Biomedical subjects

E Jauniaux

Publications and source records attributed to E Jauniaux.

At least 19 recordsLinked to original sources

PubMed2005

Villous histomorphometry and placental bed biopsy investigation in Type I diabetic pregnancies.

Insulin-dependent diabetes mellitus (Type I) is associated with disregulation of the glucose and oxygen metabolic pathways during pregnancy, both of which affect placental villous development. Term complete placentas and placental bed biopsies, between 37 and 40 weeks, from 12 singleton pregnancies complicated by Type I diabetes were collected following delivery by elective Caesarean section. The controls consisted of 10 term placentas from uncomplicated pregnancies delivered by elective Caesarean section. Villous morphology was investigated using unbiased histomorphometric techniques, in relation to the degree of transformation of the spiral arteries and the presence of fetal macrosomia. A significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast was found in the diabetic group compared to the controls. A significant reduction in the villous membrane specific diffusing capacity was observed between the diabetic and control groups (1.32 vs 1.72 cm3 min(-1)mmHg(-1)kg(-1), P=0.032). A significant increase in the volume of the intermediate and terminal villi, the surface area of the villi and of the fetal capillaries, and the harmonic thickness of the villous membrane was found in the macrosomic subgroup compared to the controls. There were no differences between the hypertensive subgroup with histological evidence of partial transformation of the spiral arteries and the controls. These data indicate that placental development in insulin-dependent diabetic pregnancies is affected differentially when pregnancies complicated by fetal macrosomia are separated from those complicated by maternal hypertensive disorders with partial transformation of the spiral arteries. The reduction in the specific diffusing capacity of the villous membrane may contribute to the fetal hypoxia and increased fetal and neonatal morbidity associated with diabetes.

Arteries↗

PubMed2005

Ultrasound detection of nuchal cord prior to labor induction and the risk of Cesarean section.

OBJECTIVES: To investigate the ability of ultrasound to detect the presence of a nuchal cord immediately prior to induction of labor and the association of its presence with delivery by Cesarean section. METHODS: A transabdominal ultrasound scan using gray-scale and color Doppler imaging was performed immediately prior to induction of labor in 289 women in a prospective study to assess the presence of a nuchal cord. The presence of a nuchal cord was classified as present, absent or uncertain. The outcomes of labor, delivery and the neonates were obtained from the patient notes after delivery. RESULTS: A nuchal cord was present at 18% of deliveries. The incidence was not affected by parity, fetal position or reduced amniotic fluid volume. The sensitivity of ultrasound in diagnosing a nuchal cord was 37.5%, with specificity, positive and negative predictive values of 80%, 29% and 85%, respectively. The presence of a nuchal cord did not significantly increase the risk of delivery by Cesarean section (35% vs. 28%; relative risk = 1.22; 95% CI, 0.80-1.87), instrumental delivery for fetal distress, an abnormal cardiotocograph in labor or at delivery, an Apgar score < 7 at 1 min, arterial cord pH < 7.1 or neonatal unit admission. CONCLUSIONS: The sensitivity of the ultrasound diagnosis of a nuchal cord is low prior to induction of labor at term. A nuchal cord does not appear to increase the risk of Cesarean section or of poor neonatal outcome. The low ultrasound detection rate of a nuchal cord limits its use in decision making prior to induction of labor in high-risk pregnancies.

Cesarean Section↗

PubMed2005

A prospective study of ultrasound screening for molar pregnancies in missed miscarriages.

OBJECTIVE: To examine the relationship between ultrasound and histological features in the screening for molar changes in missed miscarriage. METHODS: A prospective cohort study was conducted on all missed miscarriages, with features suspicious of molar pregnancy, on transvaginal ultrasound and/or on histological examination over a 5-year period. All cases of molar pregnancy diagnosed histologically were examined and cross-referenced with cases diagnosed on ultrasound and with the supplementary report from the regional referral center. When available, maternal serum beta-human chorionic gonadotropin (hCG) levels were recorded. RESULTS: Fifty-one cases of suspected molar pregnancy were referred to the regional center for further histological opinion and follow-up, and five cases were subsequently excluded from the final analysis because of the diagnosis of hydropic abortion (HA). In 33 cases a molar pregnancy was suspected at the initial scan. Of these, 26 (78.8%) were confirmed on histology, resulting in a 56% detection rate using ultrasound alone. In 15 cases hCG results were available, of which nine were greater than two multiples of the median. CONCLUSIONS: The diagnosis of both complete (CHM) and partial (PHM) hydatidiform moles in first-trimester miscarriages is difficult. hCG is significantly higher in both CHM and PHM and, in conjunction with transvaginal ultrasound, could provide the screening test required to enable clinicians to counsel women more confidently towards non-surgical methods of management of their miscarriage, where histopathological examination is not available.

Abortion, Missed↗

PubMed2005

The role of ultrasound imaging in diagnosing and investigating early pregnancy failure.

The advent of high-resolution transvaginal ultrasound (TVS) has revolutionized our understanding of the pathophysiology and the management of early pregnancy failure. Knowledge of the ultrasound appearances of normal early pregnancy development and a good understanding of its pitfalls are essential for the diagnosis and management of early pregnancy failure. Ultrasound imaging has rapidly replaced all other techniques used to study normal human development in the first trimester, and ultrasound features of the early gestational sac have corroborated anatomical studies showing that the first structures to appear are the celomic cavity and the secondary yolk sac. No single ultrasound measurement of the different anatomical features in the first trimester has been shown to have a high predictive value for determining early pregnancy outcome. Similarly, Doppler studies have failed to demonstrate abnormal blood flow indices in the first-trimester uteroplacental circulation of pregnancies that subsequently end in miscarriage. Ultrasound parameters combined with maternal serum hormone levels, maternal age, smoking habits, obstetric history and the occurrence of vaginal bleeding have all been combined in multivariate analyses, with mixed results. Combined ultrasound and in-vitro experiments have demonstrated that the maternal circulation inside the placenta starts at the periphery at around 9 weeks of gestation and that this is associated with a physiological oxidative stress which could be the trigger for the formation of the placental membranes. Abnormal development of these membranes can result in subchorionic hemorrhage and threatened miscarriage with subsequent long-term consequences such as preterm rupture of the membranes and preterm labor, irrespective of the finding of a hematoma on ultrasound. In both euploid and aneuploid missed miscarriages there is clear ultrasound evidence for excessive entry of maternal blood at a very early stage inside the developing placenta resulting in oxidative stress and subsequent degeneration of villous tissue. The finding of blood flow in the intervillous space in cases of first-trimester miscarriage using color Doppler also appears to be useful in the prediction of success of expectant management. Miscarriages with blood flow within the intervillous space are up to four times more likely to complete with expectant management. TVS is considered the gold standard in the diagnosis and management of incomplete miscarriage. Expectant management of miscarriage, using ultrasound parameters to determine eligibility, could significantly reduce the number of unnecessary evacuations of the retained products of conception, depending on the criteria used.

Abortion, Incomplete↗

PubMed2005

The secretion and effect of inhibin A, activin A and follistatin on first-trimester trophoblasts in vitro.

OBJECTIVE: The objectives of this study were to investigate the effect of activin A and follistatin on first-trimester cytotrophoblast invasion in culture and to study the secretion of inhibin A, activin A and follistatin by these cells in vitro. DESIGN AND METHODS: Cytotrophoblasts were isolated from human placental chorionic villous tissue obtained from 6-8, 8-10 and 10-12 weeks gestation. Cells were cultured for 3 days on cell-culture inserts coated with gelatine for invasion studies and in 24-well culture plates for secretion studies. The effects of activin A (10 ng/ml), follistatin (100 ng/ml), interleukin 1beta (IL-1beta; 10 ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion were investigated using a non-radioactive invasion assay. Secretion of inhibin A, activin A and follistatin in the presence of EGF, IL-1beta, activin A and follistatin were measured using in-house ELISAs. RESULTS AND CONCLUSION: Activin A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast invasion from 6-10 weeks gestation. IL-1beta had a significant stimulatory effect at 8-10 weeks and a significant inhibitory effect on invasion at 10-12 weeks gestation. Follistatin also had a significant inhibitory effect on invasion at 10-12 weeks gestation. In the secretion study, activin A secretion at 8-10 weeks was significantly stimulated by IL-1beta and EGF. At 10-12 weeks, follistatin and EGF had a significant inhibitory effect on activin A secretion. Follistatin secretion was significantly increased in the presence of IL-1beta at 6-8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1beta, activin A and follistatin. These results show that activin A promotes invasion of first-trimester cytotrophoblasts until 10 weeks gestation. There is a difference in the control of secretion of these proteins dependent on the gestation, suggesting that there is a tight regulation in the function of first-trimester trophoblasts depending on the gestational age.

Activins↗

PubMed2004

Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the villous tissue of miscarriage patients.

Maternal circulating levels of inhibin A are significantly lower in patients with clinical symptoms of miscarriage. The objective of this study was to quantify relative expression of inhibin alpha, inhibin/activin betaA, betaB, betaC, follistatin, activin receptors and beta-glycan genes and content of inhibin A, activin A and follistatin protein in villous tissue of first trimester miscarriages and gestation-matched normal pregnancies. Twelve women with clinical symptoms of miscarriage were matched with 12 normal pregnancies for gestational age. Total RNA was isolated from placental samples. Complementary DNA produced by reverse transcription was used in the real-time PCR to quantify the expression of the genes. The ratio between the target and rRNA 18S was calculated to provide relative gene expression. Villous tissue homogenates were used for the determination of the content of inhibin A, activin A and follistatin protein. Maternal serum was assayed for inhibin A, activin A and follistatin. All villous samples expressed inhibin alpha, inhibin/activin betaA, betaB, betaC, follistatin, activin receptors (ACTRIA, ACTRIB, ACTRIIA, ACTRIIB) and beta-glycan genes. There was no significant difference in the relative expression of these genes between the groups. Villous content of inhibin A, activin A and follistatin were also not different between the two groups. Maternal serum levels of inhibin A were significantly lower in the miscarriage group compared to the controls. The decreased maternal levels of inhibin A in miscarriage patients could be due to a decrease in placental mass prior to embryonic demise. This finding also confirms that the trophoblast is the major source of inhibin A after the luteo-placental shift in early pregnancy.

Abortion, Spontaneous↗

PubMed2004

Procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios.

OBJECTIVE: To investigate the procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios. METHODS: We followed prospectively all patients with polyhydramnios treated with rapid amniodrainage under continuous ultrasound guidance using a vacuum wound-drainage system from 1995 to 2002 in the fetal medicine unit of a university teaching hospital. We recorded: maternal age, type of pregnancy (singleton/twin), cause of polyhydramnios, gestational age at amniocentesis, volume of amniotic fluid drained, duration of the procedure, other intrauterine procedures in addition to the amniodrainage, and procedure-related complications including placental abruption, premature rupture of membranes (PROM), chorioamnionitis, fetal bradycardia and preterm delivery within 48 h of amniodrainage. RESULTS: Seventy-four consecutive women had 134 rapid amniodrainage procedures during the study period. Four procedures were excluded because the women were already in labor at the time of amniodrainage and they delivered within 48 h of the procedure. The final database therefore consisted of 70 patients with 130 procedures. Sixty-two percent (80/130) of the procedures were performed for the treatment of twin-twin transfusion syndrome (TTTS). There were altogether four procedure-related complications (3.1%; 95% CI, 1.0-8.0%). Three of them occurred in the TTTS group (3/80 procedures, 3.8%; 95% CI, 1.0-11.0%): one case each of placental abruption, PROM and fetal bradycardia. One PROM occurred in the non-TTTS group (1/50 procedures, 2.0%; 95% CI, 0-11.0%). In both cases of PROM the women presented in labor. CONCLUSIONS: Rapid amniodrainage using a vacuum wound-drainage system is safe and efficient to treat severe polyhydramnios, with a 3.1% complication rate.

Amniocentesis↗

PubMed2004

In-vivo concentrations of inhibins, activin A and follistatin in human early pregnancy.

The aims of this study were to investigate the relationship between inhibins, activin A and follistatin in first trimester fetal fluids, maternal serum, placenta and decidua, and to investigate if these hormones are present in the circulation of the early second trimester human fetus. Amniotic and coelomic fluid, maternal serum, placental villi and decidual tissue were obtained from normal pregnancies at 8-12 weeks. Fetal blood by cardiocentesis and maternal blood were collected at 14-16 weeks gestation. Placental extracts had higher concentrations of inhibins, activin A and follistatin compared with decidual extracts. In the second trimester, inhibins and follistatin were detectable in fetal blood at 14-16 weeks gestation. Maternal serum concentrations of inhibin A (P < 0.001) and follistatin (P < 0.05) were significantly higher than fetal serum whereas inhibin B (P < 0.01) and pro-alpha C concentrations (P < 0.001) were higher in fetal serum. Inhibin B concentrations were also higher in male fetal serum samples that had higher concentrations of testosterone. The presence of all molecular forms of inhibins, activin A and follistatin in the first trimester fetal fluids, placental and decidual extracts in the first trimester confirms other reports. In the second trimester, high concentrations of inhibin B with testosterone in the fetal circulation indicate that these hormones may interact in the development of the male fetal gonads.

Activins↗

PubMed2004

Human fetal nongonadal tissues contain human chorionic gonadotropin/luteinizing hormone receptors.

Human chorionic gonadotropin (hCG), a heterodimeric glycoprotein hormone produced in abundance by placental syncytiotrophoblasts, is preferentially secreted into maternal circulation. Fetal circulation also contains low levels of hCG that are probably derived from fetal kidney, liver, anterior pituitary gland, etc. In addition, the fetus has access to hCG present in exocoelomic and amniotic fluids. hCG has been found in a number of fetal tissues known to stimulate fetal adrenal and testicular steroidogenesis and is also thought to play a role in growth and differentiation of fetal tissues. This led us to test the hypothesis that fetal nongonadal tissues, as in the adult, may also contain hCG/LH receptors. This hypothesis was tested by immunocytochemistry, Western blotting, in situ hybridization, and RT-PCR. The results demonstrate that kidney, liver, pancreas, lung, small and large intestines, and adrenals contained hCG/LH receptors. Although the role of fetal nongonadal hCG/LH receptors is not known, they may mediate the pleiotropic actions of hCG in the growing human fetus.

Blotting, Western↗

PubMed2003

Successful early in utero management of fetal hydrothorax in a twin pregnancy.

We present a case of dichorionic diamniotic twin pregnancy in which one of the fetuses was found to have a major pleural effusion at 15 weeks of gestation. A single-needle pleural fluid aspiration was performed at 15 and 16 weeks, but the fluid reaccumulated quickly after each procedure and at 16 weeks, the fetus was found to become progressively hydropic. A shunt was then successfully inserted at 17 weeks, which is the earliest gestation reported so far in the literature for such a procedure to treat isolated hydrothorax. Because we felt that the fetus would be too small for a classical double-pigtail pleuroamniotic shunt, we used a multilength double-pigtail bladder stent (Harrison drain; Cook; Spencer; Indiana; USA) via a 13-gauge echo tip trocar. This shunt could be used for both singleton and twin pregnancies presenting with fetal pleural effusion from as early as 16 to 17 weeks to prevent the development of fetal hydrops and polyhydramnios and subsequent premature delivery. Treatment at this stage of gestation would also minimize the risk of lung hypoplasia, which is the main clinical issue when shunts are inserted after 24 weeks.

Amnion↗

PubMed2003

A reappraisal of the contrasting morphological appearances of villous cytotrophoblast cells during early human pregnancy; evidence for both apoptosis and primary necrosis.

Villous cytotrophoblast cells display a range of morphological appearances that are assumed to reflect different stages of differentiation. Here we demonstrate that apoptosis and primary necrosis can also occur in these cells during normal early pregnancy, and should be included in the list of possible phenotypes. Samples from 30 placentae of 6-15 weeks gestational age were examined. Cytotrophoblast cells displaying highly condensed chromatin, but no karyorhexis, were observed detached from the basement membrane, and represented 0.49% (s.d.+/-0.36) of the total population. Their cytoplasm was heavily vacuolated, and their mitochondria swollen, indicating secondary necrosis. By contrast, extremely pale-staining cells with large rounded nuclei (volume-weighted mean volume 471.6 microm(3) compared to 250.1 microm(3) for euchromatic cells) were frequently observed (5.97% of total, s.d.+/-4.31). These cells displayed loss of euchromatin, a paucity of cytoplasmic organelles, and swelling of the mitochondrial intracristal space and endoplasmic reticulum. Nuclei of these cells displayed a significantly higher level of gold labelling using the TUNEL technique compared to euchromatic nuclei [1.0 particles/microm(2) (s.d.+/-0.13) vs 0.12 particles/microm(2) (s.d.+/-0.03),P< 0.05], confirming increased DNA fragmentation. We conclude that these cells are undergoing primary necrosis. The stimulus for both forms of cell death remains unknown, but may be associated with syncytiotrophoblastic stress.

Adult↗

PubMed2003

The human first trimester gestational sac limits rather than facilitates oxygen transfer to the foetus--a review.

Oxygen (O2) free radicals are a potential teratologic threat to the foetal tissues and are known to be involved in the pathophysiology of common human pregnancy disorders such as miscarriage and pre-eclampsia. During the first two months of human gestation, the placenta surrounds the whole gestational sac, the villi contain only a few capillaries located mainly within the centre of the mesenchymal core, the trophoblastic layer is twice the thickness it will be in the second trimester, the foetal red cells are nucleated and the exocoelomic cavity (ECC) occupies most of the space inside the gestational sac. The ECC contains no oxygen transport system, but anti-oxidant molecules that may provide additional protection to the embryo from oxidative damage are present. Ultrasound and anatomical studies have also demonstrated that the intervillous circulation starts in the periphery of the placenta at around 9 weeks of gestation, and that it becomes continuous and diffuse in the entire placenta only after 12 weeks. Overall, these anatomical features provide indirect evidence that the architecture of the human first trimester gestational sac limits foetal exposure to O2 to what is strictly necessary for its development. These results are in agreement with the concept that the placenta and foetus develop in a physiologically low O2 environment and that its metabolism must be essentially anaerobic. Because of these anatomical arrangements, different nutritional pathways to those operating during most of pregnancy must serve the first-trimester foetus. Up to 9 weeks of gestation, foetal nutrition appears to depend on uterine glandular secretions that are delivered into the intervillous space, supplemented by maternal plasma proteins and other molecules that may percolate through the trophoblastic shell. These molecules diffuse through, or are transported by, the trophoblast of the villi and the chorionic plate into the ECC. From here they are absorbed by the secondary yolk sac (SYS), in which the extraembryonic circulation is probably first established. At the end of the first trimester, the SYS and two-thirds of the placental mass degenerate, and the ECC is progressively obliterated by the enlarging amniotic cavity. The trophoblastic plugs occluding the utero-placental arteries are gradually dislocated, allowing maternal blood to flow into the intervillous space, and the uterine glands involute. These major anatomical transformations modify considerably the spatial relationships between the maternal tissues and the developing embryo, and, consequently, the materno-embryonic exchange pathways. Overall the comparison of morphological features with physiological findings reveals that the architecture of the human first trimester gestational sac is designed to limit foetal exposure to oxygen to that which is strictly necessary for its development, and that during early pregnancy alternative nutritional pathways are in use.

Anaerobiosis↗

PubMed2003

Intralobular differences in antioxidant enzyme expression and activity reflect the pattern of maternal arterial bloodflow within the human placenta.

The aim was to determine whether the activities and mRNA concentrations of antioxidant enzymes in human placental tissues reflect the prevailing oxygen tension or developmental maturity of the villi. Advantage was taken of contrasting gradients within lobules of the mature placenta. The central region is well-oxygenated compared to the periphery, owing to the direction of maternal blood flow. However, central villi are morphologically and enzymatically immature compared to peripheral villi. Activity of catalase (t=8.72, P< 0.001) and glutathione peroxidase (t=2.17,P< 0.05) was higher in central than peripheral villi, but no difference was detected for total superoxide dismutase (t=1.08, P> 0.05). The degree of change in catalase activity across the lobule correlated closely with the radius (r=-0.70, P< 0.01). The mRNA concentration was higher in the centre for catalase (t=2.81, P< 0.05) and for glutathione peroxidase (t=3.33, P< 0.05), but no differences were found for copper/zinc or manganese superoxide dismutase. In separate experiments, first trimester villi cultured under 10 per cent oxygen contained higher concentrations of catalase mRNA than controls maintained under 2.5 per cent oxygen. We conclude that the activities of catalase and glutathione peroxidase reflect gradients established by the pattern of maternal intralobular bloodflow, and that oxygen tension is one regulatory factor in vitro.

Adult↗

PubMed2002

Evaluation of the impact of current antismoking advice in the UK on women with planned pregnancies.

Smoking during pregnancy (active or passive) is associated with increased health risks to the unborn child. Current policy on antismoking advice for pregnant women in the United Kingdom is based essentially on written information by means of leaflets given to them at the first antenatal visit. We evaluated the impact of this policy on the smoking habits of pregnant women. A sample of 180 women with planned pregnancies attending antenatal clinics at two teaching hospitals in North London was recruited over a 6-month period. All women were provided with the current antismoking counselling at their first visit at the end of the first trimester and asked to fill in a questionnaire around mid-gestation. The study population included 117 (65%) women who did not currently smoke (non-smokers) and 63 (35%) who were active smokers at the beginning of their pregnancy. Thirty-nine non-smokers were found to be passive smokers. Three women took up smoking during pregnancy. Among the smokers, 53 (84.1%) women made no change in their smoking behaviour during pregnancy, seven (11.1%) reduced their cigarette consumption and only three (4.8%) gave up smoking during the first half of pregnancy. None of the partners changed their smoking habits. All women were aware that smoking in pregnancy could be deleterious to their health and that of their fetus. Despite awareness of dangers of smoking, the prevalence of smoking among pregnant women remains very high after the first antenatal visit and the current antismoking policy based essentially on leaflets is not effective. Health-care professionals should spend more time to inform women adequately about the dangers of smoking and help them to quit before pregnancy.

Attitude to Health↗

PubMed2002

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.

Abortion, Habitual↗

PubMed2002

Down's syndrome screening in twin pregnancies by nuchal translucency measurement. Current concept.

During the last 2 decades various non-invasive Down syndrome (DS) screening methods were introduced in clinical practice. However, specific problems were encountered when these methods were applied for twin pregnancies. The current review aims to explore the problematic issue of antenatal DS screening in twins. The implication and the adjusted management in the attempt to achieve the best evaluation for this type of gestation is discussed. Overall more women with twin pregnancies (mainly those who conceived via assisted reproduction) are found false positive for DS. This is because the standard screening algorithms include maternal age. In addition, mid-trimester maternal serum screening is associated with a higher false positive rate; secondary to changes in the feto-placental endocrinologic metabolism in assisted conception pregnancies. Therefore, in twins mid-trimester maternal serum screening is of limited clinical value. In those pregnancies, DS screening by means of nuchal translucency measurements at 10-14 weeks is associated with a lower false positive rate than mid-trimester serum screening. In addition, this screening method enables to specifically identify those fetuses at risk of DS and other anomalies, and thus contributes to a better outcome.

Down Syndrome↗

PubMed2001

Parallel induction of the formation of dopamine and its metabolites with induction of tyrosine hydroxylase expression in foetal rat and human cerebral cortical cells by brain-derived neurotrophic factor and glial-cell derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF; 50 ng/ml), dopamine (DA; 10 microM) and forskolin (Fsk; 10 microM) have previously been shown by this and other laboratories to induce the tyrosine hydroxylase (TH) enzyme in foetal human and rat cerebral cortex during specified sensitive developmental periods. In the present study, these findings were extended for human and rat cells by showing that the induced TH+ cells also produce dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). In addition to this, TH induction and DA plus DOPAC production was observed in foetal human and rat cerebral cortex by using glial-cell derived neurotrophic factor (GDNF) in place of BDNF. The degree of induction by GDNF (1-10 ng/ml) was similar to that produced by BDNF and did not increase further when the two neurotrophic factors were used together. The time-course of induction in human cultures was followed: GDNF was found to cause a more rapid induction process than BDNF during the first 2 weeks. However the degree of induction after 3 weeks was the same for both neurotrophic factors. Inhibitors of transcription (actinomycin D) or of translation (cycloheximide) eliminated all the increase in DA+DOPAC contents elicited by these compounds, indicating that de novo transcription and translation were required for increased expression of the TH and other related enzymes. The intracellular pathways by which these molecules exert this dopaminergic phenotype induction effect are discussed. This study indicates a new source of dopaminergic brain tissue for use as transplants to neurosurgically treat Parkinson's disease patients.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Increased nuchal translucency as a prenatal manifestation of congenital adrenal hyperplasia.

We present two cases of pregnant women with a previous history of congenital adrenal hyperplasia. In both cases the only abnormal feature in the initial pregnancy had been increased nuchal translucency at 10-14 weeks of gestation. The fetal karyotype was normal and a diagnosis of congenital adrenal hyperplasia was made after delivery. In their current pregnancies, both fetuses also had increased nuchal translucency and normal fetal karyotype. Diagnosis of 21-hydroxylase deficiency was made prenatally by DNA analysis. These findings in four affected fetuses suggest that congenital adrenal hyperplasia should be added to the list of genetic anomalies associated with an increase in nuchal translucency.

Adrenal Hyperplasia, Congenital↗