Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Association between parental guilt and oral health problems in preschool children

Parents may feel guilty about their children's oral problems, which can affect their quality of life. The aim of this study was to assess the presence of parental guilt and its association with early childhood caries (ECC), traumatic dental injuries (TDI) and malocclusion (AMT) in preschool children. All 2 to 5 year-old children (N = 305), and their parents, seeking dental care at the University of São Paulo Dental School one-week Screening Programme, were asked to participate in the study, and 260 agreed. Children were examined by two calibrated dentists, and their parents answered a socioeconomic and ECOHIS questionnaire; the question on guilt was used as the dependent variable. Regression analyses examined the association between parental guilt and ECC, TDI, AMT and socioeconomic factors. A total of 35.8% of parents felt guilty. This was only associated with caries severity. No association was found between guilt and TDI, AMT or socioeconomic factors. ECC was present in 63.8% of the children; the mean (± sd) dmf-t score was 7.29 (± 2.78). Thus, the number of parents feeling guilty increases with the increase of their children's dental caries severity. Parental guilt is related to caries but is not associated with TDI or AMT.

Transient Benign Hyperphophatasemia - A Systematic Review of The Literature

BACKGROUND:: Sometimes, a temporary increase in alkaline phosphatase level is found in healthy infants and toddlers without evidence of liver or bone disease. The condition is customarily termed transient benign hyperphosphatasemia of infancy and early childhood. Most textbooks do not refer to the condition. METHODS:: We completed a systematic review of the literature using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS:: The 142 reports retained for analysis included 813 cases (male:female ratio = 1.1:1.0): 80 in subjects >18 years and 733 in subjects ≤18 years of age. The alkaline phosphatase ratio, calculated by dividing the measured level by the upper normal limit, was ≥5.0 in ≈70% and the duration of the elevation ≤4 months in 80% of the cases. Transient benign hyperphosphatasemia often followed a benign infection but available data fail to demonstrate a causal link. The prevalence of transient benign hyperphosphatasemia ranged 1.1-3.5% in infants 2 to 24 months of age. CONCLUSIONS:: Transient benign hyperphosphatasemia is likely the most common cause of hyperphosphatasemia among healthy infants and toddlers. Sometimes, it also occurs in older children and adults, indicating that the traditional term transient benign hyperphosphatasemia of infancy and early childhood might not be correct. The elevation in alkaline phosphatase persists for >4 months in ≈20% of the cases. Recognition of this benign condition is crucial to avoid unnecessary investigations.

The Influence of the Social and Cultural Environment on a Child's Playing in the First Three Years of Life

The research focused on children's behaviour in playing with objects both independently and in interaction with adults. It was based on studies of 40 Slovene children in 4 age groups (6,12,18 and 24 months) and of 23 Croatian children in 2 age groups (18 and 24 months). All the children were sampled proportionally by their gender and the educational level of their parents (middle and higher). Several coding check lists with satisfactory internal consistency were constructed during the study and used to analyse the video-recorded playing sessions with each child. The basic conclusion reached was that even in early childhood playing behaviour differs significantly between the infants from the two Central European countries. The difference lies not so much in the structure or the content of the playing actions, but in the way in which the infants deal playfully with the objects. This difference appears regardless of the type of object the infants are playing with and even regardless of the playing condition. It can best be described as the difference between the first significant discriminant function activity versus passivity. The Slovene infants were found to be on the active pole and the Croatians on the passive one. Social and gender differences were much less significant than cultural ones in determining the structure, the content and the way of playing. Significant age differences appeared in all three aspects, which was consistent with general trends in infants' psychological development. The group define the Slovene interactive playing style as object oriented, while the Croatian one was largely communicated oriented. Within the experimenter-infant dyads, children of both cultures played at a developmentally more advanced level than they did with their mothers, showing that the mothers were not as successful at reaching the ZPD as were the trained experimenters. In addition, the children of mothers who attributed more cognitive benefit to play played on a more advanced level than those whose mothers attributed more emotional benefit to play. The quality of the object the children were playing with was also significantly related to the structure, content and partly the way of dealing with the objects. Highly-structured objects stimulated complex play and low-structured ones stimulated simple play, regardless of playing conditions. The group concluded that both culture and the quality of the available object have an important impact on young children's play. Through the playing interaction, the infants internalise culturally specific patterns of behaviour and culturally specific meanings. These internalisations become apparent very early in their lives, even in non-social situations. On the other hand, the objects themselves have an impact on the level of infants' play. When they do not provide sufficient perceptive and functional support for a representational action, the infants' play will lag behind their actual developmental capacities.

Bilateral post-traumatic acetabular dysplasia

Traumatic disruption of the acetabular triradiate cartilage is an infrequent injury. When it occurs in early childhood, it may lead to growth changes in acetabular morphology. The morphology of this kind of acetabular dysplasia is uniform and differs significantly from that seen in classic developmental dysplasia of the hip. We present a case of bilateral post-traumatic acetabular dysplasia, which to our knowledge has not been reported. The morphology and the symptoms of impingement and periacetabular osteotomy of the hip joint are discussed.

Increased lipopolysaccharide-induced tumour necrosis factor-alpha, interferon-gamma and interleukin-10 production in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is based on a genetic predisposition, but environmental factors may trigger skin inflammation. According to the hygiene hypothesis, decreased exposure to microbial products in early childhood does not allow sufficient maturation of the immune system that is associated with an increased risk of atopic sensitization. OBJECTIVES: The effect of lipopolysaccharide (LPS) on the cytokine production of peripheral blood mononuclear cells (PBMC) of AD patients and nonatopic controls was studied. PATIENTS AND METHODS: PBMC were isolated from heparinized blood of 10 patients with AD and 10 nonatopic individuals, suspended in culture medium and stimulated with LPS. Cytokine levels in the supernatants were measured by immunoassays. Results Upon stimulation with LPS, PBMC from AD patients produced significantly higher amounts of tumour necrosis factor-alpha, interferon-gamma and interleukin (IL)-10 compared with control PBMC. LPS stimulation blocked the increased spontaneous production of IL-4 and IL-5 by PBMC from AD patients, but had no effect on IL-13 production. CONCLUSIONS: These results demonstrate that the effects of LPS stimulation depend on both the type of cytokine and the origin of PBMC. Endotoxin exposure is suggested to modulate the disease course of AD.

Methacholine responsiveness in mice from 2 to 8 wk of age

Many chronic human lung diseases have their origin in early childhood, yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh challenge. Following each MCh dose, absolute lung volume was measured plethysmographically at functional residual volume and during a slow inflation to 20-hPa transrespiratory pressure. Respiratory system impedance was measured continuously during the inflation maneuver and partitioned into airway and constant-phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in functional residual volume were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 wk of age.

Frequency of severe pulmonary hypertension complicating "isolated" atrial septal defect in infancy

Atrial septal defects (ASDs) are typically asymptomatic in infancy and early childhood, and elective defect closure is usually performed at ages of 4 to 6 years. Severe pulmonary hypertension (PH) complicating an ASD is seen in adulthood and has only occasionally been reported in small children. A retrospective study was undertaken to evaluate the incidence of severe PH complicating an isolated ASD and requiring early surgical correction. During a 10-year period (1996 to 2006), 355 pediatric patients underwent treatment for isolated ASDs either surgically or by catheter intervention at 2 tertiary referral centers. Two hundred ninety-seven patients had secundum ASDs, and 58 had primum ASDs with mild to moderate mitral regurgitation. Eight infants were found with isolated ASDs (6 with secundum ASDs and 2 with primum ASDs) associated with significant PH, accounting for 2.2% of all patients with ASDs at the centers. These 8 infants had invasively measured pulmonary artery pressures of 50% to 100% of systemic pressure. They were operated in the first year of life and had complicated postoperative courses requiring specific treatment for PH for up to 16 weeks postoperatively. The ultimate outcomes in all 8 infants were good, with persistent normalization of pulmonary pressures during midterm follow-up of up to 60 months (median 28). All other patients with ASDs had normal pulmonary pressures, and the mean age at defect closure was significantly older, at 6.2 years for secundum ASDs and 3.2 years for primum ASDs. In conclusion, ASDs were rarely associated with significant PH in infancy but then required early surgery and were associated with excellent midterm outcomes in these patients.

Long-term follow up (37-69 years) of patients with bladder exstrophy treated with ureterosigmoidostomy: uro-nephrological outcome

OBJECTIVE: To describe the urological and nephrological long-term outcome of patients born with classical bladder exstrophy treated with bilateral ureterosigmoidostomies in early childhood. PATIENTS AND METHOD: Out of 42 patients born with bladder exstrophy in Switzerland between 1937 and 1968, 25 participated in this study; seven had died, seven were lost to follow up and three refused consent. Assessment included chart review, clinical examination, and assessment of renal function and morphology. RESULTS: After a follow-up period of 37-69 years ((mean 50 years), 13 of the 25 participants (52%) had their ureterosigmoidostomy still in place. All others had different forms of urinary diversions. Fifteen (60%) patients had normal renal function or mild chronic kidney disease as assessed by estimated glomerular filtration rate. Three patients were on renal replacement therapy. MRI (n=16) showed 10 morphologically normal kidneys. One patient suffered from adenocarcinoma of the colon, five had benign colonic polyps, one urethral papillary carcinoma and 18 no evidence of tumor. CONCLUSION: The majority of our patients have normal or mildly impaired renal function and a well functioning ureterosigmoidostomy. This is remarkable, given the fact that ureterosigmoidostomies are considered to be refluxing high-pressure reservoirs at risk of renal injury and malignancy.

Longitudinal polysomnographic assessment from acute to subacute phase in infratentorial versus supratentorial stroke

Background: Regulation of sleep and sleep-related breathing resides in different brain structures. Vascular lesions can be expected to differ in their consequences on sleep depending on stroke topography. However, studies addressing the differences in sleep and sleep-related breathing depending on stroke topography are scarce. The aim of the present investigation was to compare the sleep and sleep-related breathing of patients with supratentorial versus infratentorial stroke. Methods: This study was part of the prospective multicenter study SAS-CARE-1 (Sleep-Disordered Breathing in Transient Ischemic Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE); NCT01097967). We prospectively included 14 patients (13 male, age 66 ± 6 years) with infratentorial lesions and 14 patients (14 male, age 64 ± 7 years) with supratentorial lesions, matched for age and stroke severity. Polysomnography was recorded in all during the acute phase within 9 days after stroke onset and 3 months later. Results: During the acute phase after stroke, patients with infratentorial lesions had significantly more sleep-related breathing disorders than patients with supratentorial lesions with an apnea-hypopnea index >20 observed in 8 (57%) patients with infratentorial stroke and in only 2 (14%) patients with supratentorial stroke. Sleep-related breathing improved from the acute to the subacute phase (3 months), albeit remaining elevated in a significant proportion of subjects. Sleep parameters did not differ between the two patient groups but there was a general improvement of sleep from the acute to the subacute phase which was comparable for both patient groups. Although stroke severity was mild, recovery after 3 months was worse in patients with infratentorial stroke with 12 of 14 patients with supratentorial stroke being symptom free (NIHSS = 0), while this was the case for only 6 of 14 patients with infratentorial stroke. Conclusions: Patients with infratentorial lesions are at an increased risk for sleep-related breathing disorders, which are frequent in this group. Monitoring of sleep-related breathing is therefore especially recommended in patients with infratentorial stroke. Because of the absence of reliable differences in sleep parameters between the two patient groups, polygraphy, with reduced diagnostic costs, rather than polysomnography could be considered. The higher prevalence of sleep-related breathing disorders and the poorer recovery of patients with infratentorial lesions suggest that early treatment interventions should be considered.

Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.

The ACTH receptor (MC2R) is expressed predominantly in the adrenal cortex, but is one of five G protein-coupled, seven-transmembrane melanocortin receptors (MCRs), all of which bind ACTH to some degree. Testing of MC2R activity is difficult because most cells express endogenous MCRs; hence, ACTH will elicit background activation of assayable reporter systems. Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH, also known as familial glucocorticoid deficiency (FGD). These patients are usually seen in early childhood with very low cortisol concentrations, normal mineralocorticoids, hyperpigmentation, and increased bodily growth. Several MC2R mutations have been reported in FGD, but assays of the activities of these mutants are cumbersome. We saw two patients with typical clinical findings of FGD. Genetic analysis showed that patient 1 was homozygous for the mutation R137W, and patient 2 was a compound heterozygote for S74I and Y254C. We tested the activity of these mutations in OS-3 cells, which are unresponsive to ACTH but have intact downstream cAMP signal transduction. OS-3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc) were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40-fold. Addition of ACTH to cells cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is similar to previously reported values. By contrast, the MC2R mutant R137W had low activity, and the S74I or Y254C mutants elicited no measurable response. This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity.

Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy.

We identified a new point mutation in the CYP19 gene responsible for aromatase (P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated protein that is inactive due to the absence of the functional regions of the enzyme. Aromatase deficiency was suspected prenatally because of the severe virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum estrogens, but had a normal level of serum free testosterone; in comparison with the high serum concentration of androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard GnRH stimulation tests were normal. This finding suggests that the contribution of estrogen to the hypothalamic-pituitary gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum estradiol concentrations strongly correlate with circulating inhibin levels, and thus, low inhibin levels may contribute to the striking elevation of FSH in young girls with aromatase deficiency. In contrast, estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum inhibin levels remain elevated even though levels of FSH, LH, and testosterone are decreased.

Acquiring synaesthesia: insights from training studies

Synaesthesia denotes a condition of remarkable individual differences in experience characterized by specific additional experiences in response to normal sensory input. Synaesthesia seems to (i) run in families which suggests a genetic component, (ii) is associated with marked structural and functional neural differences, and (iii) is usually reported to exist from early childhood. Hence, synaesthesia is generally regarded as a congenital phenomenon. However, most synaesthetic experiences are triggered by cultural artifacts (e.g., letters, musical sounds). Evidence exists to suggest that synaesthetic experiences are triggered by the conceptual representation of their inducer stimuli. Cases were identified for which the specific synaesthetic associations are related to prior experiences and large scale studies show that grapheme-color associations in synaesthesia are not completely random. Hence, a learning component is inherently involved in the development of specific synaesthetic associations. Researchers have hypothesized that associative learning is the critical mechanism. Recently, it has become of scientific and public interest if synaesthetic experiences may be acquired by means of associative training procedures and whether the gains of these trainings are associated with similar cognitive benefits as genuine synaesthetic experiences. In order to shed light on these issues and inform synaesthesia researchers and the general interested public alike, we provide a comprehensive literature review on developmental aspects of synaesthesia and specific training procedures in non-synaesthetes. Under the light of a clear working definition of synaesthesia, we come to the conclusion that synaesthesia can potentially be learned by the appropriate training.