[Periconceptional toxoplasmic seroconversion: about 79 cases]. / Séroconversion toxoplasmique périconceptionnelle : à propos de 79 cas.

OBJECTIVE: Toxoplasmosis is a cosmopolitan zoonose led by an intracellular protozoon, Toxoplasma gondii. Severe fetal consequences can be encountered in case of infection during pregnancy. Since 1978, a specific screening program has been implemented in France during pregnancy. The purpose of our study is to evaluate the fetal consequences of a maternal contamination during the periconceptional period. MATERIAL AND METHODS: We retrospectively analyzed, over a 10-year period, the outcome of all the pregnancies with a suspicion of periconceptional seroconversion. Periconceptional seroconversion was defined as infection occurring during the two months prior to or following the assumed date of the conception. The obstetric care, the fetal ultrasound scan and the neonatal features were all closely looked at. RESULTS: Seventy-nine patients (81 fetus) showed evidence of the diagnosis criteria of periconceptional infection. Three cases (3.8%) of congenital infection were observed: two late miscarriages (at 15 weeks and 24 weeks) and one case of an alive child with infraclinic toxoplasmosis. CONCLUSION: In our study, the rate of congenital toxoplasmosis (3.8%) in the event of a periconceptional infection is slightly above the rate previously described in the literature (0.6 to 3.3%). The rate of miscarriage is also high: 66% in case of congenital infection. A regular ultrasound follow-up until the end of the pregnancy is necessary to ensure the best care available. The decision whether to carry out an amniocentesis is discussed in that case.

[Evaluation of a proximity training program of nuchal translucency measurements and of self-scoring]. / Evaluation d'une formation de proximité à la mesure de la clarté nucale et à l'autoévaluation des clichés.

OBJECTIVE: Improvement in prenatal diagnosis of Down syndrome imposes to sonographers to realize good quality nuchal translucency measurements, which can be used for assessment of combined risk. The aim of our study was to evaluate a training program of 109 sonographers for measuring nuchal translucency and scoring their own image. STUDY DESIGN: After a proximity training program, trainees submitted 20 images scored by themselves with Herman image-scoring method. All images were reviewed by two experts. RESULTS: One hundred and nine sonographers have accomplished the training program (87.3%), collecting 2162 images. After reviewing, the mean score was 6.8+/-1.8. The rate of inacceptable scan (score< or =3) was in 6.0%. On the other hand, 48.1% of scans were excellent (score> or =8). Only 6.5% of scores were discordant for at least three points between self-scoring and reviewing. After the fourth scan, there was no significant scoring difference between self-scoring and reviewing. Finally, 84% of trainees were very satisfied of this program. CONCLUSION: As part of HAS evaluation of practitioners practices, it is possible to realize proximity training program for measuring nuchal translucency. Learning curve seems to be fast. Good handling of Herman scoring method by sonographers allows their accreditation after this kind of training program.

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.

Follow-up study of two sisters with type A syndrome of severe insulin resistance gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy outcome: a case report.

We report two sisters with profound insulin resistance associated with a novel heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor gene. The eldest was seen after puberty at age 15 and she presented a severe form of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA) mimicking a virilizing tumour. However, she has been able to ovulate under clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy was good except for a low birthweight. The youngest sister was seen earlier in life (at age 11) before puberty. First, she developed polycystic ovaries (PCO), seen under ultrasound scan, and later also developed full PCOS. This second finding gave us the opportunity to observe that PCO developed before and at the beginning of puberty despite low LH levels. We postulate that the development of PCO was the consequence of an LH-independent intra-ovarian HA likely induced by the severe hyperinsulinism in the context of genetic abnormalities.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

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).

[Trisomy 18: ultrasound aspects. Report of 40 cases]. / Trisomie 18: aspects échographiques. A propos de 40 observations.

OBJECTIVE: We describe the different ultrasound findings suggestive of trisomy 18. PATIENTS AND METHODS: We conducted a retrospective study in 40 cases of trisomy 18 diagnosed in the department of obstetrics at the Lille University Hospital between 1988 and 1998. RESULTS: Eighty percent of the women in this series were multiparous. Mean maternal age at discovery of the trisomy as 33.2 years and the mean gestational age was 20.4 weeks. Fifty-five percent of the cases were discovered during the second trimester of pregnancy, 22.5% during the third trimester and 22.5% during the first trimester. One ultrasound abnormality, at least, was detected in 36/40 cases (90%) a percentage that reached 96.8% taking into consideration the ultrasound examinations performed during the second and third trimesters (30/31 cases). The most frequently detected ultrasound abnormalities were: intra uterine growth retardation (IUGR: 50%), poly-hydramnios (42.5%), limb abnormalities (42.5%), cardiac defects (30%), facial abnormalities (37.5%), meningomyelocele (32.5%), digestive abnormalities (32.5%), urinary tract abnormalities (27.5%), lymphangiectasia and cystic hygroma (15%), and single umbilical artery (12.5%). Medical termination of pregnancy (TOP) was performed in 28 cases. There was one spontaneous miscarriage at 8 weeks and one in utero death (IUD) at 39 weeks in a patient who desired to continue her pregnancy. In 6 cases, the issue of the pregnancy was unknown because the patients were lost to follow-up. In 4 cases (10%), pregnancy was continued to delivery of live babies that only survived a few minutes to 7 days. CONCLUSION: The ultrasound signs suggestive of trisomy 18 change according to the term of pregnancy. At the first trimester, most of the signs are nonspecific, such as cystic hydroma or lymphangiectasia, and do not suggest the need for a karyotype. At the end of the second trimester, an association of various signs that alone would not be highly suspect suggest the need for further exploration in search of other signs: early IUGR, associated or not with poly-hydramnios, limb abnormalities, cardiac defects, omphalocele, diaphragmatic hernia, meningomyelocele, enlarged cisterna magna, choroid plexus cysts, single umbilical artery, facial dysmorphism, facial cleft, hydronephrosis.

[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.

[Nuchal translucency: screening for chromosomal abnormalities and congenital malformations. Multicenter study]. / Clarté nucale: dépistage des anomalies chromosomiques et des malformations congénitales. Etude multicentrique.

OBJECTIVE: To value the rate of chromosomal abnormalities and evolution of children who had a prenatal diagnosis of fetal nuchal translucency in the first trimester. MATERIAL AND METHODS: Multicenter prospective study conducted in 4,582 patients who had a first ultrasonography between 10 and 14 weeks' gestation (abdominal and/or transvaginal sonography). The measurement of fetal nuchal translucency was performed by mid-sagittal section and when it was higher than 2.5 mm a fetal karyotype was made. RESULTS: Three hundred and fifty eight nuchal translucencies (> 2.5 mm) were diagnosed and 334 karyotypes were done. We found 25 chromosomal anomalies (7.4%): 14 trisomies 21; 7 trisomies 18; 2 trisomies 13; one triploidy and one trisomy X. The postnatal examination of children detected three congenital malformations (0.9%): one facial dysmorphia, one complex abnormal heart anatomy and one renal agenesia. CONCLUSION: Nuchal translucency (> 2.5 mm) is therefore a sonography sign associated with 7.4% of chromosomal anomalies. The distribution by size and mother ages is low. It should need superior larger-scale studies are needed for representative data. But this study shows that if fetal karyotype is normal, the incidence of congenital malformations seems to be the same by comparison with the general population.