Examining the nature and directionality of the relationship between children's anxiety symptoms and the immunoendocrine systems

Abstract

Background: Preterm birth is strongly associated with mortality, morbidity and lifetime difficulties including neurodevelopmental deficits. Immaturity of the lungs at birth is a major underlying cause, thus antenatal corticosteroid therapy (ACT) is administered to pregnant women in cases of threatened preterm birth to accelerate fetal lung development in hope of lessening infant mortality and morbidity. However, ACT has become controversial due to potential side-effects of exposure to excessive corticoids for the fetus. Objective: To study the associations between antenatal exposure to corticosteroids and infant size at birth. Design, setting, and participants: Population-based cohort study of women with live singleton births in Finland from 2006 through 2010. Maternal, pregnancy, and obstetric data came from the nationwide Finnish Medical Birth Register. Methods: Two analytic strategies were compared. First, traditional multiple regression analysis was employed to test the associationsadjusted forpotential confounders. Second,propensity scorematching (PSM)was used to take into account pre-treatment factors that could influence treatment allocation and outcome. Because PSM analysis closely matches participants on treatment characteristics results are akin to a randomized control trial although observational data are used. Results: We obtained data for 278508 women and their liveborn singletons (4887 treated and 273621 untreated). Results of adjusted multiple regression analyses and PSM converged. There were no differences by treatment in birth size for infants born very early (gestational age 24-29 weeks). Preterm infants born between 30 and 37 weeks exposed to ACT were smaller than untreated infants of the samegestational age in all respects: 518g lighter birth weight, 2.68 cm shorter birth length, 0.12 lower ponderal index, and 1.77 cm smaller head circumference, according to PSM.Deficits were also statistically significant among term born infants (gestational weeks 38-41) though differences were of lower magnitude. Post-term infants were of similar size regardless of ACT exposure. Conclusions and relevance: We were able to capitalize on the clinical practice of ACT during pregnancy to test whether synthetic glucocorticoids impact on the growth potential of the developing fetus. The results showed that infantswere smaller at birth and that head circumference, indicative of brain volume,was compromised. These results lend support to the hypothesis that prenatal exposure to excessive cortisol affects infant size and neurodevelopment.