Mother-to-child Transmission Research Articles

Significance of placental pathology and CMV PCR in assessing clinical outcomes of congenital CMV infection.

Significance of placental pathology and CMV PCR in assessing clinical outcomes of congenital CMV infection.

Epidemiology and Economic Burden of Diagnosed Congenital Cytomegalovirus Infection in the First 2 Years of Life among Commercially Insured and Medicaid-Insured Individuals in the United States.

Epidemiology and Economic Burden of Diagnosed Congenital Cytomegalovirus Infection in the First 2 Years of Life among Commercially Insured and Medicaid-Insured Individuals in the United States.

Deep learning for fetal inflammatory response diagnosis in the umbilical cord.

Deep learning for fetal inflammatory response diagnosis in the umbilical cord.

Genital Herpes Simplex Virus Infections in Women-A Clinical Update.

Genital herpes is a relatively common chronic lower genital tract sexually transmitted infection caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). It is characterized by recurrent, self-limited genital ulcers, and it is the leading cause of genital ulcer disease worldwide (1). The impact of genital herpes on sexual and reproductive health, including the risk of perinatal infection, necessitates a profound understanding of its clinical presentation, diagnosis, treatment, and prevention. This chapter aims to review the critical clinical aspects of HSV in women, emphasizing relevant evidence-based data.

Congenital CMV infection and central nervous system involvement: mechanisms, treatment, and long-term outcomes

Congenital CMV infection and central nervous system involvement: mechanisms, treatment, and long-term outcomes

Role of NLRC3 in modulating inflammatory responses in neonates

ObjectiveThis study sought to investigate the role and molecular mechanisms of nucleotide-binding oligomerization domain (NOD)-like receptor family caspase activation and recruitment domain (CARD)-containing 3 (NLRC3) in the inflammatory responses of neonates, thereby developing new clinical insights into the occurrence and prevention of neonatal infections.MethodsPeripheral blood samples were collected from full-term infants (n = 49) and preterm infants (n = 41) without any signs of intrauterine infection, as well as from healthy non-pregnant adults (n = 45). A real-time polymerase chain reaction was used to assess the expression levels of NLRC3 and NOD-containing protein 1 (NOD1) in the isolated mononuclear cells. Whole blood from the adults, full-term infants, and preterm infants was stimulated for four hours with a mixture of herpes simplex virus type 60 DNA (HSV-60 DNA) and lipopolysaccharides (LPS) or LPS alone or blank medium. An enzyme-linked immunosorbent assay was employed to measure the tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β) levels in the supernatant.ResultsThe gene expression levels of NLRC3 were significantly lower in the full-term and preterm infants than in the adults, with the preterm infants showing notably lower levels when compared with the full-term infants. A positive correlation was found between the NLRC3 and NOD1 expression levels in the neonates (both full-term and preterm), indicating lower NLRC3 expression to be associated with lower NOD1 expression. After LPS stimulation, the production of TNF-α, IL-6, and IL-1β in the whole blood of the preterm and full-term infants was significantly lower than in that of the adults. Moreover, stimulation with a combination of LPS and HSV-60 DNA resulted in similar TNF-α, IL-6, and IL-1β production across the blood samples from preterm infants, full-term infants, and adults. When compared with LPS stimulation alone, the LPS and HSV-60 DNA mixture significantly reduced the release of TNF-α, IL-6, and IL-1β in the adults. In the neonates, however, only the release of TNF-α was significantly reduced, as no notable difference was observed in the IL-6 and IL-1β levels.ConclusionThe reduced expression and functional impairment of NOD-like receptors, such as NLRC3 and NOD1, in neonates, may contribute to their heightened susceptibility to severe infections. This finding indicates new avenues for the prevention and treatment of neonatal infections.

Understanding PrEP misconceptions and their impact on PrEP initiation and use among pregnant and lactating women in Malawi.

Mother-to-child transmission (MTCT) of HIV remains a challenge in Eastern and Southern Africa. Oral pre-exposure prophylaxis (PrEP) is a powerful tool to reduce MTCT, but women face barriers to effective use including those related to inaccurate comprehension of PrEP To understand women's misconceptions about PrEP and their potential impact on PrEP use, we conducted interviews with 33 pregnant and lactating women in Malawi using PrEP, and ten PrEP counselors and clinicians. The results indicate that, although pregnant women generally understood PrEP's features and functions, many held misconceptions that persisted over the course of their PrEP use and impacted their perceptions and use of the medication. Some women erroneously believed that PrEP could treat and prevent sexually transmitted infections other than HIV, which motivated some to keep taking PrEP while motivating others to stop using PrEP once their STI had resolved. Some were confused about PrEP's function, with some believing it was the same as antiretroviral therapy for HIV treatment, and others believing that PrEP could be used for overall enhancement of health. Rarer misconceptions included fears that PrEP was connected to satanic practices, could cause cancer, or was solely for individuals engaged in sex work. These misconceptions stemmed from a mix of prior knowledge, societal influences, and miscommunications during counseling sessions. Ensuring accurate knowledge and addressing common misconceptions head-on is crucial to promote continued PrEP use among women. Both clinic- and community-based communication efforts with a particular focus on the difference between PrEP, STI treatments, and ART are needed.

Association between negative T waves in lead V1 and delayed patent ductus arteriosus closure in preterm neonates

ObjectivesThe aim of this study is to determine whether the presence of a negative T wave in lead V1 within 15 h after birth is associated with delayed closure of patent ductus arteriosus (PDA) in preterm neonates within the first week of life.MethodsA retrospective cohort study was conducted involving neonates with a gestational age between 270/70/7 and 411/71/7 weeks who were less than 15 h old and had documented T-wave morphology in lead V1, with PDA confirmed by echocardiography. Neonates with asphyxia, congenital infections, structural heart defects, major malformations, or clinical sepsis were excluded. The cohort was categorized into two groups based on T-wave morphology: Group A (n = 200; normal T wave) and Group B (n = 29; negative T wave). Echocardiographic assessments of PDA closure were performed at different time intervals (days 0–2, 2–5, and 5–7).ResultsA total of 229 neonates were included, with a mean gestational age of 35.5 ± 3.23 weeks and a mean birth weight of 2.54 ± 0.78 kg. PDA was diagnosed in 54 neonates (23.6%). Negative T waves in lead V1 were observed in 29 neonates (12.7%) within 15 h after birth, of whom 15 (51.7%) had PDA. The median time to PDA closure differed significantly between Groups A and B, with closure occurring at 2 (0–2), 5 (2–5), and 7 (5–7) days, respectively (log-rank test, p < 0.01). Cox proportional hazards regression analysis identified the presence of a negative T wave in lead V1 as an independent predictor of PDA closure time (adjusted hazard ratio, 0.559; 95% confidence interval: 0.318–0.984).ConclusionThe presence of a negative T wave in lead V1 within 15 h after birth independently predicted a higher likelihood of persistent PDA at day 7 in preterm neonates.

Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy

Abstract Toxoplasma gondii, a neurotropic protozoan, causes toxoplasmosis, a prevalent zoonotic and food-borne infection, posing significant risks to immunocompromised individuals and congenital cases. The chronic phase, characterized by dormant, cyst-forming bradyzoites, is central to disease progression but is poorly understood due to the lack of serological tests to detect bradyzoite-specific antigens. This study identifies the bradyzoite serological marker (BSM) and cyst-associated BCLA as effective biomarkers for chronic toxoplasmosis. These markers showed high sensitivity and specificity in detecting cyst-bearing mice and had a positivity rate of 30% in humans with prior immunity. Bradyzoite serology helps to discriminate between recent and past infections, with BCLA improving the accuracy of the diagnosis of congenital infections. Mechanistic analyses show that the chromatin modifiers MORC and HDAC3 epistatically regulate BFD1, a key bradyzoite regulator. While BFD1 controls the expression of bradyzoite genes such as BCLA, a specific subset, including BSM, is regulated independently of BFD1. This multilayered regulation complicates the understanding of parasite persistence in humans, but offers promise for improved serologic diagnosis during pregnancy, but also in individuals with mental illness.

Cerebral Palsy - A Comprehensive Analysis of the Causes

Introduction and Purpose: Cerebral palsy (CP) is a complex motor and postural disorder resulting from damage to the developing brain. The causes of CP are diverse and can occur at various stages of a child’s life— prenatal, perinatal, and postnatal. The aim of this paper is to review the scientific literature on the causes of CP, with a particular focus on the mechanisms of brain damage at each stage. Material and methods: A comprehensive literaturere view was conducted using the PubMed database, focusing on articles published until the end of 2024. The search included the keywords:"cerebral palsy","etiology","brain damage"and "prevention" in various combinations. Relevant studies were selected based on criteria such as etiology of cerebral palsy. Results: Analysis of available studies indicates that prenatal causes predominantly include genetic abnormalities, intrauterine infections, and exposure to toxins. Perinatal causes involve asphyxia, mechanical trauma, and prematurity. In the postnatal period, infections of the nervous system, traumatic brain injuries, and perinatal complications play a significant role. These causes are often interdependent, highlighting the necessity of a comprehensive approach to CP risk analysis. Conclusion: Understanding the multifactorial etiology of CP is essential for developing effective prevention strategies. Further research into the mechanisms of brain damage may contribute to reducing the incidence of new cases and improving the quality of life for children with CP.

A Structural In Silico Analysis of Novel Epitopes from Toxoplasma gondii Proteins for the Serodiagnosis of Toxoplasmosis.

Toxoplasmosis is a widely spread zoonosis worldwide, considered one of the most important parasitic infections that affect global public health, and usually, it is not correctly diagnosed. Serological tests for the diagnosis of Toxoplasma gondii infection have limitations in differentiating acute from chronic infection, which is important to determine the appropriate clinical management and treatment, mainly in pregnant women and immunocompromised individuals infected by this parasite. The present study aimed to characterize immunogenic epitopes from T. gondii immunodominant antigens, as SAG1(SRS29B), SAG2A (SRS34A), GRA1, GRA2, GRA3, GRA5, GRA6, GRA7, MAG1, BSR4, and CCp5A, by investigating if these parasite components might emerge as alternatives to improve the diagnosis of toxoplasmosis. A detailed comparative in silico analysis was used for this purpose. Once the protein sequences were retrieved from the ToxoDB database, different parameters were calculated, including physicochemical characteristics, accessibility values, and antigenicity. Multiple sequence alignment, 3D structures modeling, and the validation of 3D structures were also performed among all 11 peptides. Considering the results from the combination of all parameters analyzed, it can be hypothesized that the linear epitopes from SAG1, GRA3, and BSR4 proteins were found to be stable and hydrophilic, with a significant antigenicity score, and accessibility on the protein surface. Also, these three selected peptides were able to detect anti-T. gondii antibodies in serum samples from pigs infected by tachyzoites, when compared with control serum samples, obtained from the same naïve animals and tested by ELISA, demonstrating remarkable difference in terms of reactivity. Taken together, as our study addresses a critical challenge in the serodiagnosis of toxoplasmosis, particularly in gestational and congenital infections, where false-positive and false-negative results often arise from the use of native or recombinant antigens of T. gondii, our findings highlight the potential of synthetic peptides derived from novel epitopes of this parasite as alternative tools for the development of more accurate immunodiagnostic assays for toxoplasmosis.

Emerging Prognostic and Predictive Biomarkers for Human Cytomegalovirus Infection During Pregnancy: Unmet Needs and Future Perspectives.

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of congenital infections worldwide, posing significant risks to fetal health. Despite advances in prenatal care, managing HCMV infection remains challenging. Early detection, accurate risk assessment, and timely intervention are critical to mitigating the adverse outcomes associated with congenital HCMV (cHCMV), such as neurodevelopmental delays and hearing loss. However, the current landscape of biomarkers for HCMV infection in pregnancy is marked by several unmet needs. These gaps in biomarker development and application limit our ability to predict fetal transmission, assess the risk of fetal damage, and prognosticate long-term outcomes. Addressing these challenges through the identification and validation of novel biomarkers could revolutionize the management of HCMV in pregnancy, leading to improved outcomes for both mothers and their children. This review examines the critical unmet needs regarding HCMV biomarkers during pregnancy, emphasizing the priority areas for further research and innovation.

Therapeutic effect of exogenous tumor necrosis factor-stimulating protein 6 intervention on lung injury in newborn rats by intrauterine infection

To investigate the therapeutic effect of exogenous tumor necrosis factor-stimulating protein 6(TSG-6) on lung injury in newborn rats induced by intrauterine infection, and to analyze its underlying mechanism. Twelve pregnant rats were randomly divided into a blank control group, a negative control group, a model group, and a TSG-6 treatment group. The blank control group was not modeled. The negative control group was injected with normal saline (NS) intraperitoneally on gestation day (E)14, and the remaining two groups were intraperitoneally injected with lipopolysaccharide at 0.6 mg/kg × body weight(kg) on E14 to establish the intrauterine infection model. The negative control and model groups were injected with NS via the tail vein on E16, and the TSG-6 treatment group was injected with TSG-6 at 0.25 mg/kg × body weight(kg) via the tail vein on E16. After delivery, the placentas of pregnant rats and the right lungs of newborn rats on postnatal day (P) 3, 7, and 14 were stained with hematoxylin-eosin to observe the inflammatory infiltration of placentas, the pathology of the lungs, and the radical alveolar count (RAC) was performed. The left lung tissues of newborn rats were collected on P3, P7d, and P14. Using Enzyme-linked immunosorbent assay (ELISA) kits to measure the levels of TSG-6, tumor necrosis factor-α(TNF-α), vascular endothelial growth factor (VEGF), and Interleukin-6 (IL-6) in lung tissues of newborn rats. Compared with the model group, the growth of the control group and the TSG-6 treatment group was better, the bronchial epithelial structure of the control and TSG-6 treatment group was intact, and the epithelial cells were normal and closely arranged. The levels of RAC, VEGF, and TSG-6 in the TSG-6 treatment group were significantly increased, and the levels of IL-6 and TNF-α were significantly decreased at the early stage of life compared with the model group; the differences were statistically significant (P < 0.05). TSG-6 intervention can reduce the inflammatory response of pregnant rats with intrauterine infection and significantly improve the pathological degree of lung injury in newborn rats caused by intrauterine infection. Its mechanism may be related to promoting the increase of TSG-6 and VEGF levels, regulating the balance of inflammatory factors and promoting tissue repair.

Obstetric Use of Prostaglandin Preparations Compared to Mechanical Methods for Cervical Ripening in Pregnancies With Premature Rupture of Membranes at Term.

Background We examined the difference in obstetric outcomes between the cases using dinoprostone and those using mechanical methods in pregnant women requiring cervical ripening following premature rupture of the membranes (PROMs) at term. Methodology During the study period, dinoprostone was used in 34 nulliparous women, while mechanical methods were used in 35 nulliparous women for cervical ripening following PROM at term. We examined the differences in the delivery outcomes between the two groups. Results On the day of induction start, 2 cases (6%) in the dinoprostone group were delivered by cesarean section due to non-reassuring fetal status (NRFS), while no cases were complicated by NRFS in the mechanical methods group (P = 0.15). However, there was no significant difference in the rate of cesarean delivery between the two groups (P = 0.73). In the mechanical methods groups, 3 cases (9%) were complicated by clinical intrauterine infection, while there was no case of clinical intrauterine infection in the dinoprostone group (P = 0.08). The clinical intrauterine infection in the cases of the mechanical methods group occurred more than 2 days after the start of cervical ripening; however, there was no case of neonatal infection in the two groups. Conclusions There were differences in the characteristics of the effects between the two methods in pregnant women with PROM who have an unfavorable cervix; however, there were no differences in the final perinatal outcome.

Bone mineral density in young patients with perinatal infection with human immunodeficiency virus

The study of the issue of impaired bone mineral density (BMD) in people living with human immunodeficiency virus (HIV) who were infected perinatally (from birth) has objective reasons for the development of osteoporosis (OP). However, information about the state of bone tissue in this group is limited and no studies have been conducted in Russia. The role of risk factors and approaches to diagnosis, treatment, and prevention of osteoporosis have not been determined. Objectives. To assess the state of BMD using densitometry in perinatal HIV-infected adults on antiretroviral therapy (ART). Material and methods. This study included patients with perinatal HIV infection (n = 38) (main group) who continue to be followed up in the adult department of a specialized center and patients with sexually acquired HIV infection (n = 36) (comparison group) who have reached adulthood but are not older than 25 years old. Both groups were not concurrently infected with HIV or HBV. Were analyzed the level of CD4+ lymphocytes and the HIV RNA. Hip and spine densitometry was performed to assess bone matrix status using the Z-score taking into account age group of study participants. Results. Patients with perinatal HIV infection had a disease duration similar to their age at the time of the study, while the duration of ART administration was 13 years with a maximum of 21 years and 5 months. BMI in the study group showed that 73.6% of indicators were within normal limits, 5 patients had low body weight and one had grade I obesity, accounting for 2.6% respectively. Currently, three (7.8%) patients had detectable levels of HIV RNA despite irregular ART intake, with no signifi cant diff erences in CD4 lymphocyte counts during analysis of this indicator. At the time of diagnosis, the proportion of patients with immunodefi ciency was 20.9%. However, at the time of the study, this proportion had increased to 23.2%. Hip and spine densitometry, two patients (5.2%) were identifi ed with signs of osteopenia. The cause of this disorder is multifactorial and includes the presence of HIV infection, duration of antiretroviral therapy, and, in one case, the presence of concurrent somatic pathology requiring constant intake of glucocorticosteroids. Conclusion. Patients with perinatal HIV infection are at risk of developing osteoporosis and require regular medical monitoring to detect bone mineral density (BMD) disorders early and treat them promptly.

CLINICAL PROFILE OF MOTHER WITH HUMAN IMMUNODEFICIENCY VIRUS AND ITS FETOMATERNAL OUTCOME

Objectives: Human immunodeficiency virus (HIV) infection carries many high-risk conditions in pregnancy. Our study aims to analyze the clinical profile of HIV-pregnant women and to determine the fetomaternal outcomes among HIV-positive pregnancies. Methods: This study is a retrospective observational study carried out at C U Shah Medical College and Hospital, Surendranagar, Gujarat, covering data of all pregnant women with HIV who delivered between January 2018 and December 2022. Results: Among a total of 8881 patients delivered from January 2018 to December 2022, 56 mothers with HIV positivity gave birth. 80% of HIV-positive mothers are between 21 and 30 years of age group. Among all HIV-positive pregnant patients, 30% were diagnosed during pregnancy, and 75% were taking regular antenatal care (ANC) visits. A total of 60% of HIV-positive patients were undergone vaginal delivery, and 40% underwent lower segment cesarean section. Among all HIV-positive pregnant patients, different maternal complications were found in 65% of the population. A total of 1.8% of babies are positive with HIV at 6-week postpartum intervals through mother-to-child transmission (MTCT). Discussion: The study analyzed the 5-year clinical profile of HIV-positive mothers and their fetomaternal outcomes. The findings from the study reveal important facets related to maternal health and neonatal outcomes, the impact of antiretroviral therapy (ART), and the prevention of MTCT of HIV. Conclusion: This study brings out the clinical profile and fetomaternal outcomes of HIV-positive mothers over 5 years, with a special emphasis on the role of ANC and ART in improving outcomes. Early diagnosis of HIV infection, regular ANC, and strict adherence to ART reduce complications and improve outcomes.

Impact of congenital cytomegalovirus infection on vestibular dysfunction and hearing outcomes in a cohort of children

This study aims to evaluate long-term vestibular function and hearing outcomes in a cohort of children with congenital cytomegalovirus infection (cCMV) using a comprehensive battery of vestibular and hearing tests, and possible relationships between vestibular and cochlear damage and relevant clinical presentation variables of cytomegalovirus (CMV) infection. A prospective cohort study was carried out from June 2016 to December 2023 and included 40 children affected by cCMV. Our sample was composed by 35% males and 65% females, with age at first vestibular assessment ranging from 3 to 8 years old, and 30% (12) were symptomatic at birth. All patients received their diagnosis during the neonatal period, with none diagnosed retrospectively through dried blood spots. The median follow-up period was 5.3 years (ranging from 4.6 to 6.0). Comparing children with and without symptoms related to CMV, the presence of hearing loss (50% vs. 0.0%, p = 0.0002), psychomotor delay (25% vs. 0.0%, p = 0.024) and vestibular dysfunction (VD) (66.7% vs. 17.9%, p = 0.0075) were significantly increased in symptomatic patients. The VD was confirmed with a reduced gain of the lateral semicircular canals (LSCC) at the video head impulse test (vHIT) (58.3% vs. 17.9%, p = 0.021), and with the absence of response at cervical vestibular evoked myogenic potentials (cVEMPs) (54.5% vs. 3.7%, p = 0.0009). Comparing children with and without VD, we found a significant presence of reduced LSCC gain during the vHIT (93.3% vs. 0.0%, p < 0.0001), of an exclusive alteration in cVEMPs (61.5% vs. 0.0%, p < 0.0001), of hearing loss (46.2% vs. 0.0%, p = 0.0004), of patients with symptoms related to cCMV at birth (61.5% vs. 14.8%, p = 0.0075), of pathological neuroimaging at onset (61.5% vs. 7.4%, p = 0.0006), presence of antiviral therapy (61.5% vs. 11.1%, p = 0.0017) and positive viremia at onset (100% vs. 63%, p = 0.018). Finally, about time of maternal CMV infection the first trimester was associated to children with VD, while the third trimester to children without VD. cCMV infection can involve the entire inner ear: vestibular function seems to be more affected than cochlear function. Therefore, vestibular evaluation should be included in the audiological work up and follow-up in children with cCMV.

Investigation of Pre- and Postnatal Abnormalities Caused by Prenatal CMV Infection-Systematic Review.

CMV (cytomegalovirus) is associated with several developmental disorders. The incidence of congenital cytomegalovirus infection is around 1%, depending on the region. Previous prospective studies have shown that certain ultrasound findings are predictive factors for prenatal CMV infection. During this systematic review, we searched PubMed and Embas. Out of 569 results, 19 met our search criteria (we included cases where prenatally positive amniocentesis PCR for CMV was performed or autopsy confirmed the CMV diagnosis). A total of 237 cases were reported from 19 studies. In 64 cases, abortion or perinatal death occurred. The most common prenatal abnormalities were small for gestational age (n = 47), ventriculomegaly (n = 51), and hyperechogenic bowels (n = 39). A subependymal cyst was the most common prenatal MRI abnormality (n = 20). Hearing loss was observed in 61 cases (42 mild, 19 severe). Among prenatal signs, we found a correlation between hearing loss and ventriculomegaly (Fisher's exact test, p = 0.0052). The most common neurological complication was speech delay. We were able to demonstrate a prenatal association with neurological complications and subependymal cyst (Fisher's exact test, p = 0.00003547), but this pattern could only be reliably seen with MRI. In prenatally diagnosed CMV infection, ultrasound signals may be suitable for estimating the outcome. Conducting a prospective study and establishing a score would be worthwhile for its clinical application. In cases of ultrasound abnormalities and suspicion of CMV, it is worth performing a prenatal MRI, even in everyday practice.

Assessment of compliance with recommendations for HIV perinatal transmission prevention, timely diagnosis and early treatment of children living with HIV in Brazil.

Strategies for perinatally transmitted HIV (PTHIV) prevention are inconsistently adopted. Moreover, delays in diagnosis and treatment initiation for children living with HIV may aggravate outcomes. We used a survey study administered to Brazilian maternities to evaluate compliance with individual PTHIV prevention interventions as well as the overall compliance using a combined endpoint. We also investigated associations with the average number of births per month and municipal social vulnerability index (SVI) using regression models. Next, using data from Brazilian HIV monitoring systems, we obtained information on age at first HIV viral load (VL) testing and age at first antiretroviral dispensation to evaluate delayed diagnosis (first VL testing ≥6 months) and delayed antiretroviral initiation (first dispensation ≥12 months) among children living with HIV, investigating associations with race/ethnicity, sex and SVI. Of 801 maternities, only 21% were compliant with the combined endpoint. Facilities located in cities with higher SVI and those with a lower number of births per month had lower odds of being compliant. Among 1152 children living with HIV, the median age at first HIV VL testing was 3 months (range 0-18) and 24% had a delayed diagnosis. Children living with HIV in cities with higher SVI had higher odds of delayed diagnosis. The median age at antiretroviral initiation was 6 months (range 1-120), and those with a delayed diagnosis had higher odds of delayed treatment initiation (aOR 4.9, 95% CI 3.5-9.9). Our study reveals significant challenges in access to PTHIV prevention, timely diagnosis and timely treatment initiation for children living with HIV, potentially related to social determinants.

Cytomegalovirus (CMV) Saliva Shedding Kinetics in Children with Congenital CMV Infection (cCMV).

Congenital CMV (cCMV) is a common congenital viral infection worldwide and the most common cause of childhood non-genetic sensorineural hearing loss (SNHL). The kinetics of CMV detection (shedding) from mucosal surfaces have not been extensively described in children with cCMV due to a lack of systematic newborn CMV screening and follow-up protocols. The aim of this study is to describe the natural history of saliva CMV shedding in a cCMV cohort, which was identified through universal newborn screening. As part of the CMV and Hearing Multicenter Screening study (CHIMES), 100,332 newborns were screened, and those confirmed to have cCMV were followed prospectively every six months for four years to determine hearing outcomes. Saliva CMV DNA shedding kinetics, including duration, viral load (VL), and intermittent shedding are described and compared between groups with and without newborn symptoms and hearing loss in children with ≥ 5 visits. The 197 children with confirmed cCMV shed CMV DNA in saliva for a median of 20 months with CMV shedding frequency decreasing from 100% at cCMV confirmation to 9.5% four years after enrollment. Similarly, median CMV DNA VL levels decreased from 8.89X106 IU/ml at the confirmation visit to 1.64X103 IU/ml at the 4-year follow-up visit. Saliva CMV shedding duration was similar between children with or without newborn symptoms (median 20 months for both groups; p = 0.57) or between those with SNHL vs normal hearing (p = 0.8). A third of the cohort intermittently shed CMV DNA in saliva (64/197, 32.5%). In this large cohort of children with cCMV identified by universal CMV newborn screening, CMV DNA was detectable in saliva for a median of 20 months, irrespective of newborn symptoms or hearing outcomes. Intermittent shedding was noted in a third of the cohort.