregnancies to define the normal ranges. The value of both tests in the management of complicated pregnancies was assessed. Serum oestriol was found to be very efficient in the diagnosis of intrauterine growth retardation. In such cases, 76% of patients had unfavourable oestriol levels. Patients with mild pre-eclampsia had HPL levels similar to normal, but values decreased significantly in the presence of fetal distress. The mean serum oestriol level in patients with pre-eclampsia were lower than normal, and were further reduced in the presence of fetal distress. The importance of measuring serum oestriol levels at each antenatal visit is stressed in the detection of developing fetal complications; in such cases, 73% of patients had subnormal values. Both tests provided accurate assessments in the 8 patients with intrauterine death. Significant fetal-placental dysfunction was present in 55 patients, and 41 (75%) were predicted by serum oestriol, 23 (42%) by HPL, and 45 (82%) by the use of both tests. In the 142 complicated pregnancies that resulted in a favourable outcome, confirmation was obtained in 102 (72%) by serum oestriol and in 121 (86%) by HPL.     

The Prognostic Value of HCG, PAPP-A, Oestradiol-170 and Progesterone in Early Human Pregnancy

Four serum parameters were assayed weekly from the 4th to the 12th week of pregnancy and finally at 16 weeks, to assess their relative prognostic values for predicting pregnancy outcome. Of 85 pregnancies generated following treatment for infertility, 16 cases had blighted ova and subsequently aborted at a mean age of 9.9 +/- 0.5 weeks. Serum HCG concentrations differentiated (p less than 0.005) between ongoing pregnancies and blighted ova as early as the 4th week which was often several weeks in advance of clinical abortion. PAPP-A, oestradiol-17 beta and progesterone did not differentiate between the 2 groups until 7 weeks (p less than 0.005, p less than 0.001 and p less than 0.001 respectively). PAPP-A measurements detected ongoing pregnancies at week 4 (16.5 +/- 5 micrograms/l) but HCG remains the more sensitive diagnostic test. The lower limits of oestradiol-17 beta and progesterone for ongoing pregnancies were 670 pmol/l and 37 nmol/l respectively. The circulating concentrations of all 4 serum markers were unaffected by administration of medroxyprogesterone acetate from 6 to 16 weeks in both ongoing and aborting pregnancies.     

Plasma β-endorphin immunoreactivity in premenstrual tension

Summary. Plasma samples were collected twice during the follicular phase and three times during the luteal phase of the menstrual cycle in 12 women with premenstrual tension (PMT) and in 14 control subjects without symptoms. Concentrations of β-endorphin (β-E) immunoreactivity, cortisol, oestradiol, progesterone and LH were determined. Comparison of the mean concentrations of LH, cortisol, oestradiol and progesterone did not reveal any statistically significant differences between the PMT and the control groups. In the early luteal phase, the mean plasma β-E immunoreactivity was lower in the PMT group (10.7, SE 0.7 pg/ml) than in the control group (14.6, SE 1.6 pg/ml, P <0.05), suggesting that endorphin secretion is decreased in PMT. No significant change in the plasma β-E level was found in the PMT patients between the follicular and luteal phase when symptoms appeared. This does not exclude the possibility that in the central nervous system abnormal changes occur in the activity of endogenous opioids in PMT.     

Plasma dopamine β-hydroxylase activity in pregnancyinduced hypertension

Summary. Plasma dopamine p-hydroxylase (DBH) activity was estimated in non-pregnant women, normotensive pregnant women during the third trimester and women with pregnancy-induced hypertension (PIH). Nonpregnant women from a high income group had significantly higher DBH activity than their low income counterparts. DBH activity was significantly elevated in women with PIH when compared with non-pregnant and normal pregnant women from a low income group, but was lower than the level in well-nourished, non-pregnant normotensive women.     

Studies on Scrum OestradioI-17-β in Normal and Hypertensive Pregnancies — Preliminary Results

Summary: Serum oestradiol-17-β was measured by a radioimmunoassay method as described by Hotchkiss et al. (1971), using antiserum against 6-oxo-oestradiol succinyl bovine serum albumin conjugate raised in sheep. One hundred and fifty-eight determinations of serum oestradiol were performed on normal pregnancy cases between the 30th and 42nd weeks of gestation. Serial serum oestradiols were assayed in 5 cases of hypertensive disorder of pregnancy in the third trimester. Serum oestradiol-17-β rose from a mean value of 12.01 ± 3.80ng./ml. (± 1 S.D.) at 30 weeks of gestation to a peak of 66.72 ± 31.39 ng./ml. (±1 S.D.) at 40 weeks. Thereafter serum oestradiol fell to 66.02 ± 26.48 ng./ml. (± 1 S.D.) at 41 weeks and 42.77 ± 18.53 ng./ml. (± 1 S.D.) at 42 weeks of gestation.
In 3 out of 5 cases of severe hypertensive disorder of pregnancy, which ended in delivery of normal healthy babies, serial serum oestradiol fell within the range of values for normal pregnancy. In 2 hypertensive cases, where the babies showed evidence of intrauterine growth retardation, serial serum oestradiol values were consistently below the range of serum oestradiol for normal pregnancy. Thus serum oestradiol 17-β could be a useful indicator of fetal well-being in pregnancies complicated by hypertension.     

A Prospective Study of βHCG Radioimmunoassay in the Diagnosis of Ectopic and Other Complicated Early Pregnancies

Summary: The β-subunit of chorionic gonadotrophin (/JHCG) was measured by radioimmunoassay in the serum of 190 consecutive patients admitted to hospital with the suspicion of ectopic pregnancy. The detection limit was set at 1 ng/ml. A urine sample was also taken for pregnancy testing on admission. A positive serum βHCG result was obtained in 36 patients (19%); pregnancy was confirmed in 32 (ectopic pregnancy 14, abortion 8, continuing normal pregnancy 7, retained products 3), giving a predictive value of 89%. There was poor correlation between serum and urine results. The serum levels were low in patients who subsequently aborted, intermediate in those with ectopic pregnancy and within the normal range in patients in whom the pregnancy continued normally. The high predictive value of the test should identify the patients for further investigation, thus avoiding unnecessary operative procedures and prolonged hospital stay.     

Correlation between Human Placental Lactogen Levels and Glucose Metabolism in Pregnant Women with Intrauterine Growth Retardation

Twenty pregnant women with fetal growth retardation and 20 pregnant women with appropriate for gestational age fetuses (controls) were recruited after the 28th week of gestation. Samples were collected for estimation of serum insulin and human placental lactogen (HPL) levels in the fasting state and a glucose tolerance test was carried out on all the subjects. The results showed the glucose and HPL levels to be significantly lower in the fetal growth retardation group compared to controls. There were no differences in the fasting serum insulin levels in the 2 groups. Fetal growth retardation appears to be linked with the absence of development of the physiological 'diabetogenic' state in the second half of pregnancy. This maternal hypoglycaemic state is associated with low HPL levels and not with raised maternal insulin levels as measured in the fasting state.     

Maternal plasma concentrations of β-lipotrophin, β-endorphin and γ-lipotrophin throughout pregnancy

Summary. Plasma β-LPH, β-EP and γ-LPH concentrations were measured by radioimmunoassay in 10 pregnant women from 12 weeks gestation until term and in nine women in the early follicular phase of the cycle. There was a progressive and significant rise in the concentration of all three peptides throughout pregnancy and by 32 weeks the concentrations of β-LPH and β-EP were greater than the corresponding concentrations in the follicular phase: γ-LPH was greater than in the follicular phase by the end of pregnancy in those women who were delivered after 40 weeks. The ratio of β-LPH to γ-LPH did not change significantly throughout pregnancy, but there was a progressive fall in the β-LPH/β-EP ratio. The possible presence of a 'big LPH' to explain this finding is discussed.     

Expression of Enzymes Regulating Placental Ammonia Homeostasis in Human Fetal Growth Restricted Pregnancies

Functional placental insufficiency results in impaired feto-placental exchange, and subsequently in fetal growth restriction (FGR). We hypothesized that reductions in placental amino acid transporter activities in FGR pregnancies may be accompanied by abnormal expression of placental ammonia-handling enzymes. Term placentas were obtained from growth restricted (N = 11) and normal (N = 17) human pregnancies, and examined for glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutaminase (GA) mRNA and protein expression. Northern and Western blots were normalized on human actin mRNA and protein expression. For GA, the presence of mRNA coding the kidney isoform, and the absence of mRNA coding the liver isoform of the enzyme were demonstrated in the human placenta. In FGR pregnancies, placental expression of GDH mRNA was reduced (P < 0.05) compared to normal pregnancies (1.576 ± 0.144 vs. 2.092 ± 0.177, respectively; mean ± SE), whereas GS and GA mRNA expression was not different between the two types of pregnancy. GDH protein expression were also reduced (P < 0.05) in FGR placentas compared to normal placentas (1.055 ± 0.079 vs. 1.322 ± 0.053, respectively; mean ± SE). The GS and GA protein expression was not different in FGR pregnancies. Our data indicate that in cases of FGR, glutamate-to-oxoglutarate transformation in the placenta is limited, yet glutamine synthesis from and decomposition to glutamate seems to be preserved. This may reflect down-regulation of GDH in response to decreased fetal liver output and reduced umbilical artery glutamate concentrations in human FGR pregnancies.     

Maternal and cord plasma concentrations of β-lipotrophin, β-endorphin and γ-lipotrophin at delivery; effect of analgesia

Summary. Maternal venous plasma concentrations of β-LPH, β-EP and γ-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein β-LPH, β-EP and γ-LPH concentrations and umbilical artery pH and positive correlations between β-LPH and β-EP but not γ-LPH and cord P _CO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.     

Serum levels of unbound 17β-oestradiol during oral and percutaneous postmenopausal replacement therapy

Summary. The metabolic effects of oestrogen therapy are influenced by the route of administration. Compared with oral treatment, percutaneous administration may have theoretical advantages with respect to liver metabolism, but there are also potential disadvantages related to the specific kinetics of this route. The increase of SHBG binding capacity is much less pronounced, which might result in excess amounts of unbound, biologically-active steroid during therapy. The serum concentrations of unbound 17β-oestradiol were calculated in two groups of postmenopausal women during replacement therapy with equivalent amounts of oral and percutaneous oestrogen. A highly significant and quite similar increase of the free fraction as well as in total 17β-oestradiol was found in both groups of women, in spite of the fact that SHBG binding capacity was unchanged during percutaneous therapy. Albumin binding and the total serum concentration of 17β-oestradiol were found to be more important for the regulation of unbound steroid concentration than variations in SHBG binding capacity. In conclusion, there was no evidence that percutaneous administration per se would carry an increased risk of over-treatment.     

Second Trimester Placental Growth Factor Levels and Placental Histopathology in Low-Risk Nulliparous Pregnancies

ObjectivePlacental growth factor (PlGF) levels are lower at delivery in pregnancies with preeclampsia or fetuses small for gestational age (SGA). These obstetrical complications are typically mediated by placental dysfunction, most commonly related to the specific placental phenotype termed placental maternal vascular malperfusion (MVM). The objective of this study was to determine the relationship between PlGF levels in the second trimester and the development of placental diseases that underlie adverse perinatal outcomes.MethodsWe performed a secondary analysis of the prospective Placental Health Study in unselected healthy nulliparous women (n = 773). Maternal demographic data, Doppler ultrasound measurements, and plasma PlGF levels at 15 to 18 weeks gestation were analyzed for association with pregnancy outcomes and placental pathology following delivery.ResultsLow PlGF levels in the second trimester (<10th percentile; <72 pg/mL) was associated with preterm delivery (<37 weeks; 26% vs. 6%, P < 0.001; unadjusted odds ratio (OR) 5.75, 95% CI 3.2–10.5), reduced mean birth weight (2998 vs. 3320 g, P < 0.001), SGA deliveries (25% vs. 11%, P = 0.001; OR 2.6, 95% CI 1.5–4.6), and preeclampsia (7% vs. 2%, P = 0.02; OR 4.3, 95% CI 1.5-12.8) relative to normal PlGF levels (≥10th percentile; ≥72 pg/mL). Low PlGF was associated with lower mean placental weight (447 vs. 471 g, P = 0.01), aberrant cord insertion (25% vs. 12%, P = 0.001) and a pathologic diagnosis of MVM (18% vs. 11%, P = 0.04; OR 1.9, 95% CI 1.01–3.55) but not with other placental pathologies.ConclusionMVM placental pathology and related adverse perinatal outcomes are associated with low PlGF in the early second trimester for healthy nulliparous women.