Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy due to LMNA (lamin A/C) mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance. Dyslipidemia and severe diabetes often occur during its evolution. Only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy. The aim of our study was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations with those of nonaffected relatives, women from the general population, and women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: Data were obtained from clinical follow-up of seven families with patients exhibiting mutations in LMNA (five R482W, one R482Q, one R439C) (14 affected among 48 women). RESULTS: The mean number of live children per woman was 1.7 in affected patients vs. 2.8 in nonaffected relatives. Fifty-four percent of LMNA-mutated women exhibited a clinical phenotype of PCOS, 28% suffered from infertility, 50% experienced at least one miscarriage, 36% developed gestational diabetes, and 14% experienced eclampsia and fetal death. Mean blood leptin level was significantly lower in LMNA-mutated patients than in nonaffected relatives (5.0 +/- 3.8 ng/ml vs 14.3 +/- 3.6; P < 0.001) despite similar body mass index (21.0 +/- 4.2 vs 22.4 +/- 2.2; P = 0.49). CONCLUSION: In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.

No loss of genomic imprinting of IGF-II and H19 in placentas of diabetic pregnancies with fetal macrosomia.

OBJECTIVES: Fetal macrosomia is a common complication of maternal diabetes mellitus and is associated with substantial morbidity, but the precise cellular and molecular mechanisms that induce fetal macrosomia are not well understood. The imprinted genes IGF-II and H19 are crucial for placental development and fetal growth. The term placentas from diabetic pregnancies express more insulin-like growth factor II (IGF-II) than those from normal pregnancies. Deregulation of their imprinting status is observed in the macrosomia-associated syndrome, the Beckwith-Wiedemann syndrome. The aim of this study was to determine whether loss of imprinting hence biallelic expression was also a hallmark of macrosomia in diabetic pregnancies. DESIGN AND METHODS: IGF-II and H19 maternal and paternal expressions were studied in placentas from two groups of type 1 diabetic mothers: one with macrosomic babies and the other with babies of normal weight. Maternal or paternal allele specific expressions were defined by using DNA polymorphic markers of the IGF-II and H19 genes. RFLP analysis was performed on PCR products from genomic DNA of the father, the mother and the child, and on RT-PCR products from placental mRNA. RESULTS: RFLP analysis showed that the IGF-II gene remains paternally expressed and the H19 gene remains maternally expressed in all placentas examined, independently of the birth weight status. CONCLUSIONS: These results suggest that, in contrast with Beckwith-Wiedemann syndrome-associated macrosomia, loss of imprinting for IGF-II or H19 is not a common feature of diabetic pregnancies associated with macrosomia.

[Is a non-invasive management allowed for maternofetal alloimmune thrombocytopenia? Experience over a 10-year period]. / Peut-on prendre en charge l'allo-immunisation plaquettaire foetomaternelle de manière non invasive? Expérience sur dix ans.

OBJECTIVES: Our purpose was to study a non-invasive management of fetomaternal alloimmune thrombocytopenia (FMAIT). PATIENTS AND METHODS: Between 1996 and 2005, 18 women were treated. The population was divided into 2 groups: patients with a history of intracranial haemorrhage (ICH) in the older sibling received weekly intravenous immunoglobulin (IVIG) therapy to the mother (1 g/kg per week) without initial cordocentesis whereas patients with a history of neonatal thrombocytopenia did not undergo any treatment. RESULTS: All pregnancies with a previous FMAIT were monitored with serial ultrasound scans without cordecentesis. 15 patients had HPA-1, 2 HPA-3 and 1 HPA-5 immunizations. Weekly intravenous immunoglobulin therapy was administered in 5 patients with a history of ICH in the older sibling. Two of these delivered thrombocytopenic children; one had a platelet count < 50 x 10(9)/l. For the 13 women (one twin) who had a sibling with neonatal thrombocytopenia, 11/14 newborns had a platelet count < 50 x 10(9)/l. Predelivery fetal blood sampling were performed in 8/18 pregnancies. The neonatal periods of the 19 children were uncomplicated and no ICHs were observed. DISCUSSION AND CONCLUSION: Our results suggest that a non-invasive strategy avoiding serial cordocentesis may be an effective therapy in patients who are at risk of fetal and neonatal alloimmune thrombocytopenia.

[Real-time quantitative PCR for toxoplasmosis diagnosis]. / Apport de la PCR quantitative en temps réel dans le diagnostic de la toxoplasmose congénitale.

Congenital toxoplasmosis results from foetus contamination by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close monitoring of mothers at risk. During the last decades, numerous advances have been made specially in the antenatal diagnosis. The congenital toxoplasmosis diagnosis relies currently on PCR test of amniotic fluid, with a sensitivity of 80%. More recently, real-time quantitative PCR has been developed to improve toxoplasmosis diagnosis. We therefore compared the diagnosis value of quantitative real-time PCR with our conventional PCR-hybridization for the diagnosis of congenital toxoplasmosis.

[Management of 103 limb reduction defects: a French-speaking fetal medicine club enquiry]. / Prise en charge de 103 anomalies réductionnelles de membre: une étude du Club Francophone de Médecine Foetale.

OBJECTIVES: Prenatal diagnosis of a limb reduction defect poses difficult medical and ethical problems. Prenatal diagnosis can be at the origin of two opposing medical attitudes, either a medical termination of pregnancy, or the specific management of the child at birth. The objective is to carry out an enquiry of practices and to determine whether there is a threshold in the gravity of the malformation from which the medical termination of pregnancy is accepted. MATERIAL AND METHOD: The study was carried out by a questionnaire addressed to the members of the French-speaking Club of Fetal Medicine. RESULTS: Outcome of 103 fetuses with limb reduction defect was described. Prenatal diagnosis and management of observed malformations were explained. CONCLUSION: Decisions concerning the outcome of the pregnancy are very variable from one couple to another and from one medical team to another. Parents making a request must be given complete information and accompanying psychological support. Collegial with a multidisciplinary team is necessary. For the parents, it is the physician's duty to avoid judgement errors related to anxiety and ignorance of the medical consequences. The physician should guide the parents towards the continuation of the pregnancy or its interruption. The proper decision proceeds from the reunion of the confidence of the couple and the conscience of the physician.

New autosomal recessive syndrome of severe microcephaly and skeletal anomalies including posterior rib-gap defects.

We describe two female fetuses conceived by a nonconsanguineous couple. The pregnancies were interrupted at 31 and 26 weeks of gestation, respectively, because of severe microcephaly. Postmortem X-ray and autopsy studies showed in both fetuses: 1) severe intrauterine growth retardation; 2) facial anomalies characterized by severe microcephaly, sloping forehead, low set and posteriorly angulated ears, prominent eyes, down-slanting palpebral fissures, large nose, small mouth with full lips, and mild microretrognathia; 3) severe brain hypoplasia that was more pronounced in the second fetus; 4) severe rib hypoplasia with posterior rib-gap defects and in case 2 hypoplasia of several bones (right clavicle, right radius and ulna, several phalanges of hands and feet); 5) contracture at large joints. No other visceral malformations were observed, and chromosomes were normal in patient 2 and parents. This phenotype has some similarities with different syndromic entities but an identical malformation syndrome seems not to have been described previously. Autosomal recessive inheritance is the most likely cause of this putative "new syndrome."

Evolution of the prematurity before the 32nd week from 1980 to 1985 in a tertiary perinatal center in Lille, France.

127 infants were born alive before the 32nd week of gestation in the H. Salengro obstetrical unit from the University Hospital of Lille from January 1980 to December 1985. During this period the annual number of deliveries was constant, 2700. Two periods were considered, 1980-1982 and 1983-1985. The number of such premature infants increased slightly: from 56 to 71. The most striking feature was the dramatic increase in infants born after induction of delivery for fetal reasons. Another finding is the statistically significant lowering of gestational age and birthweight of the spontaneously born infants. These trends counterweight the efficacy of the policy of prevention. When considering the morbidity and the mortality, hyaline membrane disease still plays a preeminent role in this population.

[Systemic sclerosis and pregnancy]. / Sclérodermie systémique et grossesse.

PURPOSE: Pregnancy in a patient with systemic sclerosis (SSc) may pose a double problem to the medical team: influence of SSc on pregnancy and consequences of pregnancy to SSc manifestations. CURRENT KNOWLEDGE AND KEY POINTS: Concepts have evolved. SSc was considered for a long time not only as not very propitious for pregnancy but also as a strict contraindication for procreation because risks for the mother and the baby were thought to be major. Currently, fertility is thought to be normal. Miscarriages and small-for-gestation age infants rate do not seem to be higher in SSc. Maternal and perinatal mortality is also not higher in SSc without severe visceral manifestations, i.e. without either pulmonary hypertension, or cardiac or respiratory insufficiency. Conversely, there is a significantly higher frequency of premature infants in SSc. As regards influence of pregnancy on SSc, the greatest fear is the occurrence of renal crisis, which may be life threatening for both mother and child. Each elevation of blood pressure, even if this increase is mild, should be considered as potentially very serious. However, pregnancy itself does not seem to increase the risk of renal crisis. Consequences of pregnancy to SSc manifestations are various but usually mild. FUTURE PROSPECTS AND PROJECTS: SSc is not a strict contraindication for pregnancy only if severe organ involvement, diffuse subset of SSc or recent onset of the disease has been ruled out. Physicians should be aware of specific problems, which SSc is possibly posing during pregnancy. Finally, it has been recently suggested that pregnancies could be involved in the pathogenesis of SSc through persisting microchimerism of fetal origin.

[Value of fetal fibronectin research for predicting premature delivery]. / Intérêt de la recherche de fibronectine foetale pour la prédiction de l'accouchement prématuré.

OBJECTIVE: To estimate the performance of the foetal fibronectin test as a predictor of preterm delivery. PATIENTS AND METHODS: This prospective study concern 61 patients who had a singleton pregnancy between 24 and 36 weeks of gestation and were hospitalized because of a threatened preterm labor without premature rupture of the membranes. For each patient the presence of foetal fibronectin in cervicovaginal secretions was determined with a rapid swab-test. RESULTS: Prematurity rate was 38% (23 patients). In case of positive result, delivery became before 37 weeks in 75% (12/16) against 24% in case of negative result (11/45). The prolongation of pregnancy after the test was on average 21 days in the positive group and 44 days in the negative group. About the prediction of preterm delivery, the results showed a sensibility of 52%, a specificity of 89%, a positive predictive value of 75%, a negative predictive value of 76%. To predict a delivery within the two weeks after the test, the sensibility was 88%, the specificity 83%, and the negative predictive value 98%. CONCLUSION: The presence of foetal fibronectin in cervicovaginal secretions represent an increased risk of preterm delivery, whereas its excellent negative predictive value allow to be reassuring, especially within a period of 15 days.

[Fetal arrhythmias: diagnosis, prognosis, treatment; apropos of 33 cases]. / Arythmies foetales: diagnostic, pronostic, traitement; à propos de 33 cas.

From October 1993 to February 1998, 33 cases of fetal cardiac arrhythmia were investigated by doppler-echocardiography at the Lille infantile and congenital cardiology department. Extrasystolic arrhythmias were the most frequently encountered disorder (25 fetuses, i.e., 76% of cases: 24 instances of extrasystolic auricular arrhythmia and one case of extrasystolic ventricular arrhythmia). They were invariably benign, and apart from one case only required standard monitoring. Tachycardia was observed in 15% of cases (three cases of supraventricular tachycardia [SVT] and two cases of auricular flutter [AF]). In no instance was a cardiopathic syndrome noted. A number of efficient treatments have been described, but the prognosis is often poor in the presence of hydrops fetalis. Direct fetal treatments (cordocentesis) are currently under evaluation, and at present can only be used as a last resort. In our series, one fetus died 15 minutes after transplacental Flecaine (flecainide) administration. Two of the three SVT and the two AF cases were successfully treated. Bradycardia, which was unassociated with extrasystolic arrhythmia, was found in 9% of cases. It is concluded that Flecaine is probably the treatment of choice for supraventricular and ventricular fetal tachycardia, as it has no teratogenic effect and crosses the placenta at a fetal concentration that is 80% of the maternal level. However, the administration of this drug is not without risk. It is known to possess certain negative side effects, and its pharmacological profile and maternal and fetal health risks have not yet been fully investigated. At present, no entirely safe and efficient treatment for fetal cardiac arrhythmia has been found.

[Cerebral fetal MRI and ventriculomegaly]. / IRM cérébrale foetale et ventriculomégalie.

OBJECTIVE: To evaluate MRI usefulness in diagnosis and management of fetuses with cerebral ventriculomegaly at US. PATIENTS AND METHODS: Sonography depicted cerebral ventriculomegaly in 61 fetuses. Management included MRI in all cases and infectious screening, and karyotype in 51 cases. Final diagnosis was supported by fetal autopsy (n=24), postnatal follow-up>6 months (n=19), infectious screening or karyotype (n=8), and MR imaging when diagnosis was obvious (n=16). RESULTS: MRI was more informative than ultrasonography in 32.8% of cases with identification of the etiology in 21.3% of cases. In 45% MRI and sonography were considered to be normal. In the remaining cases, MRI confirmed the ultrasound diagnosis of cerebral malformation. Ultrasonography never depicted more anomalies than MR imaging. The 2 false negatives were gyration disorders but MR imaging was performed too early. CONCLUSION: US is the imaging modality of choice in the evaluation of fetal anomalies but MRI has to be systematically performed in case of cerebral ventriculomegaly because MRI demonstrates its usefulness in patient counseling, even if there are a few false negative results.

[Study of developing clinical outbreak and serological rebounds in children with congenital toxoplasmosis and follow-up during the first 2 years of life]. / Etude des poussées cliniques évolutives et des rebonds sérologiques d'enfants atteints de toxoplasmose congénitale et suivis durant les 2 premières années de vie.

BACKGROUND: The survival of T gondii bradyzoites in cysts explains clinical recurrences and serological rebounds after birth in children with congenital toxoplasmosis. At the present time, management of such manifestations is not well defined. PATIENTS AND METHODS: Sixty-three infants with congenital toxoplasmosis were followed-up at the University Hospital of Lille (France) during the first two years of life. For each child, the treatment before and after birth was well defined. Clinical, ophthalmological, radiological and serological data were collected every third month. Serological assays specially adapted to this age bracket were used for the quantification of specific IgG, or for the detection of T gondii specific IgM and IgA. RESULTS: Seventy-six serological rebounds were reported in 55 of the 63 children (87%). They concerned essentially IgG (96%) and less frequently IgM (47%) or IgA (60%). At the same time, only five clinical recurrences were observed, four of them being preceded by a serological rebound. DISCUSSION: Treatment of fetuses or children with pyrimethamine and sulfonamides versus spiramycin alone was associated with a decrease in the frequency of serological rebounds during the first year of life (P < 0.001). Such a therapeutic regimen during the second year of life decreases the appearance of serological rebounds in children without rebound antecedent (P < 0.001). CONCLUSION: The increase in number of rebounds after the end of a course of pyrimethamine and sulfonamides necessitates the evaluation of such a long term treatment without interruption.

[An ischemic pulmonary malformation of the surviving fetus occurring after selective embryo reduction in bichorionic pregnancy. Report of one case and literature review]. / Une anomalie pulmonaire ischémique inhabituelle du foetus survivant après interruption sélective sur grossesse bichoriale. A propos d'un cas et revue de la littérature.

We describe, to our knowledge, the first case of a pulmonary malformation called acinar dysplasia occurring at a surviving fetus after selective embryo reduction in a bichorionic pregnancy. The chronological and histological observations suggest that this anomaly may be linked with a feticide achieved at 13 week's gestation. Literature review concerning selective embryo reduction shows rare cases of vascular connections in bichorionic pregnancies especially during the first half of gestation, that can explain in part the apparition of survivor's anomalies.

Echographic signs of trisomy 21 in the second trimester of pregnancy: actual value after analysis of the literature. / Signes échographiques de trisomie 21 au deuxième trimestre de la grossesse: valeur actuelle après analyse de la littérature.

OBJECTIVE: To evaluate the interest and to compare the major echographic signs of Down syndrome in the second trimester of pregnancy. METHODS: A bibliographic research has been performed for most of the echographic signs known and studied until now. For each study and in average for each sign, we have computed its sensitivity, its specificity, its positive and negative predictive values using the results of the different authors. Then, we have compared the benefits/risk ratio for each of these signs: the number of Down syndrome cases detected versus healthy fetus lost due to amniocentesis complications. RESULTS: The different signs can be ranked according to their benefits/risk ratio from top to bottom as follows: nuchal skinfold thickness, wide space between first and second toe, pyelectasis, large iliac angle, short humerus, short femur, hypoplasia of the middle phalanx of the fifth digit. CONCLUSION: These results suggest that second trimester echographic signs of Down syndrome must be evaluated as a function of the Down syndrome risk in the population under study. The presence of these signs does not always justify an amniocentesis; it should lead to a re-evaluation of the individual risk of a Down syndrome (a chart is given to guide this re-evaluation).

[Pathophysiology of gestational diabetes]. / Physiopathologie du diabète gestationnel.

During pregnancy, a number of maternal metabolic changes occur early and continue throughout pregnancy which help optimize the transfer of nutrients to the fetus. During normal pregnancy, there are a decrease in insulin sensibility which is physiological, progressive and reverse. For glucose tolerance to be maintained in pregnancy it is necessary for maternal insulin secretion to increase sufficiently to counteract the fall in insulin sensitivity. The metabolic characteristic of women with gestational diabetes is insufficient insulin secretion to counteract the pregnancy related fall in insulin sensitivity. There are a lot of factors that could explain the mechanism of insulin secretion and insulin sensitivity during normal pregnancy and gestational diabetes mellitus. Although glucose tolerance normalizes shortly after pregnancy with gestational diabetes in the majority of women, the risk of developing overt diabetes, especially type 2 diabetes is markedly increased. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages.

[Maternal and fetal outcome]. / Devenir de la mère et de l'enfant.

Gestational diabetes, a glucose tolerance disorder of variable severity which occurs or is diagnosed for the first time during pregnancy, constitutes a public health problem because of its frequency (1 to 6% of all pregnancies) and its short-or long term consequences for the foetus and/or the mother. There is as yet still no consensus concerning screening and diagnosis criteria, therapeutic management and the reality of the disease. This population is a high risk population of diabetes mellitus, especially of type 2 diabetes. We could think that the introduction of specific prevention programs in this group could delay or avoid diabetes mellitus and its complications. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages. It has been reported that the offspring of gestational diabetics mothers are at risk of obesity and glucose intolerance. Therapeutic management of the mother and/or the offspring should be better defined. The screening for gestational diabetes provides an opportunity of identify a large population of women and children at risk of diabetes. It should be possible to avoid diabetes mellitus by specific therapeutic programs in these populations.

[Choroid plexus cysts and risks of chromosome anomalies. Review of the literature and proposed management]. / Kyste du plexus choroïde et risque d'anomalie chromosomique. Revue de la littérature et proposition de conduite à tenir.

OBJECTIVE: We propose to specify the different criteria of estimation and management in presence of a ultrasound discovery of a choroid plexus cyst. METHOD: A detailed review of the literature about this subject allowed to better apprehend the different attitudes taken up by the authors. RESULTS: Fetal choroid plexus cysts (CPC) are potentially useful markers for trisomy 18 in as much as they are present in about 50% of affected fetuses and they are easily seen in the standard biparietal diameter view which is obtained for all routine ultrasound scans. However, advice is contradictory as to whether karyotyping should be proposed for all fetuses (1-2% of the population) where fetal CPC are diagnosed. CONCLUSION: The review of the literature show that the majority of the authors advocate amniocentesis when the CPC is associated with another ultrasound abnormality. Isolated, it imposes regular and meticulous morphologic ultrasound supervision to search for another possible associated ultrasound abnormality, if necessary, in a prenatal diagnosis center.

[Triploidies]. / Les triploïdies.

Triploidies are pregnancies that show a 69 chromosome karyotype. This chromosomal abnormality gives rise to early abortion in most cases. Triploid pregnancies, after the first three months, become molar pregnancies (molar changes inside the placenta with identifiable embryonic structures and a preeclampsia) or non molar pregnancies (isolated intauterin growth retardation). Several possibilities concerning the origin of the additional set of chromosomes exist: dispermy (the most common), diandry and digyny. The maternal and fetal clinical manifestations of this chromosomal abnormality are very diverse, which explains the difficulty of finding and recognizing this pathology. Mac Fadden's classification does not explain all the phenotypic triploid physiopathology. Formal diagnosis of triploidy depends on the fetal karyotype. The better the maternal prognosis is, the worst the fetal prognosis is. Postnatal life expectancy is not more than a few weeks. In most cases, maternal associated complications disappear with the molar evacuation. The risk of post molar tumor is discussed. However, good management of triploidy is based on an early diagnosis, before birth if that is possible.

[May-Heggelin anomaly and pregnancy. A case report, review of the literature]. / Anomalie de May-Hegglin et grossesse. A propos d'une observation, revue de la littérature.

The May-Hegglin anomaly is a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets and existence of crescent-shaped inclusions within the cytoplasm of granulocytes, eosinophils and monocytes (Döhle body). We report a case of May-Hegglin anomaly associated with a pregnancy. The pregnancy and delivery were uneventful. The child is not a carrier of this hematologic anomaly. Nine cases of complicated pregnancies with this anomaly have been reported in the literature. The risks of maternal hemorrhagic accident during pregnancy and during delivery are weak due to the fact that platelets functions are preserved. The same applies to the fetus. Nevertheless, as in the case of maternal autoimmune thrombocytopenic purpura, most reports advice performing a fetal platelet count on fetal blood sampling before birth to decide upon the mode of delivery. The risk of the cordonal approach to perform fetal blood sampling must be balanced against the small fetal hemorrhagic risk and most authors propose to allow normal delivery whilst avoiding all traumatic instrumental extraction, especially the use of vacuum extractor.

[Panorama of uropathies discovered during the prenatal period. 147 cases]. / Panorama des uropathies dépistées en période anténatale. A propos de 147 observations.

OBJECTIVES: The aim of this study was to establish the panorama of uropathies discovered during the antenatal period and to analyze the explorations performed. Pregnancy outcome and infant prognosis was also recorded. METHOD: Ultrasonographic imaging revealed dilatation in 62.5% of the cases, parenchymal anomalies in 26.3% and unilateral or bilateral agenesia in 11.2%. The percentage of abnormal karyotypes was 4.76% for all urorenal symptomatologies. These abnormal karyotypes corresponded to 10% of those performed in 17 fetuses, urine puncture was used in order to assess in utero renal function. There were 113 live births, 31 medically termined pregnancies and 3 spontaneous abortions. Among the 113 live infants, 12 died during the post-natal period. Thirty-two infants were considered to be normal and 69 had an urorenal malformation, including 2 infants with pre-end-stage renal failure at 4 and 3 years. CONCLUSION: It is uncommon to discover an urorenal malformation at prenatal ultrasonography. The main problem is antenatal management and evaluation of prognosis. Urine puncture and in utero derivation are discussed. When no other reliable factors affecting fetal prognosis are available, puncture of fetal urine provides useful information for management although the technique remains under debate.