The effect of prenatal maternal trait anxiety on atopic dermatitis and immunoglobulin E level : a prospective cohort study

Abstract

Atopic dermatitis is an inflammatory, relapsing and pruritic skin disorder and is increasing in prevalence especially in highly-developed countries. Recently, maternal distress during pregnancy is hypothesized as one of risk factors of allergic diseases. However, previous studies exhibit limitations such as outcome ascertained by maternal reports and lack of data on potential confounding factors. Moreover, the mechanism underlying the association between prenatal maternal distress and atopic dermatitis has not been investigated. The present study aimed to elucidate the effect of prenatal maternal state anxiety on the occurrence of atopic dermatitis and serum immunoglobulin E level after adjusting for postnatal depression and anxiety, and examine whether this effect was modified by nuclear factor-like 2 (Nrf2) gene polymorphisms. From August 2007 to November 2013, 1063 pregnant women were recruited for the study. Prenatal state anxiety levels were self-reported at 36th week of pregnancy using State-Trait Anxiety Inventory. At the time of analysis, the age of offspring ranged from 0 to 6 year-old. Atopic dermatitis was ascertained by physician diagnosis and mother’s report at 6 months, 1, 2, 3, and 4 year of age. IgE level was measured from cord blood and serum at 1st and 3rd year of age. Polymorphism in Nrf2 (rs6726395) was genotyped by using the TaqMan assay. Cox proportional hazards model and generalized estimating equations were conducted adjusting for potential confounders, including demographic variables and postnatal depression and anxiety. Atopic dermatitis was present in 28.0% of offspring during the first year, and 16.4% at 3rd year of age. Offspring of anxious mothers were more likely to have atopic dermatitis (physician’s diagnosis: HR 1.38, 95% CI 1.04-1.85; mother’s report: HR 1.56, 95% CI 1.20-2.03), and the association between prenatal maternal anxiety and atopic dermatitis was significant after adjusting for postnatal depression. Offspring of anxious mothers were more likely to have elevated serum immunoglobulin E level (OR 1.46, 95% CI 1.06, 2.02). When stratified for Nrf2 polymorphism and prenatal anxiety, offspring with Nrf2 GG polymorphism and anxious mother showed higher risk of having atopic dermatitis level (HR 2.43, 95% CI 1.24-4.77, interaction p-value = 0.019). Prenatal maternal state anxiety were associated with atopic dermatitis and elevated immunoglobulin E level in offspring, and this effect was modified by Nrf2 polymorphism. These findings suggest that mechanism may be mediated by reactive oxidative stress pathway. Interventions to reduce maternal anxiety during pregnancy may be helpful in preventing atopic dermatitis during infancy especially in genetically susceptible infants.