Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy.

The rate of congenital cytomegalovirus (CMV) infection was studied in newborn infants in an African population in which all adults had experienced primary CMV infection during childhood. Viruria within the first 12 hours after delivery was taken as evidence of prenatal CMV infection. 28 of 2032 newborn infants examined had viruria, giving a rate of 1.4% congenital CMV infection. The presence of meternal serum antibody therefore appears not to protect the fetus from intrauterine infection. Either reactivation of latent maternal CMV infection or recurrence of infection during pregnancy despite the presence of serum antibodies may explain these findings. Whether the long-term effects of CMV infection acquired in utero differ in cases of primary maternal infection from those due to reactivated or recurrent infection in seropositive mothers, remains undecided. Thus, the value of a live CMV vaccine to prevent prenatal CMV infection may be questioned.     

Congenital cytomegalovirus infection in preterm and full-term newborn infants from a population with a high seroprevalence rate

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infections in humans. Prematurity occurs in as many as 34% of infants with symptomatic congenital CMV infection. OBJECTIVE: To determine the clinical presentation and frequency of congenital CMV infection among preterm infants and full-term infants from a population with a high seroprevalence rate. DESIGN/METHODS: A total of 289 preterm infants (median gestational age, 34 weeks; median birth weight, 1,757 g) and 163 term infants (median gestational age, 39 weeks; median birth weight, 3,150 g) sequentially born were included in the study. Serum IgG antibodies to CMV were measured in all mothers. One urine sample was collected within the first 7 days of age from all newborns. Virus isolation in urine samples was performed by tissue culture, and viral DNA was detected by a multiplex PCR. CMV infection was diagnosed in infants with virus excretion detected by both methods on at least two occasions within the first 3 weeks of life. RESULTS: Maternal CMV seropositivity rate was 95.7%. Congenital CMV infection was detected in 6 of 289 (2.1%) (95% confidence interval, 0.84 to 4.68) preterm infants and in 3 of 163 term infants (1.8%) (95% confidence interval, 0.48 to 5.74) (P > 0.05). Four of 6 preterm infants with congenital CMV infection were symptomatic, but none of the term infants was symptomatic (P = 0.16). CONCLUSION: The frequency of congenital CMV infection in preterm newborn infants from mothers with a high seropositive rate was similar to that found in term infants. No significant difference was found between the proportion of symptomatic infants among preterm and term infants. Our finding of symptomatic congenital CMV infection underscores the need of further evaluation of correlates of congenital symptomatic infection in highly immune populations.     

Impact of asymptomatic congenital cytomegalovirus infection on size at birth and gestational duration

Cytomegalovirus (CMV) is the most common viral agent causing congenital infection in humans, affecting 0.2 to 2.4% of all live births. Symptomatic congenital CMV infection has previously been shown to cause low birth weight and prematurity. Whether or not asymptomatic congenital CMV infection, which represents the majority of cases (90 to 95%), affects intrauterine growth or gestational duration is unknown. Using a population of 146 infants with asymptomatic congenital CMV infection and 1419 controls from two socioeconomically diverse populations (biracial low income and white mid- to upper income), determinants of body size (birth weight and crown-heel length) were investigated using multiple regression techniques. We found that congenital infection following the transmission of maternal primary and "unknown" CMV infection resulted in a significant mean birth weight deficit of 163 g (P less than 0.04) for the low income term infants (blacks and whites), but not in the mid- to upper income white infants. Newborns with congenital infection following the transmission of maternal reactivated (recurrent) CMV infection were significantly shorter by a mean of 1 cm (P less than 0.03) than controls, a finding that was consistent regardless of socioeconomic status or race.     

Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity

OBJECTIVE: To define hearing outcomes in children with congenital cytomegalovirus (CMV) infection born to mothers with non-primary CMV infection. STUDY DESIGN: A cohort of 300 children with congenital CMV infection identified by newborn virologic screening at the University of Alabama Hospital and a private community hospital in which the type of maternal infection could be classified constituted the study population. Maternal infections were categorized by analyzing serum samples. Children were followed prospectively and underwent serial audiologic evaluations. RESULTS: The frequency of hearing loss was not different between children born to mothers with non-primary infection (10%) and those with primary infection (11%). Significantly more children in the primary infection group had progressive and severe/profound hearing loss compared with children in the non-primary group. The frequency of bilateral, delayed onset, high-frequency, and fluctuating hearing loss was not different between the 2 groups. The mean age of diagnosis of hearing loss was 39 +/- 53 months for children born to mothers with non-primary infection and 13 +/- 21 months for the primary infection group (P = .16). CONCLUSIONS: Maternal preexisting seroimmunity to CMV does not provide complete protection against hearing loss in infants with congenital CMV infection.     

PRIMARY AND SECONDARY MATERNAL CYTOMEGALOVIRUS INFECTIONS AND THEIR RELATION TO CONGENITAL INFECTION

ABSTRACT. 4382 new mothers were examined retrospectively with the enzymelinked immunosorbent assay (ELISA) for IgG activity to cytomegalovirus (CMV) during pregnancy. Some of them were also studied with the indirect immunofluorescence (IIF) test for CMV-IgM antibodies. All the infants had been studied for CMV excretion within the first week of life. Nineteen of them had been shown to be congenitally infected with CMV. 1218 (28 %) women lacked CMV-IgG activity at their first antenatal visit (usually in months III-IV). Fourteen of them seroconverted before parturition (primary infection). Thirteen of the seroconverters were shown to develop CMV-IgM activity. In 6 (43 %) cases the primary infection was transmitted to the offspring. The remaining 13 congenitally infected infants were born to mothers with a positive IgG-test at their first antenatal control. Only one of these mothers had a clearly positive IgM-test. She was shown to lack CMV-antibodies before conception (primary infection during the first trimester). Preconceptional sera were obtained from further 4 of the 13 seropositive mothers of congenitally infected infants; all 4 had CMV antibodies before pregnancy (secondary infection during pregnancy). The combined studies of the mothers and infants revealed that 21–63 % of the congenital infections could have been caused by secondary maternal infections. Prospectively performed, the study would only have disclosed one of the three fetal CMV infections that resulted in neurological sequelae.     

Primary and secondary maternal cytomegalovirus infections and their relation to congenital infection. Analysis of maternal sera

4 382 new mothers were examined retrospectively with the enzyme-linked immunosorbent assay (ELISA) for IgG activity to cytomegalovirus (CMV) during pregnancy. Some of them were also studied with the indirect immunofluorescence (IIF) test for CMV-IgM antibodies. All the infants had been studied for CMV excretion within the first week of life. Nineteen of them had been shown to be congenitally infected with CMV. 1 218 (28%) women lacked CMV-IgG activity at their first antenatal visit (usually in months III-IV). Fourteen of them seroconverted before parturition (primary infection). Thirteen of the seroconverters were shown to develop CMV-IgM activity. In 6 (43%) cases the primary infection was transmitted to the offspring. The remaining 13 congenitally infected infants were born to mothers with a positive IgM-test at their first antenatal control. Only one of these mothers had a clearly positive IgM-test. She was shown to lack CMV-antibodies before conception (primary infection during the first trimester). Preconceptional sera were obtained from further 4 of the 13 seropositive mothers of congenitally infected infants; all 4 had CMV antibodies before pregnancy (secondary infection during pregnancy). The combined studies of the mothers and infants revealed that 21-63% of the congenital infections could have been caused by secondary maternal infections. Prospectively performed, the study would only have disclosed one of the three fetal CMV infections that resulted in neurological sequelae.     

CMV seroconversion in pregnants and the incidence of congenital CMV infection

In this study, it was aimed to determine the ratio of CMV seroconversion in pregnant women, the prevalence of maternal CMV infection and also the incidence of congenital CMV infection in their newborns in the Antalya region of Turkey. During a one-year period, CMV-specific IgG and IgM were determined in all (n: 1027) pregnant women admitted at 8 to 20 weeks of gestation, an according to the presence or absence of anti CMV-IgM and CMV-IgG, pregnant women were classified as seropositive, seronegative and having maternal CMV infection. Differentiation of primary and recurrent CMV infection in women with both CMV-IgM (+) and CMV-IgG (+) antibody was determined by the avidity index (AI) of anti-CMV IgG. Ultrasonographic examination was done and amniocentesis was performed at 21 to 23 weeks of gestation in pregnants with primary infection. CMV DNA was investigated in the amniotic fluid by quantitative polymerase chain reaction (qPCR). Pregnants with recurrent infection were followed only by ultrasonography for the presence of fetal abnormalities. Neonates born to mothers with CMV infection were examined for the findings of congenital CMV infection and screened for anti- CMV-IgM, CMV DNA and CMV antigenemia in the first two weeks of life. The rate of seropositivity was found as 98.5% and the rate of seronegativity as 1.5% in pregnant women. The prevalence of maternal CMV infection was found as 1.2% and among these pregnant women, the incidence of primary and recurrent maternal CMV infection was 0.3% (3 women) and 0.8% (12 women), respectively. Congenital CMV infection was detected in one of the newborns born to mothers with primary infection while no infection was detected in any of the newborns of mothers with recurrent CMV infection, so the incidence of congenital CMV infection was found as 0.1% and the rate of intrauterine infection following the primary maternal infection was 33%. In conclusion, seroprevalence rate of CMV in pregnants is high and most (66%) infections are recurrent maternal CMV infection in our region. Thus, it does not seem to be cost-effective to screen all pregnant women for CMV infection, as in the other countries with high seropositivity rate.     

Clinical survey of congenital cytomegalovirus infection in Japan

Abstract Background 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.
Methods: 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.
Results. 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 in38–50% 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.
Conclusion: 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.     

Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature

Cytomegalovirus (CMV) is one of the most common causes of congenital infections in developed countries with reported incidences varying between 0.15% and 2.0%. The effects of congenital CMV infection may vary from a congenital syndrome to an asymptomatic course. Infants that are asymptomatic at birth may still present handicaps at a later age. It is generally accepted that symptoms of congenitally infected children are more severe after primary infection than after recurrent infection. In this article, we present two case reports which demonstrate that the outcome of recurrent maternal CMV infection may be severe. In the first case, early pregnancy serology showed positive IgG and IgM, but negative IgA, whereas at the time of diagnosed fetal death, 5 weeks later, there was only positive IgG. The second case showed positive IgG and negative IgM and IgA both in early pregnancy and after delivery. Since in both cases CMV was isolated from several organs, these findings are compatible with recurrent rather than primary CMV infection. In the reported patients, fetal death and necrotising enterocolitis occurred after a congenital CMV infection, with mothers having pre-existing immunity to CMV. In conclusion, these case reports and review of the literature emphasise that the outcome of recurrent maternal CMV infection may be severe and that congenital CMV infection should be considered in cases of pregnancy loss and necrotising enterocolitis with recurrent maternal CMV infection.     

Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10(3) genome equivalents (GE)/mL of females AF and 1.9 x 10(5) GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10(4) GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.     

Congenital CMV infection in symptomatic infants in Delhi and surrounding areas

Many viral infections are associated with significant maternal and fetal consequences during pregnancy among which cytomegalovirus is one of the most important agent, globally. Both primary and recurrent infection due to this virus can result in fetal infection. Samples from Congenital Anoammaled babies are referred to NICD from Delhi based Government hospitals and surrounding areas for diagnosis of congenital infections like Toxoplasm, Rubella, CMV and Herpes. In the present study, accumulated data is presented for the most common teratogenic virus—Cytomegalovirus prevalence as a causative agent for congenital infection in New Born babies at Delhi and surrounding areas. 96 samples from symptomatic babies in the age group of few days to 6 months exhibiting different congenital anomalies, were reported between 1 st Jan 04 to 30 th April/05. All the blood samples were tested for the detection of CMV (IgM) antibodies using μ-capture ELISA technique. 18(18.75%) samples from babies showed positive titres for CMV-IgM antibodies. None of the mothers of positive babies were found positive for CMV-IgM antibodies but all were serologically exposed to CMV virus previously as their serum samples were positive for CMV-IgG antibodies indicating primary infection in the past or reactivation/reinfection with a different strain of CMV in the early pregnancy.     

Predicting the outcome of symptomatic congenital cytomegalovirus infection

Abstract The prognosis of babies with symptomatic congenital cytomegalovirus (CMV) infection is worse than for those with asymptomatic CMV, but is difficult to quantify. Babies affected as a result of primary maternal CMV are at greater risk than after reactivation CMV. Chorioretinitis occurs in 10–15% of symptomatic babies and almost always indicates significant mental impairment. Microcephaly occurs in around 50% at birth, but does not always persist, and does not necessarily imply later neurological handicap. Investigative findings that increase the likelihood of handicap include radiographic or computerized tomography scan finding of intracranial calcification and raised cerebrospinal fluid protein. Late deafness is always unpredictable and all babies with congenital CMV infection should have an audiological follow up. The mortality of symptomatic congenital CMV infection is about 30%.     

Congenital cytomegalovirus infection

Congenital cytomegalovirus is the most common intrauterine infection and the leading non-genetic cause of sensorineural hearing loss. Worldwide, the birth prevalence is estimated at 7 per 1000 with the highest rates seen in developing countries. The highest intrauterine transmission rates and risk of neurodevelopmental sequelae are associated with primary maternal infections. Transmission occurs less frequently after non primary maternal infections due to reactivation or reinfection. 10–15% of infected infants are symptomatic at birth, with neurological symptoms present in two-thirds. Infants who are asymptomatic at birth may go on to develop late neurodevelopmental sequelae, with sensorineural hearing loss being the commonest late consequence. Prenatal, neonatal and retrospective diagnosis can be challenging. Early treatment of symptomatic neonates with the antiviral drug valganciclovir can reduce the long-term neurodevelopmental sequelae. Universal or targeted screening for congenital CMV is not currently advocated. The development of an effective vaccine appears to be some years away. This review highlights the important considerations for clinicians regarding the diagnosis, investigation and management of children with possible or confirmed congenital CMV infection.     

Transmission du cytomégalovirus par le lait maternel cru aux enfants prématurés : étude épidémiologique pilote

Transmission of cytomegalovirus (CMV) infection from mothers to preterm infants during breastfeeding may be symptomatic and long term consequences are unknown. This study evaluated the kinetics of CMV load in breastmilk and the rate of postnatal CMV transmission via breastmilk from mothers to their preterm infants.MethodsProspective study of mother-child pairs after preterm delivery before 33 weeks. Exclusion of donor breast milk and of CMV-seropositive blood products. Material used was maternal CMV serostatus, ear swab of the infant at birth, weekly screened breast milk and children's urine by rapid viral culture.ResultsDuring a 5-month period 28 mother-infant pairs with 34 preterm infants were studied. Eighteen women (64.3%) were CMV-seronegative at birth; breastmilk samples and the infants' urine remained CMV-negative. Eight of the 10 seropositive mothers, who had 11 preterm infants, excreted CMV into breast milk (80%). CMV excretion into breast milk was detected during the first week after delivery in 66% cases and was at its peaked between 3 to 5 weeks after delivery. Out of the 7 CMV-exposed infants, CMV transmission was confirmed in only one asymptomatic case. Total quantity of breast milk intake did not seem discriminative for CMV transmission.ConclusionIn CMV-seropositive mothers of preterm infants a high incidence of CMV excretion into breast milk was detected. Despite this high rate, symptomatic infection did not occur. However, potential risk and severity of infection may be difficult to establish. Because breastfeeding is beneficial, new procedures for gentle virus inactivation of seropositive breast milk should be assessed.     

Cytomegalovirus infection

Although commonly asymptomatic, congenital CMV infection is the leading cause of nonhereditary SNHL. Other sequelae that may be evident only after the neonatal period can include chorioretinitis, neurodevelopmental delay with mental or motor impairment, and microcephaly. (13) ? Congenital CMV infection is confirmed by detection of the virus in urine, blood, or saliva within the first 3 weeks of life by culture or polymerase chain reaction. A positive test does not necessarily confirm symptomatic CMV disease or need for treatment. (13) ? Postnatal CMV infections transmitted through human milk have been reported and may be clinically relevant in extremely premature infants; however, the risk-benefit ratio of pasteurizing human milk for the prevention of postnatal CMV infection is unclear. ? Ganciclovir, valganciclovir, foscarnet, cidofovir, and CMV hyperimmune globulin are effective in treating or preventing CMV infections in the immunocompromised host, but require close monitoring for associated toxicities. Treatment for congenital CMV is associated with significant toxicity and uncertain effectiveness. ? Based on strong evidence, anticipatory guidance for congenital CMV infection should include hearing tests and neurodevelopmental assessments until school age. (3) In patients with symptomatic congenital CMV infection, lifelong ophthalmologic screening should be included. (4) ? Based primarily on consensus, owing to lack of relevant clinical studies, it is not recommended to withhold human milk produced by CMV-seropositive mothers from healthy term infants. (5)(6) ? Based on some research evidence, as well as consensus, treatment for congenital CMV is recommended only in symptomatic infants with central nervous system involvement. (9)     

Prevalence and clinical aspects of congenital cytomegalovirus infection

OBJECTIVES: The objectives of the present study were to determine the prevalence of congenital CMV infection, as well as to evaluate the importance of this agent as cause of congenital disease, and to describe the clinical manifestations in children attended at a General Hospital in Ribeir?o Preto, SP, Brazil. POPULATION AND METHODS: A first group including 189 newborns and their mothers was evaluated for the prevalence of the congenital CMV infection. A second group including 130 newborns and 74 infants who presented clinical manifestations of congenital disease were also investigated to evaluate the importance of the CMV as a cause of this disease and to describe the clinical findings. Diagnosis of congenital CMV infection was established by detecting the virus using viral isolation in tissue culture, polymerase chain reaction DNA amplification in urine samples and detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test. RESULTS: The prevalence of congenital CMV infection was 2.6% and the prevalence of CMV antibodies in mothers was 95%. In the first group, none of the 5 congenitally infected presented clinical apparent disease at birth, although one of them had intracranial calcifications. In the second group, CMV was recognized as a causative of congenital disease in 12 children (5.9%). Of these, 10(83%) were identified after the neonatal period. The clinical findings included hepatosplenomegaly (75%), jaundice with direct hyperbilirubinemia (42%), neurologic disease consisting of microcephaly and intracranial calcifications in 42% of these children. CONCLUSIONS: The prevalence of congenital CMV infection was similar to that reported in other studies about highly immune populations. Infants with asymptomatic congenital CMV infection may have diseases of the central nervous system that are not clinically evident at birth, such as punctate calcifications. CMV infected patients who are symptomatic at birth have a multisystem disease, and the differential diagnosis of any newborn with clinical abnormalities including involvement of the hepatobiliary, hematopoietic and central nervous systems should include congenital CMV infection. CMV was an important agent of these abnormalities, and the majority of symptomatic patients were identified after the neonatal period, making the diagnosis more difficult.     

Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is a major public health problem because 30,000 to 40,000 neonates with the infection are born each year in the United States. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic, and developmental sequelae. The current study describes the audiologic outcome of 59 infants with asymptomatic congenital CMV infection compared with 26 control infants. Eight of 59 infected infants had congenital sensorineural hearing loss (SNHL) but none of the control subjects did. Longitudinal audiologic assessments revealed that 5 of the 8 infants had further deterioration of their SNHL; a ninth infant with initially normal hearing experienced a unilateral SNHL during the first year of life, with further deterioration subsequently. The frequency of SNHL was similar for infected infants born to mothers with recurrent CMV infections during pregnancy (2 of 9) and for those born to mothers who experienced primary CMV infections (5 of 26). There was a significant difference between the occurrence of hearing loss in infected infants with normal computed tomographic scans (2 of 40) compared with those with either periventricular radiolucencies (4 of 13) or calcifications (1 of 3). Children with SNHL often have no identified cause of the loss; thus, it is likely that many of these children had asymptomatic congenital CMV infection. Given the progressive nature of SNHL associated with asymptomatic congenital CMV infection, longitudinal audiologic assessments are mandatory.     

Perinatal or early-postnatal cytomegalovirus infection in preterm infants under 34 weeks gestation born to CMV-seropositive mothers within a high-seroprevalence population

In a prospective study, we evaluated the frequency, correlates, and clinical significance of perinatal or early-postnatal cytomegalovirus (CMV) infection in <34-week-gestation infants (n=95) born to CMV-seropositive mothers. None had congenital CMV infection. Overall, 21 (22.1%; 95% CI=14.2-31.8) infants were found to be infected; 10 excreted CMV at <60 days, and 11 had later excretion. Blood transfusion, birth weight, and vaginal delivery were not associated factors. Receiving natural breast milk within the first 30 days (OR=4.5, P=.02) or for >30 days (OR=7.9, P <.01) was associated with infection. Only one (4.8%) of the infected infants was symptomatic. For <34-week-gestation infants, frequency of perinatal and early-postnatal CMV infection is high. Early or prolonged exposure to breast milk is an associated factor. However, most infections are asymptomatic, indicating that CMV infection in preterm infants within such a population is a serious problem infrequently.     

Cytomegalovirus DNA detection on Guthrie cards in patients with neonatal cholestasis.

AIM: To time the onset of cytomegalovirus (CMV) infection in patients (n = 39) with CMV associated neonatal cholestasis by analysing CMV DNA on Guthrie cards sampled at 3 days of age. METHODS: CMV infection was diagnosed by serology/urine isolation or by CMV DNA detection (polymerase chain reaction) in liver biopsy specimens. In order to time the infection dry blood filter paper discs were punched out from stored Guthrie cards. After phenol-choloroform extraction CMV DNA was detected by nested polymerase chain reaction. RESULTS: All cards from control children (n = 8) with congenital CMV tested positive; none of the negative controls (n = 4) did so. Two of 39 cholestatic infants were CMV DNA positive; their mothers had serological signs compatible with infection during the second half of the pregnancy. All other cholestatic infants tested negative. CONCLUSIONS: CMV DNA was not detected in most of the children using Guthrie cards, suggesting that infection developed at or soon after birth.     

Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?

OBJECTIVE: To predict whether universal newborn auditory screening will identify most infants with sensorineural hearing loss (SNHL) caused by congenital cytomegalovirus (CMV) infection. STUDY DESIGN: A cohort of 388 children born between 1980 and 1996 at one hospital and identified during the newborn period as having congenital CMV infection received repeated hearing evaluations to assess whether hearing loss had occurred. RESULTS: SNHL was detected in 5.2% of all infants at birth. Late-onset SNHL occurred among the children throughout the first 6 years of life. By the age of 72 months, the cumulative incidence of SNHL was 15.4% in the cohort. Children with clinically apparent disease at birth had significantly more SNHL than children without any apparent disease (22.8% vs 4.0% at 3 months and 36.4% vs 11.3% at 72 months of age). CONCLUSIONS: Universal screening of hearing in neonates will detect less than half of all SNHL caused by congenital CMV infection. Because most infants with congenital CMV infection are without symptoms at birth, these children are unlikely to be recognized as being at risk for SNHL and will not receive further hearing evaluations to detect late-onset hearing loss. A combined approach of universal screening of neonates for hearing, as well as for detection of congenital CMV infection, needs to be considered.