Mother-to-child Transmission Research Articles

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.

Frequency and Clinical characteristics of congenital cytomegalovirus infection among low-birth-weight newborn in a tertiary care hospital, Dhaka, Bangladesh

Frequency and Clinical characteristics of congenital cytomegalovirus infection among low-birth-weight newborn in a tertiary care hospital, Dhaka, Bangladesh

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

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

A study to assess the effectiveness of planned teaching program on knowledge regarding the prevention of TORCH infections among antenatal mothers in selected hospitals Bangalore, India

A study to assess the effectiveness of planned teaching program on knowledge regarding the prevention of TORCH infections among antenatal mothers in selected hospitals Bangalore, India

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).

Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

Passive second stage of labor: Does a fourth hour increase maternal morbidity in nulliparous patients at term with epidural?

ObjectivesProlonging the passive second stage of labor could increase vaginal birth rate, but the data concerning maternal and fetal morbidity are contradictory. The French guidelines did not specify a maximum duration of the passive second stage. Our objective was to assess if allowing a 4th hour after full dilatation before pushing increased maternal morbidity, compared to 3 h after full dilatation. Study designThis single-center, retrospective, observational cohort study took place from January 1–December 31, 2020, in a tertiary maternity unit. All consecutive term nulliparous women who delivered under epidural anesthesia and without pathological fetal heart rate and reaching a second-stage passive phase of labor lasting at least 3 h were included. We compared 2 groups according to the duration of the passive second stage: “3-hour group” and “4-hour group”. In the "3-hour group," featuring a second-stage passive phase of up to 3 h, pushing is initiated for favorable conditions, while a cesarean section is performed if conditions are deemed unfavorable. In the "4-hour group", obstetric conditions not justifying immediate pushing after three hours, and the obstetric team believed that an additional hour of expectant management could lead to a successful vaginal delivery. The principal endpoint was a composite criterion of maternal morbidity including obstetric anal sphincter injuries, postpartum hemorrhage, transfusion and intrauterine infection. ResultsWe included 111 patients in the “4-hour group” and 349 in the “3-hour group”. Composite maternal morbidity did not increase in the “4-hour group” compared to the “3-hour group” (21 (18.9 %) versus 61 (17.5 %); p = 0.73). Neonatal morbidity was similar between the two groups. In the “4-hour group, 91 (82 %) patients had vaginal deliveries”, 62 (55,9 %) by spontaneous vaginal delivery and 29 (26,1 %) with instrumental assistance. ConclusionFor selected patients, waiting for 4 h at full dilation can be beneficial due to the high rate of vaginal delivery and low incidence of maternal and fetal complications.

Congenital cytomegalovirus infection: new answers to old problems

Congenital cytomegalovirus infection is one of the most common TORCH infections, characterized by a wide range of clinical manifestations, predominantly with multiple organ lesions and often a disabling course. The result of antenatal infection with cytomegalovirus is a high incidence of congenital malformations, often accompanied by disorders such as hearing loss, vision loss, motor and cognitive deficits. Despite the presence of modern domestic clinical recommendations, the study of this pathology remains relevant to the present day. Recently, significant progress has been made in the study of this disease. Every year, new research is conducted on topical issues of diagnosis, treatment and rehabilitation for congenital cytomegalovirus infection. This article provides a review of modern literature, covering the latest data on the molecular basis of pathogenesis, features of clinical manifestations, current approaches to the diagnosis and treatment of congenital cytomegalovirus infection.

Identification of novel bacterial species in the blood of patients with neonatal sepsis

BackgroundThe clinical diagnosis of neonatal sepsis remains difficult because of various challenges, such as culturing the bacteria and avoiding contamination. Therefore, this study aimed to identify bacterial pathogens in patients with clinically diagnosed neonatal sepsis by next-generation sequencing (NGS).MethodsHigh-throughput NGS and traditional culture identification were performed by comparing samples from newborns with neonatal sepsis with healthy control infants. All blood samples were separately inoculated into anaerobic and aerobic bottles and incubated for 7 days at 37 °C, the positive specimens were then identified. Novel bacteria identified through high-throughput NGS were analysed using polymerase chain reaction (PCR), PCR products were verified by Sanger sequencing. Wilcoxon rank-sum and chi-square tests were performed to assess the significance of differences in species abundance between groups. Subjects were clinically diagnosed and hospitalized at the Pediatrics Department of Shenzhen Seventh People’s Hospital and Pediatrics Department of the Longhua Branch of Shenzhen People’s Hospital. Experiments were performed at the Shenzhen Seventh People’s Hospital. The experimental group comprised 45 newborns clinically diagnosed with neonatal sepsis (age: 0–28 days; 28 males, 17 females). Fifteen normal newborns aged 0–28 days (7 males, 8 females) were included as the control group.ResultsHigh-throughput NGS showed a positivity rate of 44% (20/45) for bacteria in patients clinically diagnosed with neonatal sepsis, whereas traditional bacterial culture identification showed a positivity rate of 0% (0/45). The four main bacterial species identified were Anoxybacillus kestanbolensis, Geobacillus vulcani, Klebsiella oxytoca, and Acinetobacter guillouiae.ConclusionsA. kestanbolensis, G. vulcani, K. oxytoca, and A. guillouiae, newly discovered bacteria in patients with neonatal sepsis, were identified with high-throughput NGS. Which may result from maternal intrauterine infection or birth-canal infection and have a high clinical-cure rate. Owing to a lack of methods to culture these bacteria, their role in neonatal sepsis remains unclear. A definite diagnosis cannot rely solely on bacterial culture identification for patients with a suspected diagnosis and clinical diagnosis of neonatal sepsis and should involve other effective diagnostic techniques.

Cost-Effectiveness of Dolutegravir Compared With Efavirenz for Prevention of Perinatal Transmission in Women Presenting With HIV in Late Pregnancy in Uganda

ObjectivesDolutegravir (DTG) has proved to be more efficacious, tolerable, and safer than efavirenz (EFV) among mothers living with HIV and their infants in Uganda. This study assessed the cost-effectiveness of the DTG-based antiretroviral therapy (ART) compared with the standard of care for preventing perinatal transmissions among pregnant women initiating ART in late pregnancy in Uganda. MethodsWe used data from a randomized open-label trial (DolPHIN-2) and a 2-part cost-effectiveness model composed of a short-term decision tree to estimate the perinatal transmission rate and costs and an individual-based 3-state Markov model (HIV, advanced HIV, dead) to estimate the long-term costs and health outcomes from the Ugandan payer perspective using a lifetime horizon and a 1-year Markov cycle. The main outcomes were the mean annual costs in US dollars ($), disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratio. Both the deterministic and probabilistic sensitivity analyses were conducted to assess the effect of parameter uncertainties on the ultimate results and the model’s robustness. ResultsCompared with the EFV-based ART, the DTG-based ART was associated with fewer mean annual costs ($43.58 vs $68.44) and DALYs (0.33 vs 0.56), leading to cost savings of $110 per DALY averted. In the incremental analysis, the DTG-based ART dominated the EFV-based ART; that is, it was less costly and more effective. These results were robust to deterministic and probabilistic sensitivity analyses. ConclusionThe DTG-based ART is a highly cost-effective strategy compared with the EFV-based ART among women initiating treatment in the third trimester of pregnancy in a low-income setting.

Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection

Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: −0.51 (−0.91, −0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.

Severe COVID-19 in pregnant women: Analysis of placental features and perinatal outcomes.

Changes in placental features, such as maternal and fetal vascular malperfusion, are associated with SARS-CoV-2 infection. The anatomopathologic study of the placenta is crucial for understanding pregnancy and fetal complications. To that end, this study aimed to describe placental features and analyze the association between placental findings and perinatal outcomes in a cohort of pregnant women with severe COVID-19. This nested study within a prospective cohort study consisted of 121 singleton pregnant women with a diagnosis of severe COVID-19. Placental pathologic findings were described, and the associations between severe COVID-19 and clinical parameters and perinatal outcomes were assessed. The prevalence of maternal vascular malperfusion was 52.1%, followed by fetal vascular malperfusion at 21.5%, ascending intrauterine infections at 11.6%, and inflammatory lesions at 11.6%. Other lesions were observed in 39.7% of the placentas examined. Inflammatory lesions were an independent factor (P = .042) in 5-minute Apgar scores below 7. Ascending infection was associated with fetal death (P = .027). Maternal vascular malperfusion was the most prevalent placental feature in patients with severe COVID-19. Chorangiosis is associated with poor perinatal outcomes.

Screening for TORCH Antibodies in Croatian Childbearing-Aged Women, 2014-2023.

TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16-45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005-2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections.

Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.

Case series: Congenital enterovirus infection-associated haemophagocytic lymphohistiocytosis and subsequent neutropaenia.

Congenital enterovirus infection can be associated with a pro-inflammatory state triggering haemophagocytic lymphohistiocytosis (HLH). Enteroviruses are also known to cause transient neutropenia in healthy children. Two infants presented with temperature instability, lethargy, thrombocytopaenia, hepatosplenomegaly and evidence of hyperinflammation in the setting of perinatal maternal rash and household contacts with gastrointestinal symptoms. Whilst HLH was successfully treated in both, protracted neutropenia persisted. Immune dysregulation with enterovirus in the neonatal period can provoke the generation of autoantibodies to hematologic cells giving rise to conditions such as autoimmune neutropenia. Sustained neutropaenia, after resolution of secondary infectious forms of HLH, requires investigation for underlying aetiologies.

Effectiveness of Structured Teaching Program on Knowledge Regarding TORCH Infections during Pregnancy among Antenatal Mothers at Telungupalayam Village, Coimbatore District

Effectiveness of Structured Teaching Program on Knowledge Regarding TORCH Infections during Pregnancy among Antenatal Mothers at Telungupalayam Village, Coimbatore District