Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention.

INTRODUCTION: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women. METHODS: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women. Levels of knowledge were compared among groups. RESULTS: Of the 1,449 health professionals approached, 338 surveys were answered. 72% of professionals considered CMV a relevant problem. 47% of obstetricians and 28% of midwives (p ≤ 0.001) routinely informed pregnant women, and less than half knew the risk of fetal transmission. We observed significant differences in knowledge between obstetricians and midwives concerning the risks of recurrent infections, risk of transmission, and risk of severe infection (60.7% vs. 45.6%, p = 0.006 and 50.6% vs. 22.5%, p ≤ 0.001); and regarding maternal and neonatal symptoms and newborn sequelae (23% vs. 8.8%, p ≤ 0.001). Of the 700 women approached, we obtained a response rate of 72%. Only 23% had previously heard about CMV, 22% identified transmission routes, and 15% preventive measures. Compared to women without risk factors for CMV infection, women at greater risk had heard more about CMV (mothers of children <3 years: 36% vs. 20%, p < 0.001; occupational exposure: 43% vs. 20%, p ≤ 0.001) and had received more information (mothers of children <3 years: 18% vs. 9.5%, p ≤ 0.001; occupational exposure: 23% vs. 9.3%, p = 0.001). CONCLUSION: Health care professionals have limited knowledge about CMV and may fail to enforce preventive measures. While pregnant women have limited awareness about CMV infection, they recognize the need for information. Health campaigns should be promoted to enhance awareness about this perinatal infection.

Cardiac Remodeling and Hypertension in HIV-Uninfected Infants Exposed in utero to Antiretroviral Therapy.

BACKGROUND: We aimed to assess the postnatal pattern of cardiovascular remodeling associated with intrauterine exposure to maternal HIV and antiretroviral treatment (ART). METHODS: Prospective cohort including 34 HIV-exposed uninfected (HEU) infants and 53 non-HIV-exposed infants were evaluated from fetal life up to 6 months postnatally. A cardiovascular evaluation was performed including echocardiography, blood pressure, and carotid intima media thickness (cIMT) measurement. RESULTS: ART regimens during pregnancy included 2 nucleoside reverse transcriptase inhibitors (Abacavir + Lamivudine (32.4%), Emtricitabine + Tenofovir (41.2%), and Zidovudine + Lamivudine (20.6%)). At 6 months of age, HIV-exposed uninfected infants showed thicker myocardial walls (septal wall thickness mean 5.02 mm (SD 0.85) vs 3.98 mm (0.86); P < .001), relative systolic dysfunction with decreased mitral ring displacement (8.57 mm (2.03) vs 10.34 mm (1.84); P = .002), and decreased tricuspid S' (9.71 cm/s (1.94) vs 11.54 cm/s (2.07); P = .003) together with relative diastolic dysfunction showed by prolonged left isovolumic relaxation time (58.57 ms (13.79) vs 47.94 (7.39); P < .001). Vascular assessment showed significantly higher systolic and diastolic blood pressure (102 mmHg (16.1) vs 80 mmHg (13.9); P < .001 and 64 mmHg (14.4) vs 55 mmHg (10.2); P = .045 respectively), with 50% of HIV-exposed children meeting criteria for hypertension vs 3.77% of the non-HIV-exposed group (P < .001) and thicker mean cIMT in the HIV-exposed group (0.62 µm (0.09) vs 0.51 µm (0.09); P = .015). CONCLUSIONS: Subclinical cardiac impairment together with higher blood pressure and thicker cIMT were observed in HIV-exposed infants at 6 months of age. Half of them presented hypertension. Our findings support a possible increased cardiovascular risk in HIV uninfected infants exposed in utero to ART.

Coronavirus Disease 2019 in Pregnancy: A Clinical Management Protocol and Considerations for Practice.

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of COVID-19 in pregnancy. We briefly contemplate all relevant aspects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth.

Spontaneous Abortion Associated with Zika Virus Infection and Persistent Viremia.

We report a case of spontaneous abortion associated with Zika virus infection in a pregnant woman who traveled from Spain to the Dominican Republic and developed a rash. Maternal Zika viremia persisted at least 31 days after onset of symptoms and 21 days after uterine evacuation.

Gender-Specific Antenatal Growth Reference Charts in Monochorionic Twins.

OBJECTIVE: To create antenatal gender-specific reference growth charts in uncomplicated monochorionic diamniotic twins. MATERIALS AND METHODS: This is a prospective longitudinal study in which uncomplicated monochorionic (MC) twin pregnancies were included from 23 + 4 weeks of gestation onwards. Estimated fetal weight (EFW) and biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) were evaluated in both fetuses every 2 weeks using standardized methodology. Maternal and fetal complications were excluded. Charts were fitted for each biometric parameter and EFW in relation to gestational age and fetal gender using multilevel mixed models. RESULTS: The final analysis included a total of 456 ultrasound examinations in 62 MC twins, with a mean of 7 scans per pregnancy (range 5-8). The mean as well as 5th and 95th percentiles of each biometric parameter and EFW were adjusted in relation to gender and gestational age between 24 and 37 weeks of gestation. Male fetuses have higher reference values than females, and the disparity is larger in the upper centiles of the distribution. DISCUSSION: We provide gender-specific reference growth charts for MC twins. We suggest that these charts will improve prenatal MC twin assessment and surveillance, with a more accurate classification of normal or growth-restricted fetuses adjusted per sex.

Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: An observational study.

BACKGROUND: Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed. METHODS AND FINDINGS: In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction. CONCLUSIONS: The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.

Inflammatory Markers Related to Microbial Translocation Among HIV-Infected Pregnant Women: A Risk Factor of Preterm Delivery.

BACKGROUND: This study was performed to assess the role of lipopolysaccharide modulators as a marker of microbial translocation among human immunodeficiency virus (HIV)-infected women during pregnancy and to evaluate their association with preterm delivery. METHODS: The study had a prospective cohort design and was performed at the Hospital Clínic in Barcelona, Spain. Thirty-six pregnant women with and 36 without HIV infection, matched on the basis of age and parity, were included. Maternal blood samples were obtained during the first trimester, during the third trimester, and at delivery. Levels of soluble CD14 (sCD14), human lipopolysaccharide-binding protein (LBP), immunoglobulin M endotoxin core antibodies to lipopolysaccharide (EndoCAb), and interleukin 6 (IL-6) were determined. Fetal cord blood levels of sCD14, LBP, and IL-6 were determined. Results were compared between groups. RESULTS: First trimester sCD14 and LBP levels and third trimester sCD14 levels were significantly higher in the HIV-infected group. HIV-infected women with preterm births and spontaneous preterm births had significantly increased levels of sCD14 throughout pregnancy and significantly increased levels of LBP during the first trimester, compared with HIV-infected women with delivery at term or with HIV-negative women. On multivariate analysis, an independent association was observed between first trimester sCD14 levels and preterm delivery among HIV-infected women. CONCLUSIONS: This is the first study to assess inflammatory markers related to microbial translocation during pregnancy among HIV-infected women. Higher levels of sCD14 and LBP were observed in HIV-infected pregnant women and were associated with preterm delivery.

Antimicrobial resistance and virulence characterization among Escherichia coli clinical isolates causing severe obstetric infections in pregnant women.

The virulence markers and the antimicrobial resistance profiles of 78 Escherichia coli isolates causing obstetric infections accompanied by sepsis or not were studied. Adhesion-related virulence factors were the most prevalent markers. Low rates of resistance to the antimicrobial agents used as first-line therapy suggest their correct implementation in stewardship guidelines.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.

Corrigendum to "Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)" [The Lancet Regional Health - Europe 40 (2024) 100892].

[This corrects the article DOI: 10.1016/j.lanepe.2024.100892.].

Likelihood ratios to apply for nasal bone, ductus venosus and tricuspid flow at the 11-13 weeks' scan in down syndrome screening.

OBJECTIVE: To assess the feasibility of nasal bone (NB), ductus venosus (DV) and tricuspid flow (TF) at the 11-13 weeks' scan, calculate likelihood ratios for each of the markers and evaluate their efficacy in expanded and contingent screening strategies for Down syndrome. MATERIAL AND METHODS: NB, DV and TF were assessed in 11,261 singleton fetuses undergoing first trimester combined screening. For each marker, Down syndrome detection rate (DR), false positive rate (FPR), positive, negative and isolated likelihood ratios (PLR, NLR and iLR) were calculated. Likelihood ratios were multiplied to the combined test risk either to the entire population or to the intermediate risk group (expanded and sequential strategies, respectively). RESULTS: Down syndrome was diagnosed in 101 pregnancies. Feasibility for marker assessment ranged from 71 to 97%, DRs for isolated markers from 20 to 54% and FPRs from 1.3 to 5.3%. PLR ranged from 10 to 15, NLR from 0.5 to 0.8 and iLR from 3.9 to 5.6. When ultrasound markers were added to both strategies, a significant FPR reduction was observed. CONCLUSION: The application of NB, DV and TF likelihood ratios to the combined test risk, either in an expanded or contingent strategy, result in a FPR reduction.

Preterm Prelabour Rupture of Membranes before Viability in Twin Pregnancies: What Can We Expect?

Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study).

INTRODUCTION: Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has been implemented in Spain. A recent study has shown that early treatment with valaciclovir, initiated in the first trimester and before the onset of signs in the fetus, reduces the risk of fetal infection. This finding favours the implementation of a universal screening programme for cCMV.The aim of this study is to evaluate the performance of a universal screening programme for cCMV during the first trimester of pregnancy in a primary care setting. METHODS AND ANALYSIS: This is an observational multicentre cohort study. The study will be conducted in four primary care settings from the Northern Metropolitan Barcelona area and three related hospitals and will last 3 years and will consist of a recruitment period of 18 months.In their first pregnancy visit, pregnant women will be offered to add a CMV serology test to the first trimester screening tests. Pregnant women with primary infection will be referred to the reference hospital, where they will continue treatment and follow-up according to the clinical protocol of the referral hospital, which includes treatment with valacyclovir. A CMV-PCR will be performed at birth on newborns of mothers with primary infection, and those who are infected will undergo neonatal follow-up for at least 12 months of life.For the analysis, the acceptance rate, the prevalence of primary CMV infections and the CMV seroprevalence in the first trimester of pregnancy will be studied. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina Ethics Committee 22/097-P dated 27 April 2022.

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission.

INTRODUCTION: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection. METHODS: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry. RESULTS: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis. CONCLUSIONS: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission.

Maternal IgM antibody status in confirmed fetal cytomegalovirus infection detected by sonographic signs.

OBJECTIVE: To evaluate the value of maternal IgM to cytomegalovirus (CMV) as a predictive factor of fetal infection in fetuses with sonographic markers. METHODS: Observational study (2006-2011) including a consecutive series of 19 fetuses with sonographic markers of fetal infection and confirmed infection by positive CMV-DNA in amniotic fluid or fetal blood. We evaluated the status of maternal CMV IgM at the time of sonographic suspicion. RESULTS: During this 6-year study period, CMV infection was diagnosed in 19 fetuses from 18 pregnancies, including 16 singletons, both twins of a monochorionic diamniotic pregnancy and one twin of a dichorionic pregnancy. Sonographic suspicion was established on the basis of one or more of the following: brain abnormalities (14), fetal hydrops (4), hyperechogenic bowel (4), pericardial effusion (1), cardiomegaly (1), oligoanhydramnios (4), and placentomegaly (2). Maternal IgG antibodies were positive in all cases but maternal IgM antibodies were negative in 56% of pregnancies. Five of the 10 pregnancies with negative maternal IgM were diagnosed in the second trimester and five in the third trimester. CONCLUSION: In around half of fetuses with confirmed CMV infection ascertained by sonographic markers, maternal IgM antibodies are negative and should therefore not be used as a diagnostic parameter.

Latency to delivery in physical examination-indicated cerclage in twins is similar to that in singleton pregnancies.

OBJECTIVE: To compare latency to delivery and perinatal outcomes between twin and singleton pregnancies undergoing physical examination-indicated cerclage. METHODS: Retrospective observational study (2007-2017) of women who underwent physical examination-indicated cerclage at the Hospital Clinic of Barcelona. Primary outcomes were latency from cerclage to delivery and gestational age at delivery. Secondary outcomes included: neonatal morbidity and mortality, preterm prelabor rupture of membranes, clinical chorioamnionitis and cerclage displacement. Wilcoxon-test and χ2 test were used to compare continuous and categorical variables. RESULTS: Sixty women were included (17 twins and 43 singletons). There were no differences in gestational age at cerclage or presence of bulging membranes between groups. Median (25th;75th percentile) gestational age at delivery was 27.1 (24.5;32.3) weeks in the twin group and 27.6 (25.3;35.3) weeks in the singleton group (P = 0.594). There were no statistically significant differences in latency from cervical cerclage to delivery between the two groups (43 days [21;64] vs. 29 days [16;76], respectively; P = 0.938). There were no differences in neonatal mortality (2/26 [7.7%] vs. 1/33 [3.1%]; P = 0.578) or in composite neonatal morbidity (14 [53.9%] vs. 14 [42.4%]; P = 0.283) between groups, respectively. CONCLUSION: These results suggest that physical examination-indicated cerclage placement in twins could prolong latency to delivery similarly to singleton pregnancies.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection†.

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement.

Maternal high-dose valacyclovir and its correlation with newborn blood viral load and outcome in congenital cytomegalovirus infection.

BACKGROUND/OBJECTIVE: Currently, there is no validated treatment for fetal cytomegalovirus (CMV). Two studies suggest that high-dose maternal valacyclovir decreases fetal viral load and improves outcomes in moderately-symptomatic fetuses. We offered valacyclovir in cases of fetal infection lacking ultrasound abnormalities or with non-severe infection. Maternal tolerability, fetal outcome and newborn blood viral load were evaluated in pregnancies of mothers receiving valacyclovir. STUDY DESIGN: We performed a case series including 8 pregnancies with fetal CMV classified as unaffected/mildly-moderately affected. Mothers received valacyclovir (8 g/24h) from fetal infection diagnosis to delivery. Standard newborn evaluation was performed, and viremia was determined in the first 48 h of life and compared according to length of maternal treatment and presence/absence of prenatal anomalies. RESULTS: Valacyclovir was administered at a median gestational age of 26.5 weeks (23.8-33.1) in 3 cases without fetal abnormalities, and 5 with mild/moderate abnormalities. Three were 3 first trimester primary infections, one non-primary infection, and in 4 the type of infection was unknown. Valacyclovir was well-tolerated. Fetal features did not progress. Three newborns were asymptomatic, and one was severely affected (bilateral chorioretinitis). The median newborn viral load (IQR) was 502 IU/mL (231-191781) with lower levels when maternal treatment was administered ≥10 weeks, and in cases without fetal abnormalities [median 234 IU/mL (228-711) vs. 4061 (292-510500) p = .18; and 234 IU/mL (228-379500) vs. 711 IU/mL (292-4061) p = .65, respectively], these differences being non-significant. CONCLUSIONS: Fetal CMV lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/neonatal abnormalities. SUMMARY: Fetal cytomegalovirus lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/newborn abnormalities.