Gestational Age-Specific Effects of Antenatal Corticosteroids on Early Physiologic Vulnerability and Neonatal Outcomes

Gestational Age-Specific Effects of Antenatal Corticosteroids on Early Physiologic Vulnerability and Neonatal Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Gestational Age-Specific Effects of Antenatal Corticosteroids on Early Physiologic Vulnerability and Neonatal Outcomes Chae Young Kim, Abraham Kwak, Juhee Park, Tae-Gyeong Kim, Kyusang Yoo, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8754951/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objective To evaluate gestational age (GA)-specific associations between antenatal corticosteroid (ACS) exposure and early physiologic vulnerability and neonatal outcomes in preterm infants. Study Design This retrospective cohort study used Korean Neonatal Network data and included infants born between 2013 and 2021 with birth weight < 1 500 g or GA < 32 weeks. ACS exposure was categorized as complete, incomplete, or none. Multivariable logistic regression estimated adjusted odds ratios, with GA-stratified analyses and a prespecified subgroup of infants born at < 25 weeks. Results ACS exposure was associated with lower delivery room resuscitation intensity, reduced risk of severe intraventricular hemorrhage, and decreased mortality, with strongest associations observed before 32 weeks. In infants born at < 25 weeks, any ACS exposure was associated with greater physiologic stability and improved survival compared with no ACS exposure. Conclusions ACS exposure was associated with improved physiologic stability and survival in preterm infants, with benefits greater at lower GAs. Health sciences/Medical research/Epidemiology Health sciences/Diseases/Respiratory tract diseases Health sciences/Risk factors Antenatal corticosteroids Gestational age Infant Extremely premature Mortality Figures Figure 1 Figure 2 INTRODUCTION Antenatal corticosteroids (ACS) represent one of the most effective antenatal interventions for improving outcomes in preterm infants, with robust evidence demonstrating reductions in neonatal mortality and major morbidities through accelerated maturation of the fetal lung and other organ systems [ 1 , 2 ]. Based on this evidence, ACS administration has been widely incorporated into international guidelines and is routinely recommended across a broad range of gestational ages (GAs). However, much of the foundational evidence supporting ACS use is derived from heterogeneous preterm populations that are frequently analyzed as a single group, thereby limiting insight into how treatment effects vary across stages of gestational maturity [ 3 ]. Over the past two decades, advances in obstetric and neonatal care have substantially improved survival among extremely preterm infants, particularly those born before 28 weeks’ gestation [ 4 – 6 ]. As survival has increased, clinical priorities have shifted toward reducing severe morbidities—such as bronchopulmonary dysplasia, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP)—which reflect profound physiologic immaturity and vulnerability to early perinatal stressors. In this context, antenatal and immediate perinatal interventions may exert disproportionate effects on physiologic stability during the immediate postnatal transition, with important implications for subsequent clinical outcomes. Emerging evidence suggests that the benefits of ACS are not uniform across GAs and may vary according to fetal maturity, timing of administration, and early neonatal management practices [ 7 ]. Nevertheless, most prior studies have assessed ACS exposure dichotomously as present or absent, without accounting for treatment completeness. This approach is increasingly discordant with contemporary clinical practice, in which incomplete ACS courses are common owing to precipitous preterm delivery, maternal instability, or competing obstetric priorities. For clinicians managing imminent extreme preterm birth, the critical question is therefore not whether ACS is beneficial in principle, but whether partial exposure meaningfully modifies early physiologic vulnerability and survival. Moreover, extremely preterm infants are frequently grouped together in clinical research despite marked biological and clinical heterogeneity within this population. Infants born at the margins of viability differ substantially in physiologic maturity, resuscitation requirements, and capacity to tolerate perinatal stress, yet these differences are often obscured when GA-specific effects are not explicitly examined [ 8 ]. Recent studies have also suggested that ACS-associated benefits may extend into later GAs, particularly for respiratory outcomes [ 9 ], raising questions regarding the gestational threshold beyond which ACS effects attenuate. To address these gaps, we conducted a large nationwide cohort study using data from the Korean Neonatal Network (KNN) to evaluate GA-specific associations between ACS exposure and early physiologic vulnerability at birth. We focused on delivery room resuscitation intensity as an indicator of early postnatal adaptation and examined how these associations varied across clinically relevant GA strata, including a prespecified analysis of infants born before 25 weeks’ gestation. By explicitly distinguishing between complete and incomplete ACS exposure, this study aimed to reflect real-world antenatal treatment patterns and to provide clinically relevant insight into GA-dependent treatment effects across the spectrum of prematurity. METHODS Study Design and Data Source This retrospective cohort study used data from the KNN, a nationwide, prospective registry of very low birth weight infants (birth weight < 1 500 g) admitted to 70 tertiary neonatal intensive care units across South Korea. Infants born between January 1, 2013, and December 31, 2021, were eligible for inclusion. Infants were included if they met either of the following criteria at birth: (1) birth weight < 1 500 g regardless of GA, or (2) GA < 32 weeks’ gestation irrespective of birth weight. Multiple gestations were included. Infants were excluded if they had major congenital anomalies, chromosomal abnormalities, or unknown ACS exposure status. Stillbirths are not captured in the KNN registry and were therefore not included. GA was determined using the obstetric estimate based on the last menstrual period and early ultrasound findings. Definitions of ACS Exposure ACS exposure was categorized as complete, incomplete, or none based on maternal corticosteroid administration within 7 days before delivery, consistent with international guidelines recommending delivery within this interval for optimal fetal lung maturation [ 2 , 10 , 11 ]. Complete ACS exposure was defined as maternal receipt of either (1) two 12-mg intramuscular doses of betamethasone administered 24 h apart or (2) four 6-mg intramuscular doses of dexamethasone administered 12 h apart. Incomplete ACS exposure included any corticosteroid administration that did not meet the criteria for a complete regimen, including partial dosing, single-dose therapy, or dosing intervals deviating from the recommended schedule. No ACS exposure was defined as the absence of any maternal corticosteroid administration before delivery. The KNN registry does not capture information on rescue ACS, repeat courses, or precise dose-to-delivery intervals; therefore, these factors could not be evaluated. Outcome Measures The primary outcome was mortality before hospital discharge. Key secondary outcomes included delivery room resuscitation intensity—defined as the need for endotracheal intubation, chest compressions, or epinephrine administration according to Neonatal Resuscitation Program guidelines [ 12 ]—as an operational marker of early physiologic vulnerability, as well as major neonatal morbidities. Respiratory distress syndrome (RDS) was defined by a clinical diagnosis supported by radiographic findings. Patent ductus arteriosus was defined by the receipt of medical or surgical treatment. Moderate to severe bronchopulmonary dysplasia was defined according to the 2001 National Institute of Child Health and Human Development criteria. Pulmonary hypertension was defined by echocardiographic or clinical diagnosis prompting initiation of pharmacologic treatment; only infants receiving treatment were classified as having pulmonary hypertension. Severe IVH was defined as Papile grade ≥ 3, NEC as modified Bell stage ≥ II, and retinopathy of prematurity as stage ≥ 2. Sepsis was defined according to the KNN registry criteria as the presence of both a positive blood culture and a requirement for systemic antibiotic therapy for at least 5 days and was analyzed as a composite outcome without distinction between early- and late-onset sepsis. GA-Stratified Analyses GA-stratified analyses were performed to assess potential effect heterogeneity in the associations between ACS exposure and neonatal outcomes according to fetal maturity. GA categories were defined a priori based on established differences in physiologic maturity, baseline risk of adverse neonatal outcomes, and anticipated responsiveness to ACS, as supported by prior neonatal and perinatal studies [ 7 ]. Infants were stratified into three GA groups: extremely preterm infants born before 28 weeks’ gestation; very preterm infants born at 28 to < 32 weeks’ gestation; and infants born at ≥ 32 weeks’ gestation [ 13 ]. In addition to these primary stratified analyses, a prespecified subgroup analysis was conducted among infants born before 25 weeks’ gestation, a population in whom clinical decision-making regarding resuscitation and intensive care is particularly complex. Statistical Analysis Continuous variables were compared using the Student t test or the Wilcoxon rank-sum test, as appropriate, and categorical variables were compared using the chi-square test or Fisher’s exact test. No formal sample size calculation was performed;all eligible infants in the KNN during the study period were included in the analysis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for associations between ACS exposure categories (none, incomplete, and complete) and neonatal outcomes. Models were adjusted a priori for GA, birth weight, infant sex, maternal age, parity, mode of delivery, maternal hypertension, maternal diabetes, chorioamnionitis, and preterm rupture of membranes. Baseline balance between exposure groups was assessed using standardized mean differences. Because baseline standardized mean differences for key covariates were generally small to moderate and propensity score matching would have reduced the sample size, we analyzed all eligible infants using multivariable logistic regression with covariate adjustment rather than restricting analyses to matched subsets. GA-stratified analyses were performed using prespecified categories (< 28, 28 to < 32, and ≥ 32 weeks’ gestation), with an additional prespecified subgroup analysis among infants born before 25 weeks’ gestation. Effect modification by GA was assessed using interaction terms, and sensitivity analyses examined GA as a continuous variable. All analyses were performed using R software (version 4.3.2), and a two-sided p -value < 0.05 was considered statistically significant. Code Availability No custom computer code was used to generate results that are central to the conclusions of this study. RESULTS Study Population During the study period, 18,094 infants were identified in the KNN (Fig. 1 ). After excluding infants with major congenital anomalies, chromosomal abnormalities, or missing information on ACS exposure, 17,388 infants were included in the final analytic cohort. Of these, 3,109 infants (17.9%) received no ACS, 6,279 (36.1%) received an incomplete ACS course, and 8,000 (46.0%) received a complete ACS course. Among infants with available information on the specific corticosteroid administered, 5,289 (30.4%) were exposed to betamethasone and 2,770 (15.9%) to dexamethasone; the specific agent was not recorded for 9,329 infants (53.7%). Baseline Characteristics Baseline maternal and neonatal characteristics differed across ACS exposure groups (Table 1 ). Compared with infants who received no ACS, those exposed to incomplete or complete ACS were born at earlier GAs (mean GA, 28.7–28.8 vs. 29.4 weeks) and had lower birth weights (approximately 1,100–1,110 g vs. 1,170 g), indicating greater baseline physiologic immaturity. Despite this higher degree of prematurity, markers of immediate postnatal adaptation improved progressively with increasing ACS exposure: Apgar scores were lowest among infants without ACS and highest among those receiving a complete ACS course. Maternal conditions associated with preterm delivery, including preterm rupture of membranes and clinical chorioamnionitis, were more prevalent in the ACS-exposed groups. Cesarean delivery was most frequent among mothers who received a complete ACS course. Overall, infants exposed to ACS—particularly those receiving complete courses—represented a population with greater antenatal and perinatal vulnerability at baseline. Table 1 Baseline maternal and neonatal characteristics according to antenatal corticosteroid (ACS) exposure. Baseline maternal, obstetric, and neonatal characteristics stratified by ACS exposure (none, incomplete, and complete). Continuous variables are presented as mean ± standard deviation, and categorical variables as number (%). No (n = 3 111) Incomplete (n = 6 272) Complete (n = 8 005) p value Gestational age, week 29.4 ± 3.8 28.7 ± 2.8 28.8 ± 2.8 < .0001 Birth weight, g 1 170.0 ± 298.2 1 110.5 ± 240.3 1 100 ± 243.9 < .0001 Birth height, cm 36.8 ± 3.8 36.5 ± 3.6 36.3 ± 3.6 < .0001 Birth head circumference, cm 26.2 ± 2.7 25.9 ± 2.4 25.78 ± 2.4 < .0001 Apgar score at 1 min 4.5 ± 2.3 4.7 ± 2.0 4.9 ± 2.0 < .0001 Apgar score at 5 min 6.6 ± 2.1 6.6 ± 2.1 7.0 ± 1.8 < .0001 Multiple gestation 1 061 (34.1) 2 544 (40.6) 2 901 (36.2) < .0001 Cesarean section 2 295 (73.8) 5 133 (81.8) 6 460 (80.8) < .0001 Preterm rupture of membranes 784 (26.2) 2170 (34.7) 3 062 (38.4) < .0001 Preeclampsia 581 (18.7) 1 175 (18.7) 1 775 (22.2) < .0001 Chorioamnionitis 742 (23.9) 1 832 (29.2) 2 425 (30.3) < .0001 Male sex 1 544 (49.7) 3 197 (50.9) 3 947 (49.3) 0.132 Maternal age, year 32.8 ± 4.8 33.5 ± 4.3 33.5 ± 4.1 < .0001 Continuous variables are presented as mean ± standard deviation or percentage, and categorical variables as number (percentage) Overall Neonatal Outcomes Across the full cohort, mortality before hospital discharge was highest among infants without ACS exposure, decreasing stepwisely with increasing completeness of ACS treatment (Table 2 ). Crude mortality rates decreased from 17.5% in infants without ACS to 12.8% among those with incomplete ACS and 10.2% among those with complete ACS. Table 2 Neonatal outcomes according to antenatal corticosteroid exposure (ACS). Unadjusted neonatal outcomes according to ACS exposure, including delivery room resuscitation measures, major neonatal morbidities, and mortality before hospital discharge. Data are presented as number (%). No (n = 3 111) Incomplete (n = 6 272) Complete (n = 8 005) p value Resuscitation in the delivery room 2 597 (85.8) 5 725 (91.5) 7 159 (89.7) < .0001 Intubation 1 828 (70.39) 3 717 (64.9) 4 586 (64.1) < .0001 Chest compression 250 (9.6) 237 (4.1) 232 (3.2) < .0001 Epinephrine 163 (6.3) 166 (2.9) 164 (2.3) < .0001 RDS 2 234 (71.8) 5 082 (81.0) 6 048 (75.6) < .0001 PDA (treated) 1 980 (74.0) 3 783 (69.4) 5 185 (74.3) < .0001 Moderate to severe BPD 741 (29.6) 1 655 (30.3) 2 335 (32.4) 0.008 Pulmonary hypertension 265 (8.5) 559 (8.9) 754 (9.4) 0.282 Sepsis 523 (16.9) 1 285 (20.6) 1 482 (18.6) < .0001 IVH, Grade ≥ 3 339 (11.67) 611 (10.03) 532 (6.79) < .0001 NEC, Stage ≥ II 193 (6.28) 437 (7.0) 511 (6.4) 0.272 ROP, Grade ≥ 2 508 (20.9) 1 190 (21.9) 1 609 (22.6) 0.213 Mortality 543 (17.5) 804 (12.8) 817 (10.2) < .0001 Data presented as number (percentage) RDS Respiratory distress syndrome, PDA Patent ductus arteriosus, BPD Bronchopulmonary dysplasia, IVH Intraventricular hemorrhage, NEC Necrotizing enterocolitis, ROP Retinopathy of prematurity After adjustment for GA, birth weight, and relevant maternal and obstetric factors, both incomplete and complete ACS exposure were independently associated with lower odds of mortality compared with no ACS exposure (Table 3 ). The magnitude of association was greater for complete ACS (aOR, 0.46; 95% CI: 0.39–0.53) than for incomplete ACS (aOR, 0.64; 95% CI: 0.55–0.74), indicating a graded association between treatment completeness and survival. To explore potential mechanisms underlying these survival differences, delivery room resuscitation intensity was examined as an operational marker of early physiologic vulnerability during postnatal cardiopulmonary transition. In unadjusted analyses, ACS-exposed infants appeared to require more frequent delivery room resuscitation than unexposed infants, reflecting their lower GA and greater baseline vulnerability. After multivariable adjustment, both incomplete and complete ACS exposure were correlated with lower odds of advanced delivery room resuscitation, with stronger associations observed for complete exposure (Table 3 ). Adjusted associations between ACS exposure and major neonatal morbidities in the overall cohort are shown in Table 3 . Complete ACS exposure was associated with a significantly lower risk of RDS (aOR, 0.63; 95% CI: 0.55–0.72). Both incomplete and complete ACS exposure were associated with reduced odds of severe IVH, with a stronger association observed for complete ACS (aOR, 0.51; 95% CI: 0.43–0.59) than for incomplete ACS (aOR, 0.74; 95% CI: 0.64–0.87). In contrast, ACS exposure was not significantly associated with NEC or pulmonary hypertension in the overall cohort. Sepsis occurred more frequently among ACS-exposed infants, and incomplete ACS exposure remained associated with higher adjusted odds of sepsis. Table 3 Adjusted comparisons of neonatal outcomes according to antenatal corticosteroid (ACS) exposure. Adjusted odds ratios with 95% confidence intervals for associations between ACS exposure and neonatal outcomes. Models were adjusted for gestational age, birth weight, infant sex, maternal age, parity, mode of delivery, maternal hypertension, maternal diabetes, chorioamnionitis, and preterm rupture of membranes. Outcomes Comparison with no ACS (reference) Crude model Adjusted model* OR (95% CI) P value OR (95% CI) p value Resuscitation in the delivery room Incomplete 1.79 (1.56–2.05) < .001 0.99 (0.85–1.16) 0.893 Complete 1.44 (1.27–1.64) < .001 0.83 (0.71–0.96) 0.011 Intubation Incomplete 0.78 (0.70–0.86) < .001 0.54 (0.47–0.61) < .001 Complete 0.75 (0.68–0.83) < .001 0.51 (0.45–0.58) < .001 Chest compressions Incomplete 0.41 (0.34–0.49) < .001 0.41 (0.34–0.50) < .001 Complete 0.31 (0.26–0.34) < .001 0.31 (0.26–0.38) < .001 Epinephrine Incomplete 0.45 (0.36–0.56) < .001 0.47 (0.37–0.59) < .001 Complete 0.35 (0.28–0.44) < .001 0.36 (0.29–0.46) < .001 RDS Incomplete 1.68 (1.52–1.85) < .001 0.89 (0.77–1.03) 0.107 Complete 1.21 (1.11–1.33) < .001 0.63 (0.55–0.72) < .001 PDA (treated) Incomplete 0.80 (0.72–0.89) < .001 0.90 (0.80–1.01) 0.071 Complete 1.02 (0.92–1.13) 0.749 1.12 (0.99–1.25) 0.052 Moderate to severe BPD Incomplete 1.03 (0.93–1.15) 0.527 0.77 (0.68–0.87) < .001 Complete 1.14 (1.00–1.26) 0.010 0.81 (0.72–0.92) < .001 Pulmonary hypertension Incomplete 1.05 (0.90–1.22) 0.525 1.07 (0.91–1.27) 0.412 Complete 1.12 (0.97–1.29) 0.140 1.08 (0.92–1.27) 0.332 Sepsis Incomplete 1.27 (1.13–1.42) < .001 1.24 (1.10–1.39) < .001 Complete 1.17 (1.00–1.25) 0.051 1.09 (0.97–1.22) 0.171 IVH, Grade ≥ 3 Incomplete 0.90 (0.80–1.01) 0.065 0.74 (0.64–0.87) < .001 Complete 0.55 (0.48–0.64) < .001 0.51 (0.43–0.59) < .001 NEC, Stage ≥ II Incomplete 1.13 (0.94–1.34) 0.188 1.14 (0.95–1.37) 0.162 Complete 1.02 (0.86–1.22) 0.789 1.03 (0.87–1.24) 0.711 ROP, Grade ≥ 2 Incomplete 1.06 (0.94–1.19) 0.362 0.83 (0.7–0.97) 0.019 Complete 1.10 (0.99–1.23) 0.091 0.83 (0.72–0.96) 0.014 Mortality Incomplete 0.70 (0.62–0.78) < .001 0.64 (0.55–0.74) < .001 Complete 0.54 (0.48–0.61) < .001 0.46 (0.39–0.53) < .001 *Adjusted model adjusted for gestational age, birth weight, infant sex, maternal hypertension, maternal diabetes, chorioamnionitis, and premature rupture of membranes. RDS Respiratory distress syndrome, PDA Patent ductus arteriosus, BPD Bronchopulmonary dysplasia, IVH Intraventricular hemorrhage, NEC Necrotizing enterocolitis, ROP Retinopathy of prematurity. Given the strong biological rationale for effect heterogeneity by fetal maturity, GA-stratified analyses focused on infants born before 32 weeks’ gestation (Fig. 2 ; Supplementary Table 1). Within this gestational window, ACS exposure was consistently associated with reduced early physiologic vulnerability and improved survival. Among extremely preterm infants born before 28 weeks, both incomplete and complete ACS exposure were associated with markedly lower odds of advanced delivery room resuscitation, with the greatest reductions observed among those receiving complete ACS. This GA-dependent pattern was also evident for severe IVH and mortality: incomplete ACS exposure was associated with lower mortality (aOR, 0.60; 95% CI: 0.51–0.70), whereas complete ACS exposure conferred an even greater survival advantage. Very preterm infants born at 28 to < 32 weeks’ gestation demonstrated similar but attenuated patterns, with significant reductions in mortality, severe IVH, and selected respiratory outcomes across both ACS exposure categories. In contrast, associations between ACS exposure and outcomes were limited among infants born at ≥ 32 weeks’ gestation; results for this group are presented in the Supplementary Table 1. In the prespecified subgroup of infants born before 25 weeks’ gestation (Supplementary Table 2), analyses compared any ACS exposure with no ACS exposure, reflecting the clinical realities of urgent obstetric decision-making at the margins of viability. Any ACS exposure was associated with lower odds of advanced delivery room resuscitation, including chest compression and epinephrine administration, as well as reduced risks of severe IVH and mortality. These associations were most pronounced among infants born at 23 to < 25 weeks’ gestation. Among infants born at 21 to < 23 weeks’ gestation, point estimates similarly favored ACS exposure, although CIs were wide because of small sample sizes. Overall, these findings suggest that antenatal ACS exposure is associated with improved early physiologic stability and survival among infants born at the lowest GAs, with the magnitude of benefit varying according to treatment completeness and gestational maturity. DISCUSSION In this large nationwide cohort, ACS exposure was associated with improved survival and reduced early physiologic vulnerability in preterm infants, with effects varying systematically by GA. By distinguishing complete, incomplete, and absent ACS exposure and incorporating detailed GA-stratified analyses—including a prespecified focus on infants born before 25 weeks’ gestation—this study extends prior evidence supporting ACS use and provides clinically relevant insight into GA-dependent treatment effects across the spectrum of prematurity [ 7 , 14 ]. Benefits were most evident among infants born before 32 weeks’ gestation, underscoring fetal maturity as a critical determinant of responsiveness to ACS [ 15 ]. Although infants without ACS exposure were, on average, born at slightly higher GAs and with greater birth weights—reflecting clinical selection—ACS-exposed infants demonstrated lower adjusted mortality, suggesting improved early physiologic stability during postnatal transition rather than maturity alone. Notably, while the magnitude of benefit was consistently greater with complete ACS exposure, incomplete ACS exposure was also associated with improved early physiologic stability and survival compared with no exposure, particularly at lower GAs, highlighting the clinical relevance of timely ACS administration even when a complete course cannot be achieved, without implying equivalence between incomplete and complete treatment. A central finding of this study is the GA-dependent heterogeneity in ACS effectiveness, with effect sizes increasing as GA decreases, particularly for clinically critical outcomes such as delivery room resuscitation intensity and mortality. Although formal interaction tests were not uniformly statistically significant, the consistency in direction and magnitude of associations at lower GAs aligns with prior large cohort studies [ 15 , 16 ]. The reversal of associations between ACS exposure and delivery room resuscitation intensity after adjustment underscores confounding by indication inherent in observational studies. After accounting for GA and perinatal risk factors, ACS exposure was associated with improved early cardiopulmonary adaptation among infants of comparable maturity. In contrast, among infants born at ≥ 32 weeks’ gestation, associations between ACS exposure and outcomes were attenuated, likely reflecting greater baseline physiologic maturity and reduced vulnerability during postnatal transition. Accordingly, the absence of strong associations at later GAs should be interpreted as effect attenuation rather than evidence of harm or lack of biological plausibility. ACS may plausibly reduce early physiologic vulnerability during delivery room transition through several complementary mechanisms. Beyond accelerating structural lung maturation and surfactant synthesis, ACS exposure improves lung compliance and functional residual capacity, facilitating adequate spontaneous respiration immediately after birth and reducing the need for invasive ventilatory support [ 2 , 17 ] Similarly, improved pulmonary aeration promotes a more rapid decline in pulmonary vascular resistance, enhancing pulmonary blood flow and left ventricular preload during the critical cardiopulmonary transition. Collectively, these effects may stabilize systemic perfusion and oxygen delivery, thereby reducing the need for advanced resuscitative interventions such as chest compressions and epinephrine administration. In extremely preterm infants, for whom cardiopulmonary transition is particularly fragile, even modest improvements in respiratory mechanics and pulmonary vascular adaptation may translate into clinically meaningful gains in early physiologic stability. This framework is consistent with our observation that ACS-associated reductions in delivery room resuscitation intensity were most pronounced at lower GAs and attenuated with increasing fetal maturity, where baseline physiologic reserves are greater. ACS exposure was also associated with GA-dependent reductions in selected neonatal morbidities, most notably RDS and severe IVH. Complete ACS exposure was associated with lower RDS risk among infants born before 32 weeks’ gestation, consistent with accelerated pulmonary maturation [ 2 , 17 ]. In contrast, incomplete exposure showed less consistent associations, suggesting sensitivity to treatment completeness and timing [ 18 ]. Reductions in severe IVH were observed across ACS exposure categories, particularly among the most immature infants, likely reflecting improved hemodynamic stability during early postnatal transition—with reduced cerebral blood flow fluctuations—rather than a direct neuroprotective effect of ACS [ 17 , 19 , 20 ]. At the margins of viability, effect estimates remain imprecise owing to small sample sizes, clinical heterogeneity, and institutional variability in resuscitation practices [ 8 , 16 , 21 , 22 ]. Within this context, comparing any ACS exposure with no exposure among infants born before 25 weeks’ gestation reflects a pragmatic clinical approach to an inherently uncertain decision environment; any ACS exposure was associated with improved early physiologic stability and survival, findings that are directionally consistent with prior studies when active life support is pursued [ 4 , 16 , 21 , 22 ]. Interpretation of differences between incomplete and complete ACS exposure warrants caution. Treatment completeness is primarily determined by obstetric urgency and timing of presentation, and incomplete exposure may reflect both reduced dosing and greater perinatal risk [ 7 , 18 ]. Accordingly, observed differences in effect size should not be interpreted as a simple dose–response relationship but rather as descriptive associations susceptible to residual confounding. Associations between ACS exposure and gastrointestinal or pulmonary vascular outcomes were less consistent. ACS exposure was not associated with reduced risks of NEC or pulmonary hypertension in the overall cohort, whereas higher rates of sepsis among ACS-exposed infants—particularly those with incomplete exposure—are most plausibly explained by residual confounding related to intrauterine infection rather than a direct causal effect [ 23 , 24 ]. The strengths of this study include its large, contemporary nationwide cohort, explicit differentiation of ACS exposure completeness, and detailed GA-stratified analyses using KNN data [ 25 ]. Limitations include residual confounding related to obstetric urgency, lack of information on rescue or repeat ACS courses and dose-to-delivery intervals, incomplete data on corticosteroid formulation, and restriction to short-term in-hospital outcomes. Additionally, as the KNN includes only infants admitted to neonatal intensive care units, these findings may not be generalizable to preterm infants who did not receive active postnatal care, particularly at the margins of viability, where decisions regarding admission and resuscitation may vary by clinical context. Long-term follow-up studies are needed to clarify the balance of benefits and risks of ACS exposure across GAs. CONCLUSION In this nationwide cohort, ACS exposure was associated with improved survival and reduced early physiologic vulnerability in preterm infants, with benefits most pronounced at lower GAs. Reductions in severe IVH and, among infants receiving complete courses, RDS further support the role of ACS in stabilizing early postnatal transition in the most immature infants. By explicitly addressing GA-dependent heterogeneity and the clinical realities of incomplete ACS exposure, these findings support the timely initiation of ACS when preterm birth is anticipated and underscore the importance of GA-tailored antenatal management and individualized perinatal counseling, particularly near the limits of viability. Declarations COMPETING INTERESTS: The authors declare no competing interests. ETHICS APPROVAL: Research involving human participants and human data was conducted in accordance with the principles of the Declaration of Helsinki. The Korean Neonatal Network registry has been approved by the institutional review boards of all participating hospitals, and written informed consent is obtained from parents or legal guardians at the time of enrollment. This secondary analysis of de-identified registry data was reviewed and approved by the institutional review board of the coordinating institution (Asan Medical Center, Seoul, Korea; IRB No. 2025-1380). DATA AVAILABILITY: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. FUNDING: This research received no external funding. AUTHOR CONTRIBUTIONS: AK and CYK conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript. EJ and BSL contributed to the conceptualization and design of the study, interpreted the data, and critically reviewed and revised the manuscript. JP, TGK, KY, JIK, JHR, JML, HNL, JJ, and SHK contributed to data acquisition and interpretation and critically reviewed and revised the manuscript. All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work. ACKNOWLEDGMENTS: We thank the participating hospitals, physicians, and research coordinators of the Korean Neonatal Network for their dedication to data collection and maintenance of the registry. We would also like to thank Editage (www.editage.co.kr) for English language editing. References Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990; 97: 11–25. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3: CD004454. Mwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol 2010; 39 Suppl 1: i122–133. Edwards EM, Ehret DEY, Soll RF, Horbar JD. Survival of infants born at 22 to 25 weeks' gestation receiving care in the NICU: 2020-2022. Pediatrics 2024; 154: e2024065963. Venkatesan T, Rees P, Gardiner J, Battersby C, Purkayastha M, Gale C, et al. National trends in preterm infant mortality in the United States by race and socioeconomic status, 1995-2020. JAMA Pediatr 2023; 177: 1085–1095. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314: 1039–1051. Travers CP, Clark RH, Spitzer AR, Das A, Garite TJ, Carlo WA. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study. BMJ 2017; 356: j1039. Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015; 372: 1801–1811. Yenuberi H, Ross B, Sasmita Tirkey R, Benjamin SJ, Rathore S, Karuppusami R, et al. Late-preterm antenatal steroids for reduction of neonatal respiratory complications: a randomized controlled trial. Obstet Gynecol 2024; 143: 468–474. American College of OGCoOP, Society for Maternal- Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2016; 128: e187–194. World Health Organization. WHO recommendations on: antenatal corticosteroids for improving preterm birth outcomes. World Health Organization: Geneva, 2022. American Academy of Pediatrics, American Heart Association. Textbook of neonatal resuscitation. 7th ed. American Academy of Pediatrics: Elk Grove Village, IL, 2016. Kearsey EOR, Been JV, Souter VL, Stock SJ. The impact of the antenatal late preterm steroids trial on the administration of antenatal corticosteroids. Am J Obstet Gynecol 2022; 227: 280 e281–280 e215. Travers CP, Carlo WA, McDonald SA, Das A, Bell EF, Ambalavanan N, et al. Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids. Am J Obstet Gynecol 2018; 218: 130 e131–130 e113. Kim JK, Hwang JH, Lee MH, Chang YS, Park WS. Mortality rate-dependent variations in antenatal corticosteroid-associated outcomes in very low birth weight infants with 23-34 weeks of gestation: a nationwide cohort study. PLoS One 2020; 15: e0240168. Ehret DEY, Edwards EM, Greenberg LT, Bernstein IM, Buzas JS, Soll RF, et al. Association of antenatal steroid exposure with survival among infants receiving postnatal life support at 22 to 25 weeks' gestation. JAMA Netw Open 2018; 1: e183235. Siew ML, Te Pas AB, Wallace MJ, Kitchen MJ, Islam MS, Lewis RA, et al. Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits. Pediatr Res 2011; 70: 50–55. Chawla S, Wyckoff MH, Lakshminrusimha S, Rysavy MA, Patel RM, Chowdhury D, et al. Short Duration of Antenatal Corticosteroid Exposure and Outcomes in Extremely Preterm Infants. JAMA Netw Open 2025; 8: e2461312. Chakkarapani AA, Roehr CC, Hooper SB, Te Pas AB, Gupta S, ESPR Neonatal Resuscitation section writing group. Transitional circulation and hemodynamic monitoring in newborn infants. Pediatr Res 2024; 96: 595–603. Sarkar S, Bhagat I, Dechert R, Schumacher RE, Donn SM. Severe intraventricular hemorrhage in preterm infants: comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage. Am J Perinatol 2009; 26: 419–424. Mori R, Kusuda S, Fujimura M, Neonatal Research Network Japan. Antenatal corticosteroids promote survival of extremely preterm infants born at 22 to 23 weeks of gestation. J Pediatr 2011; 159: 110–114 e111. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126: 443–456. Yao TC, Chang SM, Wu CS, Tsai YF, Sheen KH, Hong X, et al. Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study. BMJ 2023; 382: e075835. Yang Y. Prenatal dexamethasone exposure and the risk of early-onset sepsis in preterm infants. Front Pediatr 2025; 13: 1673813. Chang YS, Park HY, Park WS. The Korean neonatal network: an overview. J Korean Med Sci 2015; 30 Suppl 1: S3–S11. Additional Declarations There is NO conflict of interest to disclose. Supplementary Files SupplementaryInformationJoP.pdf Gestational Age–Specific Associations Between Antenatal Corticosteroid Exposure and Neonatal Outcomes Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: revise 09 Mar, 2026 Review # 2 received at journal 07 Mar, 2026 Review # 1 received at journal 04 Mar, 2026 Reviewer # 2 agreed at journal 22 Feb, 2026 Reviewer # 1 agreed at journal 13 Feb, 2026 Reviewers invited by journal 11 Feb, 2026 Submission checks completed at journal 02 Feb, 2026 Editor assigned by journal 01 Feb, 2026 First submitted to journal 01 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8754951","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":589870818,"identity":"cd84596d-06f9-426a-a764-4d2bbf56bfbb","order_by":0,"name":"Chae Young Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDACCRBRAedaQAQIazmDxCVOC2MbKVr4Zzc/fPBxnl00fwM7kNEmwSA5+wABS+4cMzacuS05d8YBHiADqEWaLwG/FgOJBDNp3m3MuRsYeNikeYFa5HgIOMxAIv37b9459UAt7M9/E6klx4yZt+EwUAsDkAFyGCEtEjdyiiVnHDueO+Mwj7HkjHMSPJI9BLTwz0jf+OFDTXVuf3v7ww8fymzkJM4Q0IIAzBCKkLNGwSgYBaNgFBADAOTJOGDjIfOAAAAAAElFTkSuQmCC","orcid":"","institution":"Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Chae","middleName":"Young","lastName":"Kim","suffix":""},{"id":589870819,"identity":"eb0041da-6360-4fa9-8378-d1d51a1c0822","order_by":1,"name":"Abraham Kwak","email":"","orcid":"https://orcid.org/0000-0002-8161-333X","institution":"Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Abraham","middleName":"","lastName":"Kwak","suffix":""},{"id":589870820,"identity":"4f476476-1639-46cc-ba04-1853bcdebf85","order_by":2,"name":"Juhee Park","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Juhee","middleName":"","lastName":"Park","suffix":""},{"id":589870821,"identity":"8b327233-6828-42da-861f-9c2adab7d55a","order_by":3,"name":"Tae-Gyeong Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tae-Gyeong","middleName":"","lastName":"Kim","suffix":""},{"id":589870822,"identity":"bb25601c-2516-4865-bd8e-8a1cb83e8f48","order_by":4,"name":"Kyusang Yoo","email":"","orcid":"https://orcid.org/0009-0005-6952-961X","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kyusang","middleName":"","lastName":"Yoo","suffix":""},{"id":589870823,"identity":"0af2aae8-e1d5-407c-b185-f4f0485d9ff4","order_by":5,"name":"Jung Il Kwak","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jung","middleName":"Il","lastName":"Kwak","suffix":""},{"id":589870824,"identity":"9529bcb5-4717-49a5-af95-893fab37063d","order_by":6,"name":"Joo Hyung Roh","email":"","orcid":"https://orcid.org/0009-0006-7965-4980","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Joo","middleName":"Hyung","lastName":"Roh","suffix":""},{"id":589870825,"identity":"b267d107-5953-404c-8175-d39f5a8a061d","order_by":7,"name":"Jeong Min Lee","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jeong","middleName":"Min","lastName":"Lee","suffix":""},{"id":589870826,"identity":"659718e2-dd3d-460a-9836-43c6d24e0f15","order_by":8,"name":"Ha Na Lee","email":"","orcid":"https://orcid.org/0000-0002-0217-1773","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ha","middleName":"Na","lastName":"Lee","suffix":""},{"id":589870827,"identity":"34a2a2e9-01bf-47c5-bdbd-6c8922ad56f5","order_by":9,"name":"Ji Yoon Jeong","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"Yoon","lastName":"Jeong","suffix":""},{"id":589870828,"identity":"95e9a0c9-f3ae-43e4-952b-1857aede1969","order_by":10,"name":"Soo Hyun Kim","email":"","orcid":"","institution":"Asan Medical Center Children's Hospital, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Soo","middleName":"Hyun","lastName":"Kim","suffix":""},{"id":589870829,"identity":"3adac4f0-075d-47d9-8ec2-4247cc301820","order_by":11,"name":"Euiseok Jung","email":"","orcid":"https://orcid.org/0000-0003-0693-5627","institution":"Asan Medical Center Children's Hospital, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Euiseok","middleName":"","lastName":"Jung","suffix":""},{"id":589870830,"identity":"e6b857c1-91d4-4359-81d0-3dd777a042d5","order_by":12,"name":"Byong Sop Lee","email":"","orcid":"","institution":"Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Byong","middleName":"Sop","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2026-02-01 08:55:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8754951/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8754951/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102862129,"identity":"5cefb803-45f6-43e0-94c5-6d5a5a716fb1","added_by":"auto","created_at":"2026-02-17 16:15:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":74371,"visible":true,"origin":"","legend":"\u003cp\u003eStudy participants. Flow diagram showing cohort selection from the Korean Neonatal Network registry (2013–2021) and classification by antenatal corticosteroid exposure.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8754951/v1/96253bd502c3d453684cd38c.png"},{"id":102862131,"identity":"4ee777a0-c5cc-49c5-96ce-55a6ffdf7fd0","added_by":"auto","created_at":"2026-02-17 16:15:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50220,"visible":true,"origin":"","legend":"\u003cp\u003eGestational age-specific associations with neonatal outcomes. Gestational age-specific associations with (a) delivery room resuscitation intensity and mortality and (b) major neonatal morbidities.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8754951/v1/166c022b03bc835b6f5f3663.png"},{"id":103049643,"identity":"d07dddb1-51d9-43bb-a6cd-967e090a451a","added_by":"auto","created_at":"2026-02-20 07:44:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":835407,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8754951/v1/f4613348-53be-49e2-91d5-60bc910dbaad.pdf"},{"id":102862123,"identity":"bc2878f4-01ed-45ca-9a9d-7bb1ec9eb515","added_by":"auto","created_at":"2026-02-17 16:15:31","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":496509,"visible":true,"origin":"","legend":"Gestational Age\u0026#x2013;Specific Associations Between Antenatal Corticosteroid Exposure and Neonatal Outcomes","description":"","filename":"SupplementaryInformationJoP.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8754951/v1/5ef71e7d6f56ef09309fc431.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Gestational Age-Specific Effects of Antenatal Corticosteroids on Early Physiologic Vulnerability and Neonatal Outcomes","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAntenatal corticosteroids (ACS) represent one of the most effective antenatal interventions for improving outcomes in preterm infants, with robust evidence demonstrating reductions in neonatal mortality and major morbidities through accelerated maturation of the fetal lung and other organ systems [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Based on this evidence, ACS administration has been widely incorporated into international guidelines and is routinely recommended across a broad range of gestational ages (GAs). However, much of the foundational evidence supporting ACS use is derived from heterogeneous preterm populations that are frequently analyzed as a single group, thereby limiting insight into how treatment effects vary across stages of gestational maturity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the past two decades, advances in obstetric and neonatal care have substantially improved survival among extremely preterm infants, particularly those born before 28 weeks\u0026rsquo; gestation [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. As survival has increased, clinical priorities have shifted toward reducing severe morbidities\u0026mdash;such as bronchopulmonary dysplasia, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP)\u0026mdash;which reflect profound physiologic immaturity and vulnerability to early perinatal stressors. In this context, antenatal and immediate perinatal interventions may exert disproportionate effects on physiologic stability during the immediate postnatal transition, with important implications for subsequent clinical outcomes.\u003c/p\u003e \u003cp\u003eEmerging evidence suggests that the benefits of ACS are not uniform across GAs and may vary according to fetal maturity, timing of administration, and early neonatal management practices [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nevertheless, most prior studies have assessed ACS exposure dichotomously as present or absent, without accounting for treatment completeness. This approach is increasingly discordant with contemporary clinical practice, in which incomplete ACS courses are common owing to precipitous preterm delivery, maternal instability, or competing obstetric priorities. For clinicians managing imminent extreme preterm birth, the critical question is therefore not whether ACS is beneficial in principle, but whether partial exposure meaningfully modifies early physiologic vulnerability and survival. Moreover, extremely preterm infants are frequently grouped together in clinical research despite marked biological and clinical heterogeneity within this population. Infants born at the margins of viability differ substantially in physiologic maturity, resuscitation requirements, and capacity to tolerate perinatal stress, yet these differences are often obscured when GA-specific effects are not explicitly examined [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Recent studies have also suggested that ACS-associated benefits may extend into later GAs, particularly for respiratory outcomes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], raising questions regarding the gestational threshold beyond which ACS effects attenuate.\u003c/p\u003e \u003cp\u003eTo address these gaps, we conducted a large nationwide cohort study using data from the Korean Neonatal Network (KNN) to evaluate GA-specific associations between ACS exposure and early physiologic vulnerability at birth. We focused on delivery room resuscitation intensity as an indicator of early postnatal adaptation and examined how these associations varied across clinically relevant GA strata, including a prespecified analysis of infants born before 25 weeks\u0026rsquo; gestation. By explicitly distinguishing between complete and incomplete ACS exposure, this study aimed to reflect real-world antenatal treatment patterns and to provide clinically relevant insight into GA-dependent treatment effects across the spectrum of prematurity.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Data Source\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study used data from the KNN, a nationwide, prospective registry of very low birth weight infants (birth weight\u0026thinsp;\u0026lt;\u0026thinsp;1 500 g) admitted to 70 tertiary neonatal intensive care units across South Korea. Infants born between January 1, 2013, and December 31, 2021, were eligible for inclusion.\u003c/p\u003e \u003cp\u003eInfants were included if they met either of the following criteria at birth: (1) birth weight\u0026thinsp;\u0026lt;\u0026thinsp;1 500 g regardless of GA, or (2) GA\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks\u0026rsquo; gestation irrespective of birth weight. Multiple gestations were included. Infants were excluded if they had major congenital anomalies, chromosomal abnormalities, or unknown ACS exposure status. Stillbirths are not captured in the KNN registry and were therefore not included. GA was determined using the obstetric estimate based on the last menstrual period and early ultrasound findings.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinitions of ACS Exposure\u003c/h3\u003e\n\u003cp\u003eACS exposure was categorized as complete, incomplete, or none based on maternal corticosteroid administration within 7 days before delivery, consistent with international guidelines recommending delivery within this interval for optimal fetal lung maturation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Complete ACS exposure was defined as maternal receipt of either (1) two 12-mg intramuscular doses of betamethasone administered 24 h apart or (2) four 6-mg intramuscular doses of dexamethasone administered 12 h apart. Incomplete ACS exposure included any corticosteroid administration that did not meet the criteria for a complete regimen, including partial dosing, single-dose therapy, or dosing intervals deviating from the recommended schedule. No ACS exposure was defined as the absence of any maternal corticosteroid administration before delivery. The KNN registry does not capture information on rescue ACS, repeat courses, or precise dose-to-delivery intervals; therefore, these factors could not be evaluated.\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was mortality before hospital discharge. Key secondary outcomes included delivery room resuscitation intensity\u0026mdash;defined as the need for endotracheal intubation, chest compressions, or epinephrine administration according to Neonatal Resuscitation Program guidelines [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u0026mdash;as an operational marker of early physiologic vulnerability, as well as major neonatal morbidities. Respiratory distress syndrome (RDS) was defined by a clinical diagnosis supported by radiographic findings. Patent ductus arteriosus was defined by the receipt of medical or surgical treatment. Moderate to severe bronchopulmonary dysplasia was defined according to the 2001 National Institute of Child Health and Human Development criteria. Pulmonary hypertension was defined by echocardiographic or clinical diagnosis prompting initiation of pharmacologic treatment; only infants receiving treatment were classified as having pulmonary hypertension. Severe IVH was defined as Papile grade\u0026thinsp;\u0026ge;\u0026thinsp;3, NEC as modified Bell stage\u0026thinsp;\u0026ge;\u0026thinsp;II, and retinopathy of prematurity as stage\u0026thinsp;\u0026ge;\u0026thinsp;2. Sepsis was defined according to the KNN registry criteria as the presence of both a positive blood culture and a requirement for systemic antibiotic therapy for at least 5 days and was analyzed as a composite outcome without distinction between early- and late-onset sepsis.\u003c/p\u003e\n\u003ch3\u003eGA-Stratified Analyses\u003c/h3\u003e\n\u003cp\u003eGA-stratified analyses were performed to assess potential effect heterogeneity in the associations between ACS exposure and neonatal outcomes according to fetal maturity. GA categories were defined \u003cem\u003ea priori\u003c/em\u003e based on established differences in physiologic maturity, baseline risk of adverse neonatal outcomes, and anticipated responsiveness to ACS, as supported by prior neonatal and perinatal studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInfants were stratified into three GA groups: extremely preterm infants born before 28 weeks\u0026rsquo; gestation; very preterm infants born at 28 to \u0026lt;\u0026thinsp;32 weeks\u0026rsquo; gestation; and infants born at \u0026ge;\u0026thinsp;32 weeks\u0026rsquo; gestation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In addition to these primary stratified analyses, a prespecified subgroup analysis was conducted among infants born before 25 weeks\u0026rsquo; gestation, a population in whom clinical decision-making regarding resuscitation and intensive care is particularly complex.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were compared using the Student \u003cem\u003et\u003c/em\u003e test or the Wilcoxon rank-sum test, as appropriate, and categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test. No formal sample size calculation was performed;all eligible infants in the KNN during the study period were included in the analysis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for associations between ACS exposure categories (none, incomplete, and complete) and neonatal outcomes. Models were adjusted \u003cem\u003ea priori\u003c/em\u003e for GA, birth weight, infant sex, maternal age, parity, mode of delivery, maternal hypertension, maternal diabetes, chorioamnionitis, and preterm rupture of membranes. Baseline balance between exposure groups was assessed using standardized mean differences. Because baseline standardized mean differences for key covariates were generally small to moderate and propensity score matching would have reduced the sample size, we analyzed all eligible infants using multivariable logistic regression with covariate adjustment rather than restricting analyses to matched subsets. GA-stratified analyses were performed using prespecified categories (\u0026lt;\u0026thinsp;28, 28 to \u0026lt;\u0026thinsp;32, and \u0026ge;\u0026thinsp;32 weeks\u0026rsquo; gestation), with an additional prespecified subgroup analysis among infants born before 25 weeks\u0026rsquo; gestation. Effect modification by GA was assessed using interaction terms, and sensitivity analyses examined GA as a continuous variable. All analyses were performed using R software (version 4.3.2), and a two-sided \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCode Availability\u003c/h2\u003e \u003cp\u003eNo custom computer code was used to generate results that are central to the conclusions of this study.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eDuring the study period, 18,094 infants were identified in the KNN (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). After excluding infants with major congenital anomalies, chromosomal abnormalities, or missing information on ACS exposure, 17,388 infants were included in the final analytic cohort. Of these, 3,109 infants (17.9%) received no ACS, 6,279 (36.1%) received an incomplete ACS course, and 8,000 (46.0%) received a complete ACS course. Among infants with available information on the specific corticosteroid administered, 5,289 (30.4%) were exposed to betamethasone and 2,770 (15.9%) to dexamethasone; the specific agent was not recorded for 9,329 infants (53.7%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics\u003c/h2\u003e \u003cp\u003eBaseline maternal and neonatal characteristics differed across ACS exposure groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Compared with infants who received no ACS, those exposed to incomplete or complete ACS were born at earlier GAs (mean GA, 28.7\u0026ndash;28.8 vs. 29.4 weeks) and had lower birth weights (approximately 1,100\u0026ndash;1,110 g vs. 1,170 g), indicating greater baseline physiologic immaturity. Despite this higher degree of prematurity, markers of immediate postnatal adaptation improved progressively with increasing ACS exposure: Apgar scores were lowest among infants without ACS and highest among those receiving a complete ACS course. Maternal conditions associated with preterm delivery, including preterm rupture of membranes and clinical chorioamnionitis, were more prevalent in the ACS-exposed groups. Cesarean delivery was most frequent among mothers who received a complete ACS course. Overall, infants exposed to ACS\u0026mdash;particularly those receiving complete courses\u0026mdash;represented a population with greater antenatal and perinatal vulnerability at baseline.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline maternal and neonatal characteristics according to antenatal corticosteroid (ACS) exposure. Baseline maternal, obstetric, and neonatal characteristics stratified by ACS exposure (none, incomplete, and complete). Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and categorical variables as number (%).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3 111)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6 272)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8 005)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age, week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight, g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 170.0\u0026thinsp;\u0026plusmn;\u0026thinsp;298.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 110.5\u0026thinsp;\u0026plusmn;\u0026thinsp;240.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 100\u0026thinsp;\u0026plusmn;\u0026thinsp;243.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth height, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth head circumference, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar score at 1 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar score at 5 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple gestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 061 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 544 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 901 (36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 295 (73.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 133 (81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 460 (80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm rupture of membranes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e784 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2170 (34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 062 (38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreeclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e581 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 175 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 775 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChorioamnionitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e742 (23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 832 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 425 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 544 (49.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 197 (50.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 947 (49.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eContinuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or percentage, and categorical variables as number (percentage)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOverall Neonatal Outcomes\u003c/h2\u003e \u003cp\u003eAcross the full cohort, mortality before hospital discharge was highest among infants without ACS exposure, decreasing stepwisely with increasing completeness of ACS treatment (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Crude mortality rates decreased from 17.5% in infants without ACS to 12.8% among those with incomplete ACS and 10.2% among those with complete ACS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNeonatal outcomes according to antenatal corticosteroid exposure (ACS). Unadjusted neonatal outcomes according to ACS exposure, including delivery room resuscitation measures, major neonatal morbidities, and mortality before hospital discharge. Data are presented as number (%).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3 111)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6 272)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8 005)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResuscitation in the delivery room\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 597 (85.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 725 (91.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 159 (89.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 828 (70.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 717 (64.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 586 (64.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest compression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e250 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e237 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e232 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpinephrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e163 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e166 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e164 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 234 (71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 082 (81.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 048 (75.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA (treated)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 980 (74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 783 (69.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 185 (74.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate to severe BPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e741 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 655 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 335 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e265 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e559 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e754 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.282\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e523 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 285 (20.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 482 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVH, Grade\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e339 (11.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e611 (10.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e532 (6.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNEC, Stage\u0026thinsp;\u0026ge;\u0026thinsp;II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e193 (6.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e437 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e511 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROP, Grade\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e508 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 190 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 609 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e543 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e804 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e817 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData presented as number (percentage)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eRDS\u003c/em\u003e Respiratory distress syndrome, \u003cem\u003ePDA\u003c/em\u003e Patent ductus arteriosus, \u003cem\u003eBPD\u003c/em\u003e Bronchopulmonary dysplasia, \u003cem\u003eIVH\u003c/em\u003e Intraventricular hemorrhage, \u003cem\u003eNEC\u003c/em\u003e Necrotizing enterocolitis, \u003cem\u003eROP\u003c/em\u003e Retinopathy of prematurity\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter adjustment for GA, birth weight, and relevant maternal and obstetric factors, both incomplete and complete ACS exposure were independently associated with lower odds of mortality compared with no ACS exposure (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The magnitude of association was greater for complete ACS (aOR, 0.46; 95% CI: 0.39\u0026ndash;0.53) than for incomplete ACS (aOR, 0.64; 95% CI: 0.55\u0026ndash;0.74), indicating a graded association between treatment completeness and survival. To explore potential mechanisms underlying these survival differences, delivery room resuscitation intensity was examined as an operational marker of early physiologic vulnerability during postnatal cardiopulmonary transition. In unadjusted analyses, ACS-exposed infants appeared to require more frequent delivery room resuscitation than unexposed infants, reflecting their lower GA and greater baseline vulnerability. After multivariable adjustment, both incomplete and complete ACS exposure were correlated with lower odds of advanced delivery room resuscitation, with stronger associations observed for complete exposure (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Adjusted associations between ACS exposure and major neonatal morbidities in the overall cohort are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Complete ACS exposure was associated with a significantly lower risk of RDS (aOR, 0.63; 95% CI: 0.55\u0026ndash;0.72). Both incomplete and complete ACS exposure were associated with reduced odds of severe IVH, with a stronger association observed for complete ACS (aOR, 0.51; 95% CI: 0.43\u0026ndash;0.59) than for incomplete ACS (aOR, 0.74; 95% CI: 0.64\u0026ndash;0.87). In contrast, ACS exposure was not significantly associated with NEC or pulmonary hypertension in the overall cohort. Sepsis occurred more frequently among ACS-exposed infants, and incomplete ACS exposure remained associated with higher adjusted odds of sepsis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdjusted comparisons of neonatal outcomes according to antenatal corticosteroid (ACS) exposure. Adjusted odds ratios with 95% confidence intervals for associations between ACS exposure and neonatal outcomes. Models were adjusted for gestational age, birth weight, infant sex, maternal age, parity, mode of delivery, maternal hypertension, maternal diabetes, chorioamnionitis, and preterm rupture of membranes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eComparison with no ACS (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eCrude model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eAdjusted model*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eResuscitation\u003c/p\u003e \u003cp\u003ein the delivery room\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.79 (1.56\u0026ndash;2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99 (0.85\u0026ndash;1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.44 (1.27\u0026ndash;1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83 (0.71\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78 (0.70\u0026ndash;0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54 (0.47\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75 (0.68\u0026ndash;0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51 (0.45\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChest compressions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41 (0.34\u0026ndash;0.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41 (0.34\u0026ndash;0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31 (0.26\u0026ndash;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.31 (0.26\u0026ndash;0.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEpinephrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.45 (0.36\u0026ndash;0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.47 (0.37\u0026ndash;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35 (0.28\u0026ndash;0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.36 (0.29\u0026ndash;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.68 (1.52\u0026ndash;1.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.89 (0.77\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.21 (1.11\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63 (0.55\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePDA (treated)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.80 (0.72\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.90 (0.80\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02 (0.92\u0026ndash;1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.12 (0.99\u0026ndash;1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eModerate to severe BPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03 (0.93\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77 (0.68\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.14 (1.00\u0026ndash;1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.81 (0.72\u0026ndash;0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePulmonary hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05 (0.90\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.525\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.07 (0.91\u0026ndash;1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12 (0.97\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.08 (0.92\u0026ndash;1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.27 (1.13\u0026ndash;1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.24 (1.10\u0026ndash;1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.17 (1.00\u0026ndash;1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09 (0.97\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIVH, Grade\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.90 (0.80\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74 (0.64\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.55 (0.48\u0026ndash;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51 (0.43\u0026ndash;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNEC, Stage\u0026thinsp;\u0026ge;\u0026thinsp;II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.13 (0.94\u0026ndash;1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.14 (0.95\u0026ndash;1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02 (0.86\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03 (0.87\u0026ndash;1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eROP, Grade\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06 (0.94\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83 (0.7\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.10 (0.99\u0026ndash;1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83 (0.72\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.70 (0.62\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.64 (0.55\u0026ndash;0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.54 (0.48\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46 (0.39\u0026ndash;0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*Adjusted model adjusted for gestational age, birth weight, infant sex, maternal hypertension, maternal diabetes, chorioamnionitis, and premature rupture of membranes.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eRDS\u003c/em\u003e Respiratory distress syndrome, \u003cem\u003ePDA\u003c/em\u003e Patent ductus arteriosus, \u003cem\u003eBPD\u003c/em\u003e Bronchopulmonary dysplasia, \u003cem\u003eIVH\u003c/em\u003e Intraventricular hemorrhage, \u003cem\u003eNEC\u003c/em\u003e Necrotizing enterocolitis, \u003cem\u003eROP\u003c/em\u003e Retinopathy of prematurity.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGiven the strong biological rationale for effect heterogeneity by fetal maturity, GA-stratified analyses focused on infants born before 32 weeks\u0026rsquo; gestation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table\u0026nbsp;1). Within this gestational window, ACS exposure was consistently associated with reduced early physiologic vulnerability and improved survival. Among extremely preterm infants born before 28 weeks, both incomplete and complete ACS exposure were associated with markedly lower odds of advanced delivery room resuscitation, with the greatest reductions observed among those receiving complete ACS. This GA-dependent pattern was also evident for severe IVH and mortality: incomplete ACS exposure was associated with lower mortality (aOR, 0.60; 95% CI: 0.51\u0026ndash;0.70), whereas complete ACS exposure conferred an even greater survival advantage. Very preterm infants born at 28 to \u0026lt;\u0026thinsp;32 weeks\u0026rsquo; gestation demonstrated similar but attenuated patterns, with significant reductions in mortality, severe IVH, and selected respiratory outcomes across both ACS exposure categories. In contrast, associations between ACS exposure and outcomes were limited among infants born at \u0026ge;\u0026thinsp;32 weeks\u0026rsquo; gestation; results for this group are presented in the Supplementary Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the prespecified subgroup of infants born before 25 weeks\u0026rsquo; gestation (Supplementary Table\u0026nbsp;2), analyses compared any ACS exposure with no ACS exposure, reflecting the clinical realities of urgent obstetric decision-making at the margins of viability. Any ACS exposure was associated with lower odds of advanced delivery room resuscitation, including chest compression and epinephrine administration, as well as reduced risks of severe IVH and mortality. These associations were most pronounced among infants born at 23 to \u0026lt;\u0026thinsp;25 weeks\u0026rsquo; gestation. Among infants born at 21 to \u0026lt;\u0026thinsp;23 weeks\u0026rsquo; gestation, point estimates similarly favored ACS exposure, although CIs were wide because of small sample sizes. Overall, these findings suggest that antenatal ACS exposure is associated with improved early physiologic stability and survival among infants born at the lowest GAs, with the magnitude of benefit varying according to treatment completeness and gestational maturity.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this large nationwide cohort, ACS exposure was associated with improved survival and reduced early physiologic vulnerability in preterm infants, with effects varying systematically by GA. By distinguishing complete, incomplete, and absent ACS exposure and incorporating detailed GA-stratified analyses\u0026mdash;including a prespecified focus on infants born before 25 weeks\u0026rsquo; gestation\u0026mdash;this study extends prior evidence supporting ACS use and provides clinically relevant insight into GA-dependent treatment effects across the spectrum of prematurity [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Benefits were most evident among infants born before 32 weeks\u0026rsquo; gestation, underscoring fetal maturity as a critical determinant of responsiveness to ACS [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although infants without ACS exposure were, on average, born at slightly higher GAs and with greater birth weights\u0026mdash;reflecting clinical selection\u0026mdash;ACS-exposed infants demonstrated lower adjusted mortality, suggesting improved early physiologic stability during postnatal transition rather than maturity alone. Notably, while the magnitude of benefit was consistently greater with complete ACS exposure, incomplete ACS exposure was also associated with improved early physiologic stability and survival compared with no exposure, particularly at lower GAs, highlighting the clinical relevance of timely ACS administration even when a complete course cannot be achieved, without implying equivalence between incomplete and complete treatment.\u003c/p\u003e \u003cp\u003eA central finding of this study is the GA-dependent heterogeneity in ACS effectiveness, with effect sizes increasing as GA decreases, particularly for clinically critical outcomes such as delivery room resuscitation intensity and mortality. Although formal interaction tests were not uniformly statistically significant, the consistency in direction and magnitude of associations at lower GAs aligns with prior large cohort studies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The reversal of associations between ACS exposure and delivery room resuscitation intensity after adjustment underscores confounding by indication inherent in observational studies. After accounting for GA and perinatal risk factors, ACS exposure was associated with improved early cardiopulmonary adaptation among infants of comparable maturity. In contrast, among infants born at \u0026ge;\u0026thinsp;32 weeks\u0026rsquo; gestation, associations between ACS exposure and outcomes were attenuated, likely reflecting greater baseline physiologic maturity and reduced vulnerability during postnatal transition. Accordingly, the absence of strong associations at later GAs should be interpreted as effect attenuation rather than evidence of harm or lack of biological plausibility.\u003c/p\u003e \u003cp\u003eACS may plausibly reduce early physiologic vulnerability during delivery room transition through several complementary mechanisms. Beyond accelerating structural lung maturation and surfactant synthesis, ACS exposure improves lung compliance and functional residual capacity, facilitating adequate spontaneous respiration immediately after birth and reducing the need for invasive ventilatory support [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Similarly, improved pulmonary aeration promotes a more rapid decline in pulmonary vascular resistance, enhancing pulmonary blood flow and left ventricular preload during the critical cardiopulmonary transition. Collectively, these effects may stabilize systemic perfusion and oxygen delivery, thereby reducing the need for advanced resuscitative interventions such as chest compressions and epinephrine administration.\u003c/p\u003e \u003cp\u003eIn extremely preterm infants, for whom cardiopulmonary transition is particularly fragile, even modest improvements in respiratory mechanics and pulmonary vascular adaptation may translate into clinically meaningful gains in early physiologic stability. This framework is consistent with our observation that ACS-associated reductions in delivery room resuscitation intensity were most pronounced at lower GAs and attenuated with increasing fetal maturity, where baseline physiologic reserves are greater.\u003c/p\u003e \u003cp\u003eACS exposure was also associated with GA-dependent reductions in selected neonatal morbidities, most notably RDS and severe IVH. Complete ACS exposure was associated with lower RDS risk among infants born before 32 weeks\u0026rsquo; gestation, consistent with accelerated pulmonary maturation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, incomplete exposure showed less consistent associations, suggesting sensitivity to treatment completeness and timing [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Reductions in severe IVH were observed across ACS exposure categories, particularly among the most immature infants, likely reflecting improved hemodynamic stability during early postnatal transition\u0026mdash;with reduced cerebral blood flow fluctuations\u0026mdash;rather than a direct neuroprotective effect of ACS [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. At the margins of viability, effect estimates remain imprecise owing to small sample sizes, clinical heterogeneity, and institutional variability in resuscitation practices [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Within this context, comparing any ACS exposure with no exposure among infants born before 25 weeks\u0026rsquo; gestation reflects a pragmatic clinical approach to an inherently uncertain decision environment; any ACS exposure was associated with improved early physiologic stability and survival, findings that are directionally consistent with prior studies when active life support is pursued [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInterpretation of differences between incomplete and complete ACS exposure warrants caution. Treatment completeness is primarily determined by obstetric urgency and timing of presentation, and incomplete exposure may reflect both reduced dosing and greater perinatal risk [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Accordingly, observed differences in effect size should not be interpreted as a simple dose\u0026ndash;response relationship but rather as descriptive associations susceptible to residual confounding.\u003c/p\u003e \u003cp\u003eAssociations between ACS exposure and gastrointestinal or pulmonary vascular outcomes were less consistent. ACS exposure was not associated with reduced risks of NEC or pulmonary hypertension in the overall cohort, whereas higher rates of sepsis among ACS-exposed infants\u0026mdash;particularly those with incomplete exposure\u0026mdash;are most plausibly explained by residual confounding related to intrauterine infection rather than a direct causal effect [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe strengths of this study include its large, contemporary nationwide cohort, explicit differentiation of ACS exposure completeness, and detailed GA-stratified analyses using KNN data [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Limitations include residual confounding related to obstetric urgency, lack of information on rescue or repeat ACS courses and dose-to-delivery intervals, incomplete data on corticosteroid formulation, and restriction to short-term in-hospital outcomes. Additionally, as the KNN includes only infants admitted to neonatal intensive care units, these findings may not be generalizable to preterm infants who did not receive active postnatal care, particularly at the margins of viability, where decisions regarding admission and resuscitation may vary by clinical context. Long-term follow-up studies are needed to clarify the balance of benefits and risks of ACS exposure across GAs.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this nationwide cohort, ACS exposure was associated with improved survival and reduced early physiologic vulnerability in preterm infants, with benefits most pronounced at lower GAs. Reductions in severe IVH and, among infants receiving complete courses, RDS further support the role of ACS in stabilizing early postnatal transition in the most immature infants. By explicitly addressing GA-dependent heterogeneity and the clinical realities of incomplete ACS exposure, these findings support the timely initiation of ACS when preterm birth is anticipated and underscore the importance of GA-tailored antenatal management and individualized perinatal counseling, particularly near the limits of viability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL:\u0026nbsp;\u003c/strong\u003eResearch involving human participants and human data was conducted in accordance with the principles of the Declaration of Helsinki. The Korean Neonatal Network registry has been approved by the institutional review boards of all participating hospitals, and written informed consent is obtained from parents or legal guardians at the time of enrollment. This secondary analysis of de-identified registry data was reviewed and approved by the institutional review board of the coordinating institution (Asan Medical Center, Seoul, Korea; IRB No. 2025-1380).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY:\u0026nbsp;\u003c/strong\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING:\u0026nbsp;\u003c/strong\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS:\u0026nbsp;\u003c/strong\u003eAK and CYK conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript. EJ and BSL contributed to the conceptualization and design of the study, interpreted the data, and critically reviewed and revised the manuscript. JP, TGK, KY, JIK, JHR, JML, HNL, JJ, and SHK contributed to data acquisition and interpretation and critically reviewed and revised the manuscript. All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS:\u0026nbsp;\u003c/strong\u003eWe thank the participating hospitals, physicians, and research coordinators of the Korean Neonatal Network for their dedication to data collection and maintenance of the registry. We would also like to thank Editage (www.editage.co.kr) for English language editing.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCrowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990; 97: 11\u0026ndash;25.\u003c/li\u003e\n\u003cli\u003eRoberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3: CD004454.\u003c/li\u003e\n\u003cli\u003eMwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol 2010; 39 Suppl 1: i122\u0026ndash;133.\u003c/li\u003e\n\u003cli\u003eEdwards EM, Ehret DEY, Soll RF, Horbar JD. Survival of infants born at 22 to 25 weeks\u0026apos; gestation receiving care in the NICU: 2020-2022. Pediatrics 2024; 154: e2024065963.\u003c/li\u003e\n\u003cli\u003eVenkatesan T, Rees P, Gardiner J, Battersby C, Purkayastha M, Gale C, et al. National trends in preterm infant mortality in the United States by race and socioeconomic status, 1995-2020. JAMA Pediatr 2023; 177: 1085\u0026ndash;1095.\u003c/li\u003e\n\u003cli\u003eStoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314: 1039\u0026ndash;1051.\u003c/li\u003e\n\u003cli\u003eTravers CP, Clark RH, Spitzer AR, Das A, Garite TJ, Carlo WA. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study. BMJ 2017; 356: j1039.\u003c/li\u003e\n\u003cli\u003eRysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015; 372: 1801\u0026ndash;1811.\u003c/li\u003e\n\u003cli\u003eYenuberi H, Ross B, Sasmita Tirkey R, Benjamin SJ, Rathore S, Karuppusami R, et al. Late-preterm antenatal steroids for reduction of neonatal respiratory complications: a randomized controlled trial. Obstet Gynecol 2024; 143: 468\u0026ndash;474.\u003c/li\u003e\n\u003cli\u003eAmerican College of OGCoOP, Society for Maternal- Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2016; 128: e187\u0026ndash;194.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. WHO recommendations on: antenatal corticosteroids for improving preterm birth outcomes. World Health Organization: Geneva, 2022.\u003c/li\u003e\n\u003cli\u003eAmerican Academy of Pediatrics, American Heart Association. Textbook of neonatal resuscitation. 7th ed. American Academy of Pediatrics: Elk Grove Village, IL, 2016.\u003c/li\u003e\n\u003cli\u003eKearsey EOR, Been JV, Souter VL, Stock SJ. The impact of the antenatal late preterm steroids trial on the administration of antenatal corticosteroids. Am J Obstet Gynecol 2022; 227: 280 e281\u0026ndash;280 e215.\u003c/li\u003e\n\u003cli\u003eTravers CP, Carlo WA, McDonald SA, Das A, Bell EF, Ambalavanan N, et al. Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids. Am J Obstet Gynecol 2018; 218: 130 e131\u0026ndash;130 e113.\u003c/li\u003e\n\u003cli\u003eKim JK, Hwang JH, Lee MH, Chang YS, Park WS. Mortality rate-dependent variations in antenatal corticosteroid-associated outcomes in very low birth weight infants with 23-34 weeks of gestation: a nationwide cohort study. PLoS One 2020; 15: e0240168.\u003c/li\u003e\n\u003cli\u003eEhret DEY, Edwards EM, Greenberg LT, Bernstein IM, Buzas JS, Soll RF, et al. Association of antenatal steroid exposure with survival among infants receiving postnatal life support at 22 to 25 weeks\u0026apos; gestation. JAMA Netw Open 2018; 1: e183235.\u003c/li\u003e\n\u003cli\u003eSiew ML, Te Pas AB, Wallace MJ, Kitchen MJ, Islam MS, Lewis RA, et al. Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits. Pediatr Res 2011; 70: 50\u0026ndash;55.\u003c/li\u003e\n\u003cli\u003eChawla S, Wyckoff MH, Lakshminrusimha S, Rysavy MA, Patel RM, Chowdhury D, et al. Short Duration of Antenatal Corticosteroid Exposure and Outcomes in Extremely Preterm Infants. JAMA Netw Open 2025; 8: e2461312.\u003c/li\u003e\n\u003cli\u003eChakkarapani AA, Roehr CC, Hooper SB, Te Pas AB, Gupta S, ESPR Neonatal Resuscitation section writing group. Transitional circulation and hemodynamic monitoring in newborn infants. Pediatr Res 2024; 96: 595\u0026ndash;603.\u003c/li\u003e\n\u003cli\u003eSarkar S, Bhagat I, Dechert R, Schumacher RE, Donn SM. Severe intraventricular hemorrhage in preterm infants: comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage. Am J Perinatol 2009; 26: 419\u0026ndash;424.\u003c/li\u003e\n\u003cli\u003eMori R, Kusuda S, Fujimura M, Neonatal Research Network Japan. Antenatal corticosteroids promote survival of extremely preterm infants born at 22 to 23 weeks of gestation. J Pediatr 2011; 159: 110\u0026ndash;114 e111.\u003c/li\u003e\n\u003cli\u003eStoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126: 443\u0026ndash;456.\u003c/li\u003e\n\u003cli\u003eYao TC, Chang SM, Wu CS, Tsai YF, Sheen KH, Hong X, et al. Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study. BMJ 2023; 382: e075835.\u003c/li\u003e\n\u003cli\u003eYang Y. Prenatal dexamethasone exposure and the risk of early-onset sepsis in preterm infants. Front Pediatr 2025; 13: 1673813.\u003c/li\u003e\n\u003cli\u003eChang YS, Park HY, Park WS. The Korean neonatal network: an overview. J Korean Med Sci 2015; 30 Suppl 1: S3\u0026ndash;S11.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Antenatal corticosteroids, Gestational age, Infant, Extremely premature, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-8754951/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8754951/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate gestational age (GA)-specific associations between antenatal corticosteroid (ACS) exposure and early physiologic vulnerability and neonatal outcomes in preterm infants.\u003c/p\u003e\u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study used Korean Neonatal Network data and included infants born between 2013 and 2021 with birth weight\u0026thinsp;\u0026lt;\u0026thinsp;1 500 g or GA\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks. ACS exposure was categorized as complete, incomplete, or none. Multivariable logistic regression estimated adjusted odds ratios, with GA-stratified analyses and a prespecified subgroup of infants born at \u0026lt;\u0026thinsp;25 weeks.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eACS exposure was associated with lower delivery room resuscitation intensity, reduced risk of severe intraventricular hemorrhage, and decreased mortality, with strongest associations observed before 32 weeks. In infants born at \u0026lt;\u0026thinsp;25 weeks, any ACS exposure was associated with greater physiologic stability and improved survival compared with no ACS exposure.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eACS exposure was associated with improved physiologic stability and survival in preterm infants, with benefits greater at lower GAs.\u003c/p\u003e","manuscriptTitle":"Gestational Age-Specific Effects of Antenatal Corticosteroids on Early Physiologic Vulnerability and Neonatal Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-17 16:15:26","doi":"10.21203/rs.3.rs-8754951/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2026-03-09T12:53:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-07T15:50:54+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-05T03:38:13+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-02-22T17:54:16+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-02-13T14:30:47+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-02-11T21:35:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-02T11:16:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-01T08:52:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2026-02-01T08:52:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b1065a98-0182-48a7-9abd-4ad0336a8f2c","owner":[],"postedDate":"February 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62768667,"name":"Health sciences/Medical research/Epidemiology"},{"id":62768668,"name":"Health sciences/Diseases/Respiratory tract diseases"},{"id":62768669,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-05-02T13:10:36+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-17 16:15:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8754951","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8754951","identity":"rs-8754951","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}