Fig. 6. Preterm infants who received antenatal GCs out-of-phase show altered behavior.

a Distribution of the number of 5-year-old preterm infants included in the analysis. Data were collected in three centers included in the German Neonatal Network; Lübeck, Cologne and Essen. Depending on the difference (in hours) between the time of maternal physiological cortisol peak (estimated at 8:00,⁷⁴) and the time of antenatal betamethasone injection, preterm infants were divided into two groups; the in-phase group, injected between 4:00 and 12:00 (green shading) and the out-of-phase group, injected between 18:00 and 0:00 (pink shading). b A compound behavioral score (0 to 10) was used to quantify stress compensation capacity, infants with high score are reported to have more features indicating poor stress compensation capacity⁵¹. In total, 53 behavioral scores of 5-year-old preterm infants from the three centers were included in the in-phase (n = 33) and out-of-phase groups (n = 20) (i.e. 54 children out of n = 107 belong to the middle group whose mothers were injected from 12:00 to 18:00 and from 0:00 to 4:00). Data are expressed as means ± SEM; *indicates p = 0.031 [β = .65, t (49) = 2.18, partial η² = 0.08; two-sided, uncorrected p-value for parameter estimate resulting from an ordinary-least squares linear regression model predicting the behavioral score from in-phase/out-of-phase antenatal GCs while adjusting for mode of delivery, the only confounding factor; see Table 1]. Note that this parameter estimates for the out-of-phase/in-phase difference holds when including data from all preterm infants into the model, including the additional N = 54 from the middle group [two-sided, uncorrected p = 0.035, β = .63, t (101) = 2.14, partial η² = 0.05; identical model specifications]. Source data are provided as a Source Data file.