Prenatal maternal psychosocial stress and risk of asthma and allergy in their offspring: protocol for a systematic review and meta analysis
BACKGROUND Asthma and allergic disorders are of global concern, with asthma estimated to affect 334 million people and 14% of children worldwide. Although the prevalence of asthma may have plateaued at 8 12% in some economically developed countries, the global burden remains substantial. Although the prevalence of allergic disorders in childhood, such as atopic eczema and allergic rhinitis, varies substantially, the prevalence of atopic eczema appears to be increasing in Europe, Asia and Africa. In addition to genetic predisposition, urbanisation, reduced gastrointestinal flora biodiversity in infancy, early life exposure to cigarette smoke, allergens and reduced exposure to respiratory infections are established risk factors for the development of asthma and allergy in childhood. A recent randomised controlled clinical trial has also demonstrated early introduction of peanuts into infants' diets to be protective against subsequent peanut allergy. However, many factors remain unclear, and discerning causal pathways and potential targets for intervention is part of the World Health Organization's strategy for the prevention and control of asthma and allergy. There is evidence that the susceptibility for developing asthma and allergy is established in utero. Certain prenatal exposures are known to influence fetal development, including alcohol, smoking, illicit drugs and teratogenic medications. The concept of fetal programming describes how intrauterine factors can have an impact on subsequent offspring's physiology and development, affecting the risk of chronic diseases later in life. Childhood asthma and allergy are thought to be similarly influenced, as adaptive immunity develops prenatally with allergen specific immune responses demonstrable in newborns. Umbilical cord blood has been shown to contain fetally derived immunoglobulin E. Prenatal psychosocial stress, mediated through increased activity of the hypothalamic pituitary axis, has been postulated as an intrauterine exposure that may influence asthma and allergy susceptibility in the offspring. The hypothalamic pituitary axis is a biochemical pathway in which hormones secreted by the hypothalamus and pituitary gland in the brain stimulate the release of cortisol, adrenaline and noradrenaline from the adrenal glands in the abdomen. During pregnancy, these substances can be transmitted to the fetus and influence its development. Maternal prenatal psychosocial stress increases the risk of prematurity, low birthweight, offspring neurodevelopmental and cognitive delay, attention deficit hyperactivity disorder, and other mental health disorders in both animals and humans. Maternal prenatal psychosocial stress may also cause epigenetic effects with DNA methylation and altered gene expression in the placenta, although the significance of this has yet to be determined. In addition, there is some evidence that prenatal stress exposure can influence the composition of offspring's intestinal microbiota and also result in increased susceptibility to asthma. Animal studies have demonstrated that high levels of cortisol generated by prenatal psychosocial stress can increase airway responsiveness in the offspring and potentiate cell differentiation from T helper cell type 1 (Th1) to Th2 phenotype. Epidemiological studies have now investigated the potential impact of different indicators of maternal psychosocial stress during pregnancy, including bereavement, exposure to natural disasters, anxiety and depression symptoms, on the risk of asthma and allergy in the offspring. However, to better appreciate the underlying evidence base on the role of psychosocial stress in the development of asthma and allergy in the offspring, it is important to undertake a synthesis of primary studies that have emerged on this topic. This will provide the opportunity to identify key indicators of psychosocial stress that may influence the risk of asthma and allergy in children and the effects of which may be modified through development of evidence based and tailored primary prevention interventions.
npj Primary Care Respiratory Medicine