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.

European Society of Paediatric Radiology Computed Tomography and Dose Task Force: European guidelines on diagnostic reference levels for paediatric imaging.

The recent European Council Directive 2013/59/EURATOM requires the establishment of diagnostic reference levels (DRLs) to optimise radiation dose in diagnostic and interventional radiology procedures. At the time this directive was enacted, just a few European countries had already set paediatric DRLs and many of these were outdated. For this reason, the European Commission launched a project addressing European Guidelines on Diagnostic Reference Levels for Paediatric Imaging that was awarded to a consortium led by the European Society of Radiology with the collaboration of the European Society of Paediatric Radiology and other European stakeholders involved in the radiation protection of children. The main aims of this project were to establish European DRLs to be used by countries without their own national paediatric DRLs and to provide a consistent method to establish new DRLs in the future. These European guidelines have been very recently endorsed by the European Commission and published in issue N° 185 of the Radiation Protection series. The purpose of this article is to introduce these guidelines to the wide community of paediatric radiologists.

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.

[When is chest radiography indicated in a child?]. / Milloin otan lapselta keuhkokuvan?

Chest radiography is the most common radiological examination in children. The indications are severe or complicatec pneumonia, exclusion of other diseases when diagnosing asthma, and suspected foreign body aspiration if emergency bronchoscopy is not performed. Community-acquired pneumonia can be diagnosed on the basis of clinical symptoms anc findings alone, but if hospitalization is needed for pneumonia, the diagnosis needs to be confirmed with chest radiography Imaging is the only reliable method to assess the severity of pneumonia and to detect the complications.

Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential.

AIM: Children with refractory or high-risk malignancies frequently suffer from poor quality of life during palliative care. This study explored the effect of metronomic drug administration on survival and quality of life in paediatric patients with various refractory or high-risk tumours. METHODS: We treated 17 patients with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression-free survival, changes in the Karnofsky-Lansky scores from baseline to the end of the study therapy and radiological responses. RESULTS: The median overall survival after the start of the study therapy was 6.2 months (range 2.0-57.7), and the six-, 12- and 24-month survival rates were 59%, 18% and 18%, respectively. The median progression-free survival was 3.2 months (range 0.3-17.8). The Karnofsky-Lansky scores increased significantly during the study therapy (p = 0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III-V adverse events occurred in 76% of the patients. CONCLUSION: Metronomic therapy may increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events.

Finnish guidelines for the treatment of community-acquired pneumonia and pertussis in children.

UNLABELLED: Evidence-based guidelines are needed to harmonise and improve the diagnostics and treatment of children's lower respiratory tract infections. Following a professional literature search, an interdisciplinary working group evaluated and graded the available evidence and constructed guidelines for the treatment of community-acquired pneumonia and pertussis. CONCLUSION: The clinical guidelines state that chest radiography is not needed if the child is diagnosed with pneumonia and treated at home. Complications should be considered if there is no improvement after antimicrobial therapy and a paroxysmal cough can indicate pertussis, which is life-threatening in unvaccinated infants and can lead to respiratory failure.

Finnish guidelines for the treatment of laryngitis, wheezing bronchitis and bronchiolitis in children.

UNLABELLED: Evidence-based guidelines are needed to harmonise and improve the diagnostics and treatment of children's lower respiratory tract infections. Following a professional literature search, an interdisciplinary working group evaluated and graded the available evidence and constructed guidelines for treating laryngitis, bronchitis, wheezing bronchitis and bronchiolitis. CONCLUSION: Currently available drugs were not effective in relieving cough symptoms. Salbutamol inhalations could relieve the symptoms of wheezing bronchitis and should be administered via a holding chamber. Nebulised adrenaline or inhaled or oral glucocorticoids did not reduce hospitalisation rates or relieve symptoms in infants with bronchiolitis and should not be routinely used.

Fetal radiation dose in computed tomography.

The connection between recorded volumetric CT dose index (CTDI vol) and determined mean fetal dose (Df) was examined from metal-oxide-semiconductor field-effect transistor dose measurements on an anthropomorphic female phantom in four stages of pregnancy in a 64-slice CT scanner. Automated tube current modulation kept the mean Df fairly constant through all pregnancy stages in trauma (4.4-4.9 mGy) and abdomino-pelvic (2.1-2.4 mGy) protocols. In pulmonary angiography protocol, the mean Df increased exponentially as the distance from the end of the scan range decreased (0.01-0.09 mGy). For trauma protocol, the relative mean Df as a function of gestational age were in the range 0.80-0.97 compared with the mean CTDI vol. For abdomino-pelvic protocol, the relative mean Df was 0.57-0.79 and for pulmonary angiography protocol, 0.01-0.05 compared with the mean CTDI vol, respectively. In conclusion, if the fetus is in the primary beam, the CTDI vol can be used as an upper estimate of the fetal dose. If the fetus is not in the primary beam, the fetal dose can be estimated by considering also the distance of the fetus from the scan range.

Postnatal ovarian activation has effects in estrogen target tissues in infant girls.

CONTEXT: Shortly after birth, pituitary gonadotropin secretion transiently activates in both sexes, and this surge is more robust in preterm (PT) than in full-term (FT) infants. In boys, the gonadotropin surge is associated with testicular activity and is considered an important part of normal reproductive development. In contrast, gonadal activation and its consequences in infant girls are poorly understood. OBJECTIVE: Our objective was to evaluate the association of postnatal ovarian activity with simultaneous changes in estrogen target tissues in FT and PT girls. PATIENTS AND METHODS: We measured urinary estradiol (E2) levels in 29 FT and 34 PT girls using a mass spectrometric method from 1 week (D7) to 6 months of age (M1-M6). To assess the contribution of ovarian E2 on urinary E2 levels, the levels in girls were compared with the levels of boys of similar cohorts (29 FT and 33 PT boys). E2 levels were compared with simultaneous changes in estrogenic target tissues including mammary glands in both sexes and uterus and vulvar epithelium in girls. RESULTS: Median urinary E2 levels increased after D7 in girls, but not in boys. Mammary gland diameter was larger in girls than in boys from M4 in FT (P < .001) and M2 in PT infants (P < .0001). In PT girls, E2 levels increased at term and were then higher than those in FT girls (P < .0001). Urinary E2 levels in PT girls were positively associated with mammary gland and uterine growth. CONCLUSIONS: These findings indicate that gonadal steroidogenesis activates during the postnatal gonadotropin surge in girls. In addition, the resulting elevated E2 levels affect target tissues, suggesting that postnatal pituitary-ovarian activation plays a role in normal female reproductive development.

How tracking radiologic procedures and dose helps: experience from Finland.

OBJECTIVE: The purpose of our study was to review the experience of tracking radiologic procedures and radiation dose for individual patients in terms of impact on justification and optimization. MATERIALS AND METHODS: Examples were collected at the Hospital for Children and Adolescents in Helsinki, Finland, through a PACS system that covers 33 institutions in the Helsinki-Uusimaa Hospital District in which reviewing previous radiologic procedures or radiation doses helped in either avoiding the next procedure or provided insight that helped to strengthen dose optimization for CT. RESULTS: With the help of four case reports, our results show that availability of previous imaging studies and radiation dose figures helped to avoid additional new CT examinations by providing required information from previously performed CT examinations, indicate the need for imaging parameter optimization in one facility in view of a better situation detected in another facility, observe the need for further optimization with a specific CT unit and validate the outcome of successful optimization, and make a value judgment in a situation in which a patient has already undergone a number of CT examinations and a critical evaluation could avoid another one. Patient-specific optimization provides a more reliable and effective method than that of comparing average patient group values. Collective dose for a patient was not used in any situation in decision making. CONCLUSION: Patient-specific justification and optimization becomes possible using the tracking of radiologic procedures and radiation dose of individual patients.

Organ dose calculation in CT based on scout image data and automatic image registration.

BACKGROUND: Computed tomography (CT) has become the main contributor of the cumulative radiation exposure in radiology. Information on cumulative exposure history of the patient should be available for efficient management of radiation exposures and for radiological justification. PURPOSE: To develop and evaluate automatic image registration for organ dose calculation in CT. MATERIAL AND METHODS: Planning radiograph (scout) image data describing CT scan ranges from 15 thoracic CT examinations (9 men and 6 women) and 10 abdominal CT examinations (6 men and 4 women) were co-registered with the reference trunk CT scout image. 2-D affine transformation and normalized correlation metric was used for image registration. Longitudinal (z-axis) scan range coordinates on the reference scout image were converted into slice locations on the CT-Expo anthropomorphic male and female models, following organ and effective dose calculations. RESULTS: The average deviation of z-location of studied patient images from the corresponding location in the reference scout image was 6.2 mm. The ranges of organ and effective doses with constant exposure parameters were from 0 to 28.0 mGy and from 7.3 to 14.5 mSv, respectively. The mean deviation of the doses for fully irradiated organs (inside the scan range), partially irradiated organs and non-irradiated organs (outside the scan range) was 1%, 5%, and 22%, respectively, due to image registration. CONCLUSION: The automated image processing method to registrate individual chest and abdominal CT scout radiograph with the reference scout radiograph is feasible. It can be used to determine the individual scan range coordinates in z-direction to calculate the organ dose values. The presented method could be utilized in automatic organ dose calculation in CT for radiation exposure tracking of the patients.

Postnatal developmental changes in the pituitary-ovarian axis in preterm and term infant girls.

CONTEXT: Postnatal pituitary-testicular activation in infant boys is well characterized. However, the ovarian response to pituitary activation in infancy is less well understood. OBJECTIVE: The aim of the study was to compare postnatal developmental changes in the pituitary-ovarian axis in preterm and term infant girls. PARTICIPANTS AND DESIGN: Sixty-three infant girls, divided into three groups according to gestational age (GA) [i.e. full term (FT; n = 29; GA, 37-42 wk), near term (NT; n = 17; GA, 34-37 wk), and preterm (PT; n = 17; GA, 24-34 wk)] were examined monthly from 1 wk (D7) to 6 months (M1-M6) of age and reexamined at the corrected age of 14 months (cM14). MAIN OUTCOME MEASURES: We performed a longitudinal follow-up of urinary FSH and serum anti-Müllerian hormone (AMH) levels and the number of follicles in transabdominal ovarian ultrasonography. RESULTS: The postnatal FSH surge was stronger and more prolonged in NT and PT girls than in FT girls (P ≤ 0.001). Increased folliculogenesis and a rise in AMH levels were observed in all three groups after the FSH surge. In NT and PT girls, follicular development was delayed in comparison with FT girls, and a decrease in high FSH levels around the 40th postmenstrual week was temporally associated with the appearance of antral follicles in ultrasonography and an increase in AMH levels. CONCLUSIONS: The postnatal FSH surge results in transient ovarian stimulation in term and preterm girls. A delay in ovarian folliculogenesis shown in ovarian ultrasonography and by low serum AMH levels may provide an explanation for the exaggerated FSH surge in NT and PT girls.

Increased activity of the hypothalamic-pituitary-testicular axis in infancy results in increased androgen action in premature boys.

CONTEXT: Transient activation of the hypothalamic-pituitary-gonadal (HPG) axis is observed in boys during the first months of life. Previous research suggests increased HPG axis activation in premature infants, but the physiological significance of this has not been studied. OBJECTIVE: The objective of this study was to evaluate the differences in reproductive hormone levels and their biological effects between full-term (FT) and preterm (PT) infant boys. STUDY DESIGN AND PARTICIPANTS: Twenty-five FT and 25 PT (gestational age 24.7-36.6 wk) boys were recruited at birth and followed up monthly from 1 wk to 6 months of age (d 7, months 1-6). Nineteen FT and 20 PT boys were reexamined at 14 months of age. MAIN OUTCOME MEASURES: Urinary gonadotropins and testosterone were measured in serial urine samples and compared with testicular and penile growth. Urinary prostate-specific antigen was measured as an androgen biomarker. RESULTS: LH and testosterone levels were higher in PT boys (P < 0.001 for both) than FT boys. Compared with FT boys, FSH levels were lower at d 7 (P = 0.002) but higher from month 1 to month 3 (P = 0.002-0.030) in PT boys. This was associated with significantly faster testicular and penile growth in PT boys compared with FT boys. Transient increase in the prostate-specific antigen levels in both groups indicated androgen action in the prostate. CONCLUSIONS: Postnatal HPG axis activation in infancy is increased in PT boys and associated with faster testicular and penile growth compared with FT boys. Possible long-term consequences of hyperandrogenism in PT infant boys warrant further research.

Osteonecrosis in children treated for lymphoma or solid tumors.

PURPOSE: The purpose of this study was to find out the incidence of and clinical risk factors for magnetic resonance imaging (MRI)-detected osteonecrosis (ON) in children treated for lymphoma or solid tumors. PATIENTS AND METHODS: The development of ON was studied in 32 childhood cancer patients who underwent MRI scanning of the lower extremities at the end of their treatment. The underlying malignancy was Wilms tumor in 8 patients, non-Hodgkin lymphoma (NHL) in 8, Hodgkin disease (HD) in 7, rhabdomyosarcoma in 6, and other occasional solid tumors in 3 patients. RESULTS: Six of the 32 patients (19%) had ON. The mean age of the patients with ON at diagnosis was 12.7 years compared with 5.8 years for the patients without ON (P<0.001). All the patients with ON had either HD (4 patients) or NHL (2 patients). Two (33%) of the patients with ON were symptomatic. CONCLUSIONS: ON in MRI was found to be a common complication in children after treatment for HD or NHL. The risk for ON seems to be very low in patients with other solid tumors even when they receive high cumulative doses of dexamethasone.

High body mass index increases the risk for osteonecrosis in children with acute lymphoblastic leukemia.

PURPOSE: The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. PATIENTS AND METHODS: Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. RESULTS: Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). CONCLUSION: ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.

Cloacal anomaly simulating megalocystis in the first trimester.

We present a case of cloacal anomaly that simulated megalocystis in the first trimester of gestation of a female fetus. During the second trimester, repeated paracentesis was necessary to treat increasing ascites, oligohydramnios, and hydronephrosis. Our data support findings that ascites presenting with a multiloculated cystic structure on sonography during the second trimester may be typical for cloacal anomalies. Active treatment of the fetal ascites is recommended to improve the child's prospects for survival.

Vertebral artery insufficiency as a possible mechanism for sudden infant death--in vivo evidence does not support findings from postmortem studies.

Recent postmortem studies have suggested that sudden infant death syndrome (SIDS) might involve an underlying, gradual brain stem injury caused by repeated episodes of transiently compromised brain stem circulation. Autopsy studies have also reported that vertebral artery occlusion due to head rotations, such as occurs, e.g. during prone sleeping, would be a physiological phenomenon of infant atlantooccipital junction. The present study was undertaken to examine whether vertebral artery insufficiency does truly occur in live infants during such head rotations. We studied by transcranial doppler sonography the blood flow velocity of the basilar artery (BA) in 27 infants during head rotation from straight position to maximal rotation in three directions (left, right, dorsiflexion). No significant change in BA blood flow was seen between any head positions. Weight and gestational age, but not arterial pressure or hematocrit, of the infants were correlated with blood flow velocity. Our results suggest that brain stem circulation in live infants may not be compromised due to changing the head position, which is inconsistent with the postmortem findings showing insufficiency of brain stem circulation in both controls and those succumbed to SIDS. We hence propose that the brain stem pathology observed with SIDS is likely caused by other factors (e.g. systemic disturbance) rather than by mechanical obstruction of brain stem circulation.