Prevalence and clinical aspects of CMV congenital Infection in a low-income population
© The Author(s). 2016
Received: 27 June 2016
Accepted: 22 August 2016
Published: 31 August 2016
CMV is the most common cause of congenital infection in the whole world (0.2 to 2.2 %). That infection may be symptomatic or asymptomatic at birth and, although asymptomatic cases at birth are more common, some children may develop late sequelae, and require medical intervention. This study aimed to determine the prevalence of CMV congenital infections in children who were born in a public hospital in Ilhéus, Brazil, and to evaluate the clinical progression in infected newborns.
CMV congenital infection was determined by detecting viral DNA through nested PCR.
The viral DNA was detected in 25 newborns, showing a prevalence of 1.19 % (25/2100) of CMV congenital infection. In regards to the risk factors from mothers, only the variables: age of mothers (p = 0.003), number of children (p = 0.011), and use of medications (p < 0.001) were associated with the congenital infection. Approximately 12 % of children presented symptoms. One death and two auditory alterations were detected during the monitored period. Only 50 % of children diagnosed attended their medical follow.
The prevalence found confirms the findings from other studies which involved other poor populations. Two children presented impaired hearing during the monitored period; that was one of the main sequelae from the infection. It is noteworthy that there was low adherence to medical follow-up which may underestimate data on complications of the infection CMV. Late symptoms can be mistaken for other diseases or even go unnoticed.
KeywordsCongenital cytomegalovirus disease Newborn screening Epidemiology Late sequelae Medical supervision
Cytomegalovirus (CMV) infection is common worldwide and its prevalence is inversely proportional to the socioeconomic status of the population and can be higher than 90 % in developing countries including Brazil . In addition, CMV infection has been associated with ethnicity and contact with CMV sources, including people who work in daycare facilities [2, 3].
CMV is the most common cause of congenital infection worldwide and its prevalence varies between 0.2 % and 2.2 % of all infants born [4, 5]. It may be symptomatic, but in 85 – 90 % of the cases, it is asymptomatic at birth. Approximately 90 % of the symptomatic cases involve neurological impairment and unilateral or bilateral sensorineural deafness, with a significant impact on the quality of life, and these cases may progress to death [6, 7]. However, 5 – 15 % of asymptomatic children can present late symptoms and develop progressive, irreversible future sequelae, including impairment of the central nervous system, hearing, and vision, and delayed mental and psychomotor development, among other complications [8, 9].
The diagnosis of the congenital infection should be done before the third week of life because, after this period, it is not possible to assess whether viral transmission occurred through the placenta or through external sources such as the birth canal, saliva, or breast milk .
The early diagnosis of CMV congenital infection and clinical follow-up are essential to detect and manage the disease and prevent sequelae [9, 11]. Despite the importance of this infection, many children who are congenitally infected with CMV remain undetected because diagnosis is not performed by the public health system in many countries, including Brazil.
This study aimed to evaluate the prevalence of CMV congenital infections in a public hospital in Ilhéus, Brazil, and its clinical progression during the first years of life.
A total of 2100 newborns were included in this study, at any gestational age and in any clinical condition. These newborns were born between February 2010 and December 2012 in Santa Helena Maternity, São José Hospital, located in Ilhéus, southern Bahia, Brazil. Subjects whose parents or guardians refused to sign the consent form were excluded from the study. The study was approved by the Human Research Ethics Committee of the Universidade Estadual de Santa Cruz (UESC) under protocol No. 209/08.
Saliva samples from the newborns were collected with sterile swabs, which were gently placed in their mouth for 1 min to moisten the swabs and transferred to sterile plastic tubes containing 700 μL of transport medium (MEM Earle, Cultilab). After 60 min, the swabs were discarded and the medium was stored at 4 °C until further processing. Urine samples were collected aseptically in hypoallergenic collecting bags. Care was also taken to avoid contamination with meconium. We chose to also use the saliva that has been found to saliva samples seems to be a good specimens for a neonatal screening of congenital CMV due to its ease of collection and for having sensitivity and specificity similar to urine, the gold standard .
Sequence of primers used in the PCR for CMV
Product size in base pairs
5’ CAGCACCATCCTCCTCTTCCTCTGG 3’
5’ CCAAGCGGCCTCTGATAACCAAGCC 3’
5’ CCACCCGTGGTGCCAGCTCC 3’
5’ CCCGCTCCTCCTGAGCACCC 3’
To visualize the PCR products, 10 μL of each amplified product was added to 1.0 μL of GelRed dye and subjected to agarose gel electrophoresis at 2 %. The electrophoresis was conducted at 150 V for 30 min using a Tris/Borate/EDTA buffer solution (0.089 M of Tris, 0.089 M of borate, 0.01 M of EDTA, pH 7.5). Gels were photographed using a digital camera coupled with a UV transilluminator.
Clinical examinations, including measurement of weight, height, head and chest circumference, liver size, spleen size, and fundoscopy.
Complementary examinations: hemogram (including platelet count), liver function test, and measurement of total and fraction bilirubin.
To correlate maternal risk factors with the prevalence of CMV infection, the following maternal variables were collected through the application of a questionnaire: age, ethnicity, marital status, number of children, schooling, and use of legal and illegal drugs.
The prevalence of positive cases and symptoms was determined by calculating the prevalence rate.
The epidemiological data and the clinical manifestations in infected and uninfected children were compared. SPSS software version 20.0 was used for statistical analysis. The chi-squared test with Yates’ correction was used whenever applicable. The Kolmogorov-Smirnov test was conducted to assess the normality of quantitative data. P-values lower than 0.05 were considered statistically significant.
Clinical findings suggesting congenital CMV at the time of birth
General clinical aspects
Number of children
The child who presented symptoms at birth died on the seventh day due to cytomegalovirus disease. This female infant was born by normal delivery in a 36-week pregnancy, weighed 2,095 g, had a head circumference of 24 cm, chest circumference of 27.5, and body length of 44 cm. The clinical changes during disease progression included discomfort while breathing, globular and flaccid abdomen, generalized edema, jaundice, tachypnea, petechiae, sloughing, and weak reflexes. The laboratory alterations included C-reactive protein levels of 48 mg/dL (reference value of 0.1 mg/dL), marked cell atypia, serum glutamic oxaloacetic transaminase (GOT) levels of 78 URF/mL (reference value of 4–36 URF/mL), and thrombocytopenia.
Only 12 children (50 %) attended the periodic follow-up visits. Of these, only 2 children (16.7 %) presented late CMV symptoms (auditory alterations) and were referred to brainstem-evoked response audiometry (BERA). However, both children needed to relocate and were no longer monitored.
Clinic and epidemiological characteristics of mothers according to CMV infection
Mothers of CMV infected children (n = 25)
Mothers of CMV no infected children (n = 2075)
12 to 15 years old
4 (16 %)
124 (6 %)
>5 sexual partners
20 (80 %)
1773 (85.4 %)
Sexual onset before 19 years old
24 (96 %)
1776 (85.6 %)
17 (68 %)
456 (22 %)
Close contact with children < 2 years old
10 (40 %)
1108 (53.4 %)
Other infectious disease
0 (0.0 %)
230 (11.1 %)
0 (0.0 %)
45 (2.2 %)
Data from deliveries and clinical characteristics of children according to CMV infection
9 (36 %)
1056 (50.9 %)
14 (56 %)
997 (48 %)
Normal weight at birth
20 (80 %)
1799 (86.7 %)
Low body weight
4 (16 %)
162 (7.8 %)
1 (4 %)
97 (4.7 %)
22 (88 %)
849 (41 %)
0 (0.0 %)
1 (0.05 %)
Normal head circumference
19 (76 %)
1252 (60.3 %)
Decreased head circumference with deficiency
2 (8 %)
57 (2.7 %)
Increased head circumference
2 (8 %)
194 (9.3 %)
The prevalence of 1.19 % found in Ilhéus was similar to the findings of other studies conducted in low-income regions. In fact, the prevalence varied between 0.2 % and 2.2 % depending on the region and on the socioeconomic status of the population [5, 7, 15–19].
With regard to the symptoms, 87.5 % of the newborns were asymptomatic and 12.5 % showed symptoms. One of them showed symptoms at birth and two of them showed late symptoms detected during follow-up. The child who presented symptoms at birth died on the seventh day from cytomegalovirus congenital disease, which was confirmed by molecular diagnosis and by laboratory and clinical tests. This newborn was pre-term (less than 37 weeks), had low-birth weight (below the 10th percentile of the intrauterine growth curve), decreased head circumference with a trace of microcephaly (below the 10th percentile of the intrauterine growth curve), petechiae, globular abdomen, discomfort while breathing, generalized edema, jaundice, tachypnea, sloughing, and weak reflexes. Laboratory examinations indicated altered C-reactive protein levels and increased GOT.
The two children with late symptoms showed auditory alterations characterized by the lack of auditory response detected at 2 years of age, and were referred to BERA. Previous studies have reported varying rates of hearing loss associated with CMV congenital infection, time of clinical follow-up, and primary maternal infection during pregnancy [7, 20].
Only 12 mothers or guardians attended the previously scheduled post-natal follow-up visits. Some mothers discontinued the supervision for different reasons including changed telephone numbers or changed addresses. The high number of absences in follow-up visits may mask the infection symptomatology and even prevent those children from receiving proper care. Furthermore, late onset symptoms related to CMV infection may be mistaken for other diseases or even go unnoticed. The difficulty to reach patients confirms the importance of creating a health education program to educate the population about these infections and the strategies to prevent and treat them.
The maternal age and number of children were associated with CMV congenital infection. In addition, infection was more frequent in young mothers (12 – 15 years old). The early sexual maturity and lack of information concerning CMV infection may increase the risk of primary infections, which lead to a higher likelihood of vertical virus transmission as demonstrated in the literature [21, 22]. Moreover, the present study showed that most young mothers were primiparous and that primiparous women had higher likelihood of transmitting the infection vertically, thereby contributing to the increased infection rate among the newborns.
The prevalence of CMV infection in Ilhéus, Brazil, was similar to the findings of other studies conducted in low-income regions and most infected children were asymptomatic. However, late symptoms related to CMV can occur, leading to progressive and irreversible sequels. Besides, the high number of absences in follow-up visits observed in this study may mask the infection symptomatology and even prevent those children from receiving proper care. It is noteworthy that the implementation of a national educational policy and the monitoring of infected children are important strategies aimed to decrease the risk of virus transmission and detect late symptoms and sequelae.
Brainstem-evoked response audiometry
Glutamic oxaloacetic transaminase
Universidade Estadual de Santa Cruz
The authors thank the Santa Helena Maternity, São José Hospital, for its support in clinical diagnosis and UESC to have available space and give conditions to the experiment.
This study was also supported by the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB); Greant number: APP 0094/2009; and UESC number: 00220.1600.744.
Availability of data and materials
That the data will not be shared because the methods used for the experiment are standard and widely used in the scientific community.
ESCC acquired the data, reviewed the literature, interpreted the data and wrote the manuscript. MFMF and MRR acquired the data. SMBS, LDC and SRG contributed to the writing of the manuscript. LJM supervised interpretation of the data, revised the manuscript and gave final approval for publication. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent to publish
All presented cases or their legal guardian provided consent to publish according to institutional guidelines.
Ethics approval and consent to participate
All presented cases or their legal guardian provided consent to data collection and use according to institutional guidelines.
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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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