Mother-to-child Transmission Research Articles

Epilepsy in Cerebral Palsy: Unraveling Prevalence, Risk Factors, and Subtype Associations in a Large-Scale Population Study

Background and Objective: Cerebral palsy (CP) constitutes a group of enduring movement disorders arising from non-progressive brain damage, often accompanied by epilepsy. This study aims to explore the prevalence of epilepsy in CP patients, dissecting demographic characteristics, healthcare parameters, and nuanced risk factors. Materials and Methods: The study employed the National Inpatient Sample (NIS) database (2016–2019, four years). CP patients were identified through ICD-10 codes, excluding non-CP patients and those with missing values. Baseline characteristics of CP patients, such as age, subtype distribution, and types of epilepsy, were tabulated, and disparities were assessed using the chi-squared test. Univariate and multivariate logistic regression analyses were conducted to examine predictors of epilepsy according to CP subtypes and infant-related conditions. Data were presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: In this comprehensive analysis of 88,138 CP patients, 44,901 with epilepsy and 43,237 without epilepsy, disparities between those with and without epilepsy were uncovered, revealing distinct demographic patterns and healthcare characteristics. Spastic diplegic CP showed the strongest association with epilepsy (adjusted OR = 1.88, 95% CI [1.73–2.04], p < 0.0001), underscoring the significance of subtype-specific considerations. Perinatal infection emerged as a noteworthy risk factor for epilepsy development (adjusted OR = 1.61, 95% CI [1.17–2.23], p = 0.004). Conclusions: The study provides nuanced insights into the prevalence and associations of epilepsy in CP patients. Specific CP subtypes and perinatal factors play pivotal roles in epilepsy risk. These findings offer a foundation for tailored clinical management and support services, addressing the complex needs of individuals with CP and epilepsy.

Blueberry Muffin Baby Syndrome in a Patient with Congenital Leukemia: Clinical Case

Background. Blueberry muffin baby syndrome in newborns is characterized by diffuse nodular skin lesions and it is difficult for diagnosis due to diverse etiology. Etiological factors include congenital infections, intrauterine hemolytic disease, multifocal vascular abnormalities, and neoplastic conditions. Congenital neonatal leukemia is rare disease and it is usually revealed during the first month of life. Clinical case description. This clinical case presents a patient with congenital acute myeloid leukemia and severe skin manifestations. Treatment has included risk-adapted chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation from a haploidentical donor (father). Conclusion. The significance of multidisciplinary approach in management of patients with congenital leukemias consist of timely determination of the disease variant, prognostic risk group, and initiation of programmed treatment.

Congenital and Perinatal Viral Infections: Consequences for the Mother and Fetus

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.

Mother-to-child Transmission using the National HBV Perinatal Prevention Data in Korea, 2002-2021

Abstract Aims To define risk factors associated with mother-to-child transmission (MTCT) and to create supporting evidence for the National Hepatitis B Perinatal Prevention Program (HBPPP) in Korea. Methods We analyzed HBPPP mother-infant pair data enrolled from 2002 to 2021. The major outcome was the HBsAg status of the infant resulting from post-vaccination serological testing. Additionally, we used prescription records of antivirals against the hepatitis B virus (telbivudine, tenofovir disoproxil fumarate) from 2010 to 2021 by data linkage with the National Health Insurance claims data. To select significant risk factors by maternal HBeAg status based on the data from 34 to 42 weeks of pregnancy, multivariate logistic regression analysis was used. Results Data from 232,242 mother-infant pairs were analyzed. Among 154,331 (66.5%) infants with post-vaccination serological testing results, 3,620 (2.3%) were HBsAg-positive. The incidence of MTCT has shown a decreasing trend, from 4.1% in 2002 to 1.0% in 2021. However, the rate was high at 5.5% (1822/32986) for infants of HBeAg-positive mothers. Maternal antiviral prescription during the pregnancy period, old age, HBeAg negative, delivery type (C-section), and breastfeeding were significant factors in decreasing the risk of MTCT. Among the HBeAg-positive, there was a significant difference in the antiviral prescription 0.7% (11/1692) compared to the non-prescription 4.9% (789/16264) [aOR, 7.71; 95% CI, 4.24-14.02]. The result was similar for the HBeAg-negative group, 0.7% (302/44888). Conclusions To eradicate the hepatitis B virus on a national level, MTCT must be further reduced. To achieve this, it is necessary to introduce strong additional preventive measures, including quantitative HBV DNA testing for mothers with chronic hepatitis B and administering antiviral prophylaxis at the third trimester of pregnancy with HBV-DNA ≥200,000 IU/mL into the HBPPP. Key messages • The incidence of mother-to-child transmission has shown a decreasing trend, from 4.1% in 2002 to 1.0% in 2021. • Maternal antiviral prescription, old age, HBeAg negative, delivery type (C-section), and breastfeeding were significantly decrease the risk of mother-to-child transmission.

Neonatal screening for hearing loss and its associated factors: A pediatric hospital experience

Abstract Introduction Hearing impairment affects 0.6% of children worldwide, with 60% of cases being preventable. Identifying risk factors for hearing impairment would facilitate early detection and better patient prognosis. Objectives To identify factors associated with abnormalities in auditory screening in a pediatric hospital. Methods A cross-sectional study was conducted on patients assessed in the early hearing detection program at the Pediatric Tower of the High Specialty Hospital of Veracruz, Mexico, between June 2022 and 2023. Screening was performed using otoacoustic emissions initially. Those with abnormalities underwent two retests, and those positive in all three evaluations underwent confirmatory testing. Newborn screening was conducted at discharge for healthy neonates and after reaching a weight of over 1.8 kg and more than 34 gestational weeks for preterm infants. For term and low-birth-weight babies, screening occurred when they reached 2 kg, considering positive results in any of the three tests indicative of altered screening and probable hearing impairment. Results A total of 2731 patients were fully evaluated, with 1416 (51.8%) being male, and a median Apgar score of 9 at 5 minutes. The incidence of hearing impairment was 0.7%, comprising 19 patients. Evaluation of sex, 5-minute Apgar score, weight, gestational age, congenital malformations, history of neonatal asphyxia, hyperbilirubinemia, sepsis, TORCH infections, family history of hearing impairment, maternal exposure to ototoxic drugs, substances, COVID-19, gestational diabetes, or maternal hypertension obtaining values of p > 0.05 in each of them. Conclusions The prevalence of hearing loss is similar to that reported in the literature. In our population, auditory screening abnormalities are not associated with classic perinatal factors, indicating the complexity of contributors to neonatal hearing impairment. Key messages • The neonatal screening program plays a fundamental role in identifying patients with hearing loss even without any clinical factor that arouses suspicion of hearing loss. • Early diagnosis will favor timely care for patients with hearing loss, favoring their development with adequate care to improve their quality of life.

Seroepidemiological study of Epstein-Barr virus infection in reproductive age women in Bulgaria

Abstract Background At the present stage, studies on the involvement of Epstein-Barr virus (EBV) in neonatal pathology are rare. Establishing seroprevalence among women of reproductive age has important epidemiological significance in order to determine the risk of infection during pregnancy and intrauterine infection of the fetus. The aim of the study is to determine the seroepidemiological status of EBV in reproductive age women. Methods We conducted a prospective seroepidemiological study in which 96 healthy women of reproductive age (18 to 49 years) were tested during the period December 2023 - January 2024 in Medical Center “Clinical Institute for Reproductive Medicine”- Pleven, Bulgaria. Participants were surveyed on a voluntary basis. The exclusion criteria were: presence of autoimmune disorder, immunosuppressive states, malignancy and populations at risk such as persons under 18 years of age and pregnant women. The presence of specific antibodies were detected using a standardized Anti-EBV VCA IgM, Anti-EBV VCA IgG and Anti-EBV EBNA-1 IgG ELISA kits. The demographic and anamnestic data were collected for each participant in Case Report Form. Results The average age of the women was 34.41±5.44 years. Dominating were women with higher education (76.04%) living in urban areas (91.67%). The results of the seroepidemiological study of markers for EBV show that 98.96% of women of reproductive age are seropositive. There was no significant correlation between the presence of antibodies and socio-demographic indicators (living area, education and number of family members). Conclusions The results of this study imply that only 1.04% of the reproductive age women in Pleven region are susceptible to infection with EBV. Although interpretation of the serological status indicates a low risk of primary infection, active monitoring of high-risk groups pregnant women is necessary because of the possibility of EBV reactivation. Key messages • On-going monitoring of the seroepidemiological EBV status in reproductive age women is necessary to determining the possibility of EBV reactivation and to reduce the teratogenic risk of the infection. • Seroepidemiological surveillance of markers for EBV infection in reproductive age women is part of effective preventive measures at the public health level.

Early Childhood Cholestasis, Causes & Associated Factors in Children

Background: Newborn cholestasis is explained as a persisted rise of the serum conjugated bilirubin outside the first two weeks of life. There are many etiologies of newborn cholestasis that must be differentiated since immediate interference may give a better outcome. Objective: Newborn cholestasis is explained as a persisted rise of the serum conjugated bilirubin outside the first two weeks of life. There are many etiologies of newborn cholestasis that must be differentiated since immediate interference may give a better outcome. Patients and Methods: A cross-sectional research of forty-eight children consulting the Childhood Wellbeing Teaching Hospital in Baghdad/Medical City from 1st of November 2018 to the 30th of November 2021, complete evaluation by full history, physical checkup and laboratory studies. Cholestasis was demarcated as an extended raise of the levels of conjugated bilirubin outside the 1st 2 weeks of age above 1.0mg/dl(17.1µmol/l) if the whole serum bilirubin(TSB) is <5.0 mg/dL or above 20% of the TSB if the TSB is >5.0 mg/dl. Results: Out of 48 children involved in the study ,62.5% resided in Baghdad, and the remainder was belonged to other districts. The mean age of children was 11.1 months. The males constituted 58.3% of them. Eleven cases (22.9%) were caused by congenital infection, nine 18.8% had no cause detected, while 16.7% caused by biliary atresia and 16.7% had unidentified etiology, however 10.4% was related to sepsis. Biliary atresia was more frequent in boys in 62.5% compared to 37.5% in females. Family history was positive only in11.1% of idiopathic neonatal hepatitis. It was found that 81% of cholestatic jaundice were caused by congenital infection. In comparison, 62.5% caused by biliary atresia and 60% caused by sepsis appeared on the second week of the child's age, and this difference was significant statistically P-value 0.01. Conclusion: Innate infections are the most frequent source, where CMV contagion is the most commonly detected. Clinical findings included clay colored stool & elevated alkaline phosphatase concentrations observed primarily on biliary atresia. There are no specific test to identify the etiology of newborn cholestasis.

Changes in the expression profile of serum lncRNAs in pregnant women with high hepatitis B viral load during antiviral and non-antiviral treatment

ObjectiveThis research analyzes the potential of long non-coding RNAs (lncRNAs) as markers in determining the necessity of antiviral treatment in pregnant women by examining alterations in the expression profile of serum lncRNAs in pregnant women with elevated hepatitis B viral load (HBVL) under antiviral and non-antiviral treatment regimens between the second trimester and delivery.MethodsSerum was obtained from 6 s-trimester pregnant women with high HBVL and no intrauterine infection. Then, 3 of these women were randomly selected for antiviral treatment, with the remaining 3 women undergoing non-antiviral treatment as control. Serum samples were again collected from these 6 women before delivery. The expression profile of lncRNAs was analyzed with microarray technology, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The axes of hub lncRNA-miRNA-mRNA were identified based on the competing endogenous RNA (ceRNA) network.ResultsThe expression profile of serum lncRNAs in pregnant women with high HBVL changed significantly from the second trimester of pregnancy until delivery under antiviral or non-antiviral treatment. The Venn diagram was utilized to screen out the jointly up-regulated and down-regulated lncRNAs in the serum of pregnant women under antiviral and non-antiviral treatment before delivery. Additionally, the KEGG pathway enrichment analysis results showed that lncRNAs might mediate the Hippo pathway in HBV infection. Based on the ceRNA network, 3 hub lncRNAs (CATG00000076041.1, LINC01310, and G014655) were found to potentially regulate the key gene TP73 in the Hippo pathway.ConclusionIn this study, we retrieved co-differentially expressed lncRNAs in pregnant women with high HBVL under antiviral or non-antiviral treatment, which may be used as markers for evaluating whether pregnant women with high HBVL may be free of antiviral treatment. This study may provide a basis for preventing potential adverse effects of antiviral treatment on maternal and fetal health.

Molecular Biology for Diagnosis of Congenital and Neonatal Infections in the Cerebrospinal Fluid of Newborns from a Brazilian Tertiary Hospital

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations.

Predictive model development for premature infant extubation outcomes: development and analysis.

Given the knowledge of the damage caused by prolonged invasive mechanical ventilation in premature newborns, withdrawing this support as quickly as possible is important to minimize morbidity. The aim of this study was to analyze the variables associated with extubation outcomes and to develop a predictive model for successful extubation in premature newborns. Data were obtained from a multicenter study involving six public maternity hospitals. The variables with the highest correlation to the extubation outcome were used to construct the predictive model through data analysis and machine learning methods, followed by training and testing of algorithms. Data were collected from 405 premature newborns. The predictive model with the best metrics was trained and tested using the variables of gestational age, birth weight, weight at extubation, congenital infections, and time on invasive mechanical ventilation, based on 393 samples according to the extubation outcome (12 were discarded due to irretrievable missing data in important attributes). The model exhibited an accuracy of 77.78%, sensitivity of 79.41%, and specificity of 60%. These variables generated a predictive model capable of estimating the probability of successful extubation in premature newborns. Prolonged use of invasive mechanical ventilation in preterm newborns increases morbidity/mortality rates, emphasizing the importance of early withdrawal from invasive ventilatory support. However, the decision to extubate lacks tools with higher extubation outcome precision. The use of artificial intelligence through the construction of a predictive model can assist in the decision-making process for extubating preterm newborns based on real-world data. The implementation of this tool can optimize the decision to extubate preterm newborns, promoting successful extubation and reducing preterm newborns exposure to adverse events associated with extubation failure.

Maternal NO2 exposure and fetal growth restriction: Hypoxia transmission and lncRNAs-proinflammation-mediated abnormal hematopoiesis

Epidemiological studies show a strong correlation between air pollution and fetal growth restriction (FGR), but existing results are controversial due to inherent limitations, such as causality of specific pollutants, developmental origin, and maternal-fetal transmission. To address this controversy, we first conducted a retrospective analysis of 28,796 newborns and revealed that maternal nitrogen dioxide (NO2) exposure during the second trimester was positively associated with FGR, with an adjusted odds ratio of 1.075 (95% confidence interval: 1.020-1.133) per 10 μg/m3 NO2 increase for small for gestational age. Then, by establishing an animal model of prenatal NO2 exposure, we confirmed its adverse effects on embryonic growth and hematopoiesis in the yolk sac and fetal liver, primarily affecting the differentiation of hematopoietic stem and progenitor cells and erythroid maturation. By applying internal exposure analyses coupled with 15N isotope tracing, we found that maternal NO2 inhalation induced acquired methemoglobinemia through its byproducts and placental hypoxia in pregnant mice. Importantly, by combining transcriptional profiling, bioinformatics analysis, and RNA binding protein immunoprecipitation (RIP)/chromatin immunoprecipitation (CHIP), we clarified that placental-fetal hypoxia transmission activated hypoxia-inducible factors, disturbed hematopoiesis through the hypoxia-inducible factor 1β-long noncoding RNAs-CCAAT/enhancer binding protein alpha-proinflammatory signaling pathway, ultimately contributing to FGR progression. These findings provide insights for risk prevention and clinical intervention to promote child well-being in NO2-polluted areas.

Ecological aspects of studying the thyroid function of the thyroid gland in women of reproductive age living in a region with iodine deficiency (Akhtynsky district, Republic of Dagestan, Russia)

Aim. To present epidemiological aspects of the study of thyroid function of the thyroid gland.The article presents the results of a clinical and laboratory examination and epidemiological aspects of studying the thyroid function of the thyroid gland in 120 women of reproductive age living in an area with iodine deficiency (Akhtynsky district, Republic of Dagestan – located at an altitude of 1.675 metres above sea level). The women were examined for thyroid diseases and for the presence of intrauterine infections: TORCH toxoplasmosis, ornithosis, rubella, cytomegalo‐ and herpesviruses.All the examined patients had thyroid diseases (the women are registered with an endocrinologist at an Endocrinological Dispensary). All women underwent correction of iodine deficiency in the form of iodine prophylaxis by taking medications containing a daily iodine requirement of up to 250 mcg to normalize thyroid function.Intrauterine infections (IUI) were found in 76 women (69 %. of the patients examined). Intrauterine infections of women registered in the women's clinic of the district hospital were also treated.

Congenital Cytomegalovirus Infection: Update on Screening, Diagnosis and Treatment: Scientific Impact Paper No. 56.

Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected. Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2-3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2-3 weeks until birth. In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28-32 weeks of gestation (and sometimes repeated 3-4 weeks later) to assess for any signs of harm to the fetal brain. All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life. In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some. There is no licensed vaccine for CMV.

Perinatal outcomes of selective termination in dichorionic twin pregnancies: a retrospective study from a single center.

Selective termination (ST) is an appropriate procedure for managing discordant fetal anomalies in dichorionic diamniotic (DCDA) twin pregnancies. The aim of this study was to investigate the perinatal outcomes of ST at different gestational ages in DCDA twin pregnancies. This retrospective study was conducted on DCDA twin pregnancies with STs at West China Second University Hospital between January 2012 and December 2022. According to the gestational age at which ST was performed, the patients were assigned to four groups: Group 1 (13 to 17 + 6weeks), Group 2 (18 to 23 + 6weeks), Group 3 (24 to 27 + 6weeks), and Group 4 (≥ 28weeks). We identified 230 patients for this study. The overall rates of miscarriage, preterm delivery at < 32weeks, and term delivery were 1.3%, 10.5%, and 50%, respectively, while the rates of live birth and neonatal survival were 98.7% and 98.2%, respectively. The rate of term birth was highest (70.6%) and the birth weight was heaviest (2931 ± 535g) in Group 1 (p = 0.000). In the presence of a fetus subjected to feticide, the mean delivery age was earlier than that in the non-presenting group (p = 0.017); accordingly, the mean birth weight in the feticide group was lower (2366 ± 628g) than that in the non-presenting group (2590 ± 634g) (p = 0.011). When we examined the relative relationship between reduction weeks and delivery weeks of twins by correlation analysis, we observed that with regard to maternal prognosis, two pregnancies involved preterm premature rupture of membranes (PPROM) at 7days and 3days after the procedure. Intrauterine infection occurred in two patients in Group 4, but there were no maternal deaths or maternal coagulatory abnormalities. Optimal perinatal outcomes were obtained by ST of DCDA pregnancies before 18weeks, regardless of whether or not the reduced fetus was the presenting twin. However, if legally possible, late (i.e., after 28weeks) procedures can be a safe alternative for patients diagnosed after the 18th week of gestation. Overall, we herein noted a negative correlation between the procedure week and the delivery week in this study. Moreover, ST of the non-presenting twin was associated with a heavier birth weight and later gestational age at delivery.

A prospective, multicenter study of hepatitis B birth-dose vaccine with or without hepatitis B immunoglobulin in preventing mother-to-child transmission of hepatitis B virus in Ethiopia

BackgroundHistorically, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) was considered uncommon in Africa, leading to a reluctant attitude to birth-dose HBV vaccination on the continent. As a randomized trial would be unethical, real-life data are needed to assess the effect of HBV birth-dose vaccine in Africa. MethodsA multicenter, prospective, observational study of hepatitis B surface antigen (HBsAg)-positive pregnant women and their infants was carried out in Ethiopia, from January 2019 to May 2021. Pregnant women were screened for HBsAg and HIV as part of routine antenatal care and/or delivery, and HBsAg-positive HIV-negative pregnant women were included in the study. HBV birth-dose vaccine and hepatitis B immunoglobulin (HBIg) were recommended but not all newborns received it as it was not national policy. All infants, however, received the pentavalent HBV vaccine at 6, 10, and 14 weeks of age. Vaccination status was confirmed from delivery ward charts and infant vaccination certificates. Infants were tested for HBsAg at 9 months of age and a positive result was taken as evidence of MTCT. FindingsOf 290 HBsAg-positive pregnant women, 168 mother/infant pairs returned for their 9-month follow-up visit and were included in this analysis. Two of 112 (1.8 %) infants who received birth-dose vaccine with HBIg, and 2 of 23 (8.7 %) who received birth-dose vaccine alone were HBsAg positive at nine months of age, compared to 8 of 33 (24.2 %) who received neither vaccine nor HBIg at birth (p = 0.002). High maternal viral load (>200,000 IU/ml; adjusted odds ratio [AOR] 10.4; 95 % confidence interval [CI] 1.2–92.1) and not receiving HBV birth-dose vaccine nor HBIg (AOR 29.2; 95 % CI 4.0–211.3) were independent predictors of MTCT. InterpretationBirth-dose HBV vaccine with or without HBIg significantly reduced the risk of MTCT of HBV in Ethiopia. Improved coverage of birth-dose HBV vaccine should be an urgent priority.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

The value of magnetic resonance imaging in congenital cytomegalovirus infection: a systematic review.

Congenital cytomegalovirus (cCMV) infection can lead to severe neurodevelopmental and hearing impairments. Imaging techniques can be used both pre- and postnatally to assess early signs of infection. The objective was to provide a systematic review of current literature regarding magnetic resonance imaging (MRI) and its value to predict clinical outcome in children with cCMV. PubMed, Embase, and Web of Science were searched for studies investigating MRI in cCMV between 2016-2024. Risk of bias was assessed using Newcastle-Ottawa quality assessment scales. Descriptive synthesis was performed. Twenty studies were included. MRI detected brain abnormalities in 5.0-53.0% of infected patients prenatally and 26.9-69.0% postnatally. The three most frequently detected abnormalities included white matter lesions, subependymal cysts, and ventricular dilatation. Symptoms at birth, first trimester seroconversion, and high viral load were associated with abnormal MRI; however, brain abnormalities were still found in 33-37% of clinically asymptomatic patients. Prenatal MRI had a negative predictive value of 94-100% and a positive predictive value of 12-60% for predicting adverse clinical outcome. Five in six studies found an association between MRI abnormalities and neurodevelopmental impairments, five in eight with (congenital) hearing loss. MRI detected additional abnormalities in 5.6-19.4% of children with normal ultrasound.In conclusion,MRI can detect a wide range of brain abnormalities, both pre- and postnatally, in symptomatic and asymptomatic patients. MRI can be a helpful tool in the prediction of clinical impairments and seems complementary to ultrasound. Therefore, both fetal and neonatal MRI should be considered in the standard work-up of all cCMV-infected children.

Designing a novel multi-epitope antigen for diagnosing human cytomegalovirus infection: An immunoinformatics approach.

Human cytomegalovirus (HCMV) infection can lead to congenital infections and severe complications, particularly in immunocompromised individuals. Current serological tests for diagnosing HCMV infection often face limitations in sensitivity and specificity. Developing multi-epitope antigens for serological assays offers the potential for enhancing diagnostic accuracy. This study aimed to design a novel multi-epitope antigen for HCMV infection diagnosis using immunoinformatic approaches. Five tegument proteins (universal protein resource [UniProt] ID: Po8318, Po6725, F5HC97, Q6RX10, and F5HC05) were selected based on their antigenic properties and literature review. Six linear B-cell epitopes were predicted within conserved regions of each antigen sequence and linked with appropriate linkers. The designed multi-epitope antigen underwent thorough evaluation for physicochemical properties, solubility, antigenicity, and cross-reactivity. Additionally, the three-dimensional structure of the antigen was predicted, refined, and validated. The nucleotide sequence of the designed antigen was optimized for successful expression in Escherichia coli and inserted into a pET23a (+) vector. Immunoinformatic analysis revealed that the multi-epitope antigen exhibits stability, antigenicity, and lacks cross-reactivity. Our findings suggest that this multi-epitope antigen is a promising candidate for diagnosing HCMV infection. However, further validation through laboratory testing is required to confirm its diagnostic efficacy.

Discrimination of primary and chronic cytomegalovirus infection based on humoral immune profiles in pregnancy.

BACKGROUNDMost humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus varies with gestational age at the time of primary maternal infection, further research on humoral responses to primary CMV infection during pregnancy is needed.METHODSHere, systems serology tools were applied to characterize antibody responses to CMV infection in pregnant and nonpregnant women experiencing either primary or chronic infection.RESULTSWhereas strikingly different antibody profiles were observed depending on infection status, limited differences were associated with pregnancy status. Beyond known differences in IgM responses used clinically for identification of primary infection, distinctions observed in IgA and FcγR-binding antibodies and among antigen specificities accurately predicted infection status. Machine learning was used to define the transition from primary to chronic states and predict time since infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection.CONCLUSIONIn sum, this work provides insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics.FUNDINGCYMAF consortium and NIH NIAID.

Birth outcomes following bictegravir exposure during pregnancy.

Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy. We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery. The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status. A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome. These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.