[Adverse obstetric and perinatal outcome with in vitro fertilization technology: A French nationwide population-based study]. / Risques de morbidité maternelle et périnatale en fécondation in vitro : une étude nationale de cohorte française.

OBJECTIVES: The objective of this study was to quantify the risk of maternal and perinatal morbidity with in vitro fertilization (IVF) technology compared to non-IVF pregnancies in a recent French national cohort. METHOD: The data was extracted from the hospital information data system, including all pregnancies with a delivery from 2013 to 2016. The risks of preterm birth, maternal morbidity (venous and arterial thrombosis, gestational diabetes, vascular disorders, placenta previa, placenta abruption), hypotrophy and congenital malformation were compared in both groups in univariate and multivariate analysis after adjustment on the characteristics of women (age, parity, obesity, tobacco dependence, history of diabetes or high blood pressure), multiple deliveries and sex of children. RESULTS: In all, 2,875,662 pregnancies and 2,922,712 births were analyzed, of which 49,224 were derived from IVF (1.7%). In multivariate analysis, all risks were significantly higher in IVF: premature deliveries (ORajusted=1.28; CI95%=1.24-1.32), maternal morbidity (ORajusted=1.24; CI95%=1.21-2.28), (mainly for thrombosis venous, placenta previa and placenta abruption). The risks of hypotrophy (ORajusted=1.13; CI95%=1.10-1.16) and congenital malformations (ORajusted=1.11; CI95%=1.05-1.17) were slightly increased. CONCLUSION: The results of this study on a large cohort of recent births in France confirm that there was an increased risk of maternal and perinatal morbidities in IVF. These risks were similar to those published in the international literature. This study is the starting point for a forthcoming surveillance.

Fetal phenotypes in otopalatodigital spectrum disorders.

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.

Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair and teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal dominant and recessive forms occasionally occur and result from mutations in at least two other genes: EDAR and EDARADD. EDARADD interacts with the TAB2/TRAF6/TAK1 complex, which is necessary for NF-kappaB activation by EDAR. OBJECTIVES: To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED. MATERIALS AND METHODS: We have screened 28 familial or sporadic HED cases with no mutations in the EDA and EDAR genes for EDARADD, TRAF6, TAB2 and TAK1 mutations. RESULTS: We identified one EDARADD 6-bp homozygous in-frame deletion (c.402-407del, p.Thr135-Val136del) in a patient born to consanguineous parents. Functional studies showed that the p.Thr135-Val136del impaired the EDAR-EDARADD interaction and then severely inhibited NF-kappaB activity. In the remaining 27 patients, we failed to find causative mutations in EDARADD, or in TRAF6, TAB2 or TAK1. CONCLUSIONS: Our study demonstrates that EDARADD mutations are not a frequent cause of HED, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease.

First-trimester ultrasound diagnosis of skeletal dysplasia associated with increased nuchal translucency thickness.

A series of five cases of skeletal dysplasia is reported in which the diagnosis was reached at the 11-14-week routine ultrasound examination in our referral center. All five cases had increased nuchal translucency thickness (NT) associated with bone abnormalities. We review the current literature on skeletal dysplasia in the first trimester of pregnancy associated with increased NT.

Congenital erythropoietic porphyria (Günther's disease): two cases with very early prenatal manifestation and cystic hygroma.

Congenital erythropoietic porphyria (CEP) or Günther's disease is the rarest form of the porphyrias. The disease is usually diagnosed at birth or during early infancy, but rarely in utero. We describe here the first two cases of very early prenatal expression of CEP with cystic hygroma diagnosed at 14 weeks in the first fetus and at 19 weeks in the second. Both fetuses presented with severe nonimmune hydrops fetalis as early as 19 and 22 weeks, associated with intrauterine growth retardation, hyperechogenic kidneys and bones. Amniotic fluid was dark brown and uro- and coproporphyrin I was dramatically increased. Molecular screening of the CEP gene detected heterozygous C73R mutation in both fetuses, the other parental mutation being as yet unknown.

Homozygosity mapping of a Dyggve-Melchior-Clausen syndrome gene to chromosome 18q21.1.

Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental retardation, and characteristic radiological features. X rays show platyspondyly with double vertebral hump, epiphyseal dysplasia, irregular metaphyses, and a characteristic lacy appearance of the iliac crests. Electron microscopy of chondrocytes have shown widened cisternae of rough endoplasmic reticulum and biochemical analyses have shown accumulation of glucosaminoglycan in cartilage, but the pathogenesis of DMC remains unexplained. Here, we report on the homozygosity mapping of a DMC gene to chromosome 18q21.1 in seven inbred families (Zmax=9.65 at theta=0 at locus D18S1126) in the genetic interval (1.8 cM) defined by loci D18S455 and D18S363. Despite the various geographical origins of the families reported here (Morocco, Tunisia, Portugal, and Lebanon), this condition was genetically homogeneous in our series. Continuing studies will hopefully lead to the identification of the disease causing gene.

[Confined placental mosaicism: definition, consequences and outcome]. / Mosaïques confinées au placenta: définition, conséquences et conduite à tenir.

Confined placental mosaicism (CPM) occurs in approximately 2 per cent of viable pregnancies studies by chorionic villus sampling. The great majority of pregnancies with confined placental mosaicism proceed uneventfully, resulting in normal liveborn infants. However, a few specific chromosomal abnormalities have been associated with fetal growth retardation. Fetal karyotype should be checked by amniocentesis and such pregnancies should have careful ultrasound follow-up.

SHOX gene mutations and deletions in dyschondrosteosis or Leri-Weill syndrome.

Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X-Y translocations (p22,q12) in patients with dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for dyschondrosteosis. This article reports the detection of large-scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for dyschondrosteosis.

SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).

Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.

Alpha 1 isoenzyme of alkaline phosphatases. Clinical importance and value for the detection of liver metastases.

Measurement of the alpha 1 (fast liver) fraction of alkaline phosphatases in the serum for 217 cancer patients, 92 patients with nonmalignant hepatic affections and 131 controls, revealed that the alpha 1 fraction offers better global value (94%), sensitivity (96%), and specificity (93%) than gamma GT or total alkaline phosphatase determinations for the detection of liver metastases during cancer. Initial data from study of the time of appearance of the alpha 1 fraction reveals that this fraction shows up earlier than rises in the gamma GT or total alkaline phosphatases. Results of a multiparametric study conducted on the alpha 1 fraction and various hepatic enzymatic tests (SGOT, SGPT, GLDH, ALP, gamma GT) indicate that the alpha 1 fraction used alone is better than any other test or combination of tests for biological detection of liver metastases. As concerns the influence of chemotherapy on the appearance of the alpha 1 fraction, the majority of the drugs used for anticancer chemotherapy do not seem to affect measurement of the alpha 1 ALP fraction. The alpha 1 fast liver fraction of alkaline phosphatases, detected by electrophoresis on cellulose acetate, can be considered one of the best known tests for the detection of liver metastases.

[Comparative study of 2 prognostic classification systems for myeloma and examination of the correlation between initial bone marrow plasmacytosis and prognosis. A propos of a homogeneous population of 50 patients followed from diagnosis to death]. / Etude comparée de deux classifications pronostiques du myélome et recherche d'une corrélation entre la plasmocytose médullaire initiale et le pronostic. A propos d'une population homogène de 50 malades suivis du diagnostic au décès.

We report the outcome of the statistical analysis of 50 myeloma patients, making a comparison of the prognosis value of the staging systems proposed by Durie and Salmon and, more recently by Merlini, Waldenström and Jayakar. Moreover, we studied the relationship between initial percentage of bone marrow plasma cells and prognosis. All patients had a complete follow-up and received the same treatment. We excluded our cases of non excreting and solitary myeloma. The staging system proposed by Durie and Salmon still has the best prognosis significance. The system proposed by Merlini, Waldenström and Jayakar does not allow a staging of the patients in rigourous conditions. The absence of a relationship between initial bone marrow plasmocytosis and prognosis corroborates the poor reliability of this staging system.

Comparative study of gamma glutamyl transferase, alkaline phosphatase and its alpha 1 isoenzyme as biological indicators of liver metastases.

Biological detection of liver metastases represents an important factor in the surveillance of the course of cancerous affections. The authors present a report on a potential new indicator, the isoenzyme of alkaline phosphatase migrating to the alpha 1 region (alpha 1 ALP). In comparison to those tests considered the most sensitive at present-gamma glutamyl transferase and total alkaline phosphatase-this alpha 1 isoenzyme appears more sensitive and more specific, capable of detecting 97% of liver metastases with a specificity of 90%.

Residual beta cell function in insulin-dependent diabetes: evaluation by circadian determination of C-peptide immunoreactivity.

Residual beta cell function was evaluated through circadian determination of C-peptide immunoreactivity (CPR) in eighty insulin-dependent diabetics. Evaluation of beta cell activity through circadian CPR determination was in good agreement with the results obtained by glucagon test which is considered a potent stimulus of C-peptide release. The prevalence of residual beta cell function in our population was 35%. Residual beta cell function was associated with a shorter duration of diabetes, a lower dose of insulin therapy and less chronic complications. On the other hand, serum growth hormone circadian variations were more spread in diabetics without beta cell function. That is consistent with diabetes instability which has been reported more commonly insulin-dependent diabetics without beta cell function.

A sandwich method of enzyme immunoassay. III. Assay for human beta-2 microglobulin compared with radioimmunoassay.

A sandwich enzyme immunoassay has been developed to measure human beta-2 microglobulin (beta 2m) in bilogical fluids. beta 2m is first bound by specific antibody covalently coupled to microcrystalline cellulose. The solid phase is washed and reincubated with glucose oxidase-labeled anti-beta 2m antibody. After washing, the enzymic activity of the solid phase is measured by incubation with the appropriate chromogenic substrate. The OD is directly related to the quantity of beta 2m to be measured. A second sandwich assay has also been developed which uses plastic microplates coated with the IgG fraction of rabbit anti-beta 2m serum. Reproducible results are obtained in the range 2-150 and 0.75-48 microgram/l respectively. These tests detect 17 fmoles of beta 2m. Assays of 27 sera showed good agreement between these two enzyme immunoassay methods and two radioimmunoassays.

beta2-Microglobulin in lymphoproliferative disorders with special reference to gammapathies.

Plasma beta2-microglobulin ratio were calculated taking into account serum creatinine levels and were found to be elevated in a variety of lymphoproliferative disorders. Degree of elevation appeared to be proportional to the tumour mass.