Isolated corpus callosum agenesis: a ten-year follow-up after prenatal diagnosis (how are the children without corpus callosum at 10 years of age?).

BACKGROUND: Corpus callosum agenesis (CCA) is generally diagnosed in utero. Outcome appears to be better if the malformation is isolated. The aim of this study, which is the first one with a long (10 years) and standardized follow up, was to report cognitive abilities of children with isolated CCA diagnosed prenatally. METHODS: We prospectively evaluated 17 children. Clinical examinations, neuropsychological tests were performed each year. School achievement and personal and familial data were collected. RESULTS: Twelve children completed the entire follow up. One child was finally considered to have associated CCA, because signs of fetal alcohol syndrome had become obvious. Of the 11 other children, three (27%) had borderline intelligence whereas the intelligence levels of eight (73%) were in the normal range, although half of these children experienced some difficulties in scholastic achievement. Neither epilepsy nor intellectual deficiency was noted and intellectual quotient scores correlated strongly with the mother's education level. CONCLUSION: Although prenatal diagnosis of isolated CCA is reliable, false postnatal diagnoses remain possible (10-20%) even with complete prenatal screening. Outcome is mostly favorable because intelligence is within the normal range for nearly 3/4 of the children. However, they frequently have mild learning difficulties.

Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial.

BACKGROUND: Pregnant women and infants who get influenza are at increased risk for severe illness. OBJECTIVE: To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy. DESIGN: Prospective, multicenter, single-group clinical trial. (ClinicalTrials.gov registration number: NCT01024400) SETTING: Five level-3 perinatal centers in France. PATIENTS: 107 pregnant women between 22(0/7) and 32(0/7) weeks of gestation. INTERVENTION: An intramuscular dose of a nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. MEASUREMENTS: Proportion of women with an influenza antibody titer of 1:40 or greater at days 21 and 42 after vaccination, delivery, and 3 months after delivery. Seroconversion rate, fold increase in the geometric mean titer 21 days after vaccination, and proportion of neonates with an antibody titer of 1:40 or greater at birth were also assessed. RESULTS: At baseline, 19% of the women had an antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase in geometric mean titer was 67.4. At day 42, delivery, and 3 months after delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of 1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88 neonates showed an antibody titer of 1:40 or greater. The median neonate-mother antibody titer ratio was 1.4. LIMITATIONS: Only healthy pregnant women were selected. Data on hemagglutination inhibition antibody titers of infants were reported only at birth. CONCLUSION: A single dose of a nonadjuvanted influenza A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response in pregnant women and a high rate of neonatal seroprotection. PRIMARY FUNDING SOURCE: French National Institute of Health and Medical Research.

Amniocentesis performed for karyotyping after identified ultrasonographic abnormalities: what to expect?

OBJECTIVES: The aim of this study was to evaluate the relative risk of identifying fetal chromosomal anomalies after finding ultrasonographic (US) abnormalities in a high-risk population who underwent amniocentesis. METHODS: A retrospective review of a cohort of patients with single pregnancies who underwent genetic amniocentesis was undertaken. Univariate and multivariate analysis were used to determine the best correlations between US findings and chromosomal abnormalities. RESULTS: Overall, 191 chromosomal abnormalities were found in 5,604 fetuses (3.4%). Multivariate analysis showed chromosomal abnormalities were significant ly associated with anomalies of the central nervous system (OR = 4.4, 95% CI 2.2-8.7), face and neck (OR = 15.7, 95% CI 9.2-26.8), heart (OR = 5.4, 95% CI 2.6-11.2), abdomen (OR = 5.6, 95% CI 2.9-10.9), extremities (OR = 5.7, 95% CI 2.4-13.4), an increased nuchal fold (OR = 5.2, 95% CI 3.3-8.1), an intrauterine growth restriction (OR = 3.6, 95% CI 1.6-7.9) and a short femur (OR = 4.1, 95% CI 1.4-12.1). CONCLUSIONS: Our results confirm the validity of specific US markers in detecting chromosomal abnormalities in the fetus.

Fetopathologic examination for early termination of pregnancy: dogma or necessity?

OBJECTIVE: Our objective was assessment of fetopathological examination after termination of pregnancy (TOP) for fetal anomalies with normal karyotype <17 weeks of gestation. STUDY DESIGN: This was a multicenter retrospective study. Records of TOP for fetal anomalies with normal karyotype were analyzed. Primary outcomes were modifications of genetic counseling and management of next subsequent pregnancies. Medical TOPs were compared with surgical TOPs. RESULTS: In all, 59 pregnancies were included (30 aspirations, 29 inductions). Fetopathological examination modified genetic counseling for 22 patients: 62% for the medical induction group vs 13% in the vacuum aspiration group (P < .001). Management of subsequent pregnancies was modified in 17% in the medical induction group vs 3% in the aspiration group (P = .06). CONCLUSION: Fetopathological examination for early TOP with normal karyotype is relevant, especially when an intact fetus is examined. Thanks to it, genetic counseling is often modified, as is management of the next pregnancy. Medical procedures should be preferred to surgical procedures.

[Assessment of AFP in amniotic fluid: comparison of three automated techniques]. / Dosage de l'AFP dans le liquide amniotique : comparaison de trois techniques automatisées.

Ultrasound scanning is useful to detect neural tube defect (NTD) but scarcely distinguished between closed NTD and open NTD, which had very different prognosis. An amniotic fluid punction is thus mandatory to search for an increase in alpha foeto protein (AFP) levels and for the presence of acetylcholinesterase which identified open NTD. However, AFP levels fluctuate both with the gestational age and the assay used. Our aim was to establish normative values for AFP in amniotic fluid in the second half of pregnancy using three different immunoassays and to improve their clinical relevance. Amniotic fluid punctions were performed on 527 patients from 9 week of gestation (WG) to 37 WG either for maternal age, Trisomy 21 screening, increase in nucal translucency (control group, n = 527) or for suspicion of neural tube defect or abdominal defect (n = 5). AFP was measured using the immunoassay developed for serum AFP on the Access 2 system, the Immulite 2000 and the Advia Centaur. Results were expressed in ng/ml, multiple of the median (MoM) and percentiles. AFP decrease by 1.5 fold between 9 and 19 WG. When NTD was suspected, an increase in anmniotic AFP was observed (from 2.5 MoM to 9.3 MoM) confirming an open NTD. In conclusion, the assay developed on those 3 automates is suitable for the measurement of AFP in amniotic fluid.

MRI of the fetal posterior fossa.

MRI is a useful tool to complement US for imaging of the fetal posterior fossa (PF). In France, the discovery of a PF malformation in the fetus frequently leads to termination of pregnancy (80% in a personal series). However, despite improved accuracy in the diagnosis of PF abnormalities, prognosis remains uncertain. The first objective of this review is to document the normal MRI landmarks of the developing fetal PF. Because of their thinness, the visibility of the cerebellar fissures is dramatically delayed on MRI compared to macroscopic data. An important landmark is identification of the primary fissure of the vermis, normally seen at around 25-26 weeks' gestation (WG) on the sagittal slice, separating the larger posterior lobe from the anterior lobe (volume ratio around 2:1). The prepyramidal and secondary fissures are usually only identifiable after 32 WG and the hemispheric fissures are difficult to see until the end of pregnancy. Considering the signal changes, high signal on T2-weighted (T2-W) sequences is seen from 25 WG in the posterior part of the brain stem (tegmentum and ascending sensory tracts) related to myelination. The low signal intensities seen within the cerebellum on T2-W images correspond to high cellularity of grey matter (deep nuclei), as there is no myelination within the white matter before 38 WG. The second objective is to highlight the signs highly predictive of a poor neurological prognosis. Lack of pontine curvature or vermian agenesis without a PF cyst (small volume of PF) is greatly associated with poor neurological status. The third objective is to propose a diagnostic strategy in difficult cases where prognosis is important, e.g. the Dandy Walker continuum. Analysis of the cerebellum is often impossible if a PF cyst is present (whatever its nature) as the mass effect usually blurs the foliation and even impairs evaluation of the normal ratio between the posterior and anterior lobes of the vermis. Isolated cerebellar hypoplasias raise the question of prognosis and genetic counselling. Such uncertainties require an amniocentesis and a careful search for other anomalies (cerebral and extracerebral). Unilateral abnormalities of a cerebellar hemisphere can be associated with good neurological status if they are isolated. The final objective is to discuss other rare PF fetal abnormalities, such as vascular malformations and tumours.

Agenesis of corpus callosum: prenatal diagnosis and prognosis.

INTRODUCTION: Agenesis of corpus callosum (ACC) is commonly diagnosed prenatally. When isolated, it appears to carry a good prognosis but studies are often retrospective and follow-up short. We report a prospective study of 17 children (11 boys, 6 girls) with prenatally diagnosed isolated ACC. METHODS: Neuropsychological evaluation was performed each year and results at the ages of 2, 4, and 6 years were compared. RESULTS: Febrile seizures occurred in 3 patients. Median intellectual quotient (IQ) was within the normal range (80-109) and nonrelated to partial or complete ACC, sex, or febrile seizures. Lower median IQ was significantly related to low cultural status. With age, the number of children with IQ in the lower range (80-89) increased and slowness, attentional troubles, and instability appeared. CONCLUSION: This study demonstrates that if outcome of isolated ACC is favorable, a long follow-up is necessary: with age, IQ in the lower range and behavioral troubles are linked to difficulties in school.