Cost-effectiveness of screening and valacyclovir-based treatment strategies for first-trimester cytomegalovirus primary infection in pregnant women in France.

OBJECTIVE: To assess the effectiveness, cost and cost-effectiveness of four screening strategies for first-trimester (T1) cytomegalovirus (CMV) primary infection (PI) in pregnant women in France. METHODS: In a simulated pregnant population of 800 000 (approximate number of pregnancies each year in France), using costs based on the year 2022, we compared four CMV maternal screening strategies: Strategy S1, no systematic screening (current public health recommendations in France); Strategy S2, screening of 25-50% of the pregnant population (current screening practice in France); Strategy S3, universal screening (current medical recommendations in France); Strategy S4, universal screening (as in Strategy S3) in conjunction with valacyclovir in case of T1 PI. Outcomes were total cost, effectiveness (number of congenital infections, number of diagnosed infections) and incremental cost-effectiveness ratio (ICER). Two ICERs were calculated, comparing Strategies S1, S2 and S3 in terms of euros (€) per additional diagnosis, and comparing Strategies S1 and S4 in € per avoided congenital infection. RESULTS: Compared with Strategy S1, Strategy S3 enabled diagnosis of 536 more infected fetuses and Strategy S4 prevented 375 congenital infections. Strategy S1 was the least expensive strategy (€98.3m total lifetime cost), followed by Strategy S4 (€98.6m), Strategy S2 (€106.0m) and Strategy S3 (€118.9m). In the first analysis, Strategy S2 was dominated and Strategy S3 led to an additional €38 552 per additional in-utero diagnosis, compared with Strategy S1. In the second analysis, Strategy S4 led to an additional €893 per avoided congenital infection compared with Strategy S1, and was cost-saving compared with Strategy S2. CONCLUSIONS: In France, current screening practice for CMV PI during pregnancy is no longer acceptable in terms of cost-effectiveness because this strategy was dominated by universal screening. Moreover, universal screening in conjunction with valacyclovir treatment would be cost-effective compared with current recommendations and is cost-saving compared with current practice. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes.

BACKGROUND: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022). METHOD: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data. RESULTS: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, p<0.001), more frequent oxygen administration (23% vs 12%, 10% and 5%, p = 0,001) and more symptomatic patients at the time of testing with Delta and WT (75% and 71%) versus Alpha and Omicron variants (55% and 66% respectively, p<0.01). Stillbirth tended to be associated with variants (p = 0.06): WT 1/231 (<1%) vs 4/126 (3%), 3/94 (3%), and 1/35 (3%) in Alpha, Delta and Omicron cases respectively. No other difference was found. CONCLUSION: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection.

Conjunctival conveyance of SARS-CoV-2 in asymptomatic and non-severe symptomatic COVID-19 patients.

INTRODUCTION: The prevalence of ocular conveyance of SARS-CoV-2 has been well described for severe/hospitalized cases, but scarcely reported in asymptomatic and non-severe patients, who are unaware that they are carriers. MATERIAL & METHODS: This prospective cross-sectional study quantitatively evaluated SARS-CoV-2 shedding on the ocular surface (OS). Conjunctival testing was suggested to all hospital personnel being screened by nasopharyngeal (NP) SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). Disease symptoms were evaluated using a standardized questionnaire and telephone follow-up 6±3 months later for disease evolution (recovery with/without severe disease). RESULTS: Four hundred and eighty seven patients were included. From 46 NP SARS-CoV-2-positive subjects (cycle threshold [CT]=24.2±7.1), 13% tested positive at the OS (CT=36.4±2.8). Most SARS-CoV-2-positive subjects were symptomatic (n=40, 87%), while 6 were asymptomatic (being tested as contact cases). Systemic symptoms were not significantly different in OS-positive vs OS-negative subjects, although headache tended to be more frequent in OS-positives (83% vs 54%, P=0.06). None of the OS-positive subjects reported ocular symptoms and none developed severe disease requiring hospitalization or oxygen therapy. CONCLUSION: SARS-CoV-2 shedding at the OS may occur in asymptomatic and non-severe COVID-19 individuals (including those absent of ocular symptoms). However, the high RT-PCR CT values attained may indicate a low risk of transmissibility via this route.

[Monkeypox: Important facts for the ophthalmologist]. / Variole du singe : les points importants pour l'ophtalmologiste.

The current monkeypox virus (MPXV) outbreak, raging since May 2022, is the largest ever observed on a world-wide scale. Despite previously being endemic in west and central Africa with a mortality rate of up to 10%, it remained a neglected tropical disease. Along with other recent pandemics gaining much attention, this MPXV outbreak has provided an opportunity to improve our understanding of its physiopathology and better define management strategies, particularly in patients with more serious disease. From the ophthalmologist's perspective, eyelid involvement and conjunctivitis or keratoconjunctivitis are frequently observed and may precede systemic signs or even remain the major site of involvement. While the course of MPXV keratoconjunctivitis is most often favorable, severe cases pose a functional threat, in particular for immunocompromised patients. This review provides an overview of MPXV pathophysiology, diagnosis and treatment, as well as considerations for prevention of transmission. During such an epidemic, the ophthalmologist can be the first to diagnose MPXV, treat the ocular involvement, and set up adequate preventative measures in collaboration with infectious disease specialists.

New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

[SARS-Cov-2 vaccine's acceptance among pregnant women-A cross-sectional survey]. / Acceptabilité du vaccin-Sars CoV-2 chez les femmes enceintes, une enquête transversale par questionnaire.

OBJECTIVE: SARS-CoV-2 is more likely to cause severe cases in pregnant women. They were part of the priority groups since April 2021 to benefit from SARS-CoV-2 vaccination before its extent to general population. This contribution aims to evaluate, in the postpartum period, the achievement of COVID-19 vaccination and factors associated in women during their pregnancy. MATERIAL AND METHOD: Multicenter cross-sectional survey study conducted from September to December 2021 with online self-questionnaire. All postpartum patients hospitalized in one of the 6 participating maternity hospitals were invited to answer. The questionnaire asked patients about their demographic characteristics, vaccination modalities, vaccine tolerance, and their general perception of vaccination. RESULTS: Of the 371 women who responded, the vaccination rate was 65.7% (IC95% [60.8-70.4]), whom 98.8% entirely during pregnancy. Associated factors with vaccination during pregnancy were older age, higher socio-professional category, and prior information provided by health professionals. Factors that appear to motivate vaccination were personal protection and protection of the newborn. Finally, main factors negatively influencing the vaccination process were the fear of vaccine side effects and the negative perception of vaccines in general. DISCUSSION: Acceptability and information about the vaccine by health professionals is in constant improvement. Information campaigns should be continued to improve the acceptability of vaccination, in light of the accumulating data.

[Virological diagnosis of anterior herpetic ocular disease on tear sample: A simple and non-invasive technique]. / Diagnostic virologique des atteintes oculaires herpétiques antérieures sur prélèvement lacrymal : une technique simple et non invasive.

INTRODUCTION: Virological diagnosis of anterior ocular herpetic disease (AOHD) is essential for the management of these often-chronic pathologies that may require long-term therapy. PCR has become the gold standard, but the type of sampling (tears, corneal scraping, aqueous tap) has not been standardized. In this study, we studied the technique of tear sampling for the diagnosis of AOHD. MATERIALS AND METHOD: We retrospectively analyzed the medical files of patients with a positive tear sample (Schirmer strip) for herpes simplex 1 virus (HSV-1) in the Department of Ophthalmology of Paris-Saclay Bicêtre Hospital between January 2018 and December 2020. We studied the clinical and virological characteristics (viral loads) of these cases of proven AOHD. RESULTS: Thirty-six samples (33 patients) were included: 12 epithelial keratitis, 9 stromal HSK with ulceration, 5 uveitis, 4 stromal HSK without ulceration, 3 blepharitis, 1 endothelial HSK, 1 neurotrophic keratitis, and 1 conjunctivitis. The mean viral load was 3.9×105 copies/mL. Viral load was higher in cases of corneal ulceration (5.2×105±9.4×105 versus 1.2×102±1.7×102 copies/mL, P<1×10-4). There was no significant difference between primary episodes and relapses. CONCLUSION: Tear sampling using Schirmer strips is a simple, non-invasive method that can be useful for the virological diagnosis of various clinical forms of AOHD.

Universal newborn screening for congenital cytomegalovirus infection: feasibility and relevance in a French type-III maternity cohort.

OBJECTIVE: Evaluation of relevance and feasibility of universal newborn congenital cytomegalovirus infection (cCMVI) screening in saliva. DESIGN: Retrospective, population-based cohort study. SETTING: Clamart, France, 2016-2020. POPULATION: All neonates born consecutively in our level III maternity unit. METHODS: CMV PCR in saliva for all neonates at birth, and, if positive, CMV PCR in urine to confirm or exclude cCMVI. Prospective and retrospective characterisation of maternal infections. ROC curve analysis to assess saliva PCR performances. Acceptability of screening among staff members evaluated by a survey. MAIN OUTCOME MEASURES: Number of cCMVI neonates; number of expected and unexpected cCMVI. RESULTS: Among 15 341 tested neonates, 63 had cCMVI (birth prevalence of 0.4%, 95% CI 0.3-0.5). In 50% of cases, maternal infection was a non-primary infection (NPI) during pregnancy. cCMVI was expected or suspected (maternal primary infection [PI], antenatal or neonatal signs) in 24/63 neonates (38%), and unexpected in 39/63 neonates (62%). The best CMV saliva threshold to predict cCMVI was 356 (2.55 log) copies/ml [95% CI 2.52 log-3.18 log], with an area under the ROC curve of 0.97. Over 90% of the 72 surveyed staff members reported that the screening was easy and quick. No parent refused the screening. CONCLUSIONS: Universal screening for cCMVI with CMV PCR on saliva samples is feasible and highly acceptable to parents and healthcare providers. Over half (62%) of the cases had no prenatal/neonatal signs of cCMVI or a maternal history of CMV infection during pregnancy and would probably not have been diagnosed without universal screening. TWEETABLE ABSTRACT: In 62% of congenital cytomegalovirus infection cases, only universal neonatal screening in saliva can detect infection.

Positive predictive value of seroconversion or positive rubella IgM in diagnosis of maternal rubella infection: Seven-years review of French National Reference Laboratory for Rubella.

BACKGROUND: In France, as in most developed countries, childbearing age women are routinely screened for rubella antibodies to identify and vaccinate susceptible women. Immunity to rubella is usually determined by measuring the rubella virus-specific immunoglobulin G (RV-IgG). In case of seroconversion for RV-IgG and/or positive RVIgM during pregnancy, laboratories usually send serum samples to the French National Reference Laboratory (FNRL) for Rubella in order to perform complementary investigations and confirm or exclude rubella infection during pregnancy. OBJECTIVE: Our aim is to report results of these investigations during a seven-year period (2013-2019) and evaluate the positive predictive value (PPV) of RV-IgG seroconversion or positive RV-IgM to diagnose maternal rubella infection in France. STUDY DESIGN: Between 2013 and 2019, 5398 serum samples collected from 4104 pregnant women, were addressed to FNRL because of RV-IgG seroconversion (N=899) or positive RV-IgM (N=3205). Additional serological tests were performed, mainly immunoblot (to look for the presence of anti-E1 protective antibody) and RV-IgG avidity (to exclude or confirm primary infection). RESULTS: Overall, for 3724/4104 (90.8 %) women, rubella primary-infection during pregnancy was formally excluded and maternal rubella primary-infection was only confirmed in 46/4104 (1.1 %) cases. CONCLUSION: Clinicians and biologists should be particularly aware that RV-IgG seroconversion or positive RV-IgM, in the current context of low RV circulation in France are most often not rubella primary infections. PPV of seroconversion to assess maternal rubella primary infection is as low as 0.2 % (95 % CI: 0 %; 0.5 %) and PPV of positive RV-IgM is only of 1.4 % (95 % CI: 0.99 %; 1.81 %).

Evolution of awareness and knowledge of congenital cytomegalovirus infection among health care providers in France between 2011 and 2018.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic. OBJECTIVE: To evaluate health care providers' awareness of CMV maternal and congenital infection in France. STUDY DESIGN: A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study. RESULTS: Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorité de Santé) and CNGOF (Collège National des Gynécologues et Obstétriciens Français) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection. CONCLUSIONS: Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

Measles and rubella seroprevalence in a population of young adult blood donors, France 2013.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Determination of rubella virus-specific humoral and cell-mediated immunity in pregnant women with negative or equivocal rubella-specific IgG in routine screening.

BACKGROUND: Immunity to rubella-virus (RV) is commonly determined by measuring specific IgG (RV-IgG). However, RV-IgG results may be different and even discordant, depending on the assay used. Cell-mediated immunity is not routinely investigated for diagnostic purposes. OBJECTIVES: Our aim was to investigate humoral and cellular immunity of women with negative or equivocal RV-IgG before, and after post-partum vaccination. STUDY DESIGN: A total of 186 pregnant women were included in the study. During pregnancy, humoral immunity was investigated with two RV-IgG immunoassays, an immunoblot and a T-cell mediated immunity test. In the post-partum vaccination period, measuring RV-IgM and RV-IgG avidity allowed us to determine whether women raised a primary or a secondary immune response. RESULTS: Before vaccination, 52.2% women, supposed to be susceptible, had positive anti-E1 RV-IgG indicating strong evidence of previous exposure to RV. All (100%) pregant women who had a positive immunoblot before immunization raised a secondary immune response to vaccination, and 96.8% who had a negative immunoblot before immunization, raised a primary immune response to vaccination. All women who raised a primary immune response after vaccination had negative anti-E1 RV-IgG and negative cell-mediated immunity. DISCUSSION: These results indicate that individuals can have evidence of protective immunity against rubella despite negative RV-IgG.

Adverse effects of maternal enterovirus infection on the pregnancy outcome: a prospective and retrospective pilot study.

BACKGROUND: Enteroviruses account for about one billion infections worldwide each year, the majority remain asymptomatic. Data on enterovirus infections during pregnancy appear to be very rare. Several cases have been reported in the literature of fetal and neonatal complications attributed to these viruses, but prospective data on these infections during pregnancy are not available. OBJECTIVE: To estimate the prevalence of enterovirus infections in febrile syndromes in pregnant women, and in case of in utero fetal death (IUFD). METHODS: Ttri-centric observational cohort study. We performed prospective inclusion for patients with fever during a four-month period. We also analyzed the amniotic fluid in patients with unexplained IUFD retrospectively during a five-year period. Investigations of enteroviruses are made by RT-PCR from routine biological samples (amniocentesis, RT-PCR in maternal blood or CSF). RESULTS: Prospectively, 33 patients were included during the study period. We have identified 4 cases of confirmed enterovirus infection (12.4%). We have recorded a severe form of perinatal enterovirus infection involving the vital prognosis of the newborn. In the retrospective cohort of 75 IUFD cases, we had only one case of enterovirus-positive RT-PCR in amniotic fluid during 5 years, meaning a frequency of 1.3%. We did not had any positive EV case in case of early miscarriage, but the limited number of inclusions cannot help us to conclude. CONCLUSION: Enteroviruses are probably an underestimated cause of obstetric and neonatal complications. Investigation of enterovirus by PCR should be discussed during pregnancy and peripartum in case of febrile syndrome with no obvious bacterial cause, and unexplained IUFD.

Standardization of rubella immunoassays.

Currently, rubella and congenital rubella has been eliminated or is becoming a rare disease in many countries that have implemented effective vaccination programs. In most of these countries, it is recommended and of major importance to screen childbearing age women in order to identify susceptible women and offer them vaccination before pregnancy or after delivery. Immunity to rubella virus (RV) is commonly determined by measuring rubella-specific IgG (RV-IgG). However, looking at literature, it is obvious that standardization of RV-IgG assays is not effective, with different levels of International Units per milliliter (IU/mL) reported for a same sample, and consequently different interpretations of the result. This situation leads to misinterpretation of results, sometimes causing adverse clinical outcomes. This article aimed to review several factors, such as the introduction of large-scale vaccination programs and changes in epidemiology of RV infection, along with the development of new technologies that have complicated appreciation of the immune status of patients. However, there is currently no evidence that these factors may be of any influence on rubella resurgence.

Prévention et prise en charge de l'infection herpétique au cours de la grossesse et de l'accouchement : recommandations pour la pratique clinique ­ texte des recommandations (texte court).

OBJECTIVE: Identify measures to diagnose, prevent and treat genital herpes infection during pregnancy and childbirth and neonatal infection. METHODS: Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines. RESULTS: Genital herpes lesion is most often due to HSV2 (LE2). The risk of HSV seroconversion during pregnancy is 1 to 5% (LE2). Genital herpes ulceration during pregnancy in a woman with history of genital herpes corresponds with a recurrence. In this situation, there is no need for virologic confirmation (grade B). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type specific IgG (Professional consensus). In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) can be administered (grade C). The risk of neonatal herpes is estimated between 25% and 44% in case of initial episode (LE2) and 1% in case of recurrence (LE3) at the time of delivery. Antiviral prophylaxis should be offered for women with first episode genital herpes or recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (grade B). In case of a history of genital herpes without episode of recurrence during pregnancy, it is not recommended routinely offer a prophylactic treatment (professional consensus). A cesarean section should be performed if there is a suspicion of first episode genital herpes at the onset of labor (grade B), in the event of premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and vaginal delivery will be all the more considered in case of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE 3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous acyclovir (60mg/kgs/day 3 times daily) (grade A) prior to the results of HSV PCR (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, the risk of recurrence term and the cesarean rate performed to decrease the risk of neonatal herpes.

[Genital herpes and pregnancy: Serological and molecular diagnostic tools. Guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF)]. / Herpès génital et grossesse : outils du diagnostic virologique. Recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français (CNGOF).

OBJECTIVES: To describe serological and molecular tools available for genital and neonatal herpes, and their use in different clinical situations. METHODS: Bibliographic investigations from MedLine database and consultation of international clinical practice guidelines. RESULTS: Virological confirmation of genital herpes during pregnancy or neonatal herpes must rely on PCR (Professional consensus). HSV type-specific serology (IgG) will allow determining the immune status of a patient (in the absence of clinical lesions). However, there is currently no evidence to justify universal HSV serological testing during pregnancy (Professional consensus). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type-specific IgG in order to distinguish a true primary infection, a non-primary infection associated with first genital manifestation, from a recurrence (Grade C). HSV IgM is useless for diagnosis of genital herpes (Grade C). If a pregnant woman has personal history of genital herpes but no lesions, whatever the gestational age, it is not recommended to perform genital sampling nor serology (Professional consensus). In case of recurrence, if the lesion is characteristic of herpes, virological confirmation is not necessary (Professional Agreement). However, if the lesion is not characteristic, virological confirmation by PCR should be performed (Professional consensus). At birth, HSV PCR samples should be collected as soon as neonatal herpes is suspected (symptomatic neonate) (best before beginning antiviral treatment but must not delay the treatment), or after 24hours of life in case of asymptomatic neonate born to a mother with herpes lesions at delivery (Professional consensus). Clinical samples for virological confirmation should include at least blood and a peripheral location. In case of clinical manifestations of herpes in the neonate, first samples PCR positive, preterm birth, or maternal primary infection or non-primary infection associated with first genital manifestation at delivery, CSF should also be collected as well as samples of lesions in the neonate if present (Professional consensus). Sampling should be repeated in case of PCR negative but strong evidence of neonatal herpes (Professional consensus). HSV serology is useless for diagnosis of neonatal herpes (Grade C). CONCLUSIONS: Virological confirmation for diagnosis of genital herpes during pregnancy or neonatal herpes must rely on PCR. PCR assays available in France are very reliable. Specific IgG are dedicated to restricted indications.

[Enterovirus infection during pregnancy: Underestimated cause of fetal and neonatal complications?] / L'infection à entérovirus durant la grossesse : une cause sous-estimée de complications fœtale et néonatale ?

Enteroviruses are responsible for about one billion infections every year in the world. The clinical expression is in the vast majority asymptomatic cases (90%). Its consequences during pregnancy are rarely described. From the Medline database, we selected and analyzed 34 articles ranging from 1965 to 2015, to analyse the current knowledge of enterovirus infection consequences during pregnancy. We found that enterovirus infections may be the cause of fetal loss. The enterovirus infections during the 2nd and 3rd trimester may also lead to in utero fetal anomalies and death, but also to severe neonatal infections. PCR enterovirus detection should be performed during pregnancy and the peripartum in case of unexplained fever, specific fetal anomalies or unexplained fetal demise.

Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis?

Diagnosis of cytomegalovirus (CMV) primary infection is reliable, but diagnosis of CMV non-primary infection (NPI) is questionable. Our aim is to highlight the difficulties met in diagnosis of CMV NPI. We illustrate that in proven cases of CMV NPI, very different serologic and molecular patterns may be observed and that routine serologic testing may fail to help with diagnosis. These results point out that many data available in literature concerning the prevalence of NPI, materno-fetal transmission rates and consequences of NPI may be wrong. We need to know how frequently they occur, are transmitted and cause fetal damages. Diagnosis of NPI must be improved, along with our understanding of the mechanisms leading to intrauterine CMV transmission and congenital infection in babies born to women with preexisting immunity.

[Zika virus infection during pregnancy]. / Infection par le virus Zika chez la femme enceinte.

A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman.

[Detailed in utero ultrasound description of 34 cases of congenital cytomegalovirus infection]. / Étude descriptive de signes échographiques anténataux de 34 cas d'infections congénitales à cytomégalovirus.

OBJECTIVES: To describe precisely prenatal ultrasound features in congenital cytomegalovirus (CMV) infection. MATERIAL AND METHODS: We retrospectively evaluated the ultrasound descriptions of cases of congenital CMV infection between 2004 and 2013. RESULTS: In 74 congenital CMV infections, related ultrasound abnormalities were reported in 34 cases (45.9%). Abnormalities reported were either cerebral (11 cases), either extracerebral (6 cases), or associated (17 cases). A total of 22/34 cases presented extracerebral features of 11 different sorts of abnormalities, mainly intra-uterine growth retardation (11 cases) and hyperechogenic bowel (10 cases) and 26/34 cases presented cerebral features of 14 different sorts, mainly brain calcifications (12 cases) and occipital horn cavity (12 cases). MRI was performed in 25 cases and have found additional abnormalities in 8 cases. These abnormalities are not specific to CMV infection. However, a frequent finding attracted our attention: the anechogenic cavity located on the extremity of the occipital horn. CONCLUSION: A potentially specific sign, inexistent in other fetal pathologies, is an anechogenic cavity located on the extremity of the occipital and/or temporal horn, a germinal region which contains numerous proliferating and differentiating germinal cells. A better understanding of these signs could increase the sensitivity of ultrasound, and clarify the pathophysiology of congenital CMV infection.