Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis

Background

Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.

Methods and Findings

Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%.Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding.

Conclusions

There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.

Review Registration

PROSPERO CRD42013004965 Please see later in the article for the Editors'' Summary     

恒毅力养成：针对城市学龄前儿童的一种自然教育

恒毅力是一种基础性的人格特征。恒毅力对于人一生的健康和福祉都有着重要的积极影响。大量研究证明接触自然对当代人恒毅力的养成有显著的促进作用。根据人类身心发展的规律,以恒毅力为主要目标的自然教育最好从学龄前儿童期（5~6岁）开始进行。遗憾的是,关于此类自然教育的理论及实践知识仍然处于分散和不足的状态。因而,发展相对完整的自然教育体系以培养学龄前儿童的恒毅力是十分紧急且重要的。从恒毅力自然教育的理论框架、关键要素及其权重、自然教育及体验活动智库、对自然教育场所及活动的策略性设计这4部分探讨该类自然教育的理论体系和实践策略,或可为研究者提供儿童恒毅力的未来研究趋势,为教育者提供自然教育的实践启示,为设计师提供自然体验的新思路。     

RNA-Mediated Disease Mechanisms in Neurodegenerative Disorders

RNA is accurately entangled in virtually all pathways that maintain cellular homeostasis. To name but a few, RNA is the “messenger” between DNA encoded information and the resulting proteins. Furthermore, RNAs regulate diverse processes by forming DNA::RNA or RNA::RNA interactions. Finally, RNA itself can be the scaffold for ribonucleoprotein complexes, for example, ribosomes or cellular bodies. Consequently, disruption of any of these processes can lead to disease. This review describes known and emerging RNA-based disease mechanisms like interference with regular splicing, the anomalous appearance of RNA–protein complexes and uncommon RNA species, as well as non-canonical translation. Due to the complexity and entanglement of the above-mentioned pathways, only few drugs are available that target RNA-based disease mechanisms. However, advances in our understanding how RNA is involved in and modulates cellular homeostasis might pave the way to novel treatments.     

A Model for a Proportional Treatment Effect on Disease Progression

Treatments intended to slow the progression of chronic diseases are often hypothesized to reduce the rate of further injury to a biological system without improving the current level of functioning. In this situation, the treatment effect may be negligible for patients whose disease would have been stable without the treatment but would be expected to be an increasing function of the progression rate in patients with worsening disease. This article considers a variation of the Laird Ware mixed effects model in which the effect of the treatment on the slope of a longitudinal outcome is assumed to be proportional to the progression rate for patients with progressive disease. Inference based on maximum likelihood and a generalized estimating equations procedure is considered. Under the proportional effect assumption, the precision of the estimated treatment effect can be increased by incorporating the functional relationship between the model parameters and the variance of the outcome variable, particularly when the magnitude of the mean slope of the outcome is small compared with the standard deviation of the slopes. An example from a study of chronic renal disease is used to illustrate insights provided by the proportional effect model that may be overlooked with models assuming additive treatment effects.