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Antenatal Corticosteroids and Infectious Diseases Throughout Childhood
Fabienne Decrue1, Emily M Frier2, Chun Lin1
1Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Insights
Antenatal corticosteroids (ACS) increase infection risk in full-term children, but not in preterm infants born before 34 weeks. More precise ACS administration guidelines are needed to mitigate adverse effects.
Area of Science:
- Obstetrics and Gynecology
- Neonatal Research
- Pediatric Infectious Diseases
Background:
- International guidelines recommend antenatal corticosteroids (ACS) for pregnancies at risk of preterm birth before 34 weeks' gestation.
- The long-term impact of ACS exposure on childhood and adult infection susceptibility remains largely unknown.
Purpose of the Study:
- To investigate the association between antenatal corticosteroid (ACS) exposure and the risk of respiratory and nonrespiratory infections in children.
- To compare infection susceptibility between ACS-exposed and unexposed children born at various gestational ages.
Main Methods:
- Population-based cohort study utilizing nationwide registries from Finland and Scotland (Consortium for the Study of Pregnancy Treatments).
- Included singleton births between 1997-2018 (Finland) and 2006-2018 (Scotland), followed until 2018.
- Outcomes included first diagnosis of respiratory or nonrespiratory infections, stratified by gestational age at birth.
Main Results:
- ACS exposure was associated with increased risks of respiratory and nonrespiratory infections in children born full-term (37-41 weeks) and late preterm (34-36 weeks).
- No significant association between ACS exposure and infection risk was observed in very preterm infants (born <34 weeks' gestation).
- Incidence rates of infections were higher in ACS-exposed children compared to unexposed children.
Conclusions:
- Antenatal corticosteroid (ACS) exposure is linked to a higher risk of infections in full-term children up to age 21.
- No increased infection risk was found in preterm infants exposed to ACS before 34 weeks' gestation.
- Stricter criteria for ACS administration and improved preterm birth prediction are necessary to minimize potential adverse effects.
Importance:
International guidelines recommend the use of antenatal corticosteroids (ACS) in pregnancies at risk of imminent preterm birth before 34 weeks' gestation. However, whether ACS leads to long-term risk of infection from childhood to adulthood is unknown.
Objective:
To determine whether preterm (<37 weeks' gestation) and full-term (37-41 weeks' gestation) children exposed to ACS are more susceptible to respiratory and nonrespiratory infections compared with ACS-unexposed children throughout childhood and adolescence.
Design, Setting, And Participants:
This population-based cohort study used data from the multicenter Consortium for the Study of Pregnancy Treatments (Co-OPT) study, including data from nationwide registries for mothers and their children in Finland and Scotland. Singleton children born from 1997 to 2018 and 2006 to 2018 in Scotland and Finland, respectively, were followed up until 2018, death, or first infection. Data were analyzed between June 2022 and October 2023.
Exposures:
Maternal ACS treatment.
Main Outcomes And Measures:
Primary and secondary outcomes were the first diagnosis of respiratory or nonrespiratory infection after birth-related hospital discharge. Outcomes were stratified by gestational age at birth.
Results:
Among 1 548 538 included mother-child pairs (mean [SD] maternal age, 29.4 [5.7] years; mean [SD] gestational age at birth, 39.2 [1.7] weeks; 759 082 [49.0%] female neonates), 49 263 children (3.2%) were ACS-exposed, of whom 34 806 (70.7%) were preterm and 14 457 (29.3%) were full term at birth. ACS-exposed children had more respiratory and nonrespiratory infections than nonexposed children (incidence rate, 65.2 vs 39.8 and 30.0 vs 17.9 per 1000 person-years, respectively). Compared with nonexposed children, higher risks for respiratory and nonrespiratory infections were found among ACS-exposed children born at 34 weeks 0 days to 36 weeks 6 days' gestation (adjusted hazard ratios [HRs], 1.10 [95% CI, 1.06-1.14] and 1.19 [95% CI, 1.15-1.24]), 37 0/7 to 38 6/7 weeks' gestation (adjusted HRs, 1.27 [95% CI, 1.21-1.32] and 1.17 [95% CI, 1.11-1.23]), and 39 weeks 0 days to 41 weeks 6 days' gestation (adjusted HRs, 1.23 [95% CI, 1.16-1.30] and 1.31 [95% CI, 1.22-1.40]). However, ACS-exposed children born at 28 weeks 0 days to 31 weeks 6 days' gestation and 32 weeks 0 days to 33 weeks 6 days' gestation showed no association between ACS exposure and respiratory and nonrespiratory infections.
Conclusion And Relevance:
In this cohort study, exposure to ACS was associated with increased risks of infections in full-term children until age 21 years. In preterm children born before 34 weeks' gestation, no association between ACS and infections was found. To minimize the adverse effects of ACS treatment, more stringent criteria for ACS administration and better prediction tools for preterm birth are required.
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