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Antenatal corticosteroid treatment and infectious diseases in children: a nationwide observational study
Katri Räikkönen1,2, Mika Gissler3,4,5, Eero Kajantie6,7,8,9
1Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Insights
Antenatal Corticosteroid Treatment (ACT) in mothers was linked to increased infectious disease hospitalizations in term and late preterm infants. However, very-to-moderate preterm infants showed no increased risk, suggesting careful consideration of ACT benefits and risks.
Area of Science:
- Neonatal Medicine
- Pediatric Infectious Diseases
- Immunology
Background:
- Antenatal Corticosteroid Treatment (ACT) is crucial for preterm infant outcomes but may impact immune development and disease risk.
- The association between ACT and infectious diseases in term and preterm infants requires further investigation.
Purpose of the Study:
- To investigate the association between maternal ACT and infectious diseases in children born at term, late preterm, and very-to-moderate preterm.
- To assess the impact of ACT on inpatient treatment days, episodes, and specialized care visits for infectious diseases up to age 4.
Main Methods:
- A nationwide cohort study in Finland (2006-2021) included all singleton live births.
- Maternal ACT was the exposure; primary outcomes included infectious disease diagnoses, inpatient days, episodes, and outpatient visits.
- Term-born co-sibling comparisons were used to control for unmeasured familial factors.
Main Results:
- Term and late preterm infants exposed to ACT had significantly more inpatient treatment days, episodes, and specialized care visits for infectious diseases.
- Very-to-moderate preterm infants exposed to ACT showed similar outcomes to nonexposed infants, with fewer inpatient days/episodes at 3-4 years.
- Term-born co-sibling analyses confirmed the increased infectious disease burden associated with ACT.
Conclusions:
- ACT exposure is associated with an increased risk of infectious diseases in term and late preterm infants.
- The findings support careful consideration of the risks and benefits of ACT, particularly regarding potential long-term immune effects.
- Further research may be warranted to understand the mechanisms behind these observed associations.
Background:
Antenatal Corticosteroid Treatment (ACT) improves the outcome of preterm infants, but may influence immune system development and risk of immune-related diseases. We investigated whether ACT is associated with infectious diseases in children born at term (≥37 gestational weeks), and very-to-moderate (<34 gestational weeks), and late (34-36 completed gestational weeks) preterm.
Methods:
All singleton live births in Finland between 01/01/2006 and 31/12/2021, were followed-up until 31/12/2021. Exposure was maternal ACT. Primary outcomes were numbers of inpatient treatment days, episodes, and specialized care outpatient visits with any infectious disease diagnoses between ages 0 and 4 years. We considered mother- and child-related covariates, and conducted term-born co-sibling comparisons.
Findings:
Data comprised 855,234 children. Of the 20,858 (2.4%) treatment-exposed children, 5981 (28.2%) were very-to-moderate preterm-born, 5809 (27.9%) late preterm-born, and 9069 (43.5%) term-born. Of the 271,767 term-born co-sibling pairs, 5010 (1.8%) were treatment-exposure-discordant, and 266,522 (98.1%) nonexposure-concordant. Among the term- and late preterm-born, treatment-exposed children had more inpatient treatment days than nonexposed children (term: 0.87 vs. 0.56 day/y, adjusted mean difference [aMD] 0.19, 95% CI 0.17-0.28; late preterm: 1.35 vs. 1.00 days/y, aMD 0.31,0.13-0.31), more inpatient treatment episodes (term: 0.43 vs. 0.33 episodes/y, aMD 0.06, 0.06-0.11; late preterm: 0.55 vs. 0.48 episodes/y, aMD 0.12, 0.06-0.18), and specialized care treatment visits (term: 1.46 vs. 0.95 visits/y, aMD 0.38; 0.34-0.43; late preterm: 1.63 vs. 1.28 visits/y, aMD 0.22, 0.12-0.32). Treatment-exposed and nonexposed very-to-moderate preterm-born children were similar in these outcomes, though they had less inpatient treatment days and episodes at 3-4 years. Differences remained in term-born co-sibling comparisons.
Interpretation:
These findings reinforce previous suggestions for careful consideration of risks and benefits of ACT.
Funding:
Academy of Finland, HiLIFE Fellows-Programme.
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