Risk of severe maternal morbidity associated with in vitro fertilisation: a population-based study.

OBJECTIVE: To investigate the association between in vitro fertilisation IVF and severe maternal morbidity (SMM) and to explore the role of multiple pregnancy as an intermediate factor. DESIGN: Population-based cohort-nested case-control study. SETTING: Six French regions in 2012/13. POPULATION: Cases were 2540 women with SMM according to the EPIMOMS definition; controls were 3651 randomly selected women who gave birth without SMM. METHODS: Analysis of the associations between IVF and SMM with multivariable logistic regression models, differentiating IVF with autologous oocytes (IVF-AO) from IVF with oocyte donation (IVF-OD). The contribution of multiple pregnancy as an intermediate factor was assessed by path analysis. MAIN OUTCOME MEASURES: Severe maternal morbidity overall and SMM according to its main underlying causal condition and by severity (near misses). RESULTS: The risk of SMM was significantly higher in women with IVF (adjusted OR = 2.5, 95% CI 1.8-3.3). The risk of SMM was significantly higher with IVF-AO, for all-cause SMM (aOR = 2.0, 95% CI 1.5-2.7), for near misses (aOR = 1.9, 95% CI 1.3-2.8), and for intra/postpartum haemorrhages (aOR = 2.3, 95% CI 1.6-3.2). The risk of SMM was significantly higher with IVF-OD, for all-cause SMM (aOR = 18.6, 95% CI 4.4-78.5), for near misses (aOR = 18.1, 95% CI 4.0-82.3), for SMM due to hypertensive disorders (aOR = 16.7, 95% CI 3.3-85.4) and due to intra/postpartum haemorrhages (aOR = 18.0, 95% CI 4.2-77.8). Path-analysis estimated that 21.6% (95% CI 10.1-33.0) of the risk associated with IVF-OD was mediated by multiple pregnancy, and 49.6% (95% CI 24.0-75.1) of the SMM risk associated with IVF-AO. CONCLUSION: The risk of SMM is higher in IVF pregnancies after adjustment for confounders. Exploratory results suggest higher risks among women with IVF-OD; however, confidence intervals were wide, so this finding needs to be confirmed. A large part of the association between IVF-AO and SMM appears to be mediated by multiple pregnancy. TWEETABLE ABSTRACT: The risk of severe maternal morbidity is higher in IVF-conceived pregnancies than in pregnancies conceived by other means.

Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders.

Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecting the route of administration. Delivery of AAVs into the cerebrospinal fluid (CSF) represents an attractive approach to target the central nervous system (CNS) and bypass the BBB. In this study, we investigated the efficacy of intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice via intracisternal (iCist) or intralumbar (it-Lumb) administration. It-Lumb ssAAV9 delivery resulted in greater diffusion throughout the entire spinal cord and green fluorescent protein (GFP) expression mainly in the cerebellum, cortex and olfactory bulb. By contrast, iCist delivery led to strong GFP expression throughout the entire brain. Comparison of the transduction efficiency of ssAAV9-CAG-GFP versus ssAAV9-SYN1-GFP following it-Lumb administration revealed widespread and specific GFP expression in neurons and motoneurons of the spinal cord and brain when the neuron-specific synapsin 1 (SYN1) promoter was used. Our findings demonstrate that it-Lumb ssAAV9 delivery is a safe and highly efficient means of targeting the CNS in adult mice.

Invasive therapies for primary postpartum haemorrhage: a population-based study in France.

OBJECTIVE: To describe the characteristics, management, and outcomes of women undergoing invasive therapies for primary postpartum haemorrhage (PPH). DESIGN: A population-based observational study. SETTING: All 106 maternity units of six French regions. POPULATION: A total of 146 781 women delivering between 2004 and 2006. METHODS: Prospective identification of women with PPH managed with invasive therapies, including uterine suture, pelvic vessel ligation, arterial embolisation, and hysterectomy. MAIN OUTCOME MEASURES: Rate of use and failure rate of invasive therapies, with 95% confidence intervals (95% CIs). RESULTS: An invasive therapy was used in 296 of 6660 women with PPH (4.4%, 95% CI 4.0-5.0), and in 0.2% of deliveries (95% CI 0.18-0.23). A hysterectomy was performed in 72/6660 women with PPH (1.1%, 95% CI 0.8-1.4%), and in 0.05% of deliveries (95% CI 0.04-0.06). A conservative invasive therapy was used in 262 women, including 183 (70%) who underwent arterial embolisation and 79 (30%) who had conservative surgery as the first-line therapy. Embolisation was more frequently used after vaginal than caesarean delivery, and when arterial embolisation was available on site. The failure rate of conservative invasive therapies was 41/262 (15.6%, 95% CI 11.5-20.6) overall, and was higher after surgical than after embolisation procedures, in particular for vaginal deliveries. CONCLUSIONS: Both maternal mortality as a result of obstetric haemorrhage and the rate of invasive therapies used for PPH are high in France. These findings suggest flaws in the initial management of PPH and/or the inadequate use of invasive procedures. TWEETABLE ABSTRACT: Maternal mortality as a result of haemorrhage and the rate of invasive therapies used for PPH are high in France.

Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid (CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied the effect of the age at injection on neurotropism. IV delivery is more efficient in neonates and targets predominantly Purkinje cells of the cerebellum and sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF administration of AAVrh10, single strand or oversized self-complementary, is efficient for the targeting of neurons in the cerebral hemispheres, cerebellum, brainstem and spinal cord. Green fluorescent protein (GFP) expression is more widespread in neonates when compared with adults. More than 50% of motor neurons express GFP in the three segments of the spinal cord in neonates and in the cervical and thoracic regions in adults. Neurons are almost exclusively transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are targeted in adults. These results expand the possible routes of delivery of AAVrh10, a serotype that has shown efficacy and safety in clinical trials concerning neurodegenerative diseases.

Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron transduction in the whole central nervous system of cats.

Systemic and intracerebrospinal fluid delivery of adeno-associated virus serotype 9 (AAV9) has been shown to achieve widespread gene delivery to the central nervous system (CNS). However, after systemic injection, the neurotropism of the vector has been reported to vary according to age at injection, with greater neuronal transduction in newborns and preferential glial cell tropism in adults. This difference has not yet been reported after cerebrospinal fluid (CSF) delivery. The present study analyzed both neuronal and glial cell transduction in the CNS of cats according to age of AAV9 CSF injection. In both newborns and young cats, administration of AAV9-GFP in the cisterna magna resulted in high levels of motor neurons (MNs) transduction from the cervical (84±5%) to the lumbar (99±1%) spinal cord, demonstrating that the remarkable tropism of AAV9 for MNs is not affected by age at CSF delivery. Surprisingly, numerous oligodendrocytes were also transduced in the brain and in the spinal cord white matter of young cats, but not of neonates, indicating that (i) age of CSF delivery influences the tropism of AAV9 for glial cells and (ii) AAV9 intracisternal delivery could be relevant for both the treatment of MN and demyelinating disorders.

Understanding regional differences in maternal mortality: a national case-control study in France.

OBJECTIVES: To assess the risk of postpartum maternal death associated with region, and to examine whether the quality of care received by the women who died differed by region. DESIGN: A national case-control study. SETTING: France. POPULATION: Selected from recent nationwide surveys, 328 postpartum maternal deaths from 2001 through 2006 as cases; and a representative sample (n = 14 878) of women who gave birth in 2003 as controls. METHODS: Crude and adjusted odds ratios (aOR) of maternal death associated with region were calculated with logistic regression, and the quality of care for women who died was compared according to region with chi-square tests or Fisher's exact tests. MAIN OUTCOME MEASURES: Risk of postpartum maternal death associated with region, and quality of care. RESULTS: After adjustment for maternal age and nationality, the risk of maternal death was higher in the Ile-de-France region (aOR 1.6, 95% CI 1.2-2.0) and the overseas districts (aOR 3.5, 95% CI 2.4-5.0) than in the group for the rest of continental France. In both regions, the excess risk of death from haemorrhage, amniotic fluid embolism and hypertensive disorders was significant. In continental France, after further controlling for women's obstetric characteristics, the risk of maternal death in Ile-de-France remained higher (aOR 1.8. 95% CI 1.3-2.6). The women in the cases groups received suboptimal care more frequently in Ile-de-France than in the other continental regions (64% versus 43%, P = 0.01). CONCLUSIONS: These results suggest that quality of care and organisation of health services may play a role in the differential risk of maternal mortality between regions in France. Research on severe maternal morbidity and its determinants is needed to clarify the mechanisms involved.

What about the mothers? An analysis of maternal mortality and morbidity in perinatal health surveillance systems in Europe.

OBJECTIVE: To assess capacity to develop routine monitoring of maternal health in the European Union using indicators of maternal mortality and severe morbidity. DESIGN: Analysis of aggregate data from routine statistical systems compiled by the EURO-PERISTAT project and comparison with data from national enquiries. SETTING: Twenty-five countries in the European Union and Norway. POPULATION: Women giving birth in participating countries in 2003 and 2004. METHODS: Application of a common collection of data by selecting specific International Classification of Disease codes from the 'Pregnancy, childbirth and the puerperium' chapter. External validity was assessed by reviewing the results of national confidential enquiries and linkage studies. MAIN OUTCOME MEASURES: Maternal mortality ratio, with distribution of specific obstetric causes, and severe acute maternal morbidity, which included: eclampsia, surgery and blood transfusion for obstetric haemorrhage, and intensive-care unit admission. RESULTS: In 22 countries that provided data, the maternal mortality ratio was 6.3 per 100,000 live births overall and ranged from 0 to 29.6. Under-ascertainment was evident from comparisons with studies that use enhanced identification of deaths. Furthermore, routine cause of death registration systems in countries with specific systems for audit reported higher maternal mortality ratio than those in countries without audits. For severe acute maternal morbidity, 16 countries provided data about at least one category of morbidity, and only three provided data for all categories. Reported values ranged widely (from 0.2 to 1.6 women with eclampsia per 1000 women giving birth and from 0.2 to 1.0 hysterectomies per 1000 women). CONCLUSIONS: Currently available data on maternal mortality and morbidity are insufficient for monitoring trends over time in Europe and for comparison between countries. Confidential enquiries into maternal deaths are recommended.

Association between fibrinogen level and severity of postpartum haemorrhage: secondary analysis of a prospective trial.

BACKGROUND: The aim of the study was to determine whether the fibrinogen level at diagnosis of postpartum haemorrhage (PPH) is associated with the severity of bleeding. METHODS: This is a secondary analysis of a population-based study in 106 French maternity units identifying cases of PPH prospectively. PPH was defined by a blood loss exceeding 500 ml during the 24 h after delivery or a peripartum haemoglobin decrease of more than 20 g litre(-1). This analysis includes 738 women with PPH after vaginal delivery. Fibrinogen levels were compared in patients whose PPH worsened and became severe and those whose PPH remained non-severe. Severe PPH was defined as haemorrhage by occurrence of one of the following events: peripartum haemoglobin decrease ≥ 40 g litre(-1), transfusion of concentrated red cells, arterial embolization or emergency surgery, admission to intensive care, or death. RESULTS: The mean fibrinogen concentration at diagnosis was 4.2 g litre(-1) [standard deviation (sd)=1.2 g litre(-1)] among the patients without worsening and 3.4 g litre(-1) (sd=0.9 g litre(-1)) (P<0.001) in the group whose PPH became severe. The fibrinogen level was associated with PPH severity independently of other factors [adjusted odds ratio=1.90 (1.16-3.09) for fibrinogen between 2 and 3 g litre(-1) and 11.99 (2.56-56.06) for fibrinogen <2 g litre(-1)]. CONCLUSIONS: The fibrinogen level at PPH diagnosis is a marker of the risk of aggravation and should serve as an alert to clinicians.

[French hospital discharge database: data production, validity, and origins of errors in the field of severe maternal morbidity]. / Le programme de médicalisation du système d'information (PMSI) - processus de production des données, validité et sources d'erreurs dans le domaine de la morbidité maternelle sévère.

BACKGROUND: The organization of obstetric care in France brings all women in contact with the hospital system. Thus, hospital discharge data from the Program of Medicalization of the Information System (PMSI) constitute a potentially valuable source of information, particularly regarding rare events such as severe maternal morbidity. These data cover a large population but their quality has not been assessed in that field. Our objectives were to study the processes of production and the validity of PMSI data related to severe maternal morbidity. METHODS: The study was conducted in four French tertiary teaching hospitals (Caen, Cochin [AP-HP, Paris], Grenoble and Lille). First, the organization of each step of the medical information process -production, formatting, verification and processing- was detailed in each center with a standardized form. Second, the validation study was based on the comparison of data related to severe maternal morbid events in the PMSI from these centers for 2006 and 2007, with the content of medical records which constituted the gold standard. Indicators of sensitivities and positive predictive values of PMSI were calculated. RESULTS: The processes of PMSI data production showed major differences between the four centers. In hospital discharge data, diagnoses (eclampsia and pulmonary embolism) had a high proportion of false-positives (68%). Inversely, procedures (four procedures for management of severe haemorrhage) had less than 1% of false-positives, but a low sensitivity with 37% false-negatives which could be corrected in 95%. Regarding intensive care provision, all indicators of hospital data quality were very high. In addition, the validity of hospital data in centers 1 and 2 was higher for all events. CONCLUSION: The heterogeneity of the process of PMSI data production is associated with a variable quality of these data. Intensive care provision can be used in the PMSI, as well as procedures after correction. For diagnoses, the quality of the PMSI data is better in centers having both computerized medical records and steps for verification of medical information.

Histopathologic changes of the ear in canine models of mucopolysaccharidosis types I and VII.

Mucopolysaccharidosis (MPS) types I and VII are inborn errors of metabolism caused by mutation of enzymes involved in glycosaminoglycan catabolism, which leads to intralysosomal accumulation of glycosaminoglycans. In children, severe forms of MPS I and VII are characterized by somatic and neurologic manifestations, including a poorly understood hearing loss. The purpose of this study is to describe the age-related histopathologic changes of the ear in spontaneous canine models of MPS I and VII. Pathologic changes in the ear were assessed in MPS I and VII dogs ranging from 1.6 to 9.3 months of age. Paraffin-embedded sections of the whole ear and Epon-embedded semithin sections of the cochlea were examined. The following lesions were blindly scored in the middle and inner ear: inflammation, cells vacuolization, thickening of osseous and membranous structures, perivascular vacuolated macrophages infiltration, and bone resorption. All dogs had lysosomal storage within cells of tympanic membrane, ossicles, tympanic bone and mucosa, cochlear bone, spiral ligament, limbus, and stria vascularis. The MPS I dogs mainly had progressive cochlear lesions. The MPS VII dogs had severe and early middle ear lesions, including chronic otitis media and bone resorption. The MPS I dog only partially recapitulates the pathology seen in humans; specifically, the dog model lacks inflammatory middle ear disease. In contrast, the MPS VII dog has severe inflammatory middle ear disease similar to that reported in the human. In conclusion, the canine MPS VII model appears to be a good model to study MPS VII-related deafness.

Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial.

OBJECTIVE: Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. DESIGN: Cluster-randomised trial. POPULATION: 106 maternity units in six French regions. METHODS: Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe incidents, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. MAIN OUTCOME MEASURES: The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin decrease of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. RESULTS: The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units-help from senior staff (P = 0.005), or tended to - second-line pharmacological treatment (P = 0.06), timely blood test (P = 0.09). CONCLUSION: This educational intervention did not affect the rate of severe PPH as compared with control units, although it improved some practices.

Practices for prevention, diagnosis and management of postpartum haemorrhage: impact of a regional multifaceted intervention.

OBJECTIVE: To evaluate the effectiveness of a multifaceted intervention on practices for prevention, diagnosis and management of postpartum haemorrhage (PPH) and on the prevalence of major PPH in a French perinatal network. DESIGN: Quasi-experimental before-and-after survey. SETTING: All maternity units (n = 19) of a French administrative region, operating as a perinatal network. SAMPLE: One representative sample of all women delivering in the network, one representative sample of women with PPH deliveries and an exhaustive sample of women with major PPH. METHODS: The multifaceted intervention took place between February 2003 and March 2004. Information was retrospectively collected for two periods, 2002 (before the intervention) and 2005 (after). MAIN OUTCOME MEASURES: Practices for prevention, diagnosis and management of PPH and prevalence of major PPH. RESULTS: After the intervention, the pharmacological prevention of PPH increased from 58.8% to 75.9% of vaginal deliveries (P < 10(-4)), and the use of blood collecting bags from 3.9% to 76.3% (P < 10(-4)), but initial PPH management did not change significantly. However, the median delay for second-line pharmacological treatment was significantly shortened [from 80 min (35-130) in 2002 to 32.5 min (20-75) in 2005]. An increase was observed in the use of surgery for PPH (0.06% versus 0.12% of deliveries; P = 0.03) and in blood transfusions (0.18% versus 0.33%; P = 0.01). The prevalence of major PPH did not change (0.80% versus 0.86% of deliveries; P = 0.62). CONCLUSIONS: The intervention was effective at improving PPH-related preventive and diagnostic practices in a perinatal network. Improving management practices and reducing the prevalence of major PPH might require a different intervention design.

Policies for manual removal of placenta at vaginal delivery: variations in timing within Europe.

The length of the third stage of labour is a potential modifiable risk factor for postpartum haemorrhage at vaginal delivery, but there is no definitive evidence that early intervention to remove the placenta manually will prevent postpartum haemorrhage. We report a wide variation between countries in Europe in policies about the timing of manual removal of placenta. Two groups of countries with clearly divergent policies were identified. A randomised controlled trial is needed to provide definitive evidence on the risks and benefits of manual removal of placenta at different timings after vaginal delivery.

[Impact of a new regional management for postpartum hemorrhages by an audit of severe cases: a before and after study (2002-2005)]. / Evaluation de la mise en place d'une prise en charge régionale des hémorragies du postpartum par un audit des cas graves : étude avant-après (2002-2005).

BACKGROUND: Postpartum haemorrhage (PPH) is still the first cause of maternal mortality in France. Most of these cases include inappropriate management. In 2004, regional guidelines were diffused to all the birthplaces in Basse-Normandie. To assess the impact of this regional management, an epidemiological study "before-after" (2002-2005) has been performed. Part of this study was the evaluation of the management of severe PPH. OBJECTIVE: This study assessed the quality of care for major PPH and the correct follow-up of the guidelines before and after 2004. MATERIAL AND METHODS: A clinical audit has been conducted in all the birthplaces from the region to assess the management of all severe PPH identified during 2002 and 2005. PPH were considered as severe when they presented one or more of the following: blood transfusion, uterine embolisation, hemostatic surgery, difference in hemoglobin rates greater than 4 g / dl, or maternal death. All of these cases have been analysed except those defined by hemoglobin difference. Assessment has been carried out by pairs of practitioners (obstetrician and anesthetist) blinded to the origin of the case. Criteria assessed were the quality of care for major PPH, the correct follow-up of the guidelines and the degree of severity of the PPH which was estimated as moderate or severe on clinical arguments. RESULTS: The number of severe PPH was 34 in 2002 and 63 in 2005. The quality of care was increased with rates of inadequate management falling from 32 to 13% (p < 0,02), respectively. The follow-up of the guidelines was correct in the whole area, most of the criteria having been respected in about 90% of cases in 2005. However, active management of the third stage of delivery was only conducted in 71% of cases. The rates of severe PPH were not significantly different between 2002 (44%) and 2005 (38%). CONCLUSION: The originality from this study is that the modifications of the practices were conducted at a regional level in order to enhance the management of PPH. The assessment which was performed showed that quality of care was improved all over the area but that there is still place to progress.

[Delay in the management of obstetric complications: study in 7 maternity units in Cameroon]. / Délai de prise en charge des complications obstétricales: étude dans 7 maternités au Cameroun.

The purpose of this retrospective, descriptive study conducted in 7 third-level maternity units in Cameroon was to determine maternal mortality rates associated with obstetrical complications and correlate these data with competency of health-care staff and time-to-care. Consolidated data for the year 2004 were used to calculate various indicators of maternal health. During the study period 16,005 deliveries were performed with 15,322 live births. Obstetrical complications occurred in 2847 cases leading to a total of 112 maternal deaths. Overall maternal mortality was 699 deaths for 100,000 live births. The complication fatality rate was 3.3 % and was correlated with both competency of health-care-staff and time-to-care (p < 0.05). In addition delayed for treatment was a determinant factor in maternal mortality since the risk of death increased with longer time-to-care.

Dry potato extracts improve water holding capacity, shelf life, and sensory characteristics of fresh and precooked beef patties.

The objective was to examine shelf stability, cooked product yield, and sensory characteristics of beef patties that had no binder (Control), incorporated soy flour (Textured Vegetable Protein; TVP) or one of three dry potato extracts: X-TRATOS™ (potato extract), X-TRATOS™ O (potato extract with mustard), or X-TRATOS™ W (potato extract with sodium acid pyrophosphate). In retail display patties, all binders decreased discoloration and lipid oxidation compared to Control, and X-TRATOS™ O was superior (P < 0.05) to all other treatments. Cooking yield was higher (P < 0.05) in patties containing potato extracts compared with patties containing TVP, which had higher yield than Control patties. Beef patties with potato extracts were juicier (P < 0.05) than Control and TVP patties and had higher (P < 0.05) overall acceptability than Control patties. We conclude that potato extracts are effective binders for use in fresh or precooked beef patties because they improve retail shelf life, cooked product yield, and sensory characteristics.

[Maternal mortality among women with Marfan syndrome or vascular Ehlers-Danlos syndrome in France, 2001-2012]. / Mortalité maternelle chez les patientes atteintes de syndromes de Marfan ou d'Ehlers-Danlos vasculaire en France, 2001­2012.

OBJECTIVE: To describe maternal deaths in France associated with Marfan's syndrome or vascular Ehlers-Danlos syndrome. STUDY DESIGN: A retrospective descriptive study based on data from the national confidential enquiry into maternal deaths, in France, during 2001-2012. Characteristics of the patients, their pregnancies and details of their deaths were analysed. The specific maternal mortality ratio by Marfan's syndrome or vascular Ehlers-Danlos syndrome was estimated. RESULTS: Among 973 maternal deaths that occurred during the study period, five (0.4%) had a Marfan's syndrome (n=3) or a vascular Ehlers-Danlos syndrome (n=2), confirmed or suspected. The maternal mortality ratio due to Marfan's syndrome or vascular Ehlers-Danlos syndrome between 2001 and 2012 was 0.04/100,000 live births (IC 95% [0.011-0.2]). Three maternal deaths were caused by aortic dissections and two by other arterial ruptures. The deaths have occurred after 37 weeks of pregnancy for 4 patients, and at fifteen days of post-partum for one patient. The median age of death was 30 years. Three patients were nulliparous. Marfan's syndrome and vascular Ehlers-Danlos syndrome were not identified before the death of these five patients. CONCLUSION: Five patients with, or suspected to have, Marfan's syndrome or vascular Ehlers-Danlos syndrome were identified. Early diagnosis of these syndromes in pregnant women before life threatening events is very important, especially to refer them to appropriate care.

Can excess maternal mortality among women of foreign nationality be explained by suboptimal obstetric care?

OBJECTIVES: To test the hypothesis that the risk of postpartum maternal death in France remains significantly higher for women of foreign nationality after individual characteristics are taken into account and to examine whether the quality of care received by the women who died differs according to nationality. DESIGN: A national case-control study. SETTING: Metropolitan France. POPULATION: A total of 267 women who died of maternal death from 1996 to 2001 as cases and a representative sample (n = 13 186) of women who gave birth in 1998 as controls. METHODS: Crude and adjusted odd ratios were calculated with multivariate logistic regression, and the quality of care for cases was compared according to nationality with chi-square tests or Fisher's exact tests. MAIN OUTCOME MEASURES: Odd ratio for postpartum maternal death associated with nationality and quality of care. RESULTS: After taking individual characteristics into account, the risk of postpartum maternal death was twice as high for foreign women. The odds ratio was 5.5 (95% CI: 3.3-9.0) for women from sub-Saharan Africa and 3.3 (95% CI: 1.7-6.5) for those from Asia, North and South America. There was no significant excess risk of postpartum maternal death for the other European and North Africa women. The risk of dying from hypertensive disorder or infection was four times higher for foreign women. Among women who died, care was more often considered not optimal for foreign women (78 versus 57%). CONCLUSIONS: The excess risk of postpartum maternal death persisted for foreign women after individual characteristics were taken into account and was especially important for some nationalities and for some causes of death, primarily hypertensive disorders. These results point to an immediate need to pay special attention to early enrollment in prenatal care, screening and prenatal management of hypertension, especially in women of sub-Saharan African nationality.

Spinal cryptococcoma in an immunocompetent cat.

This report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.

[Impact of advanced maternal age on fecundity and women's and children's health]. / Impact de l'âge maternel élevé sur la fertilité, la santé de la mère et la santé de l'enfant.

OBJECTIVE: There has been a consistent trend towards delayed childbearing in most Western countries. We present a review of the current epidemiological understanding of the effects of advanced maternal age on fecundity, maternal and child health. MATERIALS AND METHODS: A narrative review of the literature based mostly on the key population-based studies on the subject. RESULTS: Delayed childbearing results in a substantial decrease in fecundity and a considerable increase in fetal loss; risk of the latter is doubled between 20-24 and 40-44 years of age. Other risks include those related to maternal health (maternal mortality and morbidity) and adverse pregnancy outcomes (multiple births, preterm delivery, fetal growth retardation and congenital anomalies). CONCLUSION: Risks associated with delayed childbearing become significant for maternal age greater than 35 years, and are particularly high for women aged 40 years and greater. Knowledge about the risks associated with advancing age can be helpful for couples in their decisions regarding childbearing.