Long-term outcome of vestibular function and hearing in children with congenital cytomegalovirus infection: a prospective cohort study.

PURPOSE: Congenital cytomegalovirus infection (cCMV) is the most frequent nonhereditary cause for sensorineural hearing loss (SNHL) in children. Data on vestibular function in children with cCMV are, however, scarce, although some evidence for cCMV-associated vestibular dysfunction exists. In this prospective cohort study, we evaluated long-term vestibular function and hearing outcomes in a cohort of children with cCMV. METHODS: Participants were 6-7-year-old children with cCMV from a large population-based screening study. Controls were age and gender matched healthy children, who were CMV-negative at birth. Hearing was examined with pure tone audiometry. Definition of hearing loss was pure-tone average > 20 dB. Vestibular function was assessed using the video head impulse test that provides a measure of semicircular canal function. Definition of vestibular dysfunction was lateral semicircular canal gain < 0.75. RESULTS: Vestibular dysfunction occurred in 7/36 (19.4%) of children with cCMV and in 1/31 (3.2%) of controls (p = 0.060). SNHL was recorded in 4/38 (10.5%) of children with cCMV and in 0/33 of controls (p = 0.118). Hearing loss was unilateral in all cases. In cCMV group, the two children with bilateral vestibular dysfunction also had SNHL, whereas those with unilateral vestibular dysfunction (n = 5) had normal hearing. CONCLUSIONS: In this cohort of children with cCMV identified using newborn screening, vestibular dysfunction was more common than SNHL at 6 years of age. Vestibular dysfunction occurred both in children with and without SNHL. Based on these data, inclusion of vestibular tests in follow-up protocol of cCMV should be considered.

Decrease in paediatric emergency room visits during the COVID-19 pandemic restrictions: A population-based study.

AIM: To investigate paediatric emergency room (ER) visits to evaluate the immediate health effects of COVID-19 pandemic restrictions on children. METHODS: We retrospectively examined paediatric ER visits in the Helsinki University Hospital (HUH) district during the first wave of the pandemic (1 March to 31 May 2020), and a 2-month period immediately before and after. These periods were compared to the corresponding time periods in 2015-2019 ('reference period'). RESULTS: The total number of ER visits decreased by 23.4% (mean 6474 during the reference period, 4960 during the pandemic period (incidence rate ratio [IRR] 0.75, 95% confidence interval 0.72-0.77; p < 0.001). This was due to a decrease in visits related to infectious diseases; visits due to surgical reasons did not decrease. The amount or proportion of patients triaged to the most urgent class (Emergency Severity Index 1) did not increase. Paediatric ER visits returned to baseline after lifting of restrictions. CONCLUSIONS: Although paediatric ER visits substantially decreased during the pandemic restrictions, children seen at the ER were not more severely ill. Our results do not indicate immediate detrimental health effects of pandemic control measures on children.

Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions.

Desmoplakin (DSP) and Desmoglein 1 (DSG1) variants result in skin barrier defects leading to erythroderma, palmoplantar keratoderma and variable [AQ4] other features. Some DSG1 variant carriers present with SAM syndrome (Severe dermatitis, multiple Allergies, Metabolic wasting) and a SAM-like phenotype has been reported in 4 subjects with different heterozygous DSP variants. We report here a patient with a novel DSP spectrin region (SR) 6 variant c.1756C>T, p.(His586Tyr), novel features of brain lesions and severe recurrent mucocutaneous herpes simplex virus infections, with a favourable response to ustekinumab. Through a review of reported cases of heterozygous variants in DSP SR6 (n = 15) and homozygous or compound heterozygous variants in DSG1 (n = 12) and SAM-like phenotype, we highlight phenotypic variability. Woolly hair, nail abnormalities and cardiomyopathy characterize patients with DSP variants, while elevated immunoglobulin E and food allergies are frequent in patients with DSG1 variants. Clinicians should be aware of the diverse manifestations of desmosomopathies.

Vaccine Responses in Congenital Cytomegalovirus Infection.

There is limited information on vaccine responses in children with congenital cytomegalovirus infection (cCMV). We studied diphtheria, tetanus, measles, mumps and rubella vaccine responses in 6-year-old children with cCMV and controls. Protective antibody levels and geometric mean concentrations did not differ significantly between the study groups. Therefore, immunizations for children with cCMV should be administrated according to established national schedules.

Hearing outcome in congenitally CMV infected children in Finland - Results from follow-up after three years age.

OBJECTIVES: Cytomegalovirus (CMV) is the most common congenital infection affecting about 0.6% of all newborns in developed countries. Vertical transmission to fetus can take place either after maternal primary or non-primary CMV infection during pregnancy. It is the most common infectious agent for sensorineural hearing loss (SNHL) in young children. The hearing loss after congenital CMV (cCMV) may be present at birth, or may develop after months or even years. In this study, we evaluated hearing outcome at 3-4 years of age in children (n 32) with cCMV identified in universal saliva CMV-PCR-based screening. METHODS: Study population consisted of mainly asymptomatic children (median age 3.1 years) with cCMV identified in newborn CMV screening. The type of maternal CMV infection (primary or non-primary) was determined by analyzing CMV antibodies (IgM, IgG and IgG avidity) from preserved maternal serum samples drawn in the end of first trimester of pregnancy. Hearing was evaluated with pure tone audiometry (PTA), or transient-evoked otoacoustic emission (TEOAE) and sound field audiometry (SF). RESULTS: Unilateral hearing loss occurred in 5/32 (16%) of the children with cCMV. None of the subjects in our cohort had bilateral hearing loss. Hearing loss occurred in 3/15 (20%) of children who were born to mothers with non-primary CMV infection during pregnancy, and in 2/10 (20%) of children whose mother had had a primary CMV infection during the 2-3 trimester. None of the additional 6 children, whose mother had primary infection in the first trimester, had hearing loss by age of 3-4 years. Two children with normal hearing at 1 years age had developed unilateral hearing loss by the age of three. CONCLUSIONS: Unilateral hearing loss was relatively common among the mainly asymptomatic children with cCMV identified in screening. Long-term follow up of children with cCMV is essential to identify the children with late-onset hearing loss.

Out-of-hospital deaths among children during COVID-19 pandemic: indicator of collateral damage?

We aimed to investigate the out-of-hospital mortality, and the actual prevalence of COVID-19 in children requiring paediatric emergency department (ED) care for infectious symptoms. There were four emergency medical services (EMS) responses concerning children (age 0-15 years) leading to death on-scene in 2 months during the pandemic, and eight during the previous 12 months in the Helsinki University Hospital area, although the number of EMS missions decreased by 18%. The prevalence of COVID-19 in children contacting a paediatric ED for any infectious symptoms during the epidemic peak was only 2.7%.

Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection.

BACKGROUND: Children with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature. METHODS: Study population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing RESULTS: At 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data CONCLUSIONS: The urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population.

The Burden of Congenital Cytomegalovirus Infection: A Prospective Cohort Study of 20 000 Infants in Finland.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and causes significant morbidity. This study was undertaken to evaluate the benefits of screening newborns for cCMV and to understand the cCMV disease burden in Finland. METHODS: Infants born in Helsinki area hospitals were screened for CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants and matched controls were monitored to determine their neurodevelopmental, audiological, and ophthalmological outcomes at 18 months of age. Griffiths Mental Development Scales, otoacoustic emission and sound field audiometry, and ophthalmologic examination were performed. RESULTS: Of the 19868 infants screened, 40 had confirmed cCMV infection (prevalence, 2 in 1000 [95% confidence interval, 1.4-2.6 in 1000]). Four (10%) infants had symptomatic cCMV. Griffiths general quotients did not differ significantly between the CMV-positive (mean, 101.0) and control (mean, 101.6) infants (P = .557), nor did quotients for any of the Griffiths subscales (locomotion, personal-social, hearing and language, eye and hand, performance) (P = .173-.721). Four of 54 CMV-positive ears and 6 of 80 CMV-negative ears failed otoacoustic emission testing (P = 1.000). The mean minimal response levels over the frequencies 500 Hz to 4 kHz in the sound field audiometry did not differ between CMV-positive (mean, 34.31-dB hearing level) and control (mean, 32.73-dB hearing level) infants (P = .338). No CMV-related ophthalmologic findings were observed. CONCLUSIONS: The prevalence of cCMV was low, and outcomes at 18 months of age did not differ between the infected infants and healthy control infants. With such a low burden in Finland, universal newborn screening for cCMV seems unwarranted.

Immunity against vaccine-preventable diseases in Finnish pediatric healthcare workers in 2015.

Healthcare workers (HCWs) pose a risk to themselves and their patients if not protected against vaccine-preventable diseases. Alarmingly, lacking immunity has been reported in several studies. We assessed the immunity against vaccine-preventable diseases in 157 pediatric HCWs in Helsinki Children's Hospital. The HCWs enrolled answered a questionnaire and gave a serum sample. Antibodies were measured with EIA against MMR-diseases, tetanus and diphtheria toxins, Hepatitis B (HBV), Hepatitis A (HAV), varicella zoster and pertussis toxin. Neutralizing antibodies against poliovirus 1, 2 and 3 were measured. All of the HCWs had antibodies against tetanus and 89.8% against diphtheria. All had measurable levels of polio antibodies to all three polioviruses. 41% had suboptimal levels of antibodies against at least one of the antigens tested: MMR-viruses, diphtheria, HBV or polio. Measles, mumps and rubella antibodies were detectable in 81.5%, 89.2% and 93%, respectively. Only one HCW had no varicella-antibodies. Hepatitis B surface antibodies (HBsAb) were detected in 89.8% of the nurses. 67.5% had HAV-antibodies. A poor correlation between detected antibody levels and reported vaccination history was noticed, indicating a need for a universal record system for registering the vaccines given to each individual.

Primary versus non-primary maternal cytomegalovirus infection as a cause of symptomatic congenital infection - register-based study from Finland.

BACKGROUND: Both primary and non-primary maternal cytomegalovirus (CMV) infection during pregnancy can lead to vertical transmission. We evaluated the proportion of maternal primary/non-primary infections among 26 babies with symptomatic congenital CMV infection born in Finland from 2000 to 2012. METHODS: We executed a database search on hospital records from all five university hospitals in Finland to identify infants with congenital CMV infection. The preserved maternal serum samples drawn at the end of the first trimester were analysed for CMV antibodies. Maternal infection was classified to be non-primary, if there was high avidity CMV immunoglobulin G (IgG) in the early pregnancy samples. Infection was considered primary in the case of either low avidity IgG (primary infection in the first trimester or near conception) or absent CMV IgG at the end of the first trimester (primary infection in the second or third trimester). RESULTS: The majority of the symptomatic congenital CMV infections (54%) were due to maternal non-primary infection, 27% due to maternal primary infection in the first trimester or near conception, and 19% during the second or third trimester. Long-term sequelae occurred in 59% of patients: in 6/7 after primary infection in the first trimester, in 0/5 after primary infection in the second or third trimester, and in 9/14 after non-primary infection. CONCLUSIONS: In this register-based cohort, non-primary infections caused the majority of symptomatic congenital CMV infections, and resulted in significant morbidity.

Decrease in seroprevalence for herpesviruses among pregnant women in Finland: cross-sectional study of three time points 1992, 2002 and 2012.

Maternal herpesvirus infections during pregnancy may cause fetal and neonatal infections. We investigated the seroprevalence of five herpesviruses: cytomegalovirus (CMV), herpes simplex virus (HSV) 1 and 2, varicella zoster virus (VZV) and Epstein-Barr virus (EBV) in randomly selected samples from pregnant Finnish women from the years 1992, 2002 and 2012. Over 20 years, the seroprevalences decreased significantly for CMV from 84.5% to 71.5% (p = 0.007) and HSV-1 from 69.5% to 45% (p < 0.001). The decrease in seroprevalence for HSV-2 (from 17.5% to 11%) was not statistically significant. The seroprevalence remained unchanged for VZV and EBV. The proportion of mothers with no antibodies to either HSV-1 or HSV-2 increased from 25.5% to 48% (p < 0.001). The seroprevalences for HSV-1 and HSV-2 increased in relation to age, which shows that women of childbearing age do contract primary HSV infections. Our findings indicate that a considerable proportion of women (48%) are at risk for primary HSV infection during pregnancy.

Retropharyngeal involvement in Kawasaki disease--a report of four patients with retropharyngeal edema verified by magnetic resonance imaging.

Kawasaki disease is an acute systemic vasculitis of childhood. The diagnosis is based on clinical criteria. Prognosis with adequate treatment is favorable. Untreated patients, however, may develop coronary manifestations predisposing to acute myocardial infarction. Retropharyngeal edema is a rare but known manifestation of Kawasaki disease. We present a case series of four Kawasaki patients presenting with clinical findings for retropharyngeal abscess and the magnetic resonance imaging findings of these patients, diagnosed during a six week period. To our knowledge, this is the first systematic report of cervical MRI findings of Kawasaki patients.