Rescue doses of antenatal corticosteroids, children's neurodevelopment, and salivary cortisol after a threatened preterm labor: a 30-month follow-up study

Abstract

Antenatal corticosteroids (ACS) reduce neonatal complications when are administered to women at risk of preterm birth. Moreover, ACS rescue doses are recommended in women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and exact timing for administering additional ACS doses since there are potential long-term negative effects on infants´ neurodevelopment and physiological stress functioning. The aims of this study were: i) to assess the long-term neurodevelopmental effects of receiving ACS rescue doses vs. receiving only the initial course; ii) to measure cortisol levels of infants that received ACS rescue doses; iii) to examine a potential dose-response effect of the number of ACS rescue doses on children´s neurodevelopment and salivary cortisol. The study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor (TPL) until the children were 30 months old, regardless of their gestational age at birth. Among the participants, 61 received only the initial course of corticosteroids (no rescue dose [NRD] group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses [RD] group). The follow-up was carried out at three different times: [T1] at TPL diagnosis, [T2] at the children´s age of 6 months, and [T3] at the children's age of 30 months, corrected age for prematurity. Neurodevelopment was assessed using the Ages & Stages Questionnaires-Third Edition. Saliva samples were collected for cortisol level determination. First, the RD group showed lower problem-solving skills at age 30-months compared to the NRD group. Second, the RD group demonstrated higher salivary cortisol levels at 30-months. Third, a dose-response effect was found, indicating that the higher number of rescue doses the RD group received, the lower the problem-solving skills and the higher the salivary cortisol levels they showed at 30 months of age. Our findings reinforce the hypothesis that additional doses provided after the initial course of ACS may have long-term effects on offspring's neurodevelopment and glucocorticoid metabolism. In this regard, the results raise concerns about the negative effects of repeated doses in addition to a full course of ACS. Further studies are necessary to confirm this hypothesis and help physicians to reassess the standard ACS treatment regimens.