The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

Emerging and re-emerging infectious diseases in pregnant women in an amazonian region: a large retrospective study from French Guiana.

PURPOSE: Over the past decade, the Amazon basin has faced numerous infectious epidemics. Our comprehension of the actual extent of these infections during pregnancy remains limited. This study aimed to clarify the clinical and epidemiological features of emerging and re-emerging infectious diseases during pregnancy in western French Guiana and along the Maroni River over the previous nine years. METHODS: This retrospective cohort study enrolled pregnant women living in west French Guiana territory and giving birth in the only local referral center after 22 weeks of gestation between 2013 and 2021. Data on symptomatic or asymptomatic biologically confirmed emerging or re-emerging diseases during pregnancy was collected. RESULTS: Six epidemic waves were experienced during the study period, including 498 confirmed Zika virus infections (2016), 363 SARS-CoV-2 infections (2020-2021), 87 chikungunya virus infections (2014), 76 syphilis infections (2013-2021), and 60 dengue virus infections (2013-2021) at different gestational ages. Furthermore, 1.1% (n = 287) and 1.4% (n = 350) of pregnant women in west French Guiana were living with HIV and HTLV, respectively. During the study period, at least 5.5% (n = 1,371) faced an emerging or re-emerging infection during pregnancy. CONCLUSION: These results highlight the diversity, abundance, and dynamism of emerging and re-emerging infectious agents faced by pregnant women in the Amazon basin. Considering the maternal and neonatal adverse outcomes associated with these infections, increased efforts are required to enhance diagnosis, reporting, and treatment of these conditions.

Trends in anti-infective use during pregnancy in France between 2010 and 2019: a nationwide population-based study.

AIMS: To describe the trends in anti-infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification systems. METHODS: We conducted a population-based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti-infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression. RESULTS: Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = -1.7%, [95%CI, -2.5 to -1.0%]). Conversely, use of antiviral agents increased during the 10-year study period for anti-herpes simplex virus agents (AAPC = 4.4%, [3.7-5.2%]), influenza agents (AAPC = 25.4%, [6.2-48.1%]) and for HIV-antiretroviral agents (AAPC = 1.3%, [0.6-2.0%]). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, [39.3-60.9%]). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti-infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC = 6.4%, [4.4-8.5%]). CONCLUSION: Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti-infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.

Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype.

OBJECTIVE: Recent studies have evaluated prenatal exome sequencing (pES) for abnormalities of the corpus callosum (CC). The objective of this study was to compare imaging phenotype and genotype findings. METHOD: This multicenter retrospective study included fetuses with abnormalities of the CC between 2018 and 2020 by ultrasound and/or MRI and for which pES was performed. Abnormalities of the CC were classified as complete (cACC) or partial (pACC) agenesis of the CC, short CC (sCC), callosal dysgenesis (CD), interhemispheric cyst (IHC), or pericallosal lipoma (PL), isolated or not. Only pathogenic (class 5) or likely pathogenic (class 4) (P/LP) variants were considered. RESULTS: 113 fetuses were included. pES identified P/LP variants for 3/29 isolated cACC, 3/19 isolated pACC, 0/10 isolated sCC, 5/10 isolated CD, 5/13 non-isolated cACC, 3/6 non-isolated pACC, 8/11 non-isolated CD and 0/12 isolated IHC and PL. Associated cerebellar abnormalities were significantly associated with P/LP variants (OR = 7.312, p = 0.027). No correlation was found between phenotype and genotype, except for fetuses with a tubulinopathy and an MTOR pathogenic variant. CONCLUSIONS: P/LP variants were more frequent in CD and in non-isolated abnormalities of the CC. No such variants were detected for fetuses with isolated sCC, IHC and PL.

Predictors of cochleovestibular dysfunction in children with congenital cytomegalovirus infection.

The purpose of this study is to assess the predictive factors of both hearing and vestibular impairment in congenitally cytomegalovirus-infected children (cCMV) through a multivariate analysis of clinical and imaging characteristics collected during pregnancy and at birth. This retrospective study was conducted between March 2014 and March 2020, including confirmed congenitally CMV-infected children with a complete vestibular and hearing assessment. Data concerning pregnancy, date of infection, clinical characteristics, and symptomatology at birth were collected. In total, 130 children were included, with a median age of 21 months. Eighty-three children (64%) presented with an inner ear impairment (both cochlear and vestibular impairment). Sex, modality of maternal infection (seroconversion or reactivation), pregnancy term, weight and head circumference at birth, neonatal clinical signs of infection, and treatment were not significantly correlated with inner ear impairment. However, multivariate analysis confirmed that there are two independent predictive factors of inner ear impairment: antenatal imaging lesions (ORa = 8.02 [1.74; 60.27], p-value = 0.01) and infection during the first trimester (ORa = 4.47 [1.21; 19.22], p-value = 0.03). Conversely, infections occurring during the second trimester were rarely associated with inner ear impairment: 4/13 (31%) in our series, with vestibular impairment alone (4/4) and no hearing loss. None of the children infected during the third trimester developed inner ear dysfunction. CONCLUSION: Besides the symptomatic status of the CMV infection at birth, we found that antenatal imaging brain damage and early infection (mainly during the first trimester) constitute the two best independent predictive factors of inner ear involvement in congenitally CMV-infected children. WHAT IS KNOWN: • Congenital cytomegalovirus infection is the leading infectious cause of neurological disabilities and sensorineural hearing loss in children and responsible of vestibular disorders, which are probably underestimated. • No articles have yet defined the predictive factors of the entire inner ear impairment (vestibule and cochlea). WHAT IS NEW: • The timing of the infection during pregnancy (first and second trimester, ORa=4.47) and antenatal imaging lesions (ORa=8.02) are independently predictive (in a multivariate analysis) of inner ear involvement. • The symptomatic status at birth is a poor predictor of inner ear impairment.

Fetal and neonatal abnormalities due to congenital syphilis: A literature review.

OBJECTIVE: The recent recrudescence of syphilis among women of childbearing age is associated with an increasing number of cases of congenital syphilis. We aimed to summarize the fetal and neonatal abnormalities due to congenital syphilis infection, particularly signs amenable to prenatal diagnosis. METHODS: Eligible studies were retrieved from the PubMed collection database. Articles focusing on postnatal and antenatal abnormalities covered the periods from 1969 to 2019 and 1975-2019, respectively. This review included cohort studies, case series and case reports reporting findings regarding congenital syphilis infections described before and/or after birth. Articles were reviewed by three experts in prenatal diagnosis, and all findings were classified as amenable or not amenable to prenatal diagnosis. RESULTS: A total of 432 cases of congenital syphilis infection were reported. Abnormalities were described antenatally in 161 cases, postnatally in 319 cases, and in both the antenatal and postnatal periods in 57 cases. The most frequently reported signs amenable to prenatal diagnosis were abdominal abnormalities (hepatomegaly, splenomegaly, and bowel abnormalities), fetal growth restriction, and elevated middle cerebral artery peak systolic velocity in the context of ascites or atypical hydrops. Brain abnormalities were rare and never isolated. In the neonatal period, the most common abnormalities were hepatosplenomegaly, bone damage and skin lesions. CONCLUSION: We found that no individual sonographic sign or pattern of signs is pathognomonic for fetal syphilis. In fetuses with ultrasound abnormalities suggestive of congenital infection, syphilis must be considered as part of the work-up.

Congenital lymphocytic choriomeningitis virus: A review.

INTRODUCTION: Lymphocytic choriomeningitis virus (LCMV) uses rodents such as mice and hamsters as its principal reservoir. When women acquire LCMV during pregnancy because of contact with rodents, it can lead to congenital LCMV infection, which is associated with high mortality and morbidity. Although the number of cases reported in the literature is increasing, LCMV is rarely mentioned because a history of exposure to rodents is uncommon and mostly unknown. OBJECTIVES: The main objective of this article was to summarize all morphological, antenatal, and postnatal abnormalities that may suggest a congenital LCMV infection. METHODS: We reviewed PubMed case reports and case series where an antenatal and/or a postnatal description of at least one case of congenital LCMV infection was documented. RESULTS: We found 70 cases of congenital LCMV infection, 68 of which had antenatal or postnatal brain abnormalities, which were mainly chorioretinitis (59/70), hydrocephaly (37/70), microcephaly (22/70), ventriculomegaly (11/70) and periventricular calcifications (11/70). Antenatal and postnatal extracerebral abnormalities were mainly small for gestational age, ascites, cardiomegaly or anemia. Other organ damage was rare, but could include skin abnormalities, hydrops or hepatosplenomegaly. Seventy percent (49/70) of cases had major cerebral abnormalities that could have been detected by antenatal ultrasound examination. Congenital LCMV infection is associated with a significant mortality rate (30%) and survivors often have severe neurologic sequelae. CONCLUSION: LCMV is a rare congenital infection, but awareness of the various prenatal ultrasound morphological abnormalities should be improved, and LCMV should be considered when first-line etiological explorations are negative, especially when the mother's medical history indicates exposure to rodents.

Severe Acute Respiratory Syndrome Coronavirus 2 and Pregnancy Outcomes According to Gestational Age at Time of Infection.

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.

Retrospective Description of Pregnant Women Infected with Severe Acute Respiratory Syndrome Coronavirus 2, France.

Fix data are available on the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a retrospective study of 100 pregnant women with SARS-CoV-2 infection in 4 obstetric units in the Paris metropolitan area of France during March 12-April 13, 2020. Among patients, 52 (52%) were hospitalized, 10 (10%) in intensive care units (ICUs). Women with higher body mass indexes (BMIs; median 30.7 kg/m2) were more likely to be hospitalized in ICUs than other women (median BMI 26.2 kg/m2). Women hospitalized in ICUs had lower lymphocyte count at diagnosis (median 0.77 × 109 cells/L) than women not hospitalized in ICUs (median lymphocyte count 1.15 × 109 cells/L). All women requiring oxygen >5 L/min were intubated. Clinical and laboratory evaluation of SARS-CoV-2-positive pregnant women at the time of diagnosis can identify patients at risk for ICU hospitalization.

Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: a literature review.

OBJECTIVE: Herpes simplex virus (HSV) infection during pregnancy can cause severe neonatal infections. It is also a rare cause of congenital infections. We aimed to describe fetal and neonatal abnormalities of congenital HSV infection in order to define the features that are accessible to prenatal diagnosis during ultrasound screening and/or during a work-up for congenital malformations. METHODS: We analysed all cases of congenital HSV infection (CHI) described before and/or after birth and identified in Pubed and classified the findings as accessible or not to prenatal diagnosis. RESULTS: Thirty-six cases of congenital herpes infection were reported, of which 15 were described prenatally and 21 postnatally. The most frequently reported malformations accessible to prenatal diagnosis were cerebral anomalies. The most common abnormalities described after birth were skin lesions and keratitis, which are not considered amenable to prenatal ultrasound detection. CHI can due to either HSV1 or HSV2 infection, whether primary or non-primary infection, with or without the presence of maternal symptoms. CONCLUSION: Prenatal ultrasound abnormalities due to CHI are rare, varied and non-specific. There is no clear role for fetal ultrasound in the routine management of women with primary or non-primary HSV infection in pregnancy. However, in fetuses with ultrasound abnormalities suggestive of congenital infection, HSV should still be considered as a differential diagnosis after the more common in utero infections, such as cytomegalovirus, are excluded.

Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

OBJECTIVE: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). METHODS: We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers. RESULTS: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion. CONCLUSION: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.

[Mother to Child SARS-CoV-2 Transmission: Fact or Fantasy]. / La transmission materno-fœtale du SARS-CoV-2 : réalité ou fantasme.

The emerging coronavirus called SARS-CoV-2 has spread rapidly around the world. Responsible for severe pneumonitis (Covid-19), there are also doubts concerning a possible mother-to-fetal transmission of this virus. Current data are patchy and obtained from small groups of patients. They tend to support the idea that the mother-to-fetal transmission of SARS-CoV-2 is very rare, but the period between infection and childbirth was often very short and may not allow sufficient replication to consider transplacental passage. Here, we reviewed the existing virological data and those remaining to explore. Thus, the natural history of SARS-CoV-2 infection in pregnant women and the risk of transmission in utero is not yet fully understood and defined. Four months from the emergence of this virus, it is therefore reasonable to wait for the results of specific studies on larger cohorts which, to be conclusive, must meet the best scientific criteria.

Prenatal sonographic description of fetuses affected by pyruvate dehydrogenase or pyruvate carboxylase deficiency.

OBJECTIVE: Pyruvate dehydrogenase deficiency (PDHD) and pyruvate carboxylase deficiency (PCD) are diseases with severe neonatal forms, and their low prevalence makes them difficult to diagnose during pregnancy. Our objective was to describe prenatal ultrasound features that may be suggestive of these diagnoses. METHODS: We analyzed 3 cases from our institution and reviewed 12 published cases of PDHD and 6 cases of PCD, recording all of the ultrasound signs, as well as magnetic resonance findings when available. Because of the small number of cases of PCD, we also included postnatal signs that could have been observed during imaging during pregnancy, for a total of 11 cases of PCD. RESULTS: We conclude that PDHD can be suggested in the presence of ventriculomegaly or paraventricular cysts, associated with an abnormality of the cerebral parenchyma such as abnormal gyration or involvement of the corpus callosum. Pyruvate carboxylase deficiency can be suggested in the presence of ventriculomegaly, frontal horn impairment associated with subependymal, and paraventricular cysts. CONCLUSION: When confronted to the ultrasound abnormalities we described, and after eliminating the most frequent etiologies, a metabolic deficiency should be considered. Furthermore, the hereditary character of these diseases makes that it is important to send the family with genetic advice in particular in case of history of a fetal death in utero or a death neonatal unexplained.

Rare cause of abdominal pain and fever in a pregnant woman.

CLINICAL PRESENTATION: A pregnant woman (third trimester) presented with intense abdominal pain, nausea and myalgia. The patient was obese (body mass index 38) and was being treated for high blood pressure, hyperuricemia and hypothyroidism. She had chronic renal deficiency related to focal segmental glomerular sclerosis requiring dialysis. The physical examination at admission revealed a fever of 39°C and an acute abdomen with abdominal guarding in the right upper quadrant without hepatomegaly or splenomegaly. There were no clinical signs of pre-eclampsia. Fetal ultrasound and a Doppler of the umbilical vessels were normal. Laboratory tests showed normal liver and liver function (total protein 95%, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin normal). The white cell count was 10×109/l (90% neutrophils), with a normal platelet count. Blood, urine and vaginal cultures were negative. Abdominal ultrasound revealed isolated thickening of the gallbladder wall without cholelithiasis. Empirical antibiotic treatment was begun with intravenous amoxicillin. Six days later, the patient's condition had worsened with increased abdominal pain, persistent fever and liver test abnormalities (AST-ALT 6N). However, bilirubin, hepatic synthesis tests, as well as leucocyte and platelet counts were still normal. A caesarean section followed by coelioscopy was decided. Coelioscopy revealed a liver with numerous necrotic spots (see figure 1).gutjnl;66/11/1911/GUTJNL2016313097F1F1GUTJNL2016313097F1Figure 1Diagnostic laparoscopy revealed a liver surface covered with numerous white necrotic spots. QUESTION: What is the diagnosis?

Varicelle et grossesse.

Varicella-zoster primary infection in a pregnant woman is an uncommon occurrence in France, but can cause concern for patients and for clinicians. Varicella (chickenpox) is usually benign, but can have serious consequences for the mother (especially in the third trimester of pregnancy), for the fetus (risk of fetal varicella syndrome particularly if maternal primary infection occurs before 20 weeks of gestation), and for the newborn (risk of congenital neonatal varicella if the mother is infected in the peripartum period). Several diagnostic tools, prophylaxis measures and antiviral treatments are currently available and help in the management of varicella during pregnancy.

In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study.

BACKGROUND: Congenital infection with human cytomegalovirus is a major cause of morbidity and mortality. A randomized controlled trial showed that high-dosage valacyclovir prevents cytomegalovirus disease in transplant recipients. Fetuses showing ultrasound features of infection are at high risk of being symptomatic at or before birth. In a pilot study, oral administration of high-dosage valacyclovir to mothers significantly decreased viral load and produced therapeutic concentrations in the blood of infected fetuses. A randomized controlled trial comparing prenatal treatment with valacyclovir against placebo in infected fetuses failed to recruit because women declined randomization. Randomized controlled trials in fetal medicine have often proven unacceptable by women who decline termination of pregnancy and are not prepared to resign themselves to the odds of the natural history of the disease. OBJECTIVE: We evaluated the efficacy of oral valacyclovir, 8 g daily, for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, targeting a high-risk group for developing both neurosensory and neurological impairment. STUDY DESIGN: We designed a multicenter, open-label, phase II study with 1 arm, using one of Simon's optimal 2-stage designs. Symptomatic fetuses were defined by the presence of measurable extracerebral or mild cerebral ultrasound symptoms. They were treated in utero from prenatal diagnosis at a median of 25.9 weeks' gestation until delivery or termination of pregnancy. Fetuses with severe brain anomalies on ultrasound were not included as were cases completely asymptomatic at presentation, because treatment was unlikely to modify either outcome. The primary endpoint was the proportion of asymptomatic neonates born to treated mothers. RESULTS: At the interim analysis, 8 of 11 women delivered an asymptomatic neonate (required: ≥7). In step 2, 32 additional cases were included for a total of 43; the final number of asymptomatic neonates was 34, more than the 31 required to indicate efficacy according to the Simon 2-stage design. They remained asymptomatic at 12 months. High-dosage valacyclovir given for a median of 89 days to pregnant women carrying a moderately infected fetus was efficient at giving birth to asymptomatic neonates. Fetal blood viral loads decreased and platelet counts increased, both significantly (P = .01 and P < .001, respectively), between treatment initiation and birth after treatment completion, regardless of duration of fetal infection. Compared with a historical cohort obtained by a metaanalysis of the literature, the use of valacyclovir (8 g daily) significantly increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment. Although the pill burden was high (16 pills a day) adherence to treatment was >90%. Finally, valacyclovir at this high dosage was extremely well tolerated. CONCLUSION: Our results indicate that high-dosage valacyclovir given in pregnancy is effective for improving the outcome of moderately symptomatic infected fetuses. Although this study is not a randomized controlled trial, this is the first study reporting the efficacy of an antiviral drug to treat cytomegalovirus-infected fetuses. Moreover, this first study will allow new trials to be conducted, using valacyclovir as a baseline safe and effective treatment in pregnancy, to be compared to the new emerging and more potent anticytomegalovirus drugs that have not currently been tested in pregnancy.

Management of Cytomegalovirus Seroconversion during Pregnancy in France.

INTRODUCTION: Guidelines for the management of cytomegalovirus (CMV) infection of the fetus are rare. Our main objective was to evaluate how health care practitioners in France manage cases of CMV seroconversion during pregnancy. MATERIAL AND METHODS: A questionnaire was e-mailed to health care practitioners potentially concerned by CMV seroconversion during pregnancy. They were asked if they would recommend amniocentesis, fetal cerebral MRI examination and fetal blood analysis (FBA), depending on the ultrasound results. They then had to indicate whether they would accept termination of pregnancy (TOP), depending on the results of these examinations. RESULTS: A total of 380 health care practitioners responded, mainly obstetricians (73.9%) and midwives (20.2%). Overall, 57% of respondents recommended amniocentesis in the case of CMV seroconversion during the first trimester of pregnancy, ultrasound findings being normal. In cases of positive amniocentesis and a major ultrasound abnormality, 84.5% of respondents would perform cerebral MRI, and 44.4% would perform FBA. In this case, the rate of acceptance of TOP was not significantly different whether the examinations were normal (337/372, 90.6%) or not performed (339/374, 93.3%; p = 0.17). DISCUSSION: Amniocentesis is too infrequently used and should be encouraged. The results of MRI and FBA are often not taken into account in the final decision concerning TOP. Guidelines are needed to clarify the management of CMV seroconversion during pregnancy.

Rubella and pregnancy: diagnosis, management and outcomes.

Rubella is a mild viral disease that typically occurs in childhood. Rubella infection during pregnancy causes congenital rubella syndrome, including the classic triad of cataracts, cardiac abnormalities and sensorineural deafness. Highly effective vaccines have been developed since 1969, and vaccination campaigns have been established in many countries. Although there has been progress, the prevention and diagnosis of rubella remain problematic. This article reviews the implications and management of rubella during pregnancy.

Prenatal and Postnatal Ocular Abnormalities Following Congenital Zika Virus Infections: A Systematic Review.

OBJECTIVE: To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons. METHODS: A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists. RESULTS: Studies reporting ocular abnormalities during the prenatal (n = 5) and postnatal (n = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed. CONCLUSION: This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.