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

BACKGROUND Antenatal corticosteroids reduce neonatal complications when administered to women at risk for preterm birth. Moreover, antenatal corticosteroid rescue doses are recommended for women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and the exact timing of administering additional antenatal corticosteroid doses because there are potential long-term negative effects on infants’ neurodevelopment and physiological stress functioning. OBJECTIVE This study aimed to (1) to assess the long-term neurodevelopmental effects of receiving antenatal corticosteroid rescue doses in comparison with receiving only the initial course; (2) to measure the cortisol levels of infants of mothers who received antenatal corticosteroid rescue doses; (3) to examine a potential dose-response effect of the number of antenatal corticosteroid rescue doses on children's neurodevelopment and salivary cortisol. STUDY DESIGN This study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor 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 group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses group). The follow-up was carried out at 3 different times, namely at threatened preterm labor diagnosis (T1), when the children were 6 months of age (T2), and when the children were 30 months of corrected age for prematurity (T3). Neurodevelopment was assessed using the Ages & Stages Questionnaires, Third Edition. Saliva samples were collected for cortisol level determination. RESULTS First, the rescue doses group showed lower problem-solving skills at 30 months of age than the no rescue doses group. Second, the rescue doses group demonstrated higher salivary cortisol levels at 30 months of age. Third, a dose-response effect was found that indicated that the more rescue doses the rescue doses group received, the lower the problem-solving skills and the higher the salivary cortisol levels at 30 months of age. CONCLUSION Our findings reinforce the hypothesis that additional antenatal corticosteroid doses provided after the initial course may have long-term effects on the neurodevelopment and glucocorticoid metabolism of the offspring. In this regard, the results raise concerns about the negative effects of repeated doses of antenatal corticosteroids in addition to a full course. Further studies are necessary to confirm this hypothesis to help physicians reassess the standard antenatal corticosteroid treatment regimens. Antenatal corticosteroids reduce neonatal complications when administered to women at risk for preterm birth. Moreover, antenatal corticosteroid rescue doses are recommended for women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and the exact timing of administering additional antenatal corticosteroid doses because there are potential long-term negative effects on infants’ neurodevelopment and physiological stress functioning. This study aimed to (1) to assess the long-term neurodevelopmental effects of receiving antenatal corticosteroid rescue doses in comparison with receiving only the initial course; (2) to measure the cortisol levels of infants of mothers who received antenatal corticosteroid rescue doses; (3) to examine a potential dose-response effect of the number of antenatal corticosteroid rescue doses on children's neurodevelopment and salivary cortisol. This study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor 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 group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses group). The follow-up was carried out at 3 different times, namely at threatened preterm labor diagnosis (T1), when the children were 6 months of age (T2), and when the children were 30 months of corrected age for prematurity (T3). Neurodevelopment was assessed using the Ages & Stages Questionnaires, Third Edition. Saliva samples were collected for cortisol level determination. First, the rescue doses group showed lower problem-solving skills at 30 months of age than the no rescue doses group. Second, the rescue doses group demonstrated higher salivary cortisol levels at 30 months of age. Third, a dose-response effect was found that indicated that the more rescue doses the rescue doses group received, the lower the problem-solving skills and the higher the salivary cortisol levels at 30 months of age. Our findings reinforce the hypothesis that additional antenatal corticosteroid doses provided after the initial course may have long-term effects on the neurodevelopment and glucocorticoid metabolism of the offspring. In this regard, the results raise concerns about the negative effects of repeated doses of antenatal corticosteroids in addition to a full course. Further studies are necessary to confirm this hypothesis to help physicians reassess the standard antenatal corticosteroid treatment regimens.