Prevalence Of Congenital Congenital Cytomegalovirus Infection Research Articles

The impact of maternal HIV and malaria infection on the prevalence of congenital cytomegalovirus infection in Western Kenya

BackgroundData on congenital cytomegalovirus (CMV) infection in Africa are limited. ObjectiveTo describe the prevalence of congenital CMV infection in a population with high prevalence of maternal HIV and malaria infection in western Kenya. Study designWe screened newborns for CMV by polymerase chain reaction assay of saliva swabs and dried blood spots (DBS), and assessed maternal CMV immunoglobulin G (IgG) status by testing serum eluted from newborn’s DBS. We calculated adjusted prevalence ratios (aPRs) using log-binomial regression models. ResultsAmong 1066 mothers, 210 (19·7%) had HIV infection and 207 (19·4%) had malaria infection; 33 (3·1%) mothers had both. Maternal CMV IgG prevalence was 93·1% (95% confidence interval [CI]: 88·3%–96·0%). Among 1078 newborns (12 sets of twins), 39 (3·6%, 95% CI: 2·7–4·9%) were CMV positive. The prevalence of congenital CMV infection by maternal HIV and malaria infection status was 5·0% (95% CI: 2·7–9·2%) for HIV only, 5·1% (95% CI: 2·7–9·4%) for malaria only, 8·8 (95% CI: 3·1–23·0) for HIV and malaria co-infection, and 2·6% (95% CI: 1·7–4·1%) for none. Congenital CMV infection was independently associated with maternal HIV infection (aPR=2·1; 95% CI: 1·0–4·2), adjusting for maternal age, parity, and malaria infection. ConclusionsThe prevalence of congenital CMV infection was higher than the 0·2–0·7% in developed countries. Maternal HIV infection may increase the risk of congenital CMV infection, but the role of maternal malaria on intrauterine transmission of CMV remains unclear.

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia

ObjectivesLittle is known about the birth prevalence and characteristics of congenital cytomegalovirus (CMV) infection in developing countries. To determine the prevalence and characteristics of congenital CMV infection in Indonesia, we conducted a prospective study in an urban birth cohort of neonates at a national referral hospital in 2016−2017, Jakarta, Indonesia. MethodsConsecutively born neonates were screened for the presence of CMV by using pan-herpesvirus nested-PCR and Sanger sequencing in saliva and/or urine specimens. Both the neonatal clinical findings as well as maternal characteristics were also evaluated. ResultsFrom a total of 411 newborns screened, congenital CMV infection was confirmed in 5.8% of the neonates. These CMV-positive newborns were more likely to have ventriculomegaly and thrombocytopenia compared to CMV-negative neonates. Notably, 67% CMV-positive neonates in our study had clinical findings that required medical intervention, from which only nine presented with symptoms suggestive of congenital CMV infection. Furthermore, congenital CMV infected babies were almost four times more likely to be born to mothers that had placenta previa and placental abruption. ConclusionsOur work highlights the high prevalence of congenital CMV infection in neonates born in one of the biggest referral hospitals in metropolitan Jakarta, Indonesia.

Prevalence and determinants of congenital cytomegalovirus infection at a rural South African central hospital in the Eastern Cape

Background: The Nelson Mandela Academic Hospital (NMAH) in Mthatha, Eastern Cape, is a rural central hospital, serving one of the poorest districts in South Africa. The prevalence of and risk factors for congenital cytomegalovirus (CMV) in this area are not known. The aim was to evaluate the prevalence of congenital CMV and associated risk factors for babies born at NMAH.Methods: This was a cross-sectional study to determine the prevalence of congenital CMV infection among babies born at Nelson Mandela Academic Hospital. Mother–baby pairs delivered consecutively from Monday to Friday, who gave informed consent, were included. Demographic information was collected on a questionnaire. All babies were tested for congenital CMV using a saliva swab PCR within the first week of life.Results: A total of 302 births were assessed. Congenital CMV was prevalent in 18 births (5.96%; 95% CI 3.29–8.63) and had an equal prevalence between HIV-exposed and HIV-unexposed newborns (prevalence ratio [PR] = 1.00; 95% CI 0.94–1.06; p = 0.869).Conclusions: The prevalence of congenital CMV of 5.96% is similar to findings from other resource-limited settings. There was no significant association between maternal HIV status and congenital CMV. With the prevalence of congenital CMV being as high as it is in the studied setting, clinicians are advised to have a high index of suspicion, especially when mothers are CMV seropositive.

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis.

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.

Prevalence of Congenital Cytomegalovirus Infection Assessed Through Viral Genome Detection in Dried Blood Spots in Children with Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are neurodevelopmental disorders without a definitive etiology in most cases. Environmental factors, such as viral infections, have been linked with anomalies in brain growth, neuronal development, and functional connectivity. Congenital cytomegalovirus (CMV) infection has been associated with the onset of ASD in several case reports. The aim of this study was to evaluate the prevalence of congenital CMV infection in children with ASD and in healthy controls. The CMV genome was tested by polymerase chain reaction (PCR) on dried blood spots collected at birth from 82 children (38 with ASD and 44 controls). The prevalence of congenital CMV infection was 5.3% (2/38) in cases and 0% (0/44) in controls (p=0.212). The infection rate was about 10-fold higher in patients with ASD than in the general Italian population at birth. For this reason, detection of CMV-DNA on dried blood spots could be considered in the work-up that is usually performed at ASD diagnosis to rule-out a secondary form. Given the potential prevention and treatment of CMV infection, this study could have intriguing consequences, at least for a group of patients with ASD.

Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China.

Congenital cytomegalovirus (CMV) infection is the leading viral cause of birth defects and developmental disabilities in developed countries. However, CMV seroprevalence and burden of congenital CMV infection are not well defined in China.Cohort of newborns from 5 birthing hospitals in 2 counties of Shandong Province, China, were enrolled from March 2011 to August 2013. Dried blood spots (DBS) and saliva were collected within 4 days after birth for IgG testing for maternal seroprevalence and real-time PCR testing for congenital CMV infection, respectively.Among 5020 newborns tested for CMV IgG, 4827 were seropositive, resulting in CMV maternal seroprevalence of 96.2% (95% confidence interval [CI]:95.6%–96.7%). Of the 10,933 newborns screened for congenital CMV infection, 75 had CMV detected, resulting in an overall prevalence of 0.7% (95% CI: 0.5%–0.9%), with prevalences of 0.4% (14/3995), 0.6% (66/10,857), and 0.7% (52/7761) for DBS, wet saliva, and dried saliva specimens screened, respectively. Prevalence of congenital CMV infection decreased with increasing maternal age (0.9%, 0.6%, and 0.3% among newborns delivered from mothers aged 16–25, 26–35, and >35 years, respectively; P = 0.03), and was higher among preterm infants than full term infants (1.3% vs 0.6%, P = 0.04), infants with intrauterine growth restriction (IUGR) than those without (1.8% vs 0.7%, P = 0.03), and twins or triplets than singleton pregnancies (2.8% vs 0.7%, P = 0.04). None of the 75 newborns exhibited symptomatic congenital CMV infection, and there was no difference in clinical characteristics and newborn hearing screening results between infants with and without congenital CMV infection at birth.Congenital CMV infection prevalence was lower and the clinical manifestations were milder in this relatively developed region of China compared to populations from other countries with similarly high maternal seroprevalence. Follow-up on children with congenital CMV infection will clarify the burden of disabilities from congenital CMV infection in China.

Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit.

Congenital cytomegalovirus (CMV) infection can cause a variety of neurological deficits of delayed onset in infants who are asymptomatic at birth. The aim of this study was to investigate the prevalence of congenital CMV infection among children with autism spectrum disorder (ASD) in Nagasaki, Japan. Twenty-nine children with ASD who were born in Nagasaki and had no other major neurological deficits were recruited. Two of the patients were excluded due to significant perinatal events. The remaining 27 children were investigated retrospectively for congenital CMV infection by analyzing dried blood spot samples or dried umbilical cords for CMV DNA using real-time PCR. CMV DNA was detected in two (7.4%) of the 27 children. Neither of the patients had perinatal histories suggestive of congenital CMV disease or other neurological deficits, including hearing impairment and epilepsy. The severity of their autistic disorders varied considerably. The rate of congenital CMV infection in this study (two of 27 children with ASD), which was significantly (p=0.004) higher than the incidence of congenital CMV infection in Nagasaki (0.31%, 10/3230 live births), suggests the involvement of congenital CMV infection in a portion of children with ASD, although definite diagnosis was not obtained due to limited clinical data of the study subjects.

Chapter 15 - Congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection, the most common congenital viral infection worldwide, occurs in approximately 1% of infants. Most congenitally infected infants have no long-term sequelae related to CMV infection. Approximately 10% have sensorineural hearing loss or neurologic deficits, including cerebral palsy, epilepsy, and cognitive impairment. Because of the high prevalence of congenital CMV infection, CMV is the most common non-genetic cause of deafness in children and an important cause of permanent neurodevelopmental disabilities. Treatment with ganciclovir has modest beneficial effects on outcome; no vaccine is currently available to prevent congenital CMV infection.

Congenital cytomegaloviral infection as a risk factor for preterm birth

Congenital cytomegalovirus (CMV) is the most common cause of congenital-acquired infection in the United States and preterm birth continues to be a world-wide public health problem. Given infection has been shown to play a role in preterm delivery; the objective of this study was to determine the prevalence of congenital CMV infection in a population of preterm infants and determine if it a risk factor for preterm birth.

Clinical profile of hearing loss in children with congenital cytomegalovirus (CMV) infection: CMV DNA diagnosis using preserved umbilical cord

Conclusions: Congenital cytomegalovirus (CMV) infection is a major cause of bilateral and unilateral sensorineural hearing loss (SNHL) in children, accounting for 9.0% of SNHL cases. The diagnostic rate using combined genetic deafness test and CMV DNA detection test was determined to be 46.4% in bilateral profound SNHL. Objectives. The present study investigated the prevalence of congenital CMV infection diagnosed retrospectively by detection of CMV DNA in dried umbilical cord specimens from children with unilateral or bilateral SNHL up to the age of 12 years. Methods: Preserved dried umbilical cords were collected from 134 children with bilateral (46 children) or unilateral (88 children) SNHL. DNA was extracted from the dried umbilical cords and CMV DNA was detected by quantitative PCR. Genetic deafness tests based on the invader assay were performed in children with bilateral SNHL. Results: CMV DNA from the dried umbilical cords was detected in 8.7% of the bilateral SNHL and 9.1% of unilateral SNHL. Deafness gene mutations were identified in 21.7% (10/46) of children with bilateral SNHL.

Maternal Human Immunodeficiency Virus Infection and Congenital Transmission of Cytomegalovirus

To determine the frequency of congenital cytomegalovirus (CMV) infection in infants born to human immunodeficiency virus (HIV)-infected mothers and assess risk factors that may facilitate intrauterine transmission of CMV, including the role of perinatal HIV infection. Retrospective cohort study of infants who were born to HIV-infected mothers at Parkland Memorial Hospital and screened for congenital CMV infection according to a standard nursery protocol between February 1, 1997 and May 31, 2005. During the 8-year study period that included 125,781 live births, there were 367 infants (0.3%) born to 303 HIV-infected mothers. Of 333 HIV-exposed infants who were screened for CMV, 10 (3%) had congenital CMV infection and 6 (60%) of these were identified only because of the CMV screening protocol. Four (1%) infants were infected with HIV, and none of these was CMV-infected. Compared with CMV-uninfected infants, CMV-infected, HIV-exposed newborns had lower mean birth weight (2508 versus 3148 g, P < 0.01), lower gestational age (37 vs. 39 weeks, P < 0.01), and higher median maternal HIV viral load at the start of prenatal care (15,411 vs. 2209 copies/mL, P = 0.02). CMV-infected infants were more likely to be born to mothers who were diagnosed with HIV during the pregnancy or at delivery (P = 0.03). The prevalence of congenital CMV infection among HIV-exposed newborns was 3%. Screening of these infants for CMV would allow identification of infants who are at risk for delayed onset of hearing loss and other neurodevelopmental impairment.

Decreased Risk of Congenital Cytomegalovirus Infection in Children Born to HIV‐1–Infected Mothers in the Era of Highly Active Antiretroviral Therapy

We evaluated the prevalence of congenital cytomegalovirus (CMV) infection before and after highly active antiretroviral therapy (HAART) availability among neonates born to human immunodeficiency virus type 1 (HIV-1)-infected mothers. We also identified maternal risk factors associated with in utero CMV transmission. Routine screening for congenital CMV infection was performed from 1993 through 2004 in children born to HIV-1-infected mothers included in the French Perinatal Cohort (Enquête Périnatale Française). Interpretable tests on urine samples collected within the first 10 days of life were available for 4797 of the 7563 live-born infants. Prevalence was estimated for different time periods. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CMV transmission in the HAART era. Among live-born children, the overall prevalence of CMV infection was 2.3% (95% confidence interval, 1.9%-2.8%). Prevalence was higher among HIV-1-infected neonates (10.3%; 95% confidence interval, 5.6%-17.0%) than among HIV-1-uninfected neonates (2.2%; 95% confidence interval, 1.8%-2.7%; P < .01). Among HIV-1-uninfected neonates, the prevalence of CMV infection decreased over time, from 3.5% in 1997-1998 to 1.2% in 2003-2004. Delivery period, maternal age, time at antiretroviral treatment initiation, and maternal CD4(+) cell count <200 cells/mm(3) close to delivery were independently associated with CMV infection in logistic regression analysis. The percentage of symptomatic CMV infections was 23.1% among HIV-1-infected newborns and 6.7% among HIV-1-uninfected neonates. The prevalence of congenital CMV infection was high and associated with high morbidity rates among HIV-1-infected neonates. Conversely, the prevalence of CMV infection decreased over time among neonates not infected with HIV-1, reaching levels similar to those observed in the general population, following the introduction and increasing use of HAART for prevention of mother-to-child HIV-1 transmission.

Congenital CMV infection: Prevalence in newborns and the impact on hearing deficit

Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was assessed by otoacoustic emission (OAE) within a newborn screening programme. 12 infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One boy among the 12 infected infants had unilateral hearing loss, indicating that the risk of hearing loss is greatly increased (about 20 times) in CMV infected infants. No child developed ocular complications such as chorioretinopathy during 3 y of follow-up. Congenital CMV has an impact on child health but can easily be overlooked due to lack of signs in the neonatal period. Surveillance for congenital CMV is important in addition to programmes for prevention and treatment.

Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection

We reviewed studies that reported results of systematic cytomegalovirus (CMV) screening on fetuses and/or live-born infants. The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live-born infants with congenital CMV infection were symptomatic, but the inter-study differences in definitions of symptomatic cases limit the interpretation of these data. Non-white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections. In summary, CMV is a common congenital infection worldwide that can lead to permanent disabilities. There is an urgent need for interventions that can reduce the substantial burden of this often overlooked disease.

Risk Factors for and Clinical Outcome of Congenital Cytomegalovirus Infection in a Peri-Urban West-African Birth Cohort

BackgroundCongenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high.Methodology/Principal FindingsAs part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child.Conclusions/SignificanceIn this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.

Clinical survey of congenital cytomegalovirus infection in Japan.

The clinical features of congenital cytomegalovirus (CMV) infection in countries with a higher percentage of maternal seropositivity for CMV has rarely been reported. We conducted a national survey for the first time in Japan to investigate the prevalence of congenital CMV infection. Questionnaires were sent in 1994 to pediatricians and obstetricians of 3398 hospitals with either more than 100 beds or a neonatal intensive care unit (NICU). The questionnaire asked for the number of new cases in 1992 and 1993, maternal status of CMV infection, diagnostic methods, clinical manifestations at birth, sequelae and prognosis. A total of 46 cases of CMV infection were reported for the years 1992 and 1993 by 1448 hospitals; of these 39 were symptomatic. The annual incidence of symptomatic disease was 1.6 cases/100,000 live births. Major clinical manifestations such as low birthweight, hepatosplenomegaly, petechiae and intracranial calcification were noted at birth in 38-50% of symptomatic neonates. Sequelae, such as hearing loss, mental retardation and motor disability developed in 71% of survivors. Thirty-five percent of the 49 infected infants had either died or had severe disability. Several clinical manifestations at birth, including petechiae/thrombocytopenia, were significantly associated with severe sequelae or a poor prognosis. The lower frequency of clinical findings at birth may be attributed to the higher seroprevalence of pregnant women in Japan than in Europe and the United States.