Prenatal Betamethasone Exposure and its Impact on Pediatric Type 1 Diabetes Mellitus: A Preliminary Study in a Spanish Cohort

Abstract

Background. Betamethasone, a glucocorticoid used to induce lung maturation when there is a risk of preterm delivery, can affect the immune system maturation and type 1 diabetes (T1D) incidence in the progeny. It has been described that prenatal betamethasone protects offspring from experimental T1D development. The main aim of this study was to evaluate the possible association between betamethasone prenatal exposure and T1D in humans. Research Design and Methods. A retrospective case-control study with a total of 945 children, including 471 patients with T1D and 474 healthy siblings, was performed. Participants were volunteers from the Germans Trias i Pujol Hospital and DiabetesCero Foundation. Parents of children enrolled in the study completed a questionnaire that included questions about weeks of gestation, preterm delivery risk, weight at birth, and prenatal betamethasone exposure of their children. Multiple logistic regression was used to detect the association between betamethasone exposure and T1D. Results. We compared T1D prevalence between subjects prenatally exposed or unexposed to betamethasone. The percent of children with T1D in the exposed group was 37.5% (21 of 56), and in the unexposed group was 49.52% (410 of 828) ( p = 0.139 ). The percentage of betamethasone-treated subjects with T1D in the preterm group (18.05%, 13 of 72) was significantly higher than that found in the control group (12.5%, 9 of 72) ( p = 0.003 ). The odds ratio for T1D associated with betamethasone in the univariate logistic regression was 0.59 (95% confidence interval, 0.33; 1.03 [ p = 0.062 ]) and in the multivariate logistic regression was 0.83 (95% confidence interval, 0.45; 1.52 [ p = 0.389 ]). Conclusions. The results demonstrate that the prenatal exposure to betamethasone does not increase T1D susceptibility, and may even be associated with a trend towards decreased risk of developing the disease. These preliminary findings require further prospective studies with clinical data to confirm betamethasone exposure effect on T1D risk.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden

“…However, in addition to the possibility of informative censoring affecting our observation, there are several other potential explanations. Data from experimental and clinical studies suggest a protective effect of prenatally administered exogenous glucocorticoids on type 1 diabetes risk in very preterm infants [ 35 , 36 ]. In addition, upregulation of the hypothalamic–pituitary–adrenal (HPA) axis occurs in very preterm infants, which has been suggested as a potential link between very preterm birth and glucose regulation [ 37 ].…”

Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells

“…These results point to a direct effect of betamethasone on HSC that will be maintained later in life. In humans, a preliminary study in a Spanish cohort shows that the developing immune system plasticity can be influenced by prenatal betamethasone, which could contribute to preventing autoimmune diabetes in subjects at risk (Perna-Barrull et al 2022 ). Based on these data, we hypothesized that betamethasone could also exert beneficial effects on HSC to improve engraftment.…”

“…Thus, a Treg increase could be crucial to avoid rejection and graft versus host disease. Since betamethasone is prenatally administered and that fact correlates with protection against autoimmunity (Gieras et al 2017 ; Perna-Barrull et al 2022 ), it is reasonable to speculate that Tregs will play a role in homeostasis. This fact suggests that betamethasone-induced changes in HSC will be long-term maintained.…”