Mother-to-child Transmission Research Articles

Detecting Hearing Loss Through Targeted Surveillance: Risk Registry and Surveillance Timeframe Recommendations.

The purpose of this study was to inform the revision of a targeted surveillance risk registry by identifying which risk factors predict postnatally identified hearing loss (PNIHL) in children who pass newborn hearing screening and to determine whether hearing surveillance beyond the age of 1 year is warranted. We used retrospective analysis of the audiological outcomes of children born in the state of Queensland, Australia, between January 1, 2010, and December 31, 2019, who passed the newborn hearing screen with risk factors. Approximately one third of children were lost to follow-up and could not be included in the analysis. Risk factors that predicted PNIHL in the analyzed cohort were as follows: syndromes associated with hearing loss, craniofacial anomalies, perinatal infections, and family history of permanent childhood hearing loss. Severe asphyxia did not predict PNIHL but yielded some cases of significant bilateral hearing loss. Hearing loss in children with a history of prolonged ventilation was mild and/or unilateral in nature (except in cases where the hearing loss was due to an unrelated etiology). There were no cases of PNIHL in children with hyperbilirubinemia or neonatal bacterial meningitis. For the risk factors that predicted PNIHL, nearly all hearing losses were detected by 1 year of age, except for children with family history where one quarter of hearing losses had a later onset. The four risk factors recommended for efficient postnatal identification of hearing loss are as follows: syndromes associated with hearing loss, craniofacial anomalies, perinatal infection, and family history of permanent childhood hearing loss. Hearing surveillance through to 1 year old is sufficient except for children with a family history, where a second phase assessment is indicated. Alternative targeted surveillance protocols and models of care are required to minimize loss to follow-up.

The Characteristic of HBV Quasispecies Is Related to Occult HBV Infection of Infants Born to Highly Viremic Mothers.

Although a combination of immunoprophylaxis and antiviral therapy can effectively prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV), a considerable number of infants born to highly viremic mothers still develop occult HBV infection (OBI). To uncover the virological factor and risk predictor for OBI in infants, we found that the diversity and complexity of maternal HBV quasispecies in the case group were lower than those in the control group. Mutations with significant differences between the two groups were most enriched in the NTCPbd and PreC regions. Genetic distance at the amino-acid level of the PreC region, especially the combination of three amino-acid mutations in the PreC region, could strongly predict the risk of OBI in infants. HBV quasispecies in OBI infants were highly complex, and the non-synonymous substitutions were mainly found in the RT and HBsAg regions. The sK47E (rtQ55R) and sP49L mutations in OBI infants might contribute to OBI through inhibiting the production of HBV DNA and HBsAg, respectively. This study found the potential virological factors and risk predictors for OBI in infants born to highly viremic mothers, which might be helpful for controlling OBI in infants.

Brain Metabolite Differences in Fetuses With Cytomegalovirus Infection: A Magnetic Resonance Spectroscopy Study.

Cytomegalovirus (CMV) is the most common intrauterine infection and may be associated with unfavorable outcomes. While some CMV-infected fetuses may show gross or subtle brain abnormalities on MRI, their clinical significance may be unclear. Conversely, normal development cannot be guaranteed in CMV-infected fetuses with normal MRI. To assess brain metabolite differences in CMV-infected fetuses using magnetic resonance spectroscopy (MRS). Retrospective. Out of a cohort of 149 cases, 44 with maternal CMV infection, amniocentesis results, and good-quality MRS were included. CMV-infected fetuses with positive polymerase chain reaction (PCR) (N = 35) were divided based on MRI results as follows: typical brain abnormalities (gross findings, N = 8), exclusive white matter hyperintense signal (WMHS) on T2-weighted images (subtle findings, N = 7), and normal MRI (N = 20). Uninfected fetuses (negative PCR) with normal MRI were included as controls (N = 9). 3 T, T2-weighted half Fourier single-shot turbo spin-echo (HASTE), T2-weighted true fast imaging with steady-state free precession (TrueFISP), T1- and T2*-weighted fast low angle shot (FLASH), and 1H-MRS single-voxel point resolved spectroscopy (PRESS) sequences. MRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel. Analysis of covariance test with Bonferroni correction for multiple comparisons was used to compare metabolic ratios between groups while accounting for gestational age. A P-value <0.05 was deemed significant. MRS was successfully acquired in 63% of fetuses. Substantial agreement was observed between radiologists (Fleiss' kappa [k] = 0.8). Infected fetuses with gross MRI findings exhibited significantly reduced tNAA/tCr ratios (0.64 ± 0.08) compared with infected fetuses with subtle MRI findings (0.85 ± 0.19), infected fetuses with normal MRI (0.8 ± 0.14) and controls (0.81 ± 0.15). No other significant differences were detected (P ≥ 0.261). Reduced tNAA/tCr within the apparently normal brain tissue was detected in CMV-infected fetuses with gross brain abnormalities, suggesting extensive brain damage. In CMV-infected fetuses with isolated WMHS, no damage was detected by MRS. 3 TECHNICAL EFFICACY: Stage 3.

Feasibility, performances and predictive value of congenital CMV neonatal screening on saliva swabs

BackgroundEarly diagnosis of congenital CMV infection (cCMVI) allows for early intervention and follow-up to detect delayed hearing loss. While CMV PCR in urine is the gold standard for cCMVI diagnosis, saliva testing is often performed. ObjectivesOur aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in “virus copies per million cells (Mc)” in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI. Materials and methodsIn our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI. ResultsCell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson's r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc). DiscussionOur results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.

THE IMPACT OF INTRAUTERINE INFECTION WITH CYTOMEGALOVIRUS ON THE FORMATION OF PLACENTAL PATHOLOGY AND PREMATURE TERMINATION OF PREGNANCY

Intrauterine infection occurs as a result of transplacental, amniotic, ascending or descending infection. The spectrum of pathogens is diverse: bacteria, viruses, fungi, protozoa, mycoplasmas, chlamydia, and combinations of pathogens. When an infection enters the body of a pregnant woman, pathological changes in the fetus and amniotic fluid structures can have varying degrees of severity, from local to generalized. Cytomegalovirus infection is a widespread infection in the human population and affects 50 to 100% of the adult population. The infection leads to miscarriage, severe complications during pregnancy, birth of severely premature babies, birth of children with congenital malformations and pathology of internal organs, autism, further lag in physical and mental development, and disability of children. Timely prevention of CMV infection before and during pregnancy, compliance with hygiene standards, knowledge of a healthy lifestyle, culture of sexual relations, contraceptive methods and methods of prevention of sexually transmitted infections, rules of care for children with disabilities and the elderly, identification and formation of risk groups among pregnant women for primary infection or relapse of a chronic process, timely laboratory diagnosis of the activity of the infectious process and specific treatment

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

Description of Babesiacoryicola sp. nov. from Florida pumas (Puma concolor coryi) from southern Florida, USA

Previously, a high prevalence of piroplasms has been reported from Florida pumas (Puma concolor coryi) from southern Florida. In the current study, we describe the biological characteristics of a novel Babesia species in Florida pumas. Ring-stage trophozoites were morphologically similar to trophozoites of numerous small babesids of felids including B. leo, B. felis, and Cytauxzoon felis. Parasitemias in Florida pumas were very low (<1%) and hematologic values of 25 Babesia-infected Florida pumas were within normal ranges for P. concolor. Phylogenetic analysis of near full-length 18S rRNA gene, β-tubulin, cytochrome c oxidase subunit I, cytochrome c oxidase subunit III, and cytochrome b gene sequences indicated that this Babesia species is a member of the Babesia sensu stricto clade and is related to groups of Babesia spp. from carnivores or ungulates, although the closest group varied by gene target. Internal transcribed spacer (ITS)-1 region sequences from this Babesia sp. from 19 Florida pumas were 85.7–99.5% similar to each other and ∼88% similar to B. odocoilei. Similarly, an ITS-2 sequence from one puma was 96% similar to B. bigemina and 92% similar to a Babesia sp. from a red panda (Ailurus fulgens). Infected pumas were positive for antibodies that reacted with B. odocoilei, B. canis, and B. bovis antigens with titers of 1:256, 1:128, and 1:128, respectively. No serologic reactivity was noted for Theileria equi. No molecular evidence of congenital infection was detected in 24 kittens born to 11 Babesia-infected female pumas. Pumas from other populations in the United States [Louisiana (n = 1), North Dakota (n = 5) and Texas (n = 28)], British Columbia, Canada (n = 9), and Costa Rica (n = 2) were negative for this Babesia sp. Collectively, these data provide morphologic, serologic, genetic, and natural history data for this novel Babesia sp. which we propose the name Babesia coryicola sp. nov. sp. This is the first description of a felid-associated Babesia species in North America.

A pilot integrated model nurse clinic increases the uptake of antiviral treatment for the prevention of mother-to-child transmission of HBV.

Mother-to-child-transmission (MTCT) of hepatitis B virus (HBV) may still occur despite birth-dose HBV vaccinations when pregnant women are positive for hepatitis B surface antigen (HBsAg) with high viral loads (HBV DNA ≥ 200 000 IU/mL). A pilot integrated model nurse clinic (IMNC) was started in 2020 to implement the pre-emptive antiviral therapy with tenofovir disoproxil fumarate (TDF). We aimed to evaluate the performance of IMNC on uptake of TDF. This was a territory-wide retrospective cohort of all consecutive HBsAg-positive women of child-bearing age with pregnancy records in public hospitals 2019-2022. Demographic characteristics, liver biochemistries and virologic parameters, and TDF use were collected. Concurrently, data from a prospective audit in Union Hospital, the private hospital with the highest number of deliveries in Hong Kong, from June 2022 to May 2023 were compared. The prevalence rate of HBV DNA ≥ 200 000 IU/mL in pregnant women with available HBV DNA records was 29.2% (66/226) in 2019, 27.3% (99/363) in 2020, 15.9% (125/784) in 2021 and 17.2% (117/679) in 2022 (p < .001), out of 2052 pregnant women who had their HBV DNA checked within 1 year prior to delivery. An increasing uptake rate of TDF by highly viraemic pregnant women (i.e. ≥ 200 000 IU/mL) was noted after the commencement of IMNC in public hospitals, with 67% (45/67) in 2019, 83% (88/106) in 2020, 91% (117/128) in 2021 and 89% (149/167) in 2022. Moreover, all highly viraemic pregnant women from Union Hospital received TDF. Continuous use of TDF was associated with a reduced risk of postpartum biochemical flare. IMNC increases the uptake of antiviral treatment in pregnant women at risk of MTCT of HBV. IMNC contributes to hepatitis elimination through a structured care plan to prevent MTCT of HBV.

Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity. Infection of the fetus often leads to fetal death, and surviving fetuses may develop vision impairment and central nervous system developmental disorders. LCMV is mainly diagnosed by serological methods using in-house indirect immunofluorescence assays. LCMV nucleic acid is detected by the nested RT-PCR method and confirmed by Sanger sequencing. In Hungary, 23 acquired lymphocytic choriomeningitis cases were diagnosed between 2017 and 2023. Ten out of 23 confirmed patients proved to be positive by the PCR method. Two cases of intrauterine LCMV infections were detected in 2019 and 2021, respectively. The IgG antibody titers measured in the infant's serum samples were much higher than the IgG titers of the maternal serum samples. Both IgM and IgA antibodies were detectable in the infants' sera. As the microbiological diagnosis of LCMV is rather challenging and the symptoms are very similar to the clinical picture of other common teratogenic pathogens such as cytomegalovirus or Toxoplasma gondii, intrauterine LCMV infections might still be underdiagnosed.

P-736 The therapeutic effect of hysteroscopic surgery on chronic endometritis in infertile women with intrauterine disorders

Abstract Study question Can chronic endometritis (CE) be treated by hysteroscopic surgery without antibiotic treatment in women with intrauterine disorders? Summary answer Most CE cases with intrauterine disorders were cured through hysteroscopic surgery without antibiotic therapy, regardless of the type of intrauterine abnormalities. What is known already Persistent inflammation of the local endometrium, CE, interferes with embryo implantation. CE is primarily caused by intrauterine infection; therefore, broad-spectrum antibiotic therapy is the current treatment for CE. Nevertheless, most cases with CE and endometrial polyps can be cured via hysteroscopic polypectomy without antibiotic therapy in our previous study. Study design, size, duration This study was a prospective cohort study approved by the Ethics Committee. To evaluate the therapeutic effect of hysteroscopic surgery on CE, the endometrial specimens for the immunohistochemistry analysis of the plasma cell marker CD138 were obtained to diagnose CE at surgery between November 2018 and June 2021. In the women diagnosed with CE, endometrial biopsy was performed without use of antibiotics in the subsequent menstrual cycle. Participants/materials, setting, methods The study population consisted of 337 consecutive infertile women who underwent hysteroscopic surgery. Eighty-nine consecutive patients without intrauterine disorders were also recruited as control group. CE was diagnosed as the presence of ≥ 5 CD138-positive cells in 10 nonoverlapping random stromal areas of high-power fields (HPF) in this study. Main results and the role of chance The prevalence of CE with ≥5 CD138-positive cells in women with no intrauterine disorder, endometrial polyps, myomas, intrauterine adhesion (IUA), and septate uterus were 15.7%, 85.7%, 69.0%, 78.9%, and 46.2%, respectively. Multivariate analysis revealed that CE was diagnosed significantly more often in the endometrial polyp (p &amp;lt; 0.0001, odds ratio [OR] 27.69, 95% confidence interval [CI] 15.01–51.08) and IUA groups (p &amp;lt; 0.0001, OR 8.85, 95%CI 3.26–24.05). The CE recovery rates by hysteroscopic surgery in the women with endometrial polyps, myomas, IUA, and septate uterus were 89.7%, 100%, 92.8%, and 83.3%, respectively (p = 0.45). Limitations, reasons for caution This study has limitations. First, some patients received a combination of estrogen and progestin or dienogest before surgery. These medicines may influence the number of CD138-positive cells. Second, ≥5 CD138-positive cells per 10 HPF were defined as the diagnosis of CE; however, different diagnostic criteria may generate different results. Wider implications of the findings CE is primarily caused by intrauterine infection due to a wide variety of microorganisms; however, most CE cases with intrauterine abnormalities were cured by hysteroscopic surgery without antibiotic use. Most CE cases associated with intrauterine abnormalities may be noninfectious CE. Trial registration number not applicable

P-450 Maternal-fetal SARS-CoV-2 antibody transfer in relation to the trimester of infection

Abstract Study question What does the maternal-fetal SARS-CoV-2 antibody transfer look like depending on the trimester of infection? Summary answer There is a statistically significant tendency for newborns of SARS-CoV-2 positive mothers to have a higher IgG antibody level compared to their mother’s at delivery. What is known already Passive maternal-fetal transfer of SARS-CoV-2 antibodies has been demonstrated, whilst the degree of transfer depending on the trimester of infection is lacking, and so far, there is no stratification on all three trimesters of SARS-CoV-2 infection in relation to maternal antibody levels in SARS-CoV-2 positive women, and the degree of transfer of SARS-CoV-2 antibodies to the newborn. It is known that for perinatal infections such as Rubella and Toxoplasmosis the timing of infection related to gestational age is crucial for the severity of fetal/obstetric outcomes, hence the trimester of SARS-CoV-2 infection could potentially be crucial. Study design, size, duration This is a large prospective cohort study with full medical record of all 3,026 participating women and 3,073 of their newborns, as well as antibody measurements on all women who participated between April 4’th 2020 until April 30’st 2021. Of the 3,026 participating women 459 were SARS-CoV-2 positive. Participants/materials, setting, methods The positive cohort consisted of women who had a positive SARS-CoV-2 PCR test, antigen test or antibody test and participated with a maternal blood sample and an umbilicalcord blood sample at delivery. The negative cohort was established at Hvidovre Hospital (CHH), where all women with a first trimester double marker blood test taken at CHH could participate, all woman attending their second trimester ultrasound or giving birth were invited to participate with a blood sample. Main results and the role of chance This prospective cohort study found a strong and statistically significant tendency for newborns of SARS-CoV-2 positive mothers to have a higher IgG antibody level compared to their mother’s IgG antibody level at delivery. In total, 87.5%, 95.3% and 60.3% of newborns of women who tested positive in their first, second and third trimester respectively, had higher IgG antibody levels than their mother’s at delivery. The higher level of antibodies in the newborns’ cord blood compared to their mother’s demonstrated in this study, correlates with findings of for instance pertussis toxin antibodies during pregnancy and aligns with general findings on maternofetal transport of immunoglobins. Our findings indicates that the fetus is either able to concentrate antibody levels or maintain the level of IgG antibodies transferred. Limitations, reasons for caution With only 40 women being SARS-CoV-2 positive in their first trimester, analysis in this group should be taken with caution. Other limitations are the 56 newborns of positive women who did not have an umbilical cord blood sample taken due to PPH, acute cesarean section or blood sample coagulated. Wider implications of the findings This knowledge of the maternal-fetal antibody transmission pattern is valuable for the basic understanding of SARS-CoV-2 in pregnancy and for future investigation on expected degree of early life protection against SARS-CoV-2 but could also be of interest if investigating the paradoxically concept of blunting when considering vaccination of neonates. Trial registration number H-20022647

Performance evaluation of the Alinity m system for quantifying cytomegalovirus DNA in samples of the respiratory, gastrointestinal, and urinary tract.

Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice as an ancillary tool for the diagnosis of CMV pneumonitis, intestinal disease, or congenital infection, respectively. Nevertheless, most commercially available CMV PCR platforms have not been validated for CMV DNA detection in these specimen types. In this study, a laboratory-developed test based on Alinity m CMV ("Alinity LDT") was evaluated. Reproducibility assessment using spiked bronchial aspirate (BAS) or urine samples showed low standard deviations of 0.08 and 0.27 Log IU/mL, respectively. Evaluating the clinical performance of Alinity LDT in comparison to a laboratory-developed test based on RealTime CMV ("RealTime LDT") showed good concordance across 200 clinical specimens including respiratory specimens, intestinal biopsies, urine, and stool. A high Pearson's correlation coefficient of r = 0.92, a low mean bias of -0.12 Log IU/mL, a good qualitative agreement of 90%, and a Cohen's kappa value of 0.76 (substantial agreement) were observed. In separate analyses of the sample types BAS, tracheal aspirates, bronchoalveolar lavage, biopsies, and urine, the assay results correlated well between the two platforms with r values between 0.88 and 0.99 and a bias <0.5 Log IU/mL. Overall, the fully automated, continuous, random access Alinity LDT yielded good reproducibility, high concordance, and good correlation to RealTime LDT in respiratory, gastrointestinal, and urine samples and may enhance patient management with rapid result reporting.IMPORTANCEIn transplant recipients, a major cause for morbidity and mortality is end-organ disease by primary or secondary CMV infection of the respiratory or gastrointestinal tract. In addition, sensorineural hearing loss and neurodevelopmental abnormalities are frequent sequelae of congenital CMV infections in newborns. Standard of care for highly sensitive detection and quantitation of the CMV DNA load in plasma and whole blood specimens is real-time PCR testing. Beyond that, there is a need for quantitative determination of CMV DNA levels in respiratory, gastrointestinal, and urinary tract specimens using a highly automated, random access CMV PCR assay with a short turnaround time to enable early diagnosis and treatment. In the present study, clinical performance of the fully automated Alinity m analyzer in comparison to the current RealTime LDT assay was evaluated in eight different off-label sample types.

Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection.

Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.

Updates in the Management of HIV During Pregnancy.

Human immunodeficiency virus in pregnant people remains a significant public health issue worldwide. The rate of perinatal transmission is 15% to 40% but can be decreased to less than 1% with appropriate antenatal management. Previous recommendations included a protease inhibitor-based antiretroviral therapy, infant prophylaxis, performance of cesarean section for uncontrolled viremia, and the use of formula for infant feeding. However, recent updates include first line of integrase inhibitor-based regimens and supporting parental choices for safe lactation. In this review, we summarize and provide updated recommendations for the care of people living with human immunodeficiency virus during pregnancy.

Bilateral developmental cataracts in a child with familial lipodystrophy

Bilateral developmental cataracts are usually caused due to hereditary metabolic disorder or intrauterine infections. Familial lipodystrophy type 7 has variable phenotypes with early-onset cataracts and lower limb spasticity, with most reports showing the onset of cataracts in the second decade of life. We report a rare case of bilateral congenital cataract in a child aged 3 years and 9 months with genetically proven familial partial lipodystrophy type 7. Bilateral developmental cataracts need complete physical examination and genetic analysis to detect unusual and rare causes like familial partial lipodystrophy.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

Cytomegalovirus congenital infection: long-term outcomes in a valaciclovir treated population.

This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The study focuses on assessing the prevalence of long-term sequelae in infants with confirmed CMV fetal infection. A retrospective analysis was conducted on 33 pregnancies corresponding to 34 fetus with confirmed CMV congenital infection. They were followed from November 2004 to December 2020. Valaciclovir treatment was initiated after confirmation of fetal infection, and fetal outcomes were monitored through serial ultrasounds, neurosonography, and fetal magnetic resonance imaging (MRI). Postnatal assessments included: PCR confirmation, symptoms evaluation at birth, and long-term follow-up protocols for visual, auditory, and neurodevelopmental assessment. Therapy was started at a median gestational age of 24weeks. Of the 34 newborns 79.4 % were asymptomatic atbirth. Median follow-up time was 6 years and 32.35 % developed long-term sequelae. Neurosensorial hearing loss (SNHL) was the predominant sequelae. In the cases which developed sequelae 54.5 % had imaging findings, and all with major findings developed long-term sequelae. In our treated population we had a higher asymptomatic rate at birth comparing with a non-treated population, similar to those found in previous studies. We had a long-term sequelae rate of 32.35 %, similar to recent studies on non-treated population, although we registered a slightly lower rate of SNHL. A larger multicenter studies with a longer follow-up time, where treatment is started in the first trimester, is of the utmost importance, so we can truly understand the correlation between these imaging findings, therapy and long-term sequelae.

Eliminating perinatal transmission of hepatitis B virus: it is time for action.

Eliminating perinatal transmission of hepatitis B virus: it is time for action.

Serological status for Toxoplasma gondii and cytomegalovirus in pregnant women

Background and objective. Toxoplasma gondii and CMV cause congenital defects in TORCH (Toxoplasmosis, Rubella virus, cytomegalovirus, and Herpes simplex virus) infections. The primary objective of the study was to estimate the seroprevalence of Toxoplasma gondii (TOXO) and cytomegalovirus (CMV) infections among pregnant women in Al Qurnah, Iraq, and identify the presence of specific Immunoglobulin M (IgM) antibodies indicating recent infections. Material and method. The study tested 1000 healthy pregnant women using VIDAS® TOXO and CMV IgM kits. Results. The findings revealed a significant seroprevalence, with 37.2% of samples positive for Toxoplasma IgM, 22.8% for CMV IgM, and 9.6% for mixed infections. The highest rate of abortions occurred in the first trimester, with a significant increase in abortion parameters among pregnant women infected with T. gondii and CMV. Our study comprised 372 pregnant women with Toxoplasma infection; 286 (76.9%) were rural and 86 (23.1%) urban. Our analysis identified CMV in 228 pregnant women, 159 rural (69.7%), and 69 urban (30.3%). Conclusion. The study suggests a higher prevalence of Toxoplasma IgM compared to CMV IgM infections in the region, emphasizing the importance of early detection and prevention, especially during the first trimester. The results also highlight the need for routine antenatal screening and educational measures to reduce the impact of these infections on pregnancy outcomes.

Chorioamnionitis: clinical, anamnestic and molecular-genetic parallels

Aim: to determine clinical, anamnestic and molecular-genetic parallels in emergence of clinical chorioamnionitis (CA) and severe forms of intrauterine infections (IUI) in high-risk pregnant women.Materials and Methods. A single-center prospective cohort comparative case-control study was conducted by examining 58 pregnant female patients aged 18 to 42 years with a verified CA diagnosis during pregnancy and childbirth at different gestation stages (main group), and 35 age-matched pregnant women with uncomplicated pregnancy and no significant extragenital pathology, aggravated factors of obstetric and gynecological history and risk factors for developing CA (control group), observed and performed a delivery in Yudin City Clinical Hospital. All women underwent clinical, anamnestic, laboratory, instrumental and molecular-genetic examitation. We studied the polymorphism of genes FCGR2A (Fc fragment of immunoglobulin G receptor IIa), IFN-γ (interferon gamma), IL-10 (interleukin-10), IL-6 (interleukin-6) and MBL2 (mannose binding lectin 2) to determine their role in assessing a risk of maternal and neonatal infection.Results. Among the patients with developed clinical CA vs. control subjects, more of them had a history of abortion and miscarriages (17.24 %), comorbid with chronic arterial hypertension (13.79 %), previous surgical interventions (27.59 %), as well as chronic inflammatory diseases (chronic tonsillitis, bronchitis, pyelonephritis, sinusitis; 27.59 % vs. 17.14 %). In addition to risk factors directly related to the infectious and inflammatory unfavorable background, they also had a significantly higher rate of obstetric complications: moderate preeclampsia – 6 (10.34 %) cases, threat of miscarriage or premature birth – 14 (24.14 %) cases vs. 1 (2.86 %) case in control group (p = 0.007), polyhydramnions – 4 (6.9 %) cases, placental insufficiency – 6 (10.34 %) cases. The frequency of premature rupture of membranes was 31.03 % in women with CA. Questionable cardiotocography (CTG) type was found in 24 (41.38 %) women with CA vs. 4 (11.4 3%) women without CA (p = 0.003), the pathological CTG type was observed only in women with CA. In the group with clinical CA and neonatal IUI, the combination of genotypes AG rs1801274 FCGR2A, ТT rs2430561 (IFN-γ)+874, GC rs1800795 (IL-6)-174 occurs in 80.65 % (25/31), whereas in women without severe neonatal IUI – in 37.04 % (10/27) (odds ratio (OR) =7.08; 95 % confidence interval (CI) = 2.166–23.166). In addition, the combination of alleles TT rs2430561 (IFN-γ)+874, GC+CC rs1800795 (IL-6)-174, AA rs1800450 MBL2 codon 54 was detected in 60.86 % (62/102) vs. 47.52 % (370/778) in main and control group (OR = 11.667; 95 % CI = 2.842–47.886), respectively.Conclusion. The study data evidence about importance of identifying genes for developing CA and neonatal septic complications to optimize and personalize management of high-risk patients (premature birth, infections during pregnancy, premature rupture of membranes).