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Eric Jauniaux

Publications and source records attributed to Eric Jauniaux.

At least 19 recordsLinked to original sources
PubMed2006

Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage.

Recurrent miscarriage (RM; > or =3 consecutive early pregnancy losses) affects around 1% of fertile couples. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with recurrent miscarriage; however, in the vast majority of cases the pathophysiology remains unknown. We have updated the ESHRE Special Interest Group for Early Pregnancy (SIGEP) protocol for the investigation and medical management of RM. Based on the data of recently published large randomized controlled trials (RCTs) and meta-analyses, we recommend that basic investigations of a couple presenting with recurrent miscarriage should include obstetric and family history, age, BMI and exposure to toxins, full blood count, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), parental karyotype, pelvic ultrasound and/or hysterosalpingogram. Other investigations should be limited to particular cases and/or used within research programmes. Tender loving care and health advice are the only interventions that do not require more RCTs. All other proposed therapies, which require more investigations, are of no proven benefit or are associated with more harm than good.

Abortion, Habitual↗
PubMed2006

Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution.

Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visualized in vivo for the first time. As a result, a new understanding of the early materno-fetal relationship has emerged and, with it, new insight into the pathogenesis of these disorders. Unifying the two is the concept of placental oxidative stress, with associated necrosis and apoptosis of the trophoblastic epithelium of the placental villous tree. In normal pregnancies, the earliest stages of development take place in a low oxygen (O2) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O2 free radicals (OFRs). In miscarriage, development of the placento-decidual interface is severely impaired leading to early and widespread onset of maternal blood flow and major oxidative degeneration. This mechanism is common to all miscarriages, with the time at which it occurs in the first trimester depending on the aetiology. In contrast, in pre-eclampsia the trophoblastic invasion is sufficient to allow early pregnancy phases of placentation but too shallow for complete transformation of the arterial utero-placental circulation, predisposing to a repetitive ischaemia-reperfusion (I/R) phenomenon. We suggest that pre-eclampsia is a three-stage disorder with the primary pathology being an excessive or atypical maternal immune response. This would impair the placentation process leading to chronic oxidative stress in the placenta and finally to diffuse maternal endothelial cell dysfunction.

Abortion, Spontaneous↗
PubMed2006

Clinical and ultrasound parameters to predict the risk of cesarean delivery after induction of labor.

OBJECTIVE: To evaluate whether factors in the maternal history and/or ultrasound parameters are useful in predicting the risk of cesarean delivery after induction of labor. METHODS: Maternal age, height, body mass index, parity, gestational age, Bishop score, ultrasonic amniotic fluid volume, fetal head position, estimated fetal weight, and transvaginal cervical length were studied prospectively in 267 women at 36 or more weeks of gestation immediately before induction of labor. Logistic regression analysis was used to determine which factors best predicted the risk of cesarean delivery. Receiver operating characteristic curves and a resampling technique were used to evaluate the model's performance. RESULTS: Eighty (30%) of these 267 women had cesarean delivery. Logistic regression was performed and a final model chosen, which included parity (odds ratio [OR] 20.56, 95% confidence interval [CI] 7.97-53.05, P < .001), body mass index (OR 6.17, 95% CI 2.10-18.13, P < .001), height (OR 0.94, 95% CI 0.89-0.98, P = .005), and ultrasonic transvaginal cervical length (OR 1.07, 95% CI 1.04-1.11, P < .001) as the best predictors of cesarean delivery. A risk score was calculated containing these 4 parameters, which predicted reasonably accurately the risk of cesarean delivery. CONCLUSION: Parity, body mass index, height, and ultrasonic transvaginal cervical length are the most accurate parameters in predicting the risk of cesarean delivery after induction of labor. A predictive model using these would allow more accurate counseling and better informed consent in the decision-making process regarding induction of labor LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2006

Threatened miscarriage as a predictor of obstetric outcome.

OBJECTIVE: To investigate prospectively the risk of adverse pregnancy outcome in women presenting with first-trimester threatened miscarriage. METHODS: A prospective cohort study was performed on 214 women presenting with bleeding in the first trimester and 214 asymptomatic age-matched controls. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcome. RESULTS: The first-trimester miscarriage rate, after confirmation of viability in the threatened miscarriage group, was 9.3%. Compared with controls, women presenting with threatened miscarriage were more likely to deliver prematurely, 5.6% compared with 11.9%, respectively, (relative risk 2.29, 95% confidence interval 1.4-4.6), and this was most likely to be between 34 and 37 weeks. They were also more likely to have preterm prelabor rupture of membranes, 1.9% compared with 7%, respectively, (relative risk 3.72, 95% confidence interval 1.2-11.2). Overall, there was no difference in mean birth weight and in the incidence of other obstetric complications between the 2 groups; however, women in the threatened miscarriage group were more likely to deliver neonates between 1,501 g and 2,000 g (P = .04). CONCLUSION: Women with threatened miscarriage in the first trimester are at increased risk of premature delivery, and this risk factor should be taken into consideration when deciding upon antenatal surveillance and management of their pregnancies. LEVEL OF EVIDENCE: II-0.

Abortion, Spontaneous↗
PubMed2006

Hypothesis: the placental 'steal' phenomenon - a possible hazard of amnioreduction.

The twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic twin pregnancies. Severe TTTS is associated with poor neonatal outcome and a relatively high rate of neurological abnormalities. Some studies have suggested this outcome to be more severe in cases treated by amnioreduction. In this paper we present a hypothesis that radical amnioreduction performed after 24 weeks of gestation might cause a shift of blood from the fetus into the placenta. This could explain some of the severe neurological outcomes, such as hypoxic ischemic brain damage, seen in these cases.

Amniotic Fluid↗
PubMed2006

Working with oxygen and oxidative stress in vitro.

Oxygen has a profound influence on the behavior of many cell types, including trophoblast. The effects are mediated in part through the generation of oxygen free radicals, which act as signaling molecules. Because of their high reactivity, free radicals are, however, potentially damaging to a wide range of biomolecules, and if concentrations exceed homeostatic levels then cellular oxidative stress results. Responses of tissues to changes in oxygen concentration may therefore range from physiological adaptations to pathological insults. Placental development is heavily modulated by the prevailing oxygen concentration, and understanding the mechanisms involved is clearly important. Equally, trophoblastic oxidative stress plays a key role in the pathogenesis of pregnancy complications such as miscarriage and preeclampsia. This chapter describes techniques by which the effects of oxygen and oxidative stress on placental tissues can be systematically investigated in vitro.

Female↗
PubMed2005

Updated and revised nomenclature for description of early pregnancy events.

The nomenclature used to describe clinical events in early pregnancy has been criticized for lack of clarity and promoting confusion. There is no agreed glossary of terms or consensus regarding important gestational milestones. In particular there are old and poorly descriptive terms such as 'missed abortion' and 'blighted ovum', which have persisted since their introduction many years ago (Robinson, 1975) and have not undergone revision despite the widespread application of ultrasound for accurate clinical assessment and diagnosis. The authors are aware of these shortcomings in terminology and are keen to provide an updated glossary. We hope that this paper will facilitate the introduction of a revised terminology in an attempt to provide clarity and to enhance uptake and use in the literature as well as clinical assessment and documentation.

Abortion, Habitual↗
PubMed2005

Scanning for chorionicity: comparison between sonographers and perinatologists.

OBJECTIVE: In most prenatal settings, twin pregnancies are initially evaluated by sonographers. Pregnancies diagnosed as monochorionic are subsequently referred to perinatologists or specialists in fetal medicine for the confirmation of chorionicity. In order to assess this screening strategy, we have compared the diagnosis of chorionicity made by the sonographers in the ultrasound department with the diagnosis done in the fetal medicine unit. METHODS: A cohort of women presenting with twin pregnancy and booked for prenatal care at University College London Hospitals over a 4-year period were investigated prospectively. All women were scanned at their initial visit at 11-14 weeks in the ultrasound department (US), and were subsequently referred to the Fetal Medicine Unit (FMU) for a second ultrasound evaluation. Ultrasound data were compared and diagnosis of chorionicity was confirmed by examination of the inter-twin membranes after delivery. RESULTS: Chorionicity was determined in 172 twin cases by the two different departments. The overall rate of concordant chorionicity determination between both units was 90.1%. The rate of discordant results in dichorionic pregnancies was extremely small, 1 in 119 pregnancies (0.8%). The rate of discordant results for monochorionic diamniotic pregnancies was 5.5%. Monoamniotic pregnancies were over-diagnosed by the US technicians. DISCUSSION: These results demonstrate that DC/DA chorionicity is accurately determined by sonographers at less than 14 weeks. In our opinion, it is both efficient and safe to rely on the diagnosis of the sonographers in DC/DA pregnancies in early pregnancy. In such pregnancies, a decision can be made either not to refer these patients for further evaluation of chorionicity by the fetal medicine team or to postpone the referral to after 14 weeks.

Chorion↗
PubMed2005

First-trimester diagnosis of conjoined twins.

Conjoined twins are a rare and complex complication of monozygotic twinning, which is associated with high perinatal mortality. Early prenatal diagnosis of conjoined twins allows better counselling of the parents regarding the management options, including continuation of pregnancy with post-natal surgery, termination of pregnancy or selective fetocide in case of a triplet pregnancy. With the introduction of high-resolution and transvaginal ultrasound imaging, accurate prenatal diagnosis of conjoined twins is possible early in pregnancy. We have reviewed the medical literature on the early prenatal diagnosis of suspected conjoined twins using a MEDLINE search. Although first-trimester diagnosis of conjoined twins is feasible, false-positive cases are common before 10 weeks because, earlier in gestation, fetal movements are limited and monoamniotic twins may appear conjoined. As most parents opt for immediate termination of pregnancy at confirmation of the diagnosis, there are limited data on the prenatal follow-up of conjoined twins. When the parents opt for conservative management, half of the fetuses die in utero and another 44% will die during the neonatal period. A detailed analysis of case reports where 3D imaging was used indicates that this modality does not improve on the diagnosis made by 2D ultrasound. Overall, very early prenatal diagnosis and first-trimester 3D imaging provide very little additional practical medical information compared to the 11-14 weeks' ultrasound examination.

Female↗
PubMed2005

Prenatal diagnosis and management of twin pregnancies complicated by a co-existing molar pregnancy.

Recent advances in ultrasound and molecular genetics have increased our understanding and hence enhanced the perinatal management of complete and partial hydatidiform mole. By contrast, the management of a twin pregnancy combining a normal pregnancy with a normal fetus and a complete hydatidiform mole (CHM) remains complex and controversial due to conflicting data from different parts of the world. The aim of this review is to analyse the international literature on twin pregnancies that include a mole, present the complications and outcome of pregnancy and to discuss the perinatal management. Management is complicated and women should be counselled about the maternal and fetal complications, and the pregnancy monitored carefully by a perinatal team with experience in high-risk obstetrics and access to neonatal care. The data reviewed here suggest that a woman who decides to continue with the pregnancy including a CHM must be aware that, overall, she only has a one in four chance of live birth and in around 35% of cases she will develop persistent trophoblastic disease (PTD) after delivery. In ongoing pregnancies, there will be, in at least 20% of the cases, an early onset of pre-eclampsia (PET) and a 29% risk of fetal loss due to late miscarriage, intrauterine death and neonatal death. Maternal serum human chorionic gonadotrophin (MShCG) could be useful in predicting outcome in twin pregnancy combining normal pregnancy and CHM, but this needs to be investigated prospectively.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2005

Early detection of fetal structural abnormalities.

Most published data on the detection of fetal anomalies at 11-14 weeks are from specialized centres with considerable experience in fetal anomaly scanning. However, there is still limited information on the feasibility and limitations of the screening of these anomalies compared with the now classical mid-gestation screening. This review indicates that overall, the detection rate of fetal anomalies at 11-14 weeks is 44% compared with 74% by the mid-pregnancy scan. Major abnormalities of the fetal head, abdominal wall and urinary tract, and of the umbilical cord and placenta, can be reliably detected at 10-11 weeks of gestation. Detection of other anomalies such as spina bifida, diaphragmatic hernia or heart defects is limited before 13 weeks of gestation. So far it cannot be stated that routine first trimester screening can be used on a large scale to evaluate the fetal spine and heart in the general population. In particular, in screening for congenital heart defects, the ability to perform a full cardiac examination increases from 20% at 11 weeks to 92% at 13 weeks. The early prenatal diagnosis of these anomalies may be improved by screening at 13-14 weeks rather than during the first trimester.

Congenital Abnormalities↗
PubMed2004

Polyol concentrations in the fluid compartments of the human conceptus during the first trimester of pregnancy: maintenance of redox potential in a low oxygen environment.

Polyols are sugar alcohols formed by the reduction of aldoses and ketoses. Production is favored under conditions of low oxygenation, when it may provide an alternative means to production of lactate for regulating the oxidation-reduction balance of pyridine nucleotides. Polyols also act as important organic osmolytes and as precursors of cell membrane components. We measured free sugar and polyol concentrations in matched samples of maternal serum, intervillous fluid, coelomic fluid, and amniotic fluid from normal human pregnancies at 5-12 wk gestational age. The concentrations of fructose, inositol, sorbitol, erythritol, and ribitol were significantly higher in coelomic and amniotic fluids than in maternal serum, but the reverse was the case for glucose and glycerol. Intervillous fluid concentrations of inositol, mannitol, and sorbitol were also significantly higher than those in maternal serum. These results demonstrate that the polyol pathway, considered vestigial in adult tissues, is highly active in the human conceptus during early pregnancy. The pathway may serve to maintain ATP concentrations and cellular redox potential while the embryo develops in a low oxygen environment. Polyols may also play important physiological roles in development of the human conceptus, possibly drawing water and solutes across the placenta and expanding the gestational sac.

Embryo, Mammalian↗
PubMed2004

The differentiation potential of human foetal neuronal progenitor cells in vitro.

Previously, this laboratory has shown that human foetal progenitor cells derived from ventral mesencephalon (VM) can be developmentally directed towards a dopaminergic lineage. In the present study, the effects are reported of several as yet untested differentiation/survival factors on the controlled conversion of neural progenitor cells to dopaminergic neurons. Positive immunoreactivity to tyrosine hydroxylase (TH) and raised levels of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), secreted into culture medium, were used to indicate the presence of the dopaminergic neuronal phenotype, i.e., active TH. Incubation with retinoic acid (RA) (0.5 microM) lead to an increase in the number of cultured cells showing positive immunoreactivity for the neuronal marker, microtubule-associated protein (MAP)-2ab. A concomitant increase in TH-positive immunoreactivity was also demonstrated. The brain-derived neurotrophic factor (BDNF) (50 ng/ml), glial-derived neurotrophic factor (GDNF) (10 ng/ml) and interleukin-1 beta (IL-1 beta) (10 ng/ml) also had positive effects in promoting neural progenitor cell differentiation towards the dopaminergic phenotype in the presence of dopamine (10 microM) and forskolin (Fsk) (10 microM). There was no synergy in this effect when progenitor cells were incubated with all of these agents simultaneously. The trans-differentiation potential of the progenitor cells to be directed towards other neurotransmitter phenotypic lineages was also investigated. It was found that, with the right cocktails of agents, serotonin (Ser) (75 microM), acidic fibroblast growth factor (aFGF) (10 ng/ml), BDNF (50 ng/ml) and forskolin (10 microM), these same cells could be directed down the serotonergic cell lineage pathway (as judged by the appearance of tryptophan hydroxylase (TPH) positive immunoreactivity, and synthesis of 5-HT and its metabolites, secreted into the culture medium). However, no cocktail containing noradrenaline (10 nM-500 microM), BDNF (50 ng/ml) and forskolin (10 microM) was found which promoted differentiation towards the noradrenergic cell phenotype as judged by the absence of any TH or D beta H positive immunoreactivity, and no formation of 3,4-dihydroxyphenylethyleneglycol (DOPEG), the principal metabolite of noradrenaline. The controlled trans-differentiation potential of these cell could pave the way for development and harvesting of large numbers of neurons of the appropriate neurotransmitter phenotype for future transplantation therapies for the treatment of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy: a morphological and immunohistochemical study.

BACKGROUND: The maternal circulation to the human placenta is not fully established until 10-12 weeks of pregnancy. During the first trimester the intervillous space is filled by a clear fluid, in part derived from secretions from the endometrial glands via openings in the basal plate. The aim was to determine the activity of the glands throughout the first trimester, and to identify components of the secretions. METHODS: Samples of human decidua basalis from 5-14 weeks gestational age were examined by transmission electron microscopy and immunohistochemically. An archival collection of placenta-in-situ samples was also reviewed. RESULTS: The thickness of the endometrium beneath the implantation site reduced from approximately 5 mm at 6 weeks to 1 mm at 14 weeks of gestation. The glandular epithelium also transformed from tall columnar cells, packed with secretory organelles, to a low cuboidal layer over this period. The lumens of the glands were always filled with precipitated secretions, and communications with the intervillous space could be traced until at least 10 weeks. The glandular epithelium reacted strongly for leukaemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, transforming growth factor beta, alpha tocopherol transfer protein, MUC-1 and glycodelin, and weakly for lactoferrin. As gestation advanced uterine natural killer cells became closely approximated to the basal surface of the epithelium. These cells were also immunopositive for epidermal growth factor. CONCLUSIONS: Morphologically the endometrial glands are best developed and most active during early human pregnancy. The glands gradually regress over the first trimester, but still communicate with the intervillous space until at least 10 weeks. Hence, they could provide an important source of nutrients, growth factors and cytokines for the feto-placental unit. The endometrium may therefore play a greater role in regulating placental growth and differentiation post-implantation than previously appreciated.

Cytokines↗
PubMed2004

Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursors.

Human neural precursors are considered to have widespread therapeutic possibilities on account of their ability to provide large numbers of cells whilst retaining multipotentiality. Application to human demyelinating diseases requires improved understanding of the signalling requirements underlying the generation of human oligodendrocytes from immature cell populations. In this study, we compare and contrast the capacity of neural precursors derived from the developing human and rodent spinal cord to generate oligodendrocytes. We show that the developing human spinal cord (6-12 weeks of gestation) displays a comparable ventrodorsal gradient of oligodendrocyte differentiation potential to the embryonic rodent spinal cord. In contrast, fibroblast growth factor 2 (FGF-2) expanded human neural precursors derived from both isolated ventral or dorsal cultures show a reduced capacity to generate oligodendrocytes, whereas comparable rodent cultures demonstrate a marked increase in oligodendrocyte formation following FGF-2 treatment. In addition, we provide evidence that candidate growth factors suggested from rodent studies, including FGF-2 and platelet-derived growth factor (PDGF) do not stimulate proliferation of human oligodendrocyte lineage cells. Finally, we show that the in vivo environment of the acutely demyelinating adult rat spinal cord is insufficient to stimulate the differentiation of immature human spinal cord cells to oligodendrocytes. These results provide further evidence for inter-species difference in the capacity of neural precursors to generate oligodendrocytes.

Animals↗
PubMed2004

Placental oxidative stress: from miscarriage to preeclampsia.

OBJECTIVE: To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia. METHODS: Review of published literature. RESULTS: Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. Once embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severely impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusion-type phenomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia. CONCLUSION: Miscarriage, missed miscarriage, and early- and late-onset preeclampsia represent a spectrum of disorders secondary to deficient trophoblast invasion.

Abortion, Spontaneous↗
PubMed2004

Prospective study of parental choice for aneuploidy screening in assisted conception versus spontaneously conceived twins.

The aim of this study was to evaluate and compare parental choice towards the use of aneuploidy screening and diagnostic techniques after assisted conception versus spontaneously conceived pregnancy. A total of 193 patients with consecutive twin pregnancies participated in the study, including 143 who spontaneously conceived and 50 who conceived following assisted reproduction treatment. Patients were investigated prospectively for their choice in the prenatal screening/diagnosis of aneuploidy. In the group of patients who conceived spontaneously, 111 (77.6%) opted initially for the non-invasive screening based on nuchal translucency measurements, whereas in the assisted conception group, 44 (88%) opted for the non-invasive screening. In the spontaneous conception group, 32 (22.4%) presented because they had a positive serum screening test or because they had opted for a chorionic villus sampling (CVS) or an amniocentesis for advanced maternal age. In the assisted conception group only six patients (12%) opted for amniocentesis. The difference in choice of noninvasive versus invasive screening between those with spontaneous and those with assisted conception was not significant, but those who had conceived spontaneously after the age of 37 years were significantly more likely (P < 0.05) to request an invasive diagnostic procedure through all maternal age groups. When needed, an amniocentesis was preferred to CVS. These data also indicate that the antenatal counselling needs to be adapted to couples presenting with an assisted conception twin pregnancy.

Adult↗