Intrauterine Cytomegalovirus Infection Research Articles

Attempts to shine light on fetal responses to intrauterine cytomegalovirus infection

Attempts to shine light on fetal responses to intrauterine cytomegalovirus infection

Клинический случай врожденной патологии центральной нервной системы: мультикистозная трансформация полушарий головного мозга (энцефаломаляция), внутренняя гидроцефалия

A case of multicystic encephalomalacia in a deceased child aged 1 month 17 days is presented. The dynamics describes changes in the general condition of the child, morphofunctional changes in the brain. The tactics of treatment and resuscitation measures in dynamics are given. A rare case of the formation of huge cysts of both hemispheres of the brain in a child born with an intrauterine cytomegalovirus infection is presented. In this observation, the relationship between a congenital infection and hypoxic dysfunction and morphology of the cerebral hemispheres is considered.

Analysis of the process leading to termination of pregnancy in the third trimester

Objective: To evaluate fetal anomalies and processes leading to termination of pregnancy in the third trimester. Methods: The study includes all cases who underwent termination of pregnancy after 28 weeks of gestation due to fetal anomalies between 2017 and 2022. Results: Forty four of third trimester terminations were carried out in our clinic due to fetal anomalies incompatible with life or associated with severe sequelae. Structural anomalies including 35 (79.5%) cases were the most common reason of terminations followed by chromosomal or genetic abnormalities in 8 (18.2%) cases and intrauterine cytomegalovirus infection in 1 (2.3%) case. The processes leading to the third trimester termination were evaluated by dividing 44 patients into 5 groups. (1) Delayed diagnosis due to inadequate prenatal care (25 patients, 56.8%); (2) patients diagnosed with late-onset findings (5 patients, 11.4%); (3) patients with abnormal findings in prenatal care or history but delayed diagnosis (5 patients, 11.4%); (4) patients with abnormal findings requiring further evaluation (4 patients, 9.0%); (5) patients with a definitive diagnosis but latency in the decision of family for termination of pregnancy (5 patients, 11.4%). Conclusion: Termination of pregnancy in the third trimester has an important role in countries where unfollowed pregnancies are common and access to health services is poor due to low socio-economic status.

Brainstem auditory pathway maturation in term neonates with congenital cytomegalovirus infection: a cohort study.

Congenital cytomegalovirus infection (cCMVi) is a leading cause of sensorineural hearing loss (SNHL) and developmental delay. Brainstem auditory evoked potentials (BAEPs) recording allows assessment of central auditory pathway maturation in neonates. We aimed to characterize the effect of cCMVi on the maturation of the brainstem auditory pathway in term neonates. We retrospectively reviewed medical records of neonates born with cCMVi in 2010-2018 and characterized their auditory pathway maturation using brainstem auditory-evoked potentials (BAEPs). We compared inter-peak latency differences (IPLDs) of the main BAEP components (I-V, I-III, and III-V) in terms of cCMVi patients and healthy controls and described their changes in cCMVi patients throughout the first year of life. Of 101 cCMVi patients, 57 (56.4%) were considered symptomatic, 6 (5.9%) were small for gestational age, 6 (5.9%) had microcephaly, 4 (4%) had thrombocytopenia, 5 (6.6%) had hepatitis, 2 (2.1%) had retinitis, 47 (49.5%) had typical abnormalities on head ultrasound, 9 (8.9%)developed SNHL, and 34 (59.6%) received antiviral therapy. No significant difference was found between IPLDs of full-term cCMVi patients compared to controls throughout the entire auditory pathway (I-III, III-V, and I-V IPLDs), for both ears (p > 0.05). On serial BAEP examinations, cCMVi patients presented decreased IPLDs throughout the first year of life (p < 0.05 ofcompared 1st, 2nd, and 3rd BAEPs in both ears). Conclusions: Intrauterine cytomegalovirus infection does not affect the auditory brainstem maturation process in term neonates. Our findings support previous studies noting the normal neurodevelopmental outcome of asymptomatic cCMVi patients, suggesting antiviral treatment is not warranted in these cases. What is Known: •cCMVi is a leading cause of developmental delay and hearing loss. Treatment is recommended for patients with symptomatic diseases who are at significant risk of long-term sequelae. • It is unknown whether cCMVi affects the central nervous system maturation process. What is New: •We performed a neurophysiological evaluation of brainstem conduction by recording the BAEPs. We found that cCMVi has no significant impact on central conduction times along the auditory pathways in the brainstem at birth nor changes the neuronal maturation process during the first year of life. •Our findings suggest that cCMVi does not universally affect central nervous system maturation, supporting a highly selective approach when considering the benefits of antiviral therapy.

Intrauterine cytomegalovirus infection: a possible risk for cerebral palsy and related to its clinical features, neuroimaging findings: a retrospective study

BackgroundAbundant clinical evidences indicate that the increased risk of cerebral palsy (CP) may be associated with the intrauterine exposure to maternal infection. Cytomegalovirus (CMV) is a common cause of CP. However, little is known about the relationship between the intrauterine exposure of the fetus to CMV infection and CP. This study aims to explore the relationships between intrauterine CMV infection and clinical symptoms, classification, intelligence development and brain neuroimaging findings in children with CP.MethodsIn this study, 147 children with CP in recent 6 years were retrospectively analyzed (average age: 14.76 ± 3.07months; sex (M/F): 103/44). 148 children had CMV IgG and IgM positive sera identified by TORCH examination were selected as the control group (average age: 15.10 ± 3.21months; sex (M/F): 102/46), which also undergo the examination of CMV-DNA in urine. The age and sex of children in the control group were matched with those in the CP group. CMV-DNA in urine was detected by CMV fluorescence quantitative PCR, and t-test was performed to analyze the number of copies. For the CP group, standardized rehabilitation treatment was performed and the function of gross motor was evaluated by GMFM scale before and after treatment. The Gesell developmental scale (GDS) was used to assess the level of intellectual development. The classification of CP was conducted and the results of magnetic resonance imaging were analyzed. Finally, the correlations between the copy number of CMV-DNA and the clinical characteristics of children with CP were evaluated by the method of Pearson and Spearman correlation analysis.ResultsThe level of CMV infection was negatively correlated with the developmental quotient (DQ) of children with CP. Negative association was found between the level of CMV infection and the level of the gross motor development. The level of CMV infection was positively related with the occurrence probability of spastic quadriplegia. However, no associations were found between the abnormalities of brain tissue and the number of CMV copies. Moreover, CMV infection might add the difficulty of the rehabilitation treatment.ConclusionsCMV infection is a risk factor for the occurrence of CP in children. Pregnancy examination should be strengthened. Early detection and control of CMV infection may contribute to the rehabilitation of children with CP and reduce the disability and social burden.

Impact of chorioamnionitis and other intrauterine pathological conditions on human foetal cytoskeleton structural protein development: An immunohistochemical study

The present study aimed to elucidate the mechanisms by which chorioamnionitis affects the intrauterine development of the human eye at the molecular level, utilising immunohistochemistry. The expression of six different proteins and glycoproteins in human foetal eyes was examined after labelling with specific antibodies. Fifteen out of 87 specimens had a normal appearance without inflammatory lesions. The rest showed chorioamnionitis of various degrees. Some of the foetuses had Down syndrome, toxoplasma or CMV (cytomegalovirus) infection, or a hydatidiform mole (partial mole). The expression of vimentin, myosin, desmin, fibronectin, tenascin-C and tenascin-R was detected and quantified. The results demonstrate that, while the expression of all five proteins and glycoproteins was entirely normal in foetuses with a low grade or no inflammation in the chorion and amnion, expression was significantly impaired in cases of at least moderate chorioamnionitis. This was especially marked in the case of previous intrauterine toxoplasma or CMV infection or Down syndrome. Our findings suggest that chorioamnionitis itself and not preterm birth alone may be, at least to some extent, directly responsible for the structural abnormalities often found in the eyes of children who survive. This is compatible with the existence of a possible direct mechanism, by which this condition might contribute to the manifestation of retinopathy of prematurity.

ЭХОСТРУКТУРНАЯ И ПАТОМОРФОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА ЛИКВОРНЫХ ПУТЕЙ ГОЛОВНОГО МОЗГА У ДОНОШЕННЫХ НОВОРОЖДЕННЫХ С ВРОЖДЕННОЙ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИЕЙ

In 36 full-term newborns who died at an early neonatal age under various conditions of intrauterine development, ultrasound examination and morphological study of the brain liquor space was conducted at the 1st-2nd days of life. The first group included 20 newborns aged 38-40 weeks, whose cause of death on the 4th -5th day of life was intranatal and postnatal hypoxia. The second group included 16 dead children of the same age with congenital cytomegalovirus infection. It was found out that immaturity (n=7, p&lt;0.05), pseudocysts of the vascular plexus of the lateral ventricles (n=9, p&lt;0.5), as well as intraventricular hemorrhages of I degree (n=8, p&lt;0.05) were more often diagnosed in the second group compared with the first one in neurosonographic study. Only in the second group there was a pronounced ventriculomegaly. A morphological study in the brain often detected a pronounced pericellular and perivascular edema, alterative changes of neurons, vasculitis (n=7), subependyma (n=3), choriocephalitis (n=3) and encephalitis (n=1) with small calcifications, ependymocyte desquamation and lymphocytic infiltration, with a pronounced hyperemia and hemorrhages. In all cases, specific cells of the "owl's eye" were not detected. The detected ultrasound and pathomorphological changes in the liquor space in intrauterine cytomegalovirus infection indicate the possibility of direct cytodestructive effect of the pathogen in the absence of markers of viral metamorphosis, as well as the indirect effect of antenatal hypoxia, endotoxemia and cytokineemia on the brain in newborns

Volumetric MRI Study of the Brain in Fetuses with Intrauterine Cytomegalovirus Infection and Its Correlation to Neurodevelopmental Outcome.

In recent years, effort has been made to study 3D biometry as a method for fetal brain assessment. In this study, we aimed to compare brain volumes of fetuses with cytomegalovirus infection and noninfected controls. Also, we wanted to assess whether there is a correlation to their neurodevelopmental outcome as observed after several years. A retrospective cohort study examined MR imaging brain scans of 42 fetuses (at 30-34 weeks' gestational age) that were diagnosed with intrauterine cytomegalovirus infection. Volumetric measurements of 6 structures were assessed using a semiautomated designated program and were compared with a control group of 50 fetuses. Data collected included prenatal history and MR imaging and sonographic and neurodevelopmental follow-up. We found that all brain volumes measured were smaller in the cytomegalovirus-infected group and that there was a correlation between smaller cerebellar volume and lower Vineland II Adaptive Behavior Scales questionnaire scores, especially in the fields of daily living and communication skills. In this study, we found that brain volumes are affected by intrauterine cytomegalovirus infection and that it has a developmental prognostic meaning. Such information, which should be supported by further research, may help clinicians further analyze imaging data to treat and make a better assessment of these fetuses.

Citomegalovirus y gestación. Reporte de un caso en gestación gemelar

El citomegalovirus (CMV) es la causa más frecuente de infección congénita en los países desarrollados y aparece entre 0,3 y 0,6% de los recién nacidos en Europa. La primoinfección durante el embarazo ocurre en 1 a 4% de las gestantes seronegativas. En este caso, el 40% de los fetos se infecta y 10% presenta síntomas al nacimiento. La mitad de estos niños y 13% de los que nacen asintomáticos desarrollan secuelas permanentes, especialmente hipoacusia neurosensorial y retraso mental. En la actualidad, la determinación de la avidez de los anticuerpos IgG maternos y la detección del virus en líquido amniótico por reacción en cadena de la polimerasa (PCR) permiten el diagnóstico de la primoinfección en la embarazada y el diagnóstico de la infección en el feto. El diagnóstico de la infección congénita en el recién nacido debe realizarse mediante el cultivo del virus en shell vial o mediante la identificación del genoma viral por PCR en una muestra de orina recogida en las 2 primeras semanas de vida. A día de hoy, solo disponemos de medidas higiénico-sanitarias para la prevención de la infección durante la gestación, a la espera de resultados en el desarrollo de una nueva vacuna contra el CMV y de estudios multicéntricos controlados que avalen el uso o no de antivirales e inmunoglobulinas en gestantes infectadas por CMV.

МОРФОЛОГИЧЕСКОЕ СТРОЕНИЕ ВИЛОЧКОВОЙ ЖЕЛЕЗЫ У НОВОРОЖДЕННЫХ С ВРОЖДЕННОЙ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИЕЙ

The aim of the work was to study the morphological structure of the thymus gland in 36 full-term newborns who died at the 2-5 day of life. The main group included 16 newborns who were diagnosed with intrauterine cytomegalovirus infection by the serological method and polymerase chain reaction. Cerebral ischemia of moderate and severe degree, subarachnoid and periventricular hemorrhages, as well as markers of local and generalized forms of congenital infection were revealed in children of this group. The comparison group was represented by 20 newborns with antenatal ontogenesis, uncomplicated by acute respiratory and herpes-virus infections, moderate and severe somatic and obstetric pathology in their mothers during pregnancy. The cause of their death was birth trauma, intranatal and postnatal hypoxia. In the description of the neonatal thymus, attention was paid to the following features: the general plan of the structure; structural changes in the capsule of the gland; the structure of the cortical and brain matter; violation of loose fibrous connective tissue and blood vessels of the organ. It was found out that the structure of the thymus gland in the main group was different from that in the comparison group, especially a predominance of neonates with increase and decrease in the organ mass. With the growth of the mass of the thymus there was frequently revealed subcapsular hemorrhage; the sharpness of borders decreased or completely disappeared between cortical and medullary substance; the areas of crust delymphatisation, Hassall’s corpuscles filled with detritus were often identified. The edema of the interlobular loose fibrous connective tissue increased, the endothelial edema and its desquamation in the lumen of blood vessels were noted. Lymphocyte clusters in the interlobular connective tissue were clearly visualized. In the case of a decrease in the body mass, small lobules, excessive formation of collagen fibers in the interlobular connective tissue, the loss of lymphocytes in the cortical substance and small Hassal’s bodies were more often recorded. Stimulation of thymus growth may be associated with the direct cytodestructive effect of the virus and intrauterine stress, leading to a drop in cortisol content. In the inhibition of immunopoesis growth, prolonged antenatal antigenic stimulation, higher level of cortisol against progressing alterative processes in glandulocyte of the cortex of suprarenal glands of the fetus play an important role.

Apparent Diffusion Coefficient Value Changes and Clinical Correlation in 90 Cases of Cytomegalovirus-Infected Fetuses with Unremarkable Fetal MRI Results.

Cytomegalovirus is the leading intrauterine infection. Fetal MR imaging is an accepted tool for fetal brain evaluation, yet it still lacks the ability to accurately predict the extent of the neurodevelopmental impairment, especially in fetal MR imaging scans with unremarkable findings. Our hypothesis was that intrauterine cytomegalovirus infection causes diffusional changes in fetal brains and that those changes may correlate with the severity of neurodevelopmental deficiencies. A retrospective analysis was performed on 90 fetal MR imaging scans of cytomegalovirus-infected fetuses with unremarkable results and compared with a matched gestational age control group of 68 fetal head MR imaging scans. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes; basal ganglia; thalamus; and pons. For neurocognitive assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was used on 58 children in the cytomegalovirus-infected group. ADC values were reduced for the cytomegalovirus-infected fetuses in most brain areas studied. The VABS-II showed no trend for the major domains or the composite score of the VABS-II for the cytomegalovirus-infected children compared with the healthy population distribution. Some subdomains showed an association between ADC values and VABS-II scores. Cytomegalovirus infection causes diffuse reduction in ADC values in the fetal brain even in unremarkable fetal MR imaging scans. Cytomegalovirus-infected children with unremarkable fetal MR imaging scans do not deviate from the healthy population in the VABS-II neurocognitive assessment. ADC values were not correlated with VABS-II scores. However, the lack of clinical findings, as seen in most cytomegalovirus-infected fetuses, does not eliminate the possibility of future neurodevelopmental pathology.

Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11–4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25–3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

Hidropesía fetal no inmunológica e infección intrauterina por citomegalovirus

Se reporta un caso de hidropesía fetal no inmunológica e infección intrauterina por citomegalovirus. La hidropesía fue diagnosticada por ultrasonografía a las 31 semanas de edad gestacional. Se describe las características ecográficas de la hidropesía fetal intraútero y del recién nacido. Se realizó otras evaluaciones y estudios para determinar malformaciones asociadas, las que al se descartadas confirmaron la sospecha diagnóstica de infección por citomegalovirus e hidropesía fetal.

Hearing impairment and language delay in infants: Diagnostics and genetics.

This overview study provides information on important phoniatric and audiological aspects of early childhood hearing and language development with the aim of presenting diagnostic and therapeutic approaches.The article first addresses the universal newborn hearing screening that has been implemented in Germany for all infants since January 2009. The process of newborn hearing screening from the maternity ward to confirmation diagnostics is presented in accordance with a decision by the Federal Joint Committee (G-BA).The second topic is pediatric audiology diagnostics. Following confirmation of a permanent early childhood hearing disorder, the search for the cause plays an important role. Hereditary hearing disorders and intrauterine cytomegalovirus (CMV) infection, probably the most common cause of an acquired hearing disorder, are discussed and compared with the most common temporary hearing disorder, otitis media with effusion, which in some cases is severe enough to be relevant for hearing and language development and therefore requires treatment.The third topic covered in this article is speech and language development in the first 3 years of life, which is known today to be crucial for later language development and learning to read and write. There is a short overview and introduction to modern terminology, followed by the abnormalities and diagnostics of early speech and language development.Only some aspects of early hearing and language development are addressed here. Important areas such as the indication for a cochlear implant in the first year of life or because of unilateral deafness are not included due to their complexity.

IMMUNOREGULATORY EFFECTS OF INTRAVENOUS IMMUNOGLOBULINS

Treatment with intravenous immunoglobulins (IVIG) is widely used in modern clinical practice inorder to cure different clinical disorders, including obstetric conditions. Currently, IVIGs have become drugs of choice for treatment of anti-phospholipid syndrome in pregnant women, like as in cases of intrauterine cytomegalovirus infection.

Schizencephaly: A study of 16 patients

ObjectiveTo present 16 patients with schizencephaly and neurological involvement, and analyse their characteristics and neuroimages. Material and methodsThe study included 16 patients, 8 males and 8 females, all of whom were diagnosed with schizencephaly at less than 3 years of age; 2 patients were diagnosed prenatally. Schizencephaly was identified by computerised tomography (CT) in 1 patient and by MR or three-dimensional MR (3DMR) with a 1.5tesla apparatus in the others. Most patients were referred for evaluation because of psychomotor delay, motor disabilities and/or seizures. ResultsFive patients had bilateral schizencephaly with open lips (2 of them had suffered intrauterine cytomegalovirus infections); 2 showed unilateral schizencephaly with separated lips, 8 presented unilateral schizencephaly with fused lips, and 1 had schizencephaly with open lips on one side and fused lips on the other. Prenatal cytomegalovirus infection was diagnosed in 2 patients. A cerebral malformation that affected the midline was diagnosed by routine ultrasound studies in 2 patients. Eight patients (50%) presented with seizures that were focal, except for one patient who showed secondary generalisation. The latter was the only patient whose disease was refractory to complete seizure control with antiepileptic medication. All patients had some degree of motor deficit, which was either unilateral (hemiparesis) or bilateral (tetraparesis). Conclusion3DMR imaging was very important in diagnosing of schizencephaly in our patients because it showed the polymicrogyria that covered the area of the cleft and permitted us to rule out porencephaly. Neuronal migration disorders such as heterotopias and, more frequently, cortical dysplasias, were observed in several patients. Half of the patients had epilepsy which was controlled with antiepileptic medication, except in 1 patient.

Differential Transmission and Postnatal Outcomes in Triplets with Intrauterine Cytomegalovirus Infection

We present a case of triplets with intrauterine cytomegalovirus (CMV) infection, each of whom showed differential transmission, placental pathology, and postnatal outcome. The first- and second-born infants were both vigorous and asymptomatic at birth, although the first-, but not the second-born, triplet had a high copy number of CMV DNA in the peripheral blood (1.2 × 10³ copy/mL). The third-born triplet suffered from symptomatic CMV infection with a high viral load (6.0 × 10⁶ copy/mL). The triamniotic-trichorionic placentas were not fused to each other. The histopathologic analysis showed that CMV-positive cells were frequently found in the decidua, villi, and amnion of the third-born triplet's placenta but were limited and scattered in the decidua or villi but not amnion of the other 2 placentas. The third-born triplet underwent ganciclovir therapy. None of the infants had physical or auditory problems at 4 years of age, whereas the third-born triplet had been diagnosed with an autistic disorder. This observation exemplifies the preventive roles of the individual placentas of triplets with regard to virus infection, thus suggesting that developing CMV disease largely depends on the placental function.

Esquisencefalia. Estudio de 16 pacientes

ObjectiveTo present 16 patients with schizencephaly and neurological involvement, and analyse their characteristics and neuroimages. Material and methodsThe study included 16 patients, 8 males and 8 females, all of whom were diagnosed with schizencephaly at less than 3 years of age; 2 patients were diagnosed prenatally. Schizencephaly was identified by computerized tomography (CT) in 1 patient and by MR or three-dimensional MR (3DMR) with a 1.5tesla apparatus in the others. Most patients were referred for evaluation because of psychomotor delay, motor disabilities and/or seizures. ResultsFive patients had bilateral schizencephaly with open lips (2 of them had suffered intrauterine cytomegalovirus infections); 2 showed unilateral schizencephaly with separated lips, 8 presented unilateral schizencephaly with fused lips, and 1 had schizencephaly with open lips on one side and fused lips on the other. Prenatal cytomegalovirus infection was diagnosed in 2 patients. A cerebral malformation that affected the midline was diagnosed by routine ultrasound studies in 2 patients. Eight patients (50%) presented with seizures that were focal, except for one patient who showed secondary generalisation. The latter was the only patient whose disease was refractory to complete seizure control with antiepileptic medication. All patients had some degree of motor deficit, which was either unilateral (hemiparesis) or bilateral (tetraparesis). Conclusion3D MR imaging was very important in diagnosing of schizencephaly in our patients because it showed the polymicrogyria that covered the area of the cleft and permitted us to rule out porencephaly. Neuronal migration disorders such as heterotopias and, more frequently, cortical dysplasias, were observed in several patients. Half of the patients had epilepsy which was controlled with antiepileptic medication, except in 1 patient.

Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age

Background: The risk of intrauterine cytomegalovirus (CMV) infection and disease in the fetus or newborn largely depends on time of primary maternal infection during pregnancy. Objectives Prospective cohort study of pregnancy outcome in relation to gestational age at primary maternal CMV infection. Study design In a total of 248 pregnancies with primary infection the onset of infection was determined by IgG seroconversion, IgG avidity and/or onset of clinical symptoms. Congenital infection was diagnosed by CMV detection in amniotic fluid, fetal tissue or urine of the neonate in the first 2 weeks of life. Clinical symptoms were retrieved from ultrasound and medical records. Results The intrauterine transmission rates following primary CMV infection in the pre- and periconceptional period were 16.7% (4/24) and 34.5% (10/29), respectively. For the first, second and third trimester of pregnancy transmission rates were 30.1% (25/83), 38.2% (29/76) and 72.2% (26/36), respectively. The rate of symptomatically infected fetuses or newborns at birth was 22.8% for any symptoms and 10.3% for severe manifestations. No symptoms were observed in infected newborns of mothers with primary infection in the preconceptional period and in the third trimester. Conclusions The risk of intrauterine transmission following primary maternal infection in the third trimester is high, but the risk of neonatal disease is low. The highest risk of severe symptoms in the fetus and newborn exists around conception and in the first trimester of pregnancy.

Early intrauterine cytomegalovirus infection: extreme sequels with good seizure control

Cytomegalovirus (CMV) is the most common congenital viral infection in humans with great propensity to infect and injure developing nervous system. The extent of damage directly depends on the time of infection. In early CMV infections, the extent of neurologic damage most likely causes fetal death. We present a child with serology indicative of acute CMV infection and neuroimaging showing signs of early congenital infection. Seizures caused by severe central nervous system damage were well controlled with phenobarbital maintained within reference values in blood. In conclusion, severe neurologic damage caused by early congenital CMV infection emphasizes the importance of CMV infection stigmata recognition with early fetal sonography, and in suspected cases with serology. This case reveals insufficient diagnostic strategies, as well as deficient treatment options including the need for developing a safe and efficient vaccine. This child is an extraordinary example of surviving infant with extreme central nervous system damage and good seizure control.