Characteristics of the study population
A total of 861 infants were delivered between 240/7 and 316/7 wk of gestation. Neonates with major neonatal malformations or congenital disease (n=2), admitted to NICU after 2 h of birth (n=11), not admitted to NICU (n=53), discharged from the hospital due to family financial difficulties, or concerns about the prognosis (n=43) were excluded. Moreover, 6 infants received multiple courses of ACS, 40 infants did not received ACS before birth, and 1 infant whose mother diagnosed as systemic lupus erythematosus were also excluded. Finally, 706 infants were included in the study: 264, 83, 292 and 67 infants were born at the ACS-to-delivery intervals of <24 h, 1-2 d, 2-7 d and >7 d, respectively (Figure 1).
The maternal infant baseline characteristics are summarized in Table 1. Of the 706 neonates, 66 (9.35%), 203 (28.75%) and 437 (61.90%) were born at the GA of 24-276/7, 28-296/7 and 30-316/7wk, respectively. Women receiving ACS <24 h before delivery were less likely to have PPROM >18 h, placenta previa, hypertension disorder, vaginal delivery and twin, while more likely to have low GA and birth weight. Significant differences in the maternal characteristics such as hypertensive disorders, placenta previa, GA at delivery, PPROM >18 h, and mode of delivery were observed among the 4 groups (Table 1). The incidence of placental abruption, gestational diabetes and fetal intrauterine distress before delivery were relatively similar among the 4 groups. The median duration of ventilation (invasive and non-invasive support) was 10 d (IQR: 2, 23 d) in the ACS interval of <24 h group and 4.5 d (IQR: 1, 13 d) in the ACS interval of >7 d group (p=0.01). The intervals from the first corticosteroid dose to delivery were remarkably different among the 4 groups, while the lengths of hospitalization were quite similar among the 4 groups (Table 1). Figure 2 shows the distribution of GA at birth for the 4 groups.
Relationships between ACS-to-birth intervals and neonatal outcomes
The infants exposed to ACS at 2-7 d before birth tended not to use surfactant and require for intubation-mechanical ventilation (17.1% and 10.3%) compared to those exposed <24 h (37.1% and 18.9%), 1-2 d (18.1% and 10.8%) and >7 d (22.4% and 13.4%) before delivery, respectively. The unadjusted cumulative incidence rates and ORs testing associations between ACS intervals and neonatal outcomes are shown in Table 2. The unadjusted incidence of NRDS, death, the need for intubation in delivery room, surfactant use and mechanical ventilation were significantly higher in the ACS interval of <24 h compared with the administration-to-birth interval of 2-7 d. There was no difference in the incidence of BPD among the 4 groups.
After adjusting these confounding factors, multivariable logistic regression analysis revealed the significantly increases in NRDS risk (aOR: 1.8, 95% CI: 1.2-2.7), mortality rate (aOR: 2.8, 95% CI: 1.1-6.8), the need for surfactant use (aOR: 2.7, 95% CI: 1.7-4.4), the need for endotracheal intubation at birth (aOR: 1.9, 95% CI: 1.0-3.7), intubation/mechanical ventilation rate (aOR: 1.9, 95% CI: 1.1-3.4) and surfactant use or intubation/mechanical ventilation rate (aOR, 2.8; 95% CI, 1.7-4.4) in the ACS-to-birth interval of <24 h group compared with the ACS-to-birth interval of 2-7 d group (Table 2). Compared with the ACS-to-birth interval of 2-7 d group, the rates of NRDS, surfactant use, intubation/mechanical ventilation and mortality were relatively similar in the ACS intervals of 1-2 d and >7 d groups (Table 2). However, no remarkable difference in the rate of BPD was found among the 4 groups after adjusting the variables.
Subgroup analysis for the association between ACS-to-birth interval of <24 h and neonatal pulmonary outcomes
Of the 264 neonates exposed to ACS <24 h before birth, 153 (23.9%), 50 (7.8%) and 61 (9.6%) were born <6 h, 6-12 h and 12-24 h, respectively. After adjusting those confounding factors, the incidence of NRDS, mortality rate, surfactant use, intubation in delivery room, rate of intubation/mechanical ventilation (aOR: 2.8, 95% CI: 1.5-5.4) and rate of surfactant use or mechanical ventilation were significantly higher in neonates delivered <6 h after ACS exposure than in those delivered within 2-7 d after ACS exposure (Table 3). Moreover, the rates of mortality, surfactant use, mechanical ventilation or surfactant use were significantly increased in the ACS-to-birth interval of 6-12 h group compared with the ACS-to-birth interval of <6 h group. However, the rates of BPD were not remarkably different among the 4 groups.