This is the first study exploring the associations of maternal lifestyle choice during pregnancy with the risk of childhood respiratory allergic diseases. Our findings demonstrated that all of the three unhealthy maternal lifestyles, including short sleep duration, lack of physical activity and too much screen exposure, were independent risk predictors. Also of concern was significant dose-response trend, the more concentrations of maternal unhealthy lifestyles during pregnancy, the greater risk of respiratory allergies in their children. Moreover, significant gender difference was identified that boys were more susceptible to the adverse effects. The results, in most cases, can be verified in the Allergen Test Subgroup and the single type of disease, which further enforced the evidence. The present study extended our attention on the association of maternal behavior exposure with immune development and allergic disease susceptibility in their offspring, in which gender difference should be taken into consideration.
The rapid increase in childhood allergic disease may be correlated to rapid economic growth or modernization.3 In developed countries, the prevalence of childhood allergic respiratory symptoms appears to have peaked and stabilized.24 China, as a developing country, is rapidly urbanizing and the prevalence of childhood respiratory allergies is now on the rise, especially in fast-growing cities such as Shanghai.3 Urbanization is accompanied by a modern style of life, electronic screen exposure is more frequent, sedentary time is increasing while sleeping time is decreasing,11 and there has been proved that pregnant women spend at least half their time on sedentary behaviors.25
Our results provided new evidence to the hypothesis that mother's lifestyle during pregnancy affects offspring’s long-term health, herein childhood respiratory allergies. Previous studies exploring the effect of lifestyle during pregnancy on the long-term health of children largely focused on the neurological and behavioral development.26–29 A rodent model found that lacking of sleeping in the third trimester can impair autonomic responses in male offspring with a long-term effect.26 Cohorts data from 83,884 mother-child pairs from five countries revealed that maternal cellphone use during pregnancy increased the risk of hyperactivity in their offspring.27 Another two prospective studies found that adequate physical activity during pregnancy could promote language development in children.28,29 This study, for the first time, focused on maternal lifestyle choice and the susceptibility of childhood allergic disease. In addition, most of previous studies only assessed one aspect of maternal life styles, and their combined effects have never been studied. In our study, a clear dose-response relationship was established, the more exposures to maternal unhealthy lifestyles during pregnancy, the higher risk of childhood respiratory allergies.
Early life exposure in utero can affect fetal airway and lung development, as well as immune function.30 As suggested by previous studies, maternal smoking, unqualified diet, vitamin D deficiency and exposure to air pollution has been found to be possible potential risk factors.7,31−34 A retrospective follow-up study was conducted among 1201 Los Angeles women between 3 and 6 months after delivery, where it was shown that children whose mothers ate more fast food during pregnancy had a relative increased risk of asthma.31 Although there existed different conclusions,32,33 a more recent meta-analysis revealed that maternal prenatal vitamin D supplementation was associated with a lower risk of allergic diseases in children.34 Compared to these studies, we focused on daily lifestyle choices, including sleep duration, physical activity and screen using, and established the relationship between them and the risk of childhood respiratory allergies with a dose-response pattern. As far as we know, to date this is the only one population-based study to explore the associations. To test the association, analysis was further applied in subgroup whose allergen test was positive, and the similar results further enforced the evidence that maternal daily lifestyle choices is involved in childhood susceptibility to respiratory allergic diseases.
Although this is the first epidemiological study to explore the relationship between maternal lifestyle choice and offspring allergies, several potential explanations were in biological mechanism to support the relationship. A number of studies have demonstrated that early life adverse exposure in utero can block the production of the immune response of fetal cytokines to Th1 type and affect the programming of fetal immune function.30,35,36 In addition, an increased stress and inflammatory response were put forward to explain the pathway. Sleep deprivation may lead to oxidative stress and inflammation, thus affecting early embryonic development;37 while regular exercise can effectively buffer stress and prevent inflammation-related diseases through the mother-fetus connection.38 Moreover, prenatal unhealthy behavioral exposure may also affect microbiota of pregnant women, thereby transferring maternal bacteria to the fetus.39 The imbalance of intestinal flora in infancy may lead to the deviation of immune function and allergic reactions.40
It was impressed that respiratory allergies were mainly prevalent in boys when their mothers were exposed to adverse lifestyle behaviors during pregnancy. In a rat model, maternal high-fat diet during pregnancy was associated with neonatal cardiac dysfunction, reduced respiratory capacity and oxidative stress only in male offspring, indicating that adverse prenatal exposures impaired dynamism with sex-divergent characteristic.35 It has been recognized that male and female possessed different immune responses, especially in T-helper cells.36 On referring to genetics, most of respiratory genes are located on sex chromosomes or are involved in the production of sex hormones. Estrogen, the primary female sex hormone, has been regarded as immune-stimulating factor.15 While testosterone, as male sex hormones, tends to have immunosuppressive effects.15 Taken together, the current progress in research indicated gender difference existed in immune response, it seemed that female offspring tended to have protective immune response under the function of estrogen.
This study has several limitations. First, information on maternal behavioral exposure was obtained from questionnaires, and thus the recall bias was inevitable. However, due to pregnancy was a special period, and the China’s one-child policy in the past decades, the recall bias can lower to a small level. Second, cross-sectional study was poor in determining causal links. However, the dependent variables and the outcome variables we analyzed were mothers' lifestyles during pregnancy and their children’s respiratory allergies respectively, which had a time sequence, thus revealing a certain causal relationship. Third, allergic diseases were not diagnosed by professionals. However, the international standard ISAAC questionnaire was applied worldwide with quite good reliability and validity.22 In addition, children with positive allergen test were analyzed as a subgroup, which further verified our findings. Finally, even though many confounding factors were taken into account, residual confounding may remain. However, given that the results were broadly consistent across all the respiratory allergies in this study, the evidence for link between maternal behavioral exposure and childhood allergic disease appeared to be robust.