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Friday, January 3, 2014

Maternal psychological distress during pregnancy affects wheezing in preschool children

Mechanisms such as social, behavioral, and environmental factors during pregnancy that may affect the risk of childhood asthma have been studied, but only few studies have assessed the relationship between maternal psychological distress and childhood wheezing.  Guxens et al performed a population-based study among children from birth to 6 years of age while assessing maternal and paternal psychological distress during pregnancy (J Allergy Clin Immunol 2014; 133(1): 59-67).  This large study of 4,848 children was embedded within the Generation R study, a population-based prospective cohort from fetal life onwards in Rotterdam, The Netherlands.  Maternal and paternal distress data was collected at 20 weeks gestation and again at 2 and 6 months, and 3 years after delivery by using the Brief Symptom Inventory questionnaire. Wheezing was annually assessed in the children up to 4 years of age. Physician diagnosed ever asthma was reported by parents at age 6 years. 

The authors point out that the association between maternal psychological distress during pregnancy and childhood asthma might be explained by developmental adaptations of the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, the lung structure and function, and immune responses in the children but also other mechanisms such as social, behavioral, or environmental factors.  To assess the role of different mechanisms, the authors assessed the associations both for the mother (unique intrauterine mechanism) and father (social, behavioral, or environmental factors), all taking into account many socioeconomic and lifestyle variables, and maternal psychological distress after the child was born. Children ultimately included in the analysis were more frequently from parents with a higher education level, and their parents had less psychological distress during pregnancy compared to those lost in follow-up. 

Guxens concludes that mothers with psychological distress during pregnancy had increased odds of overall wheezing in their children from 1 to 4 years of life, or of asthma at 6 years of age, compared to mothers that did not.  This result was similar in children of mothers with a history of asthma and atopy, compared to those without.  The authors go on to show that the robust result is independent of paternal psychological distress during pregnancy and maternal and paternal psychological distress after delivery.  These results suggest a direct intrauterine programming effect of maternal psychological distress on respiratory morbidity. To study these potential underlying biological mechanisms, markers of stress (diurnal cortisol rythm) and changes in the immune system (types of lymphocytes) could be measured. Our study has these data in a limited number of children only. Data for a genetic underlying mechanism, including interaction with environmental factors, are available and will be explored in the future. 

Implications of race and ethnicity on genetic profiles for personalized medicine

It is well known that frequencies and severity of disease can differ among races.  The mixing of African, European, and Native American ancestries has resulted in a variety of different ethnic groups with varied diversity. There is robust evidence from various clinical trials that different ethnic groups have variable responses to specific therapeutic agents.  The study of pharmacogenetics is used to personalize therapies specific to individuals from different ethnic or racial groups and it has historically been composed of mostly non-Hispanic whites of European descent. 

Ortega and Meyers summarize the genetic and epidemiologic basis for the variable genetic backgrounds observed between different, recently admixed ethnic groups such as African American or Hispanic (J Allergy Clin Immunol 2014; 133(1): 16-26). Rare genetic variants appear to be more frequent among individuals of African ancestry and could account for inter-ethnic differences in drug responses especially for rare, adverse events. Variability in phenotypes important in determining asthma severity between different ethnic groups could impact therapeutic responses to commonly used therapies.  For example, individuals with higher degrees of African ancestry have lower baseline lung function and increased risk for asthma exacerbations . In addition, African Americans are an ethnic group with an increased risk for adverse, possibly life-threatening, responses to long acting B2-adrenergic receptor agonists compared to non-Hispanic whites. 

The authors go on to explain that the genetic complexity of admixed ethnic groups is further challenged by representing only a minority of subjects enrolled in studies, cultural and habitual differences, and increased genetic diversity at an individual level.  These complex variables will require a combination of methods including genome-wide association studies, admixture-based analytical methods, and next-generation sequencing in larger populations to find and study genetic differences among ethnic groups and contribute to future pharmacogenetic studies.