"A vaccine that nonetheless remains apart": Papillomavirus and vaccination in France / « Un vaccin qui reste quand même à part ¼ : Papillomavirus et vaccination en France

Introduction: Vaccination against the human papillomavirus (HPV) is currently not widespread in France, where the vaccination rate is one of the lowest in Europe. However, this virus is encountered by 80% of the population and causes 3000 new cases of cancer per year. This vaccination constitutes a real lever for action. Purpose of research: Using a qualitative approach (semi-directive interviews), we documented the perceptions, reluctance, and obstacles of sixteen general practitioners in Ile de France. The objective was to understand the low vaccination rate and to propose sustainable solutions to increase adherence to this vaccine. Results: The HPV vaccine is different from other vaccines, which makes it more difficult for the public to understand. Firstly, because it affects the privacy of patients from a very young age. Secondly, because it has long been dedicated to a female public and the opening of vaccination to boys of the same age leads to a change in discourse and a break with its gendered image. Finally, this vaccination is taking place in a context where there is a marked reluctance to vaccinate in France, with a rapid circulation of more or less reliable information that often places the medical profession in difficulty. Conclusions: Health professionals play a key role in convincing and encouraging patients to adhere to the vaccine, and a majority of doctors are still in favor of vaccination. Relying on a wider group of health professionals could help to increase adherence to the vaccine in France.

Introduction: La vaccination contre le papillomavirus humain (HPV) est aujourd'hui peu répandue en France où le taux vaccinal est l'un des plus faibles d'Europe. Pourtant, ce virus est rencontré par 80 % de la population et entraine 3 000 nouveaux cas de cancers du col de l'utérus par an. Cette vaccination constitue un réel levier d'action, notamment par le biais des médecins généralistes. But de l'étude: L'objectif était de comprendre le faible taux vaccinal en France et de proposer des solutions durables pour augmenter l'adhésion à ce vaccin. Avec une approche qualitative, nous avons documenté les perceptions, réticences et obstacles de seize médecins généralistes en Île de France. Résultats: Le vaccin anti-HPV présente des particularités qui rendent son abord plus délicat auprès de la population. D'abord, parce qu'il touche à l'intimité des patients et ce, dès un très jeune âge. Ensuite, parce qu'il a longtemps été dédié à un public féminin ; l'ouverture de la vaccination aux garçons du même âge entraine donc une modification des discours et une rupture avec son image genrée. Enfin, cette vaccination s'inscrit dans un contexte où l'hésitation vaccinale est marquée en France, avec une circulation rapide d'informations plus ou moins fiables venant souvent mettre en difficulté le corps médical. Conclusions: Les professionnels de santé détiennent un rôle clé pour convaincre et entrainer l'adhésion des patients, et une majorité des médecins reste favorable à cette vaccination. S'appuyer sur un ensemble de professionnels de santé plus large pourrait permettre d'augmenter l'adhésion vaccinale en France.

Evaluation of Midwives' Practises on Herpetic Infections during Pregnancy: A French Vignette-Based Study.

(1) Background: One out of two pregnant women has a history of herpes infection. Initial infections have a high risk of neonatal transmission. Our objective was to analyse the professional practises of midwives regarding the management of herpes infections during pregnancy in France; (2) Methods: A national survey conducted via an online self-questionnaire, including clinical vignettes for which the midwives proposed a diagnosis, a drug treatment, a mode of birth, and a prognosis. These responses were used to evaluate the conformity of the responses to the guidelines, as well as the influence of certain criteria, such as mode of practise and experience; (3) Results: Of 728 responses, only 26.1% of the midwives reported being aware of the 2017 clinical practise guidelines. The midwives proposed taking the appropriate actions in 56.1% of the responses in the case of a recurrence, and in 95.1% of the responses in the case of a primary infection. For the specific, high-risk case of a nonprimary initial infection at 38 weeks of gestation, reporting knowledge of the recommendations improved the compliance of the proposed care by 40% (p = 0.02). However, 33.8% of the midwives underestimated the neonatal risk at term after a primary initial infection, and 43% underestimated the risk after a primary initial infection at term; (4) Conclusions: The majority of reported practises were compliant despite a low level of knowledge of the guidelines. The dissemination of guidelines may be important to improve information and adherence to appropriate therapeutic practise.

Human cytomegalovirus infection is associated with increased expression of the lissencephaly gene PAFAH1B1 encoding LIS1 in neural stem cells and congenitally infected brains.

Congenital infection of the central nervous system by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae, including mental retardation or neurodevelopmental abnormalities. The most severe complications include smooth brain or polymicrogyria, which are both indicative of abnormal migration of neural cells, although the underlying mechanisms remain to be determined. To gain better insight on the pathogenesis of such sequelae, we assessed the expression levels of a set of neurogenesis-related genes, using HCMV-infected human neural stem cells derived from embryonic stem cells (NSCs). Among the 84 genes tested, we found dramatically increased expression of the gene PAFAH1B1, encoding LIS1 (lissencephaly-1), in HCMV-infected versus uninfected NSCs. Consistent with these findings, western blotting and immunofluorescence analyses confirmed the increased levels of LIS1 in HCMV-infected NSCs at the protein level. We next assessed the migratory abilities of HCMV-infected NSCs and observed that infection strongly impaired the migration of NSCs, without detectable effect on their proliferation. Moreover, we observed increased immunostaining for LIS1 in brains of congenitally infected fetuses, but not in control samples, highlighting the clinical relevance of our findings. Of note, PAFAH1B1 mutations (resulting in either haploinsufficiency or gain of function) are primary causes of hereditary neurodevelopmental diseases. Notably, mutations resulting in PAFAH1B1 haploinsufficiency cause classic lissencephaly. Taken together, our findings suggest that PAFAH1B1 is a critical target of HCMV infection. They also shine a new light on the pathophysiological basis of the neurological outcomes of congenital HCMV infection, by suggesting that defective neural cell migration might contribute to the pathogenesis of the neurodevelopmental sequelae of infection. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Herpes simplex virus infections during pregnancy: epidemiology, clinical presentation and management]. / Infections par les virus herpes simplex pendant la grossesse : épidémiologie, aspects cliniques et prise en charge.

The incidence of herpes simplex virus (HSV) neonatal infection is estimated to be 8.9 per 100,000 live births in Europe. Early treatment with intravenous acyclovir has transformed the prognosis but this infection remains severe since, despite the treatment, mortality is frequent in disseminated diseases and neurological sequelae are frequent when central nervous system is involved. The major risk factor for transmission is the type of maternal infection. In women shedding the virus in their genital tract during childbirth, neonatal infection rates are 44 %, 25 % and 1.3 % in primary, non-primary and recurrent infections, respectively. The goals for the management of this infection during pregnancy encompass 1) the prevention of any contact between the newborn and the maternal virus by suppressing viral replication in the genital tract in late pregnancy and recommending a cesarean section in cases of genital lesions at delivery, and 2) the development of strategies allowing rapid identification and treatment of infected newborns.

Habitat patches for newts in the face of climate change: local scale assessment combining niche modelling and graph theory.

Triturus cristatus and Triturus marmoratus are two protected and declining newts occurring in the administrative department of Vienne, in France. They have limited dispersal abilities and rely on the connectivity between habitats and their suitability. In a warming climate, the locations of suitable habitats are expected to change, as is the connectivity. Here, we wondered how climate change might affect shifts in habitat suitability and connectivity of habitat patches, as connectivity is a key element enabling species to realize a potential range shift. We used ecological niche modelling (ENM), combining large-scale climate suitability with local scale, high-resolution habitat features, to identify suitable areas for the two species, under low and high warming scenarios (RCP 2.6 and RCP 8.5). We associated it with connectivity assessment through graph theory. The variable 'small ponds' contributed most to land cover-only ENMs for both species. Projections with climate change scenarios revealed a potential impact of warming on suitable habitat patches for newts, especially for T. cristatus. We observed a decrease in connectivity following a decrease in patch suitability. Our results highlight the important areas for newt habitat connectivity within the study area, and define those potentially threatened by climate warming. We provide information for prioritizing sites for acquisition, protection or restoration, and to advise landscape policies. Our framework is a useful and easily reproducible way to combine global climate requirements of the species with detailed information on species habitats and occurrence when available.

Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains.

BACKGROUND: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. METHODS: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (n = 13) and moderately affected (n = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8+, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. RESULTS: Quantities of CD8+, plasma cells, NK cells, macrophages, and HCMV+ cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all p values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. CONCLUSIONS: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.

Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: Identify measures to diagnose, prevent, and treat genital herpes infection during pregnancy and childbirth as well as neonatal herpes infection. MATERIALS AND METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: Genital herpes lesions are most often due to HSV-2 (LE2). The risk of HSV seroconversion during pregnancy is 1-5% (LE2). Genital herpes lesions during pregnancy in a woman with a history of genital herpes is a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In pregnant women with genital lesions who report they have not previously had genital herpes, virological confirmation by PCR and identifying the specific IgG type is necessary (professional consensus). A first episode of genital herpes during pregnancy should be treated with aciclovir (200 mg 5 times daily) or valaciclovir (1000 mg twice daily) for 5-10 days (Grade C), and recurrent herpes during pregnancy with aciclovir (200 mg 5 times daily) or valaciclovir (500 mg twice daily) (Grade C). The risk of neonatal herpes is estimated at between 25% and 44% if a non primary and primary first genital herpes episode is ongoing at delivery (LE2) and 1% for a recurrence (LE3). Antiviral prophylaxis should be offered to women with either a first or recurrent episode of genital herpes during pregnancy from 36 weeks of gestation until delivery (Grade B). Routine prophylaxis is not recommended for women with a history of genital herpes but no recurrence during pregnancy (professional consensus). A cesarean delivery is recommended if a first episode of genital herpes is suspected (or confirmed) at the onset of labor (Grade B) or if it occured less than 6 weeks before delivery (professional consensus) or in the event of premature rupture of the membranes at term. When a recurrence of genital herpes is underway at the onset of labor, cesarean delivery is most likely to be considered when the membranes are intact and vaginal delivery in cases of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most cases of neonatal herpes, mothers have no history of genital herpes (LE3). When neonatal herpes is suspected, various samples (blood and cerebrospinal fluid) for HSV PCR must be taken to confirm the diagnosis (professional consensus). Any newborn with suspected neonatal herpes should be treated with intravenous acyclovir (20 mg/kg 3 times daily) (grade A) before the PCR results are available (professional consensus). The duration of the treatment depends on the clinical form (professional consensus) CONCLUSION: There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes and the risk of recurrence at term, as well as cesarean rate because of herpes lesions.

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.

BACKGROUND: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. OBJECTIVE: We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. STUDY DESIGN: We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. RESULTS: In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. CONCLUSION: Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.

PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells.

Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPARγ levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPARγ agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPARγ activity. It also increased the rate of cells expressing the IE antigen in HCMV-infected NSCs. Further, we demonstrated that (1) pharmacological activation of ectopically expressed PPARγ was sufficient to induce impaired neuronogenesis of uninfected NSCs, (2) treatment of uninfected NSCs with 9-HODE impaired NSC differentiation and (3) treatment of HCMV-infected NSCs with the PPARγ inhibitor T0070907 restored a normal rate of differentiation. The role of PPARγ in the disease phenotype was strongly supported by the immunodetection of nuclear PPARγ in brain germinative zones of congenitally infected fetuses (N = 20), but not in control samples. Altogether, our findings reveal a key role for PPARγ in neurogenesis and in the pathophysiology of HCMV congenital infection. They also pave the way to the identification of PPARγ gene targets in the infected brain.

Comparison of the LIAISON(®) CMV IgG Avidity II and the VIDAS(®) CMV IgG Avidity II assays for the diagnosis of primary infection in pregnant women.

BACKGROUND: The accuracy of IgG avidity assays is crucial for the diagnosis of primary CMV infection in pregnancy. OBJECTIVE: To compare the performance of the second generation avidity assays LIAISON(®) CMV IgG Avidity II and VIDAS(®) CMV IgG Avidity II for the diagnosis of primary infection in pregnant women. STUDY DESIGN: In our laboratory, in sera of pregnant women presenting with positive CMV IgG and positive CMV IgM, the two avidity assays were run in parallel from January 2013 to April 2015. RESULTS: The results of the 2 avidity assays were analyzed in 280 sera. The correlation between the second generation LIAISON(®) and VIDAS(®) avidity results was significantly higher than between the results of the first generation assays (77% versus 49%, p<0.001). Discrepant results were mainly explained by the difficulty of the VIDAS(®) assay to reach intermediate and high avidity status over time, suggesting the superiority of the LIAISON(®) assay to achieve high avidity levels. In 4 sera from 3 pregnant women (1.4%) with documented primary infection the LIAISON(®) avidity was falsely high. In these cases the level of CMV IgG was low (<50U/mL). CONCLUSION: The LIAISON(®) CMV IgG Avidity II assay reached more rapidly higher avidity status than the VIDAS(®) CMV IgG Avidity II. However, with the LIAISON(®) CMV IgG Avidity II, we identified rare sera with high positive avidity values in documented recent seroconversion. The advantages and drawbacks of each assay must be known for a sound interpretation of the results.

Health effects of ambient air pollution: do different methods for estimating exposure lead to different results?

BACKGROUND: Spatially resolved exposure models are increasingly used in epidemiology. We previously reported that, although exhibiting a moderate correlation, pregnancy nitrogen dioxide (NO2) levels estimated by the nearest air quality monitoring station (AQMS) model and a geostatistical model, showed similar associations with infant birth weight. OBJECTIVES: We extended this study by comparing a total of four exposure models, including two highly spatially resolved models: a land-use regression (LUR) model and a dispersion model. Comparisons were made in terms of predicted NO2 and particle (aerodynamic diameter<10 µm, PM10) exposure and adjusted association with birth weight. METHODS: The four exposure models were implemented in two French metropolitan areas where 1026 pregnant women were followed as part of the EDEN mother-child cohort. RESULTS: Correlations between model predictions were high (≥ 0.70), except for NO2 between the AQMS and both the LUR (r = 0.54) and dispersion models (r = 0.63). Spatial variations as estimated by the AQMS model were greater for NO2 (95%) than for PM10 (22%). The direction of effect estimates of NO2 on birth weight varied according to the exposure model, while PM10 effect estimates were more consistent across exposure models. CONCLUSIONS: For PM10, highly spatially resolved exposure model agreed with the poor spatial resolution AQMS model in terms of estimated pollutant levels and health effects. For more spatially heterogeneous pollutants like NO2, although predicted levels from spatially resolved models (all but AQMS) agreed with each other, our results suggest that some may disagree with each other as well as with the AQMS regarding the direction of the estimated health effects.

Delivery for women with a previous cesarean: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF).

The primary cause of uterine scars is a previous cesarean. In women with a previous cesarean, the risks of maternal complications are rare and similar after a trial of labor after cesarean (TOLAC) and after an elective repeat cesarean delivery (ERCD), but the risk of uterine rupture is higher with TOLAC (level of evidence [LE]2). Maternal morbidity in women with previous cesareans is higher when TOLAC fails than when it leads to successful vaginal delivery (LE2). Although maternal morbidity increases progressively with the number of ERCD, maternal morbidity of TOLAC decreases with the number of successful previous TOLAC (LE2). The risk-benefit ratio considering the risks of short- and long-term maternal complications is favorable to TOLAC in most cases (LE3). Globally, neonatal complications are rare regardless of the mode of delivery for women with previous cesareans. The risks of fetal, perinatal, and neonatal mortality during TOLAC are low. Nonetheless, these risks are significantly higher than those associated with ERCD (LE2). The risks of mask ventilation, intubation for meconium-stained amniotic fluid, and neonatal sepsis all increase in TOLAC (LE2). The risk of transient respiratory distress increases in ERCD (LE2). To reduce this risk, and except in particular situations, ERCD must not be performed before 39 weeks (grade B). TOLAC is possible for women with a previous cesarean before 37 weeks, with 2 previous cesareans, with a uterine malformation, a low vertical incision or an unknown incision, with a myomectomy, postpartum fever, an interval of less than 6 months between the last cesarean delivery and the conception of the following pregnancy, if the obstetric conditions are favorable (professional consensus). ERCD is recommended in women with a scar in the uterine body (grade B) and a history of 3 or more cesareans (professional consensus). Ultrasound assessment of the risk of uterine rupture in women with uterine scars has not been shown to have any clinical utility and is therefore not recommended during pregnancy to help decide the mode of delivery (professional consensus). Use of X-ray pelvimetry to decide about TOLAC is associated with an increase in the repeat cesarean rate without any reduction in the rate of uterine rupture (LE2). It is unnecessary for deciding mode of delivery and for managing labor during TOLAC (grade C). TOLAC should be encouraged for women with a previous vaginal delivery either before or after the cesarean, a favorable Bishop score or spontaneous labor, and for preterm births (grade C). For women with a fetus with an estimated weight of more than 4500 g, especially in the absence of a previous vaginal delivery and those with supermorbid obesity (BMI>50), ERCD must be planned from the outset (grade C). For all of the other clinical situations envisioned (maternal age>35 years, diabetes, morbid obesity, prolonged pregnancy, breech presentation and twin pregnancy), TOLAC is possible but the available data do not allow specific guidelines about the choice of mode of delivery, in view of the low levels of proof (grade C). The decision about planned mode of delivery must be shared by the patient and her physician and made by the 8th month, taking into account the individual risk factors for TOLAC failure and uterine rupture (professional consensus). TOLAC is the preferred choice for women who do not have several risk factors (professional consensus). The availability onsite of an obstetrician and anesthetist must be pointed out to the patient. If the woman continues to prefer a repeat cesarean after adequate information and time to think about it, her preference should be honored (professional consensus). Labor should be induced in woman with a previous cesarean only for medical indications (professional consensus). Induction of labor increases the risk of uterine rupture, which can be estimated at 1% if oxytocin is used and 2% with vaginal prostaglandins (LE2). Mechanical methods of induction have not been studied sufficiently. Misoprostol appears to increase the risk of uterine rupture strongly (LE4). Based on the information now available, its use is not recommended (professional consensus). Routine use of internal tocodynamometry does not prevent uterine rupture (professional consensus). The increased risk of uterine rupture associated with oxytocin use is dose-dependent (LE3). In the active phase, it is recommended that the total duration of failure to progress should not exceed 3h; at that point, a cesarean should be performed (professional consensus). Epidural analgesia must be encouraged. The simple existence of a uterine scar is not an indication for a routine manual uterine examination after VBAC (grade C).

Prediction of fetal infection in cases with cytomegalovirus immunoglobulin M in the first trimester of pregnancy: a retrospective cohort.

BACKGROUND: Interpretation of positive cytomegalovirus (CMV) immunoglobulin M (IgM) in the first trimester of pregnancy is ill-defined. We aimed to quantify the risk of fetal transmission in women with positive CMV IgM in the first trimester. METHODS: A retrospective cohort of women (2009-2011) was tested for CMV immunoglobulin G (IgG) and IgM before 14 weeks of gestation. IgG avidity was tested with 2 assays (LIAISON and VIDAS). CMV polymerase chain reaction (PCR) was done in maternal serum, amniotic fluid, or neonatal urine at birth. RESULTS: A total of 4931 consecutive women were screened; 201 presented with positive or equivocal IgM and with high, intermediate, or low IgG avidity in 58.7%, 18.9%, and 22.3%, respectively. In 72 women with low or intermediate avidity, fetal transmission was 23.6%. In multivariate analysis, positive CMV PCR in maternal serum, decreasing avidity index with both LIAISON and VIDAS, and low IgG titers were all associated with fetal transmission (odds ratio [OR], 12.38 [95% confidence interval {CI}, 1.77-86.33], P = .011; OR, 0.16 [95% CI, .03-.95], P = .044; OR, 0.54 [95% CI, .11-.88], P = .028; and OR, 0.27 [95% CI, .29-.84], P = .010, respectively). CONCLUSION: This study demonstrates a significant association between the risk of vertical transmission and the avidity index combined with CMV PCR in maternal serum or IgG titers. This allows calculation of incremental risk of fetal transmission upon which informed choice can be based and could lead to a better pickup rate of fetal infection while decreasing unnecessary invasive procedures.