[Preterm labour after adenosine treatment for paroxysmal supraventricular tachycardia during pregnancy, a case report]. / Menace d'accouchement prématuré après administration d'adénosine pour la réduction d'une tachycardie supraventriculaire paroxystique à 30 semaines d'aménorrhée : à propos d'un cas.

Paroxysmal supraventricular tachycardia is the most frequent arrhythmia among young pregnant women. In case of failure of vagal manoeuvres, their management is preferentially intravenous infusion of adenosine. The in vitro contracturant effect of adenosine on myometrial fibres is known, but very few data are available about the in vivo effect during pregnancy. We report here the case of a 30-week gestational age pregnant woman treated successfully by adenosine for a junctional tachycardia. Adenosine administration was immediately followed by a preterm labour managed by calcium channels blockers tocolysis. Even if causal relationship remains uncertain, this observation is consistent with physiopathological data and should catch physician's attention when initiating this treatment.

[Implementing palliative care for newborns in various care settings. Part 3 of "Palliative care in the neonatal period"]. / La mise en oeuvre pratique des soins palliatifs dans les différents lieux de soins : 3(e) partie des réflexions et propositions autour des soins palliatifs en période néonatale.

Palliative care in newborns may take place in the delivery room and then continued either in maternity wards or in the neonatal unit. For babies developing a chronic condition, going home may be advantageous. The population concerned includes babies born with a severe intractable congenital malformation and certain extremely preterm newborn babies at the limits of viability. Care procedures as well as withholding and withdrawing treatments are reviewed.

[Endometriosis of the ischio-rectal excavation at the contact of the sciatic nerve: a case report of neurolysis by pararectal incision]. / Endométriose de la fosse ischiorectale au contact du nerf sciatique: à propos d'un cas de neurolyse par voie pararectale.

Localisation of endometriosis on the sciatic nerve is exceptional. We report the case of a patient presenting an endometriotic nodule of the left ischio-rectal excavation, with an extension contiguous to the sciatic nerve, responsible of invalidating sciatalgia. Two laparoscopies did not allow to localise the lesion. Finally the endometriotic nodule was treated by a direct access of the left ischio-rectal excavation through a pararectal incision. In this article we discuss the means to localise such lesion and the surgical approach to propose.

[Access to preventative care, screening and treatment of women in vulnerable socio-economic groups presenting with cervical cancer]. / Cancer du col et précarité, accès aux soins diagnostic et traitement.

AIM: The object of this study was to evaluate access to preventative care, screening and treatment of women in vulnerable socio-economic groups presenting with cervical cancer and the progression of their disease. METHOD: This is a retrospective study of 123 patients with cervical cancer treated at the hôpital Bichat (Paris) or the hôpital Verdier (Bondy) between 1st January 1996 and 31 December 2005. RESULTS: "CMU" or "AME" is the entitlement for fully state funded medical care and was used in this study to indicate social deprivation. Social deprivation is associated with homelessness (43.9 vs 1.23%; P = 0.0001) and unemployment (90 vs 30%; P = 0.0001). Women from deprived groups seldom enter screening programs (25 vs 56.1%; P = 0.008). Once symptomatic they delay seeking medical attention (1.8 months later than for non-deprived groups; P = 0.027), present more often to accident and emergency departments (51.22 vs 17.07%; P = 0.0003), and do not see any primary care practitioner (41.46 vs 8.64%; P < 0.0001). There was no significant difference with regard to treatment instituted in the two groups. The non-deprived patients residing in Bondy had similar access to care as the deprived patients treated in Paris. The average follow-up period was 30.43 months (+/- 26.64). CONCLUSION: Cervical screening is not taken up adequately throughout the general population. Access to health care is poorly tailored to the needs of the socially deprived. Social deprivation did not demonstrate an association with levels of pelvic recurrence, metastasis or death. The low doctor to patient ratio in certain geographical areas reduces access to medical care.

[Decision making on breech delivery: information as a way to reconcile maternal autonomy and medical responsibility]. / Peut-on concilier autonomie maternelle et responsabilité médicale dans les décisions de voies d'accouchement des foetus en siège? Rôle de l'information.

As far as breech vaginal delivery remains an acceptable option, each case has to be evaluated in order to determine whether in that particular situation it is medically relevant. When vaginal delivery is to be envisaged, maternal consent is needed. This implies seeking medical information that allows women to express their autonomy and to be part of the decision regarding their delivery. This article concerns a physicians reflection on medical information and on connections between the obstetrician's responsibility, that of the future mother, and autonomy. Understanding information as necessarily arising from an exchange between the care giver and the future mother is the condition that allows the coexistence of maternal autonomy and medical responsibility.

[Fetal toxicity of angiotensin-II-receptor inhibitors. Case report]. / Toxicité foetale des antagonistes des récepteurs de l'angiotensine II. A propos d'un cas.

The fetal toxicity of angiotensin-converting enzyme inhibitors (ACEI) is now well known. Sartans which are angiotensin II inhibitors, are supposed to have the same side effects on the fetus as ACEI because of their similar mechanism of action. This is supported by experimental and clinical data. Clinical presentation of fetal exposition to sartans varies from transient oligamnios to permanent renal failure, potentially complicated by Potter syndrome. According to previously reported cases, we report a case of transitory fetal oliguria secondary to the exposure to an angiotensin-II-receptor inhibitor (valsartan) between 19 and 21 weeks' gestation. We discuss the management of pregnancies exposed to angiotensin II inhibitors.

The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. OBJECTIVES: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. PATIENTS AND METHODS: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. RESULTS: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurrence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL(-1) decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL(-1) was 79% and the positive predictive value of a concentration

[Neurological outcome of children from twin pregnancies]. / Pronostic neurologique des enfants issus de grossesse gémellaire.

The neurological outcome is an important issue regarding twin pregnancies. In fact, twin pregnancy is clearly associated with an important neurological morbidity, roughly 4 times higher than singleton pregnancy. It is possible to distinguish some high-risk situations, making it possible to calculate more accurately the individual risk. The different aetiologies are analysed: hypotrophy, prematurity, malformations, prenatal occurrence of anoxic and ischemic lesions, and particularly the link with monochorionicity. The neurological outcome is mainly depending on hypotrophy and prematurity. However, the rate of long-term neurological complications is not different between twins and singletons after adjustment for term and birth weight. An increased risk of malformation is associated with twin pregnancies, essentially a high rate of abnormal neural tube closing (RR=2). Monochorionic pregnancies have a specific morbidity, not related to these aetiologies, with characteristic anoxic and ischemic lesions. Cerebral palsy is observed in 10-20% of the monochorionic pregnancies, vs 3.7% of the bichorionic ones. These complications are linked to the constant vascular anastomoses, between the circulations of the two monochorionic twins. When the twin-to-twin transfusion syndrome is severe, a poor neurological outcome is observed in 4 to 18% of the surviving children. However, this rate depends on studies, treatments, and methods of neurological evaluation. The laser destruction of anastomoses could decrease this morbidity. The stillbirth rate, either associated or not with twin to twin transfusion syndrome, is increased by monochorionicity. The death of one of the twins is associated with a 20% higher risk of neurological sequelae for the surviving co-twin.

Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome.

OBJECTIVES: To investigate if systemic hypertension occurs in fetuses with twin-to-twin transfusion syndrome (TTTS). METHODS: We conducted an observational cohort study in a tertiary care centre in 23 pregnant women with TTTS. Polyhydramnios stuck twin sequence occurred at a median gestational age of 22 weeks (range 15-27). Biventricular myocardial hypertrophy was diagnosed in 22/23 recipient fetuses. In cases with atrioventricular valve regurgitation (AVR), it was possible to estimate the fetal systolic systemic blood pressure by ultrasound, on the basis of the simplified Bernouilli equation. The diagnosis of fetal hypertension (FHT) was made when the estimated systolic arterial pressure was equal to or above 1.6-fold the expected value. RESULTS: In 10 pregnancies (group A), fetal blood pressure could be assessed in recipients with AVR. The maximum velocities ranged from 2.9 to 5 m/s, leading to estimates of systemic fetal arterial pressure from 37 to 104 mmHg, that is, 1.6- to 2.8-fold the expected values. In 13 pregnancies (group B), fetal blood pressure could not be assessed in the absence of AVR. In group A, perinatal death (16/20) and hydrops (7/20) were significantly more frequent than in group B (8/26 and 1/26 respectively). CONCLUSION: Fetal systemic hypertension may occur in recipient twins and could play a role in the pathophysiology of TTTS.

[What's new in fetal medicine?]. / Quoi de neuf en médecine foetale?

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.

Arthrogryposis multiplex congenita and cerebellopontine ischemic lesions in sibs: recurrence of prenatal disruptive brain lesions with different patterns of expression?

Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders in which prolonged decrease or absence of fetal movements results in a series of deformational anomalies. The rate of recurrence ranges from 25% in some recessive forms of myogenic arthrogryposis or of primary anterior horn cell loss, to less than 1% in anoxic-ischaemic damage. Cerebral clastic processes are considered as sporadic. We report on a non-consanguineous family in which the first child was affected by AMC and the following pregnancy was terminated because cerebellum hypoplasia was suspected at ultrasound and confirmed by fetal magnetic resonance imaging. Post-mortem findings demonstrated pontocerebellar ischaemic-haemorrhagic injuries. The occurrence of these neurologic abnormalities in the same family suggests a common mechanism, which might correspond to a same genetic defect with different patterns of expression. This is the first prenatal report suggesting that an 'ischaemic' process, usually recognised as sporadic could in fact be due to an inherited abnormality. Careful prenatal follow-up of third-trimester fetal brain development may be required in pregnant women with a family history of AMC.

Prenatal ultrasound may predict fetal response to therapy in non-hydropic fetuses with supraventricular tachycardia.

OBJECTIVE: To study the fetal response to prenatal therapy in non-hydropic fetuses with supraventricular tachycardia (SVT) as a function of fetal haemodynamic status at presentation. STUDY DESIGN: Retrospective study. MATERIAL AND METHODS: Between 1990 and 2000, 40 non-hydropic fetuses presented with SVT. Twenty-eight had reciprocating SVT and 12 had atrial flutter. Ten fetuses had significant tricuspid valve regurgitation. All fetuses were treated prenatally. The main outcome measurement was fetal response to therapy as assessed by the rate of prenatal SVT reduction and by the mean time interval to sinus rhythm restoration. RESULTS: The mean gestational age at presentation was 29 +/- 4.9 weeks. Overall, there were 39 live births and 1 intrauterine death. Reduction of SVT was achieved prenatally in 32 cases (80%). Among the 30 cases without tricuspid regurgitation, prenatal conversion to sinus rhythm was achieved in 27 cases (90%) with a mean time interval of 7 days. Among the 10 fetuses presenting with tricuspid regurgitation, the rate of prenatal conversion was significantly lower (5/10) and the mean time interval to conversion was significantly longer (24 days; p = 0.04, Mann-Whitney test). In the subgroup treated by digoxin as first-line therapy (n = 32), the interval to sinus rhythm restoration was also significantly higher in the presence of tricuspid regurgitation, with a slightly but not significantly lower reduction rate. CONCLUSION: The response to prenatal therapy may be poorer in cases presenting with tricuspid regurgitation.

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

[Allotransplantation in utero and immortalization of primate fetal hepatocytes]. / Allotransplantation in utero et immortalisation d'hépatocytes foetaux de primates.

We are developing cell therapy approaches on non-human primates as a preclinical model for the treatment of hepatic metabolic diseases. In foetuses, the tissues, including liver, are in expansion, which should facilitate hepatocytes engraftment, and the immune system becomes fully mature only after birth. We have set out conditions for isolation of fetal hepatocytes from macaca mulatta at the end of the 2nd trimester of gestation (90-100 days), their cryopreservation and retroviral transduction. Two different routes of administration of hepatocytes were evaluated: the umbilical vein which was deleterious for the foetuses, and the intraparenchymatous injection which was well tolerated by the animals. Administration of hepatocytes into the hepatic parenchyma resulted in microchimerism and allogenic cells were visualized 9 days after transplantation. Another approach has been to immortalize simian foetal hepatocytes using a retroviral vector expressing SV40 Large T flanked by lox sites. A cell line has been established for 2 years, which is not tumorigenic when injected subcutaneously into nude mice and display characteristics of bipotent hepatoblasts, precursors of hepatocytes and biliary cells. After orthotopic transplantation into nude mice via the portal vein, these cells expressed albumin until the sacrifice of the animals (17 days). The next steps will be to define conditions for transplantation of retrovirally transduced fetal primary and/or immortalized hepatocytes into young foetuses (60 days of gestation) and post-natally.

Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia.

OBJECTIVE: To study the potential for prenatal magnetic resonance imaging to predict pulmonary hypoplasia in congenital diaphragmatic hernia. DESIGN: Prospective observational study. SETTING: Tertiary care centre. PARTICIPANTS: Thirteen cases of congenital diaphragmatic hernia (11 left, 2 right) without associated anomalies and 74 controls. METHODS: Measurements by magnetic resonance imaging of fetal lung volume were achieved. In the control fetuses, a regression analysis was performed to associate fetal lung volume with gestational age. This yielded a formula allowing calculation of the expected fetal lung volume as a function of gestational age. In the cases with congenital diaphragmatic hernia, the observed/expected fetal lung volume ratio was compared with perinatal outcome. MAIN OUTCOME MEASURES: Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. RESULTS: The expected fetal lung volume was derived from the following formula: Fetal lung volume (mL) = exp (1.24722 + 0.08939 x gestational age in weeks). The observed/expected fetal lung volume ratio was significantly lower in congenital diaphragmatic hernia (median: 0.31, range: 0.06-0.63), than in controls (median: 0.99, range: 0.42-1.94). This ratio was significantly less in the infants with congenital diaphragmatic hernia who died (median: 0.26, range: 0.06-0.63) compared with those who survived (median: 0.46, range: 0.35-0.56). The observed: expected fetal lung volume ratio was significantly correlated with the post mortem lung: body weight ratio. CONCLUSION: In isolated congenital diaphragmatic hernia, fetal lung volume measurement by magnetic resonance imaging is a potential predictor of pulmonary hypoplasia and postnatal outcome. Further studies are required to establish the clinical value of magnetic resonance imaging for the prenatal assessment of fetal lungs.

Pathogenesis of twin-twin transfusion syndrome: the renin-angiotensin system hypothesis.

In spite of active perinatal management, twin-twin transfusion syndrome (TTTS) remains a severe disease with a high risk of neonatal mortality and morbidity. TTTS initially results from an unbalanced blood flow from a donor to a recipient twin. However, its pathogenesis remains unclear, although cardiovascular disturbances and regulation of fetal volemia and diuresis seem central in this syndrome. Previously, we demonstrated that the renin-angiotensin system (RAS) was up-regulated in donor twins as a consequence of hypovolemia, and down-regulated in recipients. This was the first evidence of the implication of the RAS in TTTS. We hypothesize that the RAS plays a key role in the pathogenesis of TTTS. In the donor, RAS up-regulation aggravates oligohydramnios and may increase arterial resistance, which could contribute to placental dysfunction leading to intrauterine growth restriction. In the recipient, paradoxical RAS activation, due to transfer of effectors such as angiotensin II through placental shunts, could explain fetal vascular disturbances and cardiomyopathy. According to our hypothesis, TTTS would appear similar to the classical model of hypertension referred to as '2 kidneys-1 clip' with a donor twin, comparable to the clipped kidney, intoxicating its cotwin, comparable to the normal kidney.