Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth.

A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.

First trimester prenatal diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency).

In Smith-Lemli-Opitz syndrome (SLOs), 7-dehydrocholesterol (7-DHC) accumulated because there is a block in the pathway for synthesis of cholesterol via 7-DHC. Prenatal diagnosis of SLOs has been achieved by analysis of 7-DHC in amniotic fluid obtained at 16-18 wk from pregnancies at risk. The purpose of this study was to investigate 7-DHC and cholesterol concentrations in chorionic villus (CV) samples with a view to performing first trimester prenatal diagnosis. Using a sensitive gas chromatography-mass spectrometry assay it was possible to detect 7-DHC in CV samples obtained as early as 7 wk of gestation. The ration of 7-DHC to cholesterol in placental tissue was shown to be relatively constant over the gestational period of 7-18 wk. We therefore proceeded to analyze the 7-DHC/cholesterol ration in CV samples taken at 10-12 wk of gestation from three pregnancies at risk for SLOs. The results were as follows: patient A, 1.10 x 10(-3); patient B, 1.80 x 10(-3); patient C, 0.091; control range for CVS (8-12 wk), 3.10 x 10(-4) to 1.62 x 10(-3) (mean +/- 2SD; n = 5). The fetus of patient C was diagnosed as affected by SLOs, and the parents requested termination. Analysis of cultured skin fibroblasts confirmed the diagnosis. Pregnancies A and B were diagnosed unaffected, and this was confirmed first by amniocentesis and then by the birth of normal infants at term. We conclude that synthesis of cholesterol via 7-DHC is occurring in the placenta and/or fetus at 10 wk of gestation and that prenatal diagnosis by CV biopsy is possible.

Fetal haemoglobin concentration and mean red cell volume are not related to the maternal values at 18-25 weeks' gestation.

A cross-sectional study of 64 women and their fetuses undergoing cordocentesis at 18-25 weeks showed no significant correlation between maternal and fetal Hb or MCV and no relationship between these measurements and fetal abdominal circumference. We found no evidence for a nutritional or physiological association between maternal and fetal haematological status.

Platelet size and glycoprotein Ib and IIIa expression in normal fetal and maternal blood.

OBJECTIVE: Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and maternal blood throughout pregnancy. STUDY DESIGN: A cross-sectional study was performed at the Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. Fetal and maternal blood samples were obtained from uncomplicated pregnancies at 8 to 42 weeks' gestation (n = 101 and n = 117, respectively) and from 30 nonpregnant controls. Flow cytometry was used to determine platelet size and glycoprotein Ib and IIIa expression both before and after stimulation with adenosine diphosphate. RESULTS: Mean platelet size in both fetal and maternal blood was significantly lower than that of nonpregnant controls and decreased with advancing gestation. The surface density of glycoprotein Ib in maternal and fetal platelets was significantly lower than in nonpregnant controls but did not change with gestation. Adenosine diphosphate stimulation of maternal platelets resulted in increased percentage expression and surface density of all glycoproteins, whereas stimulation of control platelets resulted in increased surface density of glycoprotein Ib and percentage expression of glycoprotein IIIa. Adenosine diphosphate stimulation of fetal platelets resulted in increased surface density of glycoprotein Ib and IIIa. CONCLUSION: Pregnancy is associated with increased thrombocytopoiesis in both the mother and fetus. Maternal platelet glycoprotein expression and responsiveness to adenosine diphosphate stimulation is increased. Fetal platelets are phenotypically mature from at least 12 weeks' gestation and respond in an adultlike fashion to stimulation with adenosine diphosphate.

Effect of dihydroergocryptine on serum prolactin levels and milk secretion in puerperal women.

The aim of the present study was to evaluate the efficacy and tolerability of the dopamine agonist drug dihydroergocryptine in the suppression of puerperal lactation. A single blind and placebo-controlled study was performed. A total of 90 postpartum women was acutely or repeatedly treated with dihydroergocryptine at different doses in order to investigate the efficacy of this drug in the suppression of puerperal lactation and to find the optimum dose for therapy. Prolactin levels, mammary symptomatology and rebound effects were monitored during the repeated treatment and also 1 and 8 days after drug discontinuation. With acute administration, dihydroergocryptine significantly reduced prolactin levels only at the dose of 10 mg and not at 5 mg. With repeated administration, a daily dose of 15 mg was more effective than 10 mg in reducing prolactin levels and in suppressing puerperal lactation. No side-effects occurred during the treatment. These results suggest that dihydroergocryptine might be considered an effective drug in the suppression of puerperal lactation.

The effect of various drugs with neuroendocrine activity and transdermal estradiol on plasma gonadotropin concentrations after ovariectomy in reproductive-aged women.

In the present study we compared the effect of different neuroactive drugs with that of estrogen treatment on the ovariectomy-induced plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) changes. A total of 35 menstruating women undergoing ovariectomy were randomly divided into five groups of 7 patients each, receiving a 4-week treatment with oral clonidine, lisuride and sodium valproate, transdermal 17 beta-estradiol, or placebo. The treatment started the day after ovariectomy. Surgery was done during the early follicular phase of the cycle. Blood samples were collected before and after 3, 5, 7, 14, 21 and 28 days of treatment. During the treatment, hot flushes were subjectively recorded. The placebo-treated group showed a progressive increase in plasma LH and FSH concentration during the month following ovariectomy. The same changes occurred in the lisuride and sodium valproate treated groups. Plasma LH levels in ovariectomized women treated with clonidine showed an increase which was higher than in placebo-treated women (p less than 0.01), while FSH levels were similar to those in the placebo group. In the estradiol-treated group the increase in both gonadotropins was significantly less (p less than 0.01) than in the placebo group. The frequency and intensity of hot flushes were high in placebo and sodium valproate treated subjects, being significantly reduced by clonidine, lisuride and estrogen treatment. Our results seem to indicate that clonidine treatment modulates the LH postcastration rise and that both neuroendocrine and gonadal mechanisms influence the changes in the activity of the GnRH-pituitary axis following ovariectomy.

Breast carcinoma metastasized in ovarian thecoma (a case report).

We describe a patient with breast cancer metastatic to ovarian thecoma. This finding, to the best of our knowledge, has yet to be reported in literature regardless of the fact that there are many gynecological neoplastic associations. Our hypothesis is that this unusual finding is not accidental, but rather benign lesions may be natural resting sites for metastatic disease. An autopsy series is required to elucidate this incidence.