Objectives

Although maternal antenatal corticosteroid treatment (ACT) improves outcomes of infants born preterm, it is associated with an increased risk of infectious diseases during infancy and early childhood. We studied whether the risk of infectious diseases related to ACT persists into adolescence and whether it differs according to gestational age at birth.

Methods

We conducted a nationwide register-based cohort study of all singleton live births in Finland between 2006 and 2017, with follow-up from age 5 to 16 years (2011–2022). Children were classified as being born either very-to-moderately preterm (<34 weeks), late preterm (34–36 weeks), or term (≥37 weeks). Exposure was receipt or not of maternal ACT. The primary outcomes were differences in the annual number of hospitalizations, inpatient treatment days, and specialized care outpatient visits for any infectious disease. We used generalized linear models to assess associations between ACT exposure and the outcomes and reported mean differences from the generalized linear models with 95% confidence intervals (CIs). A subgroup analysis restricted the analysis to late preterm-born and term-born sibling pairs who received discordant (yes or no) ACT treatment.

Results

The cohort included 669 474 children (all children had outcome data for ages 5–10 years; a subsample of 345 591 children had outcome data for ages 6–11 years). Among 6519 children born very-to-moderately preterm, 22 024 late preterm, and 640 931 term, there were 4329 (66.4%), 3786 (17.2%), and 6716 (1.1%) treated with ACT. Of these, there were 353 and 3322 sibling pairs born late preterm or term analysed in the subgroup analysis for discordant receipt of ACT. Compared with nonexposed children, late preterm and term treatment-exposed children had a higher annual number of hospitalizations (adjusted mean difference [aMD], 0.02; 95% CI, 0.00–0.04; p <0.025; and aMD, 0.01; 95% CI, 0.00–0.02; p <0.009, respectively) and specialized care outpatient visits (aMD, 0.11; 95% CI, 0.04–0.17; p <0.001; and aMD, 0.10; 95% CI, 0.07–0.14; p <0.001, respectively) for any infectious disease, between the ages of 5 and 10 years. Late preterm treatment-exposed children also had a higher annual number of inpatient treatment days (aMD, 0.06; 95% CI, 0.01–0.10; p <0.017). This was not the case for children born very-to-moderately preterm (for hospitalizations: aMD, −0.05; −0.09 to −0.01; p <0.024; for inpatient treatment days: aMD, −0.23; 95% CI, −0.44 to −0.02; p <0.035; for specialized care outpatient visits: aMD, −0.13; 95% CI, −0.25 to −0.00; p <0.050). In the subgroup analysis of discordant sibling pairs, an increased risk for infectious diseases was only observed in the late preterm group. None of the observed risks persisted between ages 11 and 16 years.

Discussion

Our results support caution when considering ACT beyond 34 gestational weeks.