The majority of congenital cytomegalovirus (cCMV) infections are asymptomatic at birth and therefore not diagnosed. Approximately 10-15% of these infants develop late-onset hearing loss and other ...developmental disorders. Implementation of a universal screening approach at birth may allow early initiation of symptomatic interventions due to a closer follow-up of infants at risk and offers the opportunity to consider treatment of late-onset disease. Real-time PCR assays for the detection of CMV DNA in buccal swab samples demonstrated feasibility and good clinical sensitivity in comparison to a rapid culture screening assay. Because most cCMV infections remain asymptomatic, a universal screening assay that stratifies CMV infected infants according to low and high risk of late-onset cCMV disease could limit the parental anxiety and reduce follow-up costs. We therefore developed and characterized a screening algorithm based on a highly-sensitive quantitative real-time PCR assay that is compatible with centralized testing of samples from universal screening and allows to determine CMV DNA load of saliva samples either as International Units (IU)/ml saliva or IU/105 cell equivalents. 18 of 34 saliva samples of newborns that tested positively by the screening algorithm were confirmed by detection of CMV DNA in blood and/or urine samples obtained during the first weeks of life. All screening samples that could not be confirmed had viral loads of <2.3x105 IU/ml saliva (median: 6.8x103) or 1.3x105 IU/105 cell equivalents (median: 4.0x102). The viral load of screening samples with confirmed cCMV infection ranged from 7.5x102 to 8.2x109 IU/ml saliva (median: 9.3x107) or 1.5x102 to 5.6x1010 IU/105 cell equivalents (median: 3.5x106). Clinical follow-up of these newborns with confirmed cCMV infection should reveal whether the risk of late-onset cCMV disease correlates with CMV DNA load in early life saliva samples and whether a cut-off can be defined identifying cCMV infected infants with or without risk for late-onset cCMV disease.
Abstract Early infant feeding and swallowing are complex motor processes involving numerous muscles in coordination, e.g. the orofacial muscles as well as the muscles of the pharynx, larynx and ...esophagus. The newborn’s reflexive drinking develops into the ability to ingest pureed complementary food as infancy progresses. Finally, in the last part of the first year of life, a differentiated eating, chewing and swallowing process develops allowing the voluntary intake of different foods of the family diet. The dietary schedule for the first year of life, which describes the recommended nutrition of infants in Germany, corresponds to these milestones in eating development. Disturbances in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere with the development of eating skills. Swallowing disorders (dysphagia) in children can have a detrimental effect on food intake and pose a serious risk to growth and development. Their prevention treatment requires a multidisciplinary approach with the aim of enabling the child to eat independently in the long term.
High-resolution optical coherence tomography (OCT) allows the detection of macular pathology and involvement of the optic nerve in a wide spectrum of diseases. For the differentiation of diseased and ...healthy status, normal values of retinal layer segmentation are critical. Yet, normative values mostly cover adult populations with only sparse data for paediatric cohorts. We present data of retinal layer characteristics via OCT in a healthy paediatric cohort. This prospective cross-sectional study screened 75 healthy children (male = 42, female = 33, range 4-17 years) without visual problems. OCT was performed with a peripapillary ring and macula scan protocol to determine paediatric normative values for routine parameters (peripapillary retinal nerve fibre layer thickness (pRNFL), total macular volume (TMV), macular retinal thickness (RT)). The macula scan (6mm grid) was segmented using the device-inherent automated segmentation software (Heidelberg Eye Explorer) for retinal layers: RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) in 9 segments each and mean of the 9 segments. We obtained OCT data of 72 children with mean age 12.49 years (standard deviation, SD, 2.18; minimum 3.93). Mean global pRNFL was 102.20 mum (SD 8.24), mean TMV 8.81 mm.sup.3 (0.30) and mean RT (all segments) 318.22 mum (10.19). Segmented macular retinal layer thicknesses (mean of all segments) were: RNFL 27.67 mum (2.14), GCL 41.94 mum (2.50), IPL 34.97 mum (2.10), INL 35.18 mum (2.15), OPL 29.06 mum (2.24), ONL 68.35 mum (6.20). The OCT is a useful non-invasive imaging technique for the examination of the retina in children with short duration, high imaging resolution and no known adverse effects. Normative values may serve as a comparator for different neuropaediatric disorders and are first presented with this study using an up-to-date and standardized OCT imaging technique.
Patients with phenylketonuria (PKU) present signs of impaired executive functioning and bone health in adolescence and adulthood, depending in part on the success of therapy in childhood. Therefore, ...nine children with well-treated PKU (4–7 years old, 22.2% ♀, seven with a full set of data, two included into partial analysis) and 18 age-, gender- and season-matched controls were analyzed for differences in executive functioning and bone parameters in plasma. Plasma was analyzed with commercially available kits. Cognitive performance in tonic alertness, visuo-spatial working memory, inhibitory control and task switching was assessed by a task battery presented on a touch screen. Regarding cognition, only the performance in incongruent conditions in inhibitory control was significantly better in children with PKU than in controls. No further differences in cognitive tests were detected. Furthermore, no significant difference in the bone turnover markers osteocalcin, undercarboxylated osteocalcin and CTX were detected between children with PKU and controls, while children with PKU had a significantly higher vitamin D concentration (69.44 ± 12.83 nmol/L vs. 41.87 ± 15.99 nmol/L, p < 0.001) and trended towards lower parathyroid hormone concentrations than controls (48.27 ± 15.16 pg/mL vs. 70.61 ± 30.53 pg/mL, p = 0.066). In this small group of well-treated preschoolers with PKU, no impairments in cognitive performance and bone turnover were observed, while vitamin D supplementation of amino acid supplements seems to be sufficient to achieve good vitamin D status.
ObjectiveTo determine the frequency and clinical-radiological associations of antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) in children presenting with neuromyelitis ...optica (NMO) and limited forms.MethodsChildren with a first event of NMO, recurrent (RON), bilateral ON (BON), longitudinally extensive transverse myelitis (LETM) or brainstem syndrome (BS) with a clinical follow-up of more than 12 months were enrolled. Serum samples were tested for MOG- and AQP4-antibodies using live cell-based assays.Results45 children with NMO (n=12), LETM (n=14), BON (n=6), RON (n=12) and BS (n=1) were included. 25/45 (56%) children had MOG-antibodies at initial presentation (7 NMO, 4 BON, 8 ON, 6 LETM). 5/45 (11%) children showed AQP4-antibodies (3 NMO, 1 LETM, 1 BS) and 15/45 (33%) were seronegative for both antibodies (2 NMO, 2 BON, 4 RON, 7 LETM). No differences were found in the age at presentation, sex ratio, frequency of oligoclonal bands or median EDSS at last follow-up between the three groups. Children with MOG-antibodies more frequently (1) had a monophasic course (p=0.018) after one year, (2) presented with simultaneous ON and LETM (p=0.004) and (3) were less likely to receive immunosuppressive therapies (p=0.0002). MRI in MOG-antibody positive patients (4) less frequently demonstrated periependymal lesions (p=0.001), (5) more often were unspecific (p=0.004) and (6) resolved more frequently (p=0.016).Conclusions67% of all children presenting with NMO or limited forms tested positive for MOG- or AQP4-antibodies. MOG-antibody positivity was associated with distinct features. We therefore recommend to measure both antibodies in children with demyelinating syndromes.
Persistent respiratory symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults are frequent, and there can be long-term impairment of pulmonary function. To date, only ...preliminary evidence is available on persistent respiratory sequelae of SARS-CoV-2 in children and adolescents. Our objective was to examine the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infections on pulmonary function in this age group in a single-center, controlled, prospective study.
Participants with serological or polymerase chain reaction-based evidence of SARS-CoV-2 infection were recruited from a population-based study of seroconversion rates. Multiple-breath washout (MBW), body plethysmography, and diffusion capacity testing were performed for children and adolescents. Participants were interviewed about their symptoms during the acute phase of infection and long-lasting symptoms. Cases were compared with SARS-CoV-2 seronegative controls from the same population-based study with and without history of respiratory infection within 6 months prior to assessment. Primary endpoints were differences in pulmonary function, including diffusion capacity and MBW, between participants with and without evidence of SARS-CoV-2 infection. Secondary endpoints included correlation between lung function and long-lasting symptoms as well as disease severity.
In total, 73 seropositive children and adolescents (5-18 years) were recruited after an average of 2.6 months (range 0.4-6.0) following SARS-CoV-2 infection. Among 19 patients (27.1%) who complained of persistent or newly emerged symptoms since SARS-CoV-2, 8 (11.4%) reported respiratory symptoms. No significant differences were detected in frequency of abnormal pulmonary function when comparing cases with 45 controls, including 14 (31.1%) with a history of previous infection (SARS-CoV-2: 12, 16.4%; controls: 12, 27.7%; odds ratio 0.54, 95% confidence interval 0.22-1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (
= 0.012) in patients with severe SARS-CoV-2 infection.
Pulmonary function is rarely impaired in children and adolescents after SARS-CoV-2 infection, except from those with severe infection, and did not differ between SARS-CoV-2 and other previous infections, suggesting that SARS-CoV-2 is not more likely to cause pulmonary sequelae than other infections. The discrepancy between persisting respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.
The present study aimed to assess the current state of breast-feeding promotion in hospitals and the prevalence of breast-feeding during the first year of life in Germany and to compare the results ...with a study 20 years earlier.
In the studies on 'breast-feeding and infant nutrition in Germany' named 'SuSe', a cross-sectional survey in hospitals was combined with a subsequent prospective survey of breast-feeding and infant nutrition during the first year of life (0·5, 2, 4, 6 and 12 months after birth) in mother-infant pairs who were recruited in the hospitals. Written questionnaires and phone calls were used in SuSe I and web-based questionnaires in SuSe II. Breast-feeding promotion and prevalence were evaluated using recommendations from the WHO and the UNICEF.
Two nationwide surveys SuSe I (1997-1998) and SuSe II (2017-2019).
In SuSe I, 177 hospitals and 1717 mother-infant pairs and in SuSe II 109 hospitals and 962 mother-infant pairs were included.
In SuSe II, hospitals implemented seven of the WHO 'Ten Steps to Successful Breastfeeding' to a greater extent than the hospitals in SuSe I. More mothers exclusively breastfed for 4 months (57 % v. 33 %) and continued breast-feeding until 6 (78 % v. 48 %) and 12 months (41 % v. 13 %). In both studies, exclusive breast-feeding decreased between 4 and 6 months of age due to the introduction of complementary feeding.
In Germany, breast-feeding habits have come closer to the recommendations over the last 20 years.
To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated ...disease (MOGAD) optic neuritis (ON).
All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGAD
) cohort and patients with ≥18 years in the adult (MOGAD
) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained.
Twenty MOGAD
(10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGAD
(34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm
, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGAD
and 31% MOGAD
ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome.
Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.
L-Arginine (Arg) is a semi-essential amino acid. Constitutive and inducible nitric oxide synthase (NOS) isoforms convert Arg to nitric oxide (NO), a potent vaso- and bronchodilator with multiple ...biological functions. Atopic dermatitis (AD) and bronchial asthma (BA) are atopic diseases affecting many children globally. Several studies analyzed NO in airways, yet the systemic synthesis of NO in AD and BA in children with BA, AD or both is elusive.
In a multicenter study, blood and urine were obtained from 130 of 302 participating children for the measurement of metabolites of the Arg/NO pathway (BA 31.5%; AD 5.4%; AD + BA 36.1%; attention deficit hyperactivity disorder (ADHD) 12.3%). In plasma and urine amino acids Arg and homoarginine (hArg), both substrates of NOS, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), both inhibitors of NOS, dimethylamine (DMA), and nitrite and nitrate, were measured by gas chromatography-mass spectrometry. Malondialdehyde (MDA) was measured in plasma and urine samples to evaluate possible effects of oxidative stress.
There were no differences in the Arg/NO pathway between the groups of children with different atopic diseases. In comparison to children with ADHD, children with AD, BA or AD and BA had higher plasma nitrite (
< 0.001) and nitrate (
< 0.001) concentrations, suggesting higher systemic NO synthesis in AD and BA. Urinary excretion of DMA was also higher (
= 0.028) in AD and BA compared to patients with ADHD, suggesting elevated ADMA metabolization.
The Arg/NO pathway is activated in atopic diseases independent of severity. Systemic NO synthesis is increased in children with an atopic disease. Plasma and urinary MDA levels did not differ between the groups, suggesting no effect of oxidative stress on the Arg/NO pathway in atopic diseases.
Preterm birth is a major risk factor for children's development. It affects children's cognitive and intellectual development and is related to impairments in IQ, executive functions, and well-being, ...with these problems persisting into adulthood. While preterm children's intellectual and cognitive development has been studied in detail, their social development and social-cognitive competencies have received less attention. Namely, preterm children show problems in interactions with others. These interaction problems are present in relationships with parents, teachers, and peers. Parents' behavior has been identified as a possible mediator of children's social behavior. Maternal sensitivity and responsiveness as well as absence of mental disorders foster children's social development. In this article, we will report on the social side of impairments that preterm children face. The review of the literature revealed that preterm infants' joint attention abilities are impaired: They are less likely to initiate joint attention with others and to respond to others' efforts to engage in joint attention. These deficits in joint attention might contribute to later impairments in social cognition, which in turn might affect social interaction skills. Based on these three domains (i.e., problems in social interaction, parental behavior, and impairments in joint attention), we suggest that preterm children's social cognitive abilities should be investigated more intensively.
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