According to the Development Origins of Health and Disease (DOHaD) theory,1 maternal prenatal stress is one of the key factors that affect the offspring’s risk of non-communicable diseases (NCD).2 Allergy is one of the representative NCD in children. Recent epidemiology studies indicate that maternal prenatal stress increases the risk of allergic diseases in offspring.3,4 No biomarker, however, is available, meaning that the exposure to stress or the possibility of allergic diseases development cannot be estimated. On the other hand, oxidative stress increases when subjects are under psychological stress5 and this elevates the risk of contracting NCD.6 Oxidative stress is thought to also be involved in allergic disease pathogenesis.4 Recently there have been clues that the leukocyte telomere length (LTL) shortening reflects the exposure to cumulative oxidative stress.7 Telomeres, the protective nucleoprotein structures with a variable number of a tandem repeat sequence that envelops the ends of linear chromosomes, are known to shorten with cell division.8 The LTL shortening is accelerated by oxidative stress and inflammation.9 This study aimed to verify whether maternal prenatal stress reduces the LTL in offspring, and whether the offspring’s LTL shortening is associated with the state of atopic dermatitis. If an association was shown, it would implicate that LTL shortening themselves, or other factors that can shorten the LTL, i.e. oxidative stress, is largely involved in the pathogenesis of prenatal stress inducing development of the offspring’s atopic dermatitis.
We selected a Korean birth cohort that demonstrated a good association between the prenatal maternal stress and offspring’s atopic dermatitis development.10 Among subjects whose cord blood and 1-year peripheral blood were both collected, 4 groups were selected according to both the level of prenatal maternal stress and later development of atopic dermatitis (high stress with later atopic dermatitis [HSWD], high stress without atopic dermatitis development [HSOD], low stress with later atopic dermatitis [LSWD], and low stress without atopic dermatitis development [LSOD] group). We evaluated cord blood and 1-year peripheral blood-LTL by measuring the mean terminal restriction fragment length using commercial kits from each group and compared them according to time points and groups.
A total of 68 subjects were sampled (22, 14, 13, and 18 for the HSWD, HSOD, LSWD, and LSOD groups, respectively). The mean 1-year peripheral blood LTL was significantly shorter than that of cord blood, which means that 1 year is a sufficient time to evaluate the change. When we divided groups according to the prenatal maternal stress, LTL were shorter in high stress groups than low stress ones, regardless of atopic dermatitis development both in cord blood and 1-year peripheral ones; this implies that prenatal stress certainly affects LTL shortening and the effect persists during the initial developmental period after birth. On the other hand, when groups were divided according to atopic dermatitis development, cord-blood LTL were not different between groups and 1-year peripheral-blood LTL presented only marginal difference between those that developed atopic dermatitis and those that did not. This demonstrates that LTL shortening is not a causal factor for developing atopic dermatitis. When we subdivided the comparison into each subgroup, the LTL did not shorten in the LSOD group, whereas in the LSWD group, LTL significantly shortened during 1 year after birth, which indicates that LTL shortening was prominent with the atopic dermatitis development.
In conclusion, prenatal stress results the LTL shortening; this may not be the causal, but the associated, factor of atopic dermatitis development. These results collectively indicate that the LTL shortening, a marker for oxidative stress exposure, reflects the complicated pathogenesis of prenatal stress associated with offspring’s atopic dermatitis development.