L-Arginine treatment for severe vascular fetal intrauterine growth restriction: a randomized double-bind controlled trial.

BACKGROUND & AIMS: Infants born with severe IUGR are exposed to higher neonatal mortality and morbidity rates, as compared with appropriate-for-gestational-age. They are exposed to a higher risk of developing chronic disease such as hypertension, coronary artery disease, obesity, and type 2 diabetes in adulthood. L-Arginine is a precursor of nitric oxide (NO) and may play a role in placental vascular mediation or local vasodilatation. OBJECTIVE: The current study was designed to determine whether oral supplementation of gravid patients suffering from severe intrauterine growth restriction (IUGR) with L-arginine, would enhance birth weight and/or decrease neonatal morbidity. PATIENTS AND METHODS: Forty-four patients with a singleton pregnancy who had been referred for IUGR detected by ultrasonic examination were included. Vascular IUGR was defined by fetal abdominal circumference less than or equal to the 3rd percentile, associated with abnormal uterine Doppler. After double-blind randomization, patients received either 14 g/day of L-arginine, or a placebo. RESULTS: The characteristics of the two groups of patients (IUGR with L-arginine vs IUGR with placebo) were similar upon randomization. There was no significant difference between the two groups concerning birth weight (1042+/-476 vs. 1068+/-452 g). At delivery, maternal and neonatal characteristics were similar in the two groups. There was no difference in the Clinical Risk Index for Babies (CRIB) score, the duration of ventilatory assistance, nor the delay between birth and full enteral feeding between the two groups. CONCLUSION: In this study which is, at the best of our knowledge, the first double-bind, multicenter, randomized trial in this condition, L-arginine is not an effective treatment for severe vascular growth restriction.

Chronic villitis of unknown etiology.

The diagnosis of chronic villitis of unknown etiology (CVUE), characterized by focal areas of inflammation with mononuclear cells and areas of fibrinoid necrosis in chorionic villi, can only be set-up after exclusion of a latent maternal-fetal transmission of infectious agents by sophisticated techniques such as polymerase chain reaction. Significant associations of CVUE with maternal body mass index, multigravidity and ethnicity were reported. While a fetal origin of the inflammatory cells has been evoked, there are many more arguments drawn from histopathology and immunohistology for a maternal immune response against the foreign fetal allograft. CVUE is detected in 7-33% of placentas, mainly after idiopathic intrauterine growth retardation, unexplained prematurity, preeclampsia, perinatal asphyxia and intrauterine fetal death. CVUE is also more frequent in pregnancies affected by autoimmune or alloimmune diseases. Considering the high rate of recurrences after an index case of CVUE, we would suggest to associate aspirine and corticosteroids in further pregnancies, a regimen that was successful in our experience but must be confirmed by other studies. The same is true for the alleviated inflammatory immunologic response recently obtained by a weekly use of maternal intravenous immunoglobulins.

Use of mifepristone to ripen the cervix and induce labor in term pregnancies.

OBJECTIVE: This study was undertaken to determine the efficacy of mifepristone for ripening the cervix and inducing labor in term pregnancies. STUDY DESIGN: In a double-blind placebo-controlled dose-finding study, 346 women received 50, 100, 200, 400, or 600 mg of mifepristone or placebo. The main endpoint for efficacy was the number of patients in whom labor occurred between 12 and 45 and 54 hours after treatment or who had a Bishop score 6 or greater. Maternal and fetal tolerability was also studied. RESULTS: No significant efficacy was observed whatever the dose of mifepristone. Mifepristone was well tolerated by the mother and fetus. CONCLUSION: Mifepristone, at doses up to 600 mg, does not induce labor within 54 hours in patients with unfavourable cervical status.

Prenatal sonographic patterns in six cases of Wolf-Hirschhorn (4p-) syndrome.

This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization.

Obstetrical complications and subsequent schizophrenia in adolescent and young adult offsprings: is there a relationship?

Schizophrenia is a psychiatric disease affecting around 1% of the population, the negative signs of which are correlated with inactivity of the prefrontal dorsolateral cortex, while an increased, more deeply localized, activity in the mesolimbic pathway may explain the positive signs. Several events occurring during pregnancy are likely to be involved in its genesis: hormonal supplementation by diethylstilbestrol, severe maternal denutrition, exposure to influenza virus, repeated psychological stress. From multicentric studies and meta-analyses in the psychiatric literature, the risk of schizophrenia appears to be multiplied by two if pregnancy is complicated, mainly by diabetes, Rhesus incompatibility, bleeding, preeclampsia, premature rupture of membranes and preterm birth. When delivery is linked to an abnormal presentation or happens via a caesarean birth for acute foetal distress, the time when the first signs of psychosis appear seems to be earlier in adolescence or in early adulthood. Cerebral imaging of schizophrenic patients shows ventriculomegaly and gray matter reduction, mainly in hippocampal volumes and in the dorsolateral prefrontal cortex. Similar alterations in the neuronal pathways have been experimentally reproduced in rats after repeated prenatal stress and perinatal hypoxia. A region on the distal portion of chromosome 1 has shown evidence for linkage to schizophrenia. Therefore, a two factor model seems to be able to explain the onset of schizophrenia in which obstetrical complications may interact with a genetic liability and in which the consequences of hypoxic events may lie on a continuum ranging from cerebral palsy in some children to subtle cognitive and behavioural disturbances in others.

Prenatal diagnosis of a 'minor' form of Brachmann-de Lange syndrome by three-dimensional sonography and three-dimensional computed tomography.

Brachmann-de Lange syndrome is a congenital disease characterized by severe mental retardation, pre- and postnatal symmetric growth delay, limb defects, visceral anomalies, hirsutism, and a typical face. The authors describe the prenatal sonographic pattern of Brachmann-de Lange syndrome suspected at 20 weeks of gestation, with severe intrauterine growth retardation, facial dysmorphism, cardiac abnormality, and micromelia without the typical defects of the upper limbs. Fetal karyotyping was normal. The diagnosis of a 'minor' form of Brachmann-de Lange syndrome was confirmed at 28 weeks of gestation by using three-dimensional sonography in order to assess precisely the facial dysmorphism and by performing a three-dimensional computed tomography of the upper limbs in order to identify the subtle abnormalities of the radial head and of the first metacarpal bone.