Abstract
Background
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.
Objective
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.
Study Design
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.
Results
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.
Conclusions
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.
Keywords
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Article info
Publication history
Accepted:
March 1,
2023
Received in revised form:
February 21,
2023
Received:
November 28,
2022
Publication stage
In Press Accepted ManuscriptIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
