Determinants of linear growth from infancy to school-aged years: a population-based follow-up study in urban Amazonian children

Background: Although linear growth during childhood may be affected by early-life exposures, few studies have examined whether the effects of these exposures linger on during school age, particularly in low-and middle-income countries. Methods: We conducted a population-based longitudinal study of 256 children living in the Brazilian Amazon, aged 0.1 y to 5.5 y in 2003. Data regarding socioeconomic and maternal characteristics, infant feeding practices, morbidities, and birth weight and length were collected at baseline of the study (2003). Child body length/height was measured at baseline and at follow-up visits (in 2007 and 2009). Restricted cubic splines were used to construct average height-for-age Z score (HAZ) growth curves, yielding estimated HAZ differences among exposure categories at ages 0.5 y, 1 y, 2 y, 5 y, 7 y, and 10 y. Results: At baseline, median age was 2.6 y (interquartile range, 1.4 y-3.8 y), and mean HAZ was -0.53 (standard deviation, 1.15); 10.2% of children were stunted. In multivariable analysis, children in households above the household wealth index median were 0.30 Z taller at age 5 y (P = 0.017), and children whose families owned land were 0.34 Z taller by age 10 y (P = 0.023), when compared with poorer children. Mothers in the highest tertile for height had children whose HAZ were significantly higher compared with those of children from mothers in the lowest height tertile at all ages. Birth weight and length were positively related to linear growth throughout childhood; by age 10 y, children weighing >3500 g at birth were 0.31 Z taller than those weighing 2501 g to 3500 g (P = 0.022) at birth, and children measuring >= 51 cm at birth were 0.51 Z taller than those measuring <= 48 cm (P = 0.005). Conclusions: Results suggest socioeconomic background is a potentially modifiable predictor of linear growth during the school-aged years. Maternal height and child's anthropometric characteristics at birth are positively associated with HAZ up until child age 10 y.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.

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.

Signaling pathway of a photoactivable Rac1-GTPase in the early stages

In modern life- and medical-sciences major efforts are currently concentrated on creating artificial photoenzymes, consisting of light- oxygen-voltage-sensitive (LOV) domains fused to a target enzyme. Such protein constructs possess great potential for controlling the cell metabolism as well as gene function upon light stimulus. This has recently been impressively demonstrated by designing a novel artificial fusion protein, connecting the AsLOV2-Jα-photosensor from Avena sativa with the Rac1-GTPase (AsLOV2-Jα-Rac1), and by using it, to control the motility of cancer cells from the HeLa-line. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their signaling pathway after photoexcitation is still in its infancy. Here, we show through computer simulations of the AsLOV2-Jα-Rac1-photoenzyme that the early processes after formation of the Cys450-FMN-adduct involve the breakage of a H-bond between the carbonyl oxygen FMN-C4O and the amino group of Gln513, followed by a rotational reorientation of its sidechain. This initial event is followed by successive events including β-sheet tightening and transmission of torsional stress along the Iβ-sheet, which leads to the disruption of the Jα-helix from the N-terminal end. Finally, this process triggers the detachment of the AsLOV2-Jα-photosensor from the Rac1-GTPase, ultimately enabling the activation of Rac1 via binding of the effector protein PAK1.

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.

[Experiences with the early treatment of osteogenesis imperfecta]

Between 1973 and 1988 twenty children with osteogenesis imperfecta were treated in the Department of Paediatric Surgery at the University of Berne, Switzerland. Our initial experience with the first 15 children, who had virtually no treatment during infancy and early childhood showed that they later developed severe soft tissue and skeletal deformities. Since resulting contractures and curvatures of the long bones are difficult to correct, we changed our therapeutic approach. Traditional therapy in OI was limited to the correction of bony malformations. Considering the fact, that the different elements of the locomotor system are part of a functional entity, we began early treatment combining physiotherapy and surgery.

Dynamics of the nasal microbiota in infancy: A prospective cohort study.

BACKGROUND Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.

Effects of Breastfeeding on Respiratory Symptoms in Infancy.

OBJECTIVE To assess the impact of potential risk factors on the development of respiratory symptoms and their specific modification by breastfeeding in infants in the first year of life. STUDY DESIGN We prospectively studied 436 healthy term infants from the Bern-Basel Infant Lung Development cohort. The breastfeeding status, and incidence and severity of respiratory symptoms (score) were assessed weekly by telephone interview during the first year of life. Risk factors (eg, pre- and postnatal smoking exposure, mode of delivery, gestational age, maternal atopy, and number of older siblings) were obtained using standardized questionnaires. Weekly measurements of particulate matter <10 μg were provided by local monitoring stations. The associations were investigated using generalized additive mixed model with quasi Poisson distribution. RESULTS Breastfeeding reduced the incidence and severity of the respiratory symptom score mainly in the first 27 weeks of life (risk ratio 0.70; 95% CI 0.55-0.88). We found a protective effect of breastfeeding in girls but not in boys. During the first 27 weeks of life, breastfeeding attenuated the effects of maternal smoking during pregnancy, gestational age, and cesarean delivery on respiratory symptoms. There was no evidence for an interaction between breastfeeding and maternal atopy, number of older siblings, child care attendance, or particulate matter <10 μg. CONCLUSIONS This study shows the risk-specific effect of breastfeeding on respiratory symptoms in early life using the comprehensive time-series approach.

Early life risk factors and puberty implications for cancer prevention

Earlier age at puberty is a known risk factor for breast cancer and suspected to influence prostate cancer; yet few studies have assessed early life risk factors for puberty. The overall objectives was to determine the relationship between birth-weight-for-gestational-age (BWGA), weight gain in infancy and pubertal status in girls and boys at 10.8 and 11.8 years and who were born of preeclamptic (PE) and normotensive (NT) mothers. Data for this study were collected from hospital and public health medical records and at a follow-up visit at 10.8 and 11.8 years for girls and boys, respectively. We used stratified analysis and multivariable logistic regression modeling to assess effect measure modifier and to determine the relationship between BWGA, weight gain in infancy and childhood and pubertal status, respectively. ^ There was no difference in the relationship between BWGA and pubertal status by maternal PE status for girls and boys; however, there was a non-significant increase in the odds of having been born small-for-gestational-age (SGA) in girls who were pubertal for breast or pubic hair Tanner stage 2+ compared to those who B1 or PH1. In contrast, boys who were pubertal for genital and pubic hair Tanner stage 2+ had lower odds of having been born SGA than those who were prepubertal for G1 or PH1. ^ In girls who were pubertal for breast development, the odds of having gained one additional unit SD for weight was highest between 3 to 6 months and 6-12 months for those who were B2+ vs. B1. For pubic hair development, weight gain between 6-12 months had the greatest effect for girls of PE mothers only. In boys, there were no statistically significant associations between weight gain and genital Tanner stage at any of the intervals; however, weight gain between 3-6 months did affect pubic hair tanner stage in boys of NT mothers. This study provide important evidence regarding the role of SGA and weight gain at specific age intervals on puberty; however, larger studies need to shed light on modifiable exposures for behavioral interventions in pregnancy, postpartum and in childhood.^

Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos

Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second most common pediatric neuromuscular disorder. Two candidate genes—survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning. However, the functional impact of these genes and the mechanism leading to a degeneration of motor neurons remain to be defined. To analyze the role of the SMN gene product in vivo we generated SMN-deficient mice. In contrast to the human genome, which contains two copies, the mouse genome contains only one SMN gene. Mice with homozygous SMN disruption display massive cell death during early embryonic development, indicating that the SMN gene product is necessary for cellular survival and function.

Attitudes of the autism community to early autism research

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.

Authentic and interesting memoirs of Mrs. Clarke, : from her infancy to the present time. : Likewise, a brief account of Mr. Wardle's charges, relative to His Royal Highness the Duke of York: : together with the minutes of evidence, as taken in the House of Commons. : From authentic documents. : Illustrated with a beautiful portrait of Mrs. Clarke.

"Authentic documents, &c. &c.," p. [31]-371, printed in two columns.

Origins and early development of human body knowledge

As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensori-motor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuospatial body knowledge in infancy. Our technique is to compare infants' responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body pictures at 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development.

Controlling feeding practices:cause or consequence of early child weight?

INTRODUCTION. The exertion of control during child feeding has been associated with both underweight and overweight during childhood. What is as-yet unclear is whether controlling child feeding practices causally affect child weight or whether the use of control may be a reactive response to concerns about high or low child weight. The aims of this study were to explore the direction of causality in these relationships during infancy. METHODS. Sixty-two women gave informed consent to take part in this longitudinal study that spanned from birth to 2 years of child age. Mothers completed the Child Feeding Questionnaire at 1 year, and their children were weighed at 1 and 2 years of age. Child weight scores were converted into standardized z scores that accounted for child age and gender. RESULTS. Controlling for child weight at 1 year, the use of pressure to eat and restriction at 1 year significantly predicted lower child weight at 2 years. CONCLUSIONS. Controlling feeding practices in infancy have an impact on children's weight at 2 years. The use of restrictive child feeding practices during infancy predicts lower child weight at age 2 years, which may reinforce mothers' use of this strategy in the longer term despite its potential association with disinhibition and greater child weight in later childhood.