Jean-Marie Jouannic

Notable contribution of large CFTR gene rearrangements to the diagnosis of cystic fibrosis in fetuses with bowel anomalies

Grade III fetal bowel hyperechogenicity and/or loop dilatation observed at the second trimester of pregnancy can be due to several disease conditions, including cystic fibrosis (CF). Screening for frequent CF mutations is performed as a first step and, in certain situations, such as when a frequent CF mutation is found in the fetus, the increased risk of CF justifies an in-depth study of the second allele. To determine the contribution of large CFTR gene rearrangements in such cases, detected using a semiquantitative fluorescent multiplex PCR (QFM-PCR) assay, we collated data on 669 referrals related to suspicion of CF in fetuses from 1998 to 2009. Deletions were found in 5/70 cases in which QFM-PCR was applied, dele19, dele22_23, dele2_6b, dele14b_15 and dele6a_6b, of which the last three remain undescribed. In 3/5 cases, hyperechogenicity was associated with dilatation and/or gallbladder anomalies. Of the total cases of CF recognized in the subgroup of first-hand referrals, deletions represent 16.7% of CF alleles. Our study thus strengthens the need to consider large CFTR gene rearrangements in the diagnosis strategy of fetal bowel anomalies, in particular in the presence of multiple anomalies.

Variability of T1-weighted signal intensity of pericallosal lipomas in the fetus

BackgroundPericallosal lipomas are often associated with corpus callosum dysgenesis. The diagnosis of lipoma, suggested on ultrasonography, relies on the classic T1 hyperintensity on magnetic resonance imaging (MRI). However, this feature may be absent prenatally.ObjectiveOur objective was to study the changes of T1 intensity in fetal lipomas with comparison to postnatal/postmortem data and to assess the factors influencing the signal variations of pericallosal lipomas on prenatal MRI.Materials and methodsPatients with callosum dysgenesis and interhemispheric hyperechogenicity suggestive of a pericallosal lipoma with available postnatal or postmortem data were included. Gestational age, lipoma size and pattern, corpus callosum size and changes in fetal fat T1 intensity were recorded. Comparison with postmortem neuropathology was available for one fetus.ResultsEleven patients with callosum dysgenesis and pericallosal lipomas (seven curvilinear and four tubulonodular) were included. All MRI scans were performed in the third trimester. Curvilinear lipomas were thinner and six cases were associated with prenatal T1 iso-intensity. Typical T1 hyperintensity appeared on postnatal MRI only. All tubulonodular lipomas were much larger and showed prenatal T1 hyperintensity. In two patients, the lipoma increased in size on postnatal MRI.ConclusionThe type and size of a lipoma influence T1 prenatal intensity. Absence of T1 intensity was observed in curvilinear lipomas only. Curvilinear lipomas are much thinner. Changes in T1 intensity may also be related to fat maturation within the lipoma and, subsequently, to gestational age. In the case of callosum dysgenesis, absence of prenatal T1 pericallosal hyperintensity should not exclude the diagnosis of pericallosal lipoma.

Relation between the quality of the ultrasound image acquisition and the precision of the measurement of the crown-rump length in the late first trimester: what are the consequences?

OBJECTIVE To assess the extent to which the distribution of crown-rump length (CRL) values may be correlated with different criteria for the quality of the CRL images. STUDY DESIGN This is a retrospective analysis of a series of 977 CRL images, by two independent observers, for the presence or the absence of 14 quality hallmarks. Inter-observer agreement for the hallmarks was assessed by the proportion of agreement and Cohens kappa. The association between the quantiles of the CRL distribution and the presence or absence of the 14 quality hallmarks was modeled using quantile regression. RESULTS The overall inter-observer agreement across the 14 hallmarks was 91.7%, kappa=0.81, 95% CI [0.80-0.82]. Distribution of CRL measurements varied considerably as a function of image quality: when the fetus was in extension, the mean CRL was +5.7mm (vs. not in extension, p<0.001), when the fetus was in flexion (vs. not), the mean CRL was -4.7mm (p<0.001) and when the image magnification was <65% (vs. >65%), the mean CRL was -4.2mm (p<0.001). There was a global trend to over-estimate the CRL for the higher deciles and to under-estimate the CRL for the lower deciles when the sagittal quality hallmarks were absent. No significant impact on CRL distribution was observed in association with the precise placement of the calipers nor with the horizontal orientation of the fetus. CONCLUSION Distribution of CRL measurements was influenced by the quality of CRL images. In particular, inadequate position of the fetus (flexion/extension) and insufficient image magnification were associated with systematic changes in the values of CRL. Our results show that as the quality of CRL images decreases, the associated variations in the distribution of CRL can have an impact on the chromosomal risk assessment and may lead to inappropriate obstetrical decisions.

Re: Perinatal outcomes after open fetal surgery for myelomeningocele repair: a retrospective cohort study

in detail, as the relative sizes of the groups and the incidence of outcomes (for example, caesarean rates or oxytocin rates) within them will help to validate the quality of the data being analysed. In addition, we would like to emphasise that although the classification has been primarily used for analysing caesarean section rates, less attention has been given to its other important quality which is that it can be used to analyse other perinatal events, outcomes, and complications, thus relating them all to each other. Caesarean section rates, for example, should never be interpreted on their own and must include other physical and patient experience outcomes. We agree that the Robson classification serves as a common starting point for further analysis, but its full potential will not be realised until we all become familiar with it and use it continuously. In order to do so, good quality routine data collection is essential, and this remains the ‘holy grail’.&