Administering antenatal steroids has become an important intervention method for preventing bronchopulmonary dysplasia in premature infants. However, it may also affect other aspects, such as fetal growth [20
], kidneys [28
], cardiovascular adaption [29
], and the immune system. In this study, we found antenatal steroid exposure to be correlated with an increased incidence of allergic diseases, particularly asthma and allergic rhinitis. These findings agree with a previous study by Pole et al. that reported that antenatal steroid therapy appears to be a risk factor for asthma among children between the ages of 36 and 72 months [15
]. The etiology of pediatric asthma includes various exposures and complex interactions. In infants, such factors include low birth body weight, gestational age, measurements at birth (body length and head circumference), malposition, and threatened labor. Maternal risk factors include maternal asthma history, smoking during pregnancy, mode of delivery, maternal age, prematurity, and breastfeeding status. Annesi-Maesano et al. reported that threatened labor could result in a significantly increased risk of asthma for the child [30
]. In Taiwan, mothers with threatened preterm labor before 34 weeks are routinely given corticosteroid to promote fetal lung maturation and prevent hyaline membrane disease in accordance with the American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice (ACOG) guidelines [31
]. While the precise mechanisms are still unclear, the priming of the Th1/Th2 system has been reported to occur during late gestation, as well as that pulmonary systems are already programmed during intrauterine life. Th1 immunity becomes markedly diminished during pregnancy, which results in maternal tolerance of the antigens derived from the paternal chromosomes. Diminished Th1 activity during pregnancy may help explain why pregnant women have a higher incidence of infections than non-pregnant women, especially with intracellular pathogens. The Th2 cytokines (IL-5) and regulatory T cytokine (Treg, IL-10) were also elevated in patients with asthma and allergic rhinitis but not atopic dermatitis in this study. The plasma levels of IP-10 were higher in atopic dermatitis, which suggests a different immune reaction between atopic dermatitis and asthma/allergic rhinitis. The modulation of the immune system may occur before 2 years old, prior to developing the allergic disease. Any allergic process may be the result of the fetus’s exposure to the mediators in utero. Whether corticosteroid therapy in the late gestation is directly associated with childhood asthma or whether it is a mediating factor of threatened labor still requires further study, but it seems to be a risk factor for childhood asthma. We first reported the increased incidence of allergic rhinitis in children with antenatal steroid exposure in this study. Dietert et al. showed that fetal exposure to dexamethasone (even at its lowest doses) provokes marked and persistent functional loss of DTH (Th1 immune response) [16
]. Other studies have indicated that inflammation in atopic dermatitis is biphasic: Th2 cells in acute atopic dermatitis; Th1 cells in chronic atopic dermatitis. This phenomenon may explain why antenatal steroids exposure in preterm infants is correlated with asthma and allergic rhinitis, which are considered Th2 cell-associated inflammatory diseases, while atopic dermatitis is not. In this study, we found no significant differences in mRNA of T-bet, RORγt, or cytokines (IL-17A, IFNγ, IL-2, and IP-10) between the prenatal exposure and non-exposure groups. This study also demonstrated no significant differences in Th2 immune response (GATA-3, IL-5, and IL-13) and Treg immune response (Foxp-3 and IL-10). A limitation of this study is the number of cases examined. Furthermore, no studies have yet discussed antenatal steroid exposure or change in cytokines from birth to 2 years old. Therefore, we will consider designing another study that focuses on this group. The impact of prenatal dexamethasone exposure on Th1/Th2/Th17 and Treg immune response needs further evaluation before a definite conclusion can be reached.
Our study also found a significantly higher MDI in the dexamethasone exposure group, but no significant differences in the PDI score between the two groups. We used the Mental Developmental Index to measure language, memory, and problem-solving abilities. Alexander et al. noted the long-lasting effects of antenatal synthetic corticosteroids exposure on hypothalamic-pituitary-adrenal reactivity in term infants, which may have significant implications with regard to the risk for stress-related physical and psychiatric disorders [32
]. This may explain the correlation between the use of antenatal corticosteroids and mental development. However, Asztalos et al. demonstrated that, in preterm infants, the neurodevelopmental outcome remained the primary factor (such as gestational age at birth), which was contributory regardless of the number of courses of antenatal synthetic corticosteroid therapy [33
]. Dexamethasone is not only used to promote fetus lung maturation but also to prevent further intraventricular hemorrhaging in preterm births before 34 weeks’ gestation [34
]. For preterm infants, the benefit offered by dexamethasone may exceed its disadvantages. However, this issue requires further study due to the limitations of our case numbers. The Psychomotor Developmental Index generally measures motor skills, but this was not related to dexamethasone exposure in our study.