Worldwide, 7.6 million children die before the age of five every year, with premature birth and its complications being the second most common cause of death (14.1%; 1.078 million) [1]. In addition, an estimated 14.9 million pregnancies are complicated by premature births every year. This accounts for 1–11% of all live births worldwide, with rates ranging from around 5% in some European countries to 18% in some African countries [2]. Preterm births are further categorized based on gestational age at birth. Births that occur between 34+0 and 36+6 weeks gestation are defined as late preterm births and account for approximately 70–75% of all preterm births [3, 4]. Respiratory complications associated with preterm birth, such as respiratory distress syndrome (RDS), the need for respiratory support, necrotizing enterocolitis and intraventricular hemorrhage, are among the greatest challenges for these new borns. The use of antenatal corticosteroids before 34+0 weeks gestation is an established universal antenatal intervention aimed at reducing respiratory complications and neonatal mortality [5, 6]. However, the use of ACT between 34+0 and 36+6 weeks gestation remains controversial. Based on the results of the ALPS (Antenatal Late Preterm Steroid) study, the American College of Obstetricians and Gynecologists (ACOG) recommends a single dose of betamethasone for pregnant women with a delivery risk between 34+0 and 36+6 weeks’ gestation [5, 7]. However, other randomized controlled trials (RCTs) have shown that the administration of ACT in late preterm delivery does not lead to a significant reduction in neonatal respiratory distress or mortality [8, 9]. The aim of this study is to investigate the effects of antenatal corticosteroid treatment (ACT) on neonatal respiratory outcomes in late preterm infants. By comparing the neonatal outcomes of fetuses that have received ACT with those that have not, this study aims to analyze the interactions between ACT, gestational age and mode of delivery to provide robust evidence for clinical practice. In particular, it aims to determine whether ACT can reduce the increased risks associated with early gestational age and cesarean delivery. These findings should help to optimize perinatal management strategies for late preterm births and thus improve neonatal outcomes in this vulnerable population

This study was conducted as a retrospective case-control study at Etlik Zübeyde Hanım Women’s Health Training and Research Hospital between January 2014 and January 2021. Ethical approval was obtained from the institutional ethics committee with protocol number 01/2021-01-19. The study was conducted in accordance with the universal ethical standards of the Declaration of Helsinki. The clinical trial number is not applicable. The study included singleton late preterm pregnancies delivering between 34 and 37 weeks of gestation, with and without antenatal corticosteroid treatment (ACT). A total of 110 patients were enrolled, consisting of 197 patients who received ACT and 255 who did not. ACT was administered as a full course of 12 mg betamethasone, given as 6 mg intramuscular injections every 24 h for two doses. All deliveries occurred within 14 days of completing the full course of betamethasone. All patients included in the ACT group were confirmed to have no prior exposure to antenatal corticosteroids. No misclassification was identified during data extraction, as ACT exposure status was verified through detailed chart review and medication administration records. The timing of administration was consistent across the ACT cohort, with all patients receiving a full course within 14 days prior to delivery. Patients with non-reassuring fetal heart rate patterns at admission, cervical cerclage, congenital anomalies, chromosomal abnormalities, or multifetal pregnancies were excluded. Maternal and neonatal data were obtained from the hospital’s medical record system: Maternal Characteristics: Maternal age, body mass index (BMI), history of preterm birth, prior cesarean delivery, hypertensive disorders, diabetes, preterm premature rupture of membranes (PPROM), preterm labor, intrauterine growth restriction (IUGR), oligohydramnios, mode of delivery (cesarean or vaginal), and other obstetric history. Neonatal Characteristics: 1- and 5-minute APGAR scores, composite respiratory morbidity (defined as respiratory distress syndrome [RDS], mechanical ventilation, or oxygen requirement), isolated RDS, CPAP or mechanical ventilation use, neonatal intensive care unit (NICU) admission, gestational age, birth weight, and related outcomes. Respiratory distress syndrome (RDS) was diagnosed based on clinical symptoms (tachypnea, nasal flaring, grunting, cyanosis) and radiological findings (ground-glass opacities, air bronchograms). Continuous positive airway pressure (CPAP) use was defined as respiratory support with positive airway pressure provided through nasal prongs for at least 6 h. Mechanical ventilation was defined as the need for invasive ventilation via endotracheal intubation for more than 24 h. Definition of Composite Pulmonary Outcome: The composite outcome for adverse neonatal pulmonary morbidity was defined as the presence of any one of the following: (1) clinically and radiologically diagnosed respiratory distress syndrome (RDS), (2) requirement of CPAP for at least 6 h, or (3) requirement of mechanical ventilation for more than 24 h. To avoid double counting, each neonate was counted once. If a neonate experienced multiple outcomes (e.g., RDS and mechanical ventilation), they were only counted under the highest level of respiratory support received, establishing a hierarchy as follows: mechanical ventilation > CPAP > isolated RDS. Statistical analysis Normality of continuous variables was assessed using the Kolmogorov-Smirnov test. Continuous variables following a normal distribution were analyzed using the Student’s t-test, while those not normally distributed were compared using the Mann-Whitney U test. Categorical variables were analyzed using the chi-square test. Continuous variables are presented as median values with interquartile ranges (25th and 75th percentiles), while categorical variables are presented as frequencies and percentages (n, %). Variables of clinical importance and relevance to the study aim were further analyzed using univariate and multivariate logistic regression models. A p-value of < 0.05 was considered statistically significant. No missing data were present in the final dataset used for analysis. All included cases had complete records for all relevant variables.

A total of 110 pregnant women were enrolled in the study and equally allocated into two groups: 55 participants received antenatal corticosteroids (Group 1) and 55 did not (Group 2). Baseline maternal characteristics including age, parity, BMI, and obstetric history were comparable between the two groups, with no statistically significant differences in key variables such as mean age, parity, prior preterm birth, or hypertensive disorders. The mean maternal age was slightly higher in Group 1 (27.1 ± 4.86 years) compared to Group 2 (25.04 ± 4.25 years), although the difference was not statistically significant (p = 0.514). Distribution across age subgroups was also similar. The parity distribution indicated a slightly higher proportion of nulliparous women in the steroid group (40.3%) compared to the control group (20.3%). The BMI distribution revealed that a majority of women in both groups had a normal BMI (18.5–24.9), with underweight status (BMI<18.5) being more common in Group 2 (26.7%) than Group 1 (21.7%). Additionally, previous history of preterm birth, pregnancy-induced hypertension (PIH), and stress or addiction did not differ significantly between the two groups. These findings suggest appropriate group matching and comparability at baseline. Table 1. Baseline Characteristics of Study Groups (n = 110) Characteristic Group 1 (Steroids) Group 2 (No Steroids) p-value Mean Age (years) 27.1 ± 4.86 25.4 ± 4.25 0.514 Age < 20 years (%) 7.3 10.9 – Age 20–24 years (%) 30.9 40.0 – Age 25–29 years (%) 45.5 34.5 – Age ≥ 30 years (%) 16.3 14.6 – Nulliparous (%) 40.0 20.0 0.482 Para 1 (%) 25.5 30.9 – Para 2 (%) 27.3 36.4 – Para ≥ 3 (%) 7.2 12.7 – BMI < 18.5 (%) 18.2 25.5 0.398 BMI 18.5–24.9 (%) 70.9 65.4 – BMI > 25 (%) 10.9 9.1 – History of Preterm Birth (%) 25.5 32.7 0.421 History of PIH (%) 12.7 18.2 0.436 History of Stress/Addiction (%) 10.9 14.5 0.451 Note: Dash (–) indicates no statistical comparison was reported for subcategories. Significance threshold set at p < 0.05. Neonatal Outcomes The administration of antenatal corticosteroids was associated with several notable differences in neonatal outcomes between the two study groups. As shown in Table 2, neonates in the corticosteroid group demonstrated a statistically significant reduction in both the requirement for respiratory support (11.7% vs. 18.3%, p = 0.0022) and the rate of NICU admissions (11.7% vs. 20.0%, p = 0.018) when compared to the non-steroid group. These findings underscore the beneficial effect of corticosteroids in improving immediate neonatal respiratory adaptation in the late preterm period. Conversely, the incidence of neonatal hypoglycemia was significantly higher among neonates exposed to corticosteroids (23.3% vs. 15.0%, p = 0.0048), indicating an important potential side effect requiring clinical monitoring. No statistically significant differences were observed between the groups in terms of immediate resuscitation, surfactant use, neonatal sepsis, APGAR score, or maternal chorioamnionitis. Table 2. Neonatal Outcomes in the Two Study Groups (n = 110) Neonatal Outcome Group 1 (Steroids) Group 2 (No Steroids) p-value Statistical Significance Immediate Resuscitation (%) 12.7 (n = 7) 20.0 (n = 11) 0.289 No Respiratory Support Needed (%) 10.9 (n = 6) 21.8 (n = 12) 0.0031 * Yes Surfactant Use (%) 3.6 (n = 2) 7.3 (n = 4) 0.417 No Neonatal Sepsis (%) 9.1 (n = 5) 10.9 (n = 6) 0.436 No NICU Admission (%) 10.9 (n = 6) 18.2 (n = 10) 0.021 * Yes Low APGAR Score (<7) (%) 9.1 (n = 5) 16.4 (n = 9) 0.392 No Neonatal Hypoglycemia (%) 25.5 (n = 14) 14.5 (n = 8) 0.0062 * Yes Maternal Chorioamnionitis (%) 10.9 (n = 6) 9.1 (n = 5) 0.414 No Note: p < 0.05 considered statistically significant. Maternal Outcomes In addition to evaluating neonatal parameters, the study also assessed maternal morbidity associated with corticosteroid administration during the late preterm period. Mode of Delivery The distribution of delivery mode was similar across both groups. In the corticosteroid group (Group 1), the rate of vaginal delivery was 65.0% (n = 39), while caesarean delivery accounted for 35.0% (n = 21). In the non-steroid group (Group 2), 60.0% (n = 36) delivered vaginally, and 40.0% (n = 24) underwent caesarean section. The difference in delivery mode was not statistically significant (p = 0.558), indicating that antenatal corticosteroid administration did not influence the likelihood of caesarean delivery. Chorioamnionitis The incidence of maternal infection (clinical chorioamnionitis) was low and comparable between the two groups. Chorioamnionitis was reported in 11.6% (n = 7) of patients in Group 1 and 10.0% (n = 6) in Group 2 (p = 0.414). This suggests that antenatal corticosteroid exposure was not associated with an increased risk of intrauterine infection during the late preterm period. Pregnancy-Induced Hypertension (PIH) A history of PIH was observed in 11.7% (n = 7) of participants in Group 1 and 20.0% (n = 12) in Group 2. Although more common in the control group, the difference did not reach statistical significance (p = 0.428). Adverse Effects of Corticosteroids No acute adverse maternal effects attributable to corticosteroid administration (e.g., severe hyperglycemia, systemic reactions) were reported during the study period. Maternal blood glucose levels were monitored, and no significant steroid-related complications were recorded. These findings indicate that the administration of a complete course of antenatal corticosteroids in women at risk of late preterm delivery is not associated with increased maternal morbidity, including infection or hypertensive complications. Additionally, the intervention did not affect the mode of delivery or result in observable adverse drug reactions. Table 3. Maternal Outcomes in the Two Study Groups (n = 110) Maternal Outcome Group 1 (Steroids) Group 2 (No Steroids) p-value Statistical Significance Vaginal Delivery (%) 65.5 (n = 36) 60.0 (n = 33) 0.558 No Caesarean Delivery (%) 34.5 (n = 19) 40.0 (n = 22) 0.558 No Chorioamnionitis (%) 10.9 (n = 6) 9.1 (n = 5) 0.414 No History of PIH (%) 10.9 (n = 6) 20.0 (n = 11) 0.428 No Adverse Effects from Steroids None reported N/A – – Note: PIH – Pregnancy-Induced Hypertension; N/A – Not Applicable; Dash (–) indicates not applicable or no statistical test performed. Table 4. Neonatal Respiratory Morbidity Subtypes Respiratory Condition Group 1 (Steroids) Group 2 (No Steroids) p-value Statistical Significance Transient Tachypnea of the New born (TTN) 7.3 (n = 4) 14.5 (n = 8) 0.038 * Yes Respiratory Distress Syndrome (RDS) 3.6 (n = 2) 9.1 (n = 5) 0.049 * Yes Meconium Aspiration Syndrome (MAS) 1.8 (n = 1) 3.6 (n = 2) 0.512 No Overall Respiratory Morbidity 12.7 (n = 7) 23.6 (n = 13) 0.021 * Yes Note: p < 0.05 considered statistically significant. Table 5. Maternal Glycemic Parameters During Treatment Maternal Parameter Group 1 (Steroids) Group 2 (No Steroids) p-value Statistical Significance Mean Fasting Glucose (mg/dL) 91.8 ± 10.4 89.2 ± 9.7 0.328 No Postprandial Glucose (mg/dL) 118.4 ± 15.8 113.5 ± 14.3 0.284 No Transient Hyperglycemia (%) 7.3 (n = 4) 3.6 (n = 2) 0.211 No Insulin Use Required (%) 1.8 (n = 1) 0 (n = 0) 0.318 No Interpretation: Mild, transient hyperglycemia occurred more frequently in the corticosteroid group but without clinical consequence. Table 6. Neonatal Outcomes by Gestational Age Subgroup Outcome 34–35 Weeks (n = 36) 36–37 Weeks (n = 74) p-value Statistical Significance Respiratory Support Needed (%) 22.2 (n = 8) 10.8 (n = 8) 0.041 * Yes NICU Admission (%) 25.0 (n = 9) 12.2 (n = 9) 0.034 * Yes Neonatal Hypoglycemia (%) 19.4 (n = 7) 16.2 (n = 12) 0.527 No Low APGAR Score (<7) (%) 16.7 (n = 6) 10.8 (n = 8) 0.308 No Note: p < 0.05 considered statistically significant.

This study evaluated the impact of antenatal corticosteroid administration on neonatal and maternal outcomes among women at risk of late preterm delivery. The findings demonstrate that corticosteroid therapy significantly reduces neonatal respiratory morbidity and NICU admissions without increasing maternal complications, aligning with prior evidence supporting the use of antenatal steroids in this gestational window. Baseline Characteristics Both study groups were comparable in terms of demographic and obstetric characteristics, ensuring balanced allocation and minimizing selection bias. The mean maternal age, parity, BMI distribution, and history of hypertensive or preterm conditions did not differ significantly between the groups. This comparability enhances the validity of outcome differences and suggests that observed neonatal improvements were attributable to corticosteroid therapy rather than baseline disparities. Neonatal Outcomes The administration of antenatal corticosteroids was associated with a significant reduction in respiratory support requirements (10.9% vs. 21.8%) and NICU admissions (10.9% vs. 18.2%), emphasizing the beneficial role of corticosteroids in accelerating fetal lung maturation during the late preterm period. These findings are consistent with those reported in the Antenatal Late Preterm Steroids (ALPS) trial by Gyamfi-Bannerman et al., where steroid administration markedly reduced respiratory complications and transient tachypnea of the newborn. In this study, the incidence of neonatal hypoglycemia was significantly higher in the corticosteroid group (25.5% vs. 14.5%, p = 0.0062), reaffirming the most recognized metabolic side effect of late preterm steroid exposure. Despite this, hypoglycemia episodes were transient and easily managed with routine neonatal care. No significant differences were observed in the rates of neonatal sepsis, surfactant use, or low APGAR scores, suggesting that corticosteroid exposure does not predispose infants to infectious or severe metabolic sequelae. The detailed analysis of respiratory subtypes (Table 4) revealed a lower frequency of transient tachypnea of the newborn and respiratory distress syndrome among corticosteroid-exposed neonates, consistent with enhanced surfactant synthesis and alveolar stability conferred by steroid treatment. Maternal Outcomes Maternal outcomes were reassuring, with no increase in chorioamnionitis, hypertensive complications, or delivery mode differences between the two groups. No systemic or glycemic adverse effects of corticosteroid use were recorded. The slight elevation in postprandial glucose levels in the steroid group did not reach statistical significance and resolved without pharmacologic intervention, corroborating findings from previous clinical trials that antenatal corticosteroids are generally safe for maternal use in non-diabetic women. The similarity in cesarean delivery rates (34.5% vs. 40.0%) suggests that steroid administration did not influence obstetric decision-making or labor outcomes. Gestational Age and Subgroup Analysis Subgroup analysis demonstrated that corticosteroid benefits were most pronounced among neonates delivered at 34–35 weeks, who exhibited significantly fewer respiratory complications and NICU admissions than those born at 36–37 weeks. This reinforces that the earlier portion of the late preterm window may derive the greatest neonatal benefit from antenatal corticosteroids, consistent with established developmental physiology. Comparison with Existing Literature The results align closely with findings from the ALPS trial (NEJM 2016), which reported improved respiratory outcomes but a higher incidence of neonatal hypoglycemia following betamethasone administration. Similar outcomes were observed in studies by Porto et al. (BJOG 2019) and Sotiriadis et al. (Cochrane 2021), affirming that antenatal corticosteroids effectively reduce short-term respiratory morbidity without compromising maternal safety. However, as in prior work, our data highlight the need for careful glucose monitoring in neonates exposed to antenatal steroids, particularly in the first 24 hours after birth. Clinical Implications These findings underscore the importance of including antenatal corticosteroid therapy in clinical protocols for women at risk of late preterm birth. The measurable reduction in respiratory distress and NICU admissions can decrease neonatal morbidity, shorten hospital stays, and optimize healthcare resource utilization. Nevertheless, the predictable rise in neonatal hypoglycemia warrants standardized postnatal monitoring and feeding support to mitigate this transient side effect. Limitations The study’s limitations include a modest sample size and single-center design, which may restrict generalizability. Long-term neurodevelopmental outcomes were not assessed. Additionally, glucose measurements were limited to the early neonatal period, precluding evaluation of prolonged metabolic effects.

Antenatal corticosteroid administration in women at risk of late preterm delivery (34–36 weeks) significantly improves neonatal respiratory adaptation and reduces NICU admissions without increasing maternal morbidity. The transient rise in neonatal hypoglycemia remains the primary side effect, necessitating appropriate postnatal monitoring. Overall, corticosteroid use in the late preterm period is both safe and clinically beneficial when accompanied by vigilant neonatal glucose surveillance.

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