Olivier Picone

Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy?: Results of a 3-year prospective study in a French hospital.

BACKGROUND Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection in developed countries. OBJECTIVES The objective of this study was to evaluate the impact of our prenatal CMV infection screening and counseling policy. STUDY DESIGN Since 2005, all pregnant women in our obstetric center have been informed about CMV infection, and if they agree, given a serological test at around 12 weeks of gestation (WG). If this first test is negative, the women and their partners are given hygiene counseling on how to prevent CMV infection, and a second test is performed at around 36 WG. RESULTS Among the 5312 women who had an unknown immune status, or were known to be seronegative when they had their first visit to our center for their current pregnancy, 97.4% agreed to CMV screening. Primary infection was detected in 11 women between 0 and 12 WG (0.42%), and seroconversion was diagnosed in five women between 12 and 36 WG (0.19%). CONCLUSIONS These results suggest that if clear information is given on CMV infection during pregnancy, the rate of seroconversion is lower following counseling than before counseling.

Twin pregnancies: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF)

The rate of twin deliveries in 2008 was 15.6 per 1000 in France, an increase of approximately 80% since the beginning of the 1970s. It is recommended that chorionicity be diagnosed as early as possible in twin pregnancies (Professional Consensus). The most relevant signs (close to 100%) are the number of gestational sacs between 7 and 10 weeks and the presence of a lambda sign between 11 and 14 weeks (Professional Consensus). In twin pregnancies, nuchal translucency is the best parameter for evaluating the risk of aneuploidy (Level B). The routine use of serum markers during the first or the second trimester is not recommended (Professional Consensus). In the case of a choice about sampling methods, chorionic villus sampling is recommended over amniocentesis (Professional Consensus). Monthly follow-up by a gynaecologist-obstetrician in an appropriate facility is recommended for dichorionic pregnancies (Professional Consensus). A monthly ultrasound examination including an estimation of fetal weight and umbilical artery Doppler is recommended (Professional Consensus). It is recommended to plan delivery of uncomplicated dichorionic diamniotic twin pregnancies from 38 weeks and before 40 weeks (Level C). Monthly prenatal consultations and twice-monthly ultrasound are recommended for monochorionic twins (Professional Consensus). It is reasonable to consider delivery from 36 weeks but before 38 weeks+6 days, with intensified monitoring during that time (Professional Consensus). Prenatal care of monochorionic pregnancies must be provided by a physician working in close collaboration with a facility experienced in the management of this type of pregnancy and its complications (Professional Consensus). The increased risk of maternal complications and the high rate of medical interventions justify the immediate and permanent availability of a gynaecologist-obstetrician with experience in the vaginal delivery of twins (Professional Consensus). It is recommended that the maternity ward where delivery takes place have rapid access to blood products (Professional Consensus). Only obstetric history (history of preterm delivery) (Level C) and transvaginal ultrasound measurement of cervical length (Level B) are predictive factors for preterm delivery. No study has shown that the identification by transvaginal sonography (TVS) of a group at risk of preterm delivery makes it possible to reduce the frequency of such deliveries in asymptomatic patients carrying twins (Professional Consensus). It is important to recognize signs of TTTS early to improve the management of these pregnancies (Professional Consensus). Treatment and counseling must be performed in a center that can offer fetoscopic laser coagulation of placental anastomoses (Professional Consensus). This laser treatment is the first-line treatment (Level B). In the absence of complications after laser treatment, planned delivery is recommended from 34 weeks and no later than 37 weeks (Professional Consensus). For delivery, it is desirable for women with a twin pregnancy to have epidural analgesia (Professional Consensus). The studies about the question of mode of delivery have methodological limitations and lack of power. Active management of the delivery of the second twin is recommended to reduce the interval between the births of the two twins (Level C). In the case of non-cephalic presentation, total breech extraction, preceded by internal version manoeuvres if the twins position is transverse, is associated with the lowest cesarean rates for second twins (Level C). In the case of high and not yet engaged cephalic presentation and if the team is appropriately trained, version by internal manoeuvres followed by total breech extraction is to be preferred to a combination of resumption of pushing, oxytocin perfusion, and artificial rupture of the membranes, because the former strategy appears to be associated with fewer cesareans for the second twin (Level C).

Evaluation of Cytomegalovirus (CMV) DNA Quantification in Dried Blood Spots: Retrospective Study of CMV Congenital Infection

ABSTRACT We compared two protocols for extracting DNA from dried blood spots for cytomegalovirus (CMV) DNA detection and quantification by real-time PCR. Both extraction methods were reliable for the retrospective diagnosis of CMV congenital infection. Quantification of CMV DNA was valuable after normalization of viral loads with albumin gene PCR amplification results.

Human Cytomegalovirus UL144 Gene Polymorphisms in Congenital Infections

ABSTRACT The human cytomegalovirus (HCMV) UL144 gene is a tumor necrosis factor-like receptor with the potential to affect HCMV virulence. HCMV strains display genetic variability in the UL144 region, and the analysis of a potential link between UL144 gene polymorphisms and disease severity has scarcely been studied. However, a correlation between the UL144 genotype and congenital-disease outcome has been reported in one previous study, with the observation that all asymptomatic infants had a single UL144 genotype. In order to confirm or refute this finding, we determined the UL144 polymorphisms of HCMV strains recovered from the amniotic fluids of 38 infected fetuses and compared them to HCMV strains obtained from 30 viremic adult controls. The UL144 sequences were distributed among five genotypes (A, B, C, AC, and AB), as previously described. We observed similar percentages of the three major genotypes A (37%), B (33%), and C (27%) in our population. The UL144 genotype distributions were similar among the group of infected adults and the group of infected fetuses and among symptomatic and asymptomatic fetuses (P < 0.05). In our series, all five UL144 genotypes could be vertically transmitted from mothers to fetuses, and all could cause symptomatic congenital infection. We concluded that determination of UL144 polymorphisms in cases of congenital infection is not relevant, since it is unlikely to help predict the outcome of the infection.

Inner ear lesions in congenital cytomegalovirus infection of human fetuses

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19–35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.

Cytomegalovirus-induced brain malformations in fetuses.

Neurologic morbidity associated with congenital cytomegalovirus (CMV) infection is a major public health concern. The pathogenesis of cerebral lesions remains unclear. We report the neuropathologic substrates, the immune response, and the cellular targets of CMV in 16 infected human fetal brains aged 23 to 28.5 gestational weeks. Nine cases were microcephalic, 10 had extensive cortical lesions, 8 had hippocampal abnormalities, and 5 cases showed infection of the olfactory bulb. The density of CMV-immunolabeled cells correlated with the presence of microcephaly and the extent of brain abnormalities. Innate and adaptive immune responses were present but did not react against all CMV-infected cells. Cytomegalovirus infected all cell types but showed higher tropism for stem cells/radial glial cells. The results indicate that 2 main factors influence the neuropathologic outcome at this stage: the density of CMV-positive cells and the tropism of CMV for stem/progenitor cells. This suggests that the large spectrum of CMV-induced brain abnormalities is caused not only by tissue destruction but also by the particular vulnerability of stem cells during early brain development. Florid infection of the hippocampus and the olfactory bulb may expose these patients to the risk of neurocognitive and sensorineural handicap even in cases of infection at late stages of gestation.

Normal fetal urine production rate estimated with 3-dimensional ultrasonography using the rotational technique (virtual organ computer-aided analysis)

OBJECTIVE The aim of this study was to assess hourly fetal urine production rates (HFUPRs) and establish a nomogram by measuring bladder volumes with 3-dimensional ultrasound. STUDY DESIGN Fetal urine bladder volume was estimated in 167 normal singleton pregnancies with neither oligohydramnios nor polyhydramnios, at a gestational age of 20-41 weeks. HFUPR was estimated in a regression analysis that included at least 3 volumes calculated during the filling phase with the Virtual Organ Computed-aided AnaLysis (VOCAL) technique. We estimated interoperator variability for HFUPR less than 10 mL/h and HFUPR greater than 10 mL/h. RESULTS Fetal urine production rates at 25, 30, 35, and 40 weeks were 7.5, 22.2, 56.1, and 125.1 mL/h, respectively. The intraclass correlation coefficients for interoperator variability were 99.2% for HFUPR less than 10 mL/hour and 97.1% for HFUPR greater than 10 mL/h. CONCLUSION Prenatal measurement of HFUPR with 3-dimensional VOCAL ultrasound is reproducible and may help to determine the cause and prognosis of amniotic fluid volume abnormalities.

Awareness of cytomegalovirus infection among pregnant women in France

BACKGROUND Cytomegalovirus (CMV) is the most frequent cause of congenital virus infection. Approximately 1% of newborns are infected by CMV at birth with severe consequences among 10% of them. Efficacy of hygienic counselling is nowadays established and should be spread. OBJECTIVE To evaluate pregnant womens awareness of cytomegalovirus infection in France. STUDY DESIGN Pregnant women receiving prenatal care, at any moment of their pregnancy, in two different obstetrics clinics with different information policies, were asked to complete a written questionnaire about CMV infection. RESULTS More than half (217/362, 60%) of the pregnant women had heard of congenital CMV infection, and most of them (72%) knew the hygiene measures to use to prevent infection. Nevertheless, most could not correctly identify the symptoms associated with congenital CMV disease. Awareness was associated with hospitals policy concerning CMV infection information, the mothers educational level, parity, and employment in health care. Indeed, when information is supposed to be given (hospital A), 74% (vs 34%) know congenital CMV infection and among them the knowledge is more precise. CONCLUSIONS This study tends to confirm that there is a large gap between knowledge of CMV and the burden of this disease. To bridge this gap, women should receive education about congenital CMV. Hospital-based prenatal education increases awareness and knowledge about CMV and CMV prevention.

Obstetrical Complications and Outcome in Two Families with Hereditary Angioedema due to Mutation in the F12 Gene

Backgroud. Hereditary angioedema (HAE) is characterized by recurrent swelling of the skin, the abdomen (causing severe acute pain), and the airways. A recently discovered type caused by mutations in the factor XII gene (designated as HAE type III) occurs mainly in women. Estrogens may play an important role, but few obstetrical complications have been reported. Case. We report the symptoms and obstetrical complications of women in two families with HAE attributable to the p. Thr328Lys mutation in the F12 gene. Clinical manifestations included acute and severe maternal abdominal pain, with transient ascites, laryngeal edema, and fetal and neonatal deaths. Patients had normal C4 levels and a normal C1 inhibitor gene. Administration of C1-inhibitor concentration twice monthly decreased the attack rate in one mother, and its predelivery administration (1000 U) led to the delivery of healthy girls. Conclusions. Obstetricians and anesthesiologists should be aware of this rare cause of unexplained maternal ascites and in utero or fetal death associated with edema.

Correlation between referral ultrasound with suspected foetal anomalies and autopsy examination in two prenatal diagnosis centres. Impact of the routine use of 3D/4D scan

To compare ultrasound diagnosis with autopsy findings in two tertiary referral foetal medicine centres, only one routinely using 3D and 4D ultrasound, and to compare results between the centres.