(Is there a place for) antenatal corticosteroid treatment after 34 weeks of gestation in twin pregnancies when late preterm delivery is inevitable

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Antenatal corticosteroid treatment (ACT) is the main intervention to improve neonatal outcomes in unavoidable preterm births. Our aim was to investigate the association between neonatal outcome and ACT in twin pregnancies with late preterm birth, where the effects of corticosteroids have not been adequately studied. Methods Women with dichorionic-diamniotic twins who had a late preterm birth between 2017 and 2021 at a large referral hospital providing tertiary care and medical training were retrospectively analyzed. Women who met the inclusion criteria were divided into three groups: No ACT (n = 209), ACT < 34 weeks' gestation (n = 76) and ACT ≥ 34 weeks' gestation (n = 67). The groups were compared with regard to adverse neonatal complications. Primary outcome measures were composite respiratory and composite neonatal outcomes. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome. Results Composite respiratory and composite neonatal outcomes which did not differ significantly between groups. Gestational age at birth, birthweight and ACT before 34 weeks' gestation were independent protective factors for composite respiratory outcome, composite neonatal outcome and admission to the neonatal intensive care unit. Female gender was an independent protective factor for both composite respiratory outcome and neonatal intensive care unit admission, while gestational age at birth and birthweight were independent protective factors for hypoglycemia. Conclusion ACT at or after 34 weeks' gestation did not improve neonatal outcomes in dichorionic-diamniotic twins born late preterm and was associated with a higher rate of neonatal hypoglycemia than those not treated with corticosteroids. Antenatal corticosteroids betamethasone hypoglycemia late preterm outcome twin pregnancy Figures Figure 1 Background Preterm birth, a major cause of neonatal morbidity and mortality, is any live birth before 37 weeks' gestation (WG). Preterm birth and its associated complications are more common in twins. According to the 2006 National Vital Statistics Report on birth data in the United States, 11.1% of singleton pregnancies and 61.9% of multiple pregnancies resulted in preterm birth [ 1 ]. The World Health Organization classifies preterm births as mild or late (34–37 WG), moderate (32–34 WG), very (28–32 WG), and extreme (< 28 WG) preterm births [ 2 ]. Late preterm births account for 60% of all live twin births [ 3 ]. Studies on preterm birth have focused mainly on preterm infants born before 34 0/7 WG who are more likely to have severe complications of prematurity. Antenatal corticosteroid treatment (ACT) to induce fetal lung maturity is the most effective intervention to improve perinatal outcomes and has long been offered to women in whom preterm birth before 34 0/7 WG is inevitable [ 4 – 6 ]. Despite lower neonatal complication and mortality rates compared with preterm infants born at lower weeks, late preterm infants have a relatively higher risk of morbidity and mortality compared with term infants [ 7 – 9 ]. In some studies, ACT was found to be a significant factor in reducing neonatal respiratory complications in the late preterm period, while according to other studies, this reduction was not significant [ 10 – 15 ]. However, there are no definitive data on the use of late preterm ACT in twin pregnancies where late preterm delivery is inevitable and ACT is not administered before 34 0/7 WG. Research is needed in this area to close the gap between knowledge and practice. In addition, there are still many questions about the side effects and benefits of ACT that need to be clarified. The aim of this study was to compare the neonatal outcomes of late preterm-born dichorionic-diamniotic twins who received ACT in the late preterm period or < 34 0/7 WG with those who did not. Methods Design of the study We conducted a retrospective cohort study of women with dichorionic-diamniotic twins who had a late preterm birth between January 1, 2017, and December 31, 2021, at a large reference hospital providing tertiary care and medical training. The Ethics Committee of University of Health Sciences Etlik Lady Zübeyde Maternity and Women's Health Education and Research Hospital, Ankara, Turkey, approved the conduct, protocol and procedures of the study (16.03.2022-04/31) and waived the requirement for written informed consent for participation due to the retrospective nature of the study. After approval, a retrospective review of the patients' medical records was carried out. Characteristics of the study population, selection of participants and definitions Twins with intrauterine demise of one or both fetuses, twins other than dichorionic-diamniotic, singletons and higher order pregnancies were not included. Pregnancies with fetal factors such as growth restriction, congenital infections, malformations and genetic abnormalities, pregnant women with diabetes, prelabor rupture of membranes, missing data and those who had received more than one course of ACT, including a rescue course, and deliveries within 48 hours after the first dose of the standard ACT regimen were excluded. All pregnant women selected for participation had reassuring fetal well-being of both fetuses at hospital admission, defined as pregnancies with a maximum vertical amniotic pocket of ≥ 2 cm and a reactive non-stress test. In addition, women who had reassuring antepartum fetal well-being at the time of hospital admission but required emergency delivery due to non-reassuring intrapartum well-being were included, while patients who had already been diagnosed with antepartum fetal distress at the time of admission were not included. During the five-year period covered by this retrospective study, a total of 69792 (100%) live births were recorded. Of these, 1462 (2.09%) were twins, 1232 (1.76%) were dichorionic-diamniotic twins, of which 580 were born late preterm. According to the inclusion criteria, a total of 352 subjects (704 newborns) were eligible, of whom 76 (152 newborns) received ACT < 34 0/7 WG; 67 (134 newborns) received late preterm ACT, and 209 (418 newborns) did not receive ACT (Fig. 1 ). Any live birth between 34 0/7 and 36 6/7 WG is designated as "late preterm" by the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the National Center for Health Statistics [ 16 – 18 ]. Gestational age was calculated from the first day of the last menstrual period (LMP) and confirmed by sonographic dating. If the two calculations differed by ≤ 7 days, gestational age was determined based on LMP; otherwise, sonographic dating was used. Sonographic findings that indicated dichorionicity were separate placental masses, different fetal sexes, and the appearance of the intertwin membrane as a "lambda" or "twin-peak" sign [ 19 ]. ACT was defined as delivery at least 48 hours after the first dose of the standard regimen, which involves the administration of two intramuscular injections of 12 mg betamethasone 24 hours apart. The indication for ACT was anticipated preterm delivery in women less than 37 0/7 WG, who had not yet been treated with antenatal corticosteroids during the current pregnancy. Rescue-dose corticosteroid treatment was defined as the administration of a single repeat course of antenatal corticosteroids in women with < 34 0/7 WG who are at risk of preterm delivery within seven days and who had received ACT more than 14 days ago [ 20 ]. The presence of uterine contractions of sufficient frequency, amplitude and duration to cause progressive cervical effacement and/or dilation between 34 0/7 and 36 6/7 WG was defined as late preterm labor. The mode of delivery was classified as either vaginal or cesarean section. If an emergency cesarean section was required to deliver the second twin after vaginal delivery of the first twin, delivery of the first fetus was classified as vaginal delivery, while delivery of the second twin was classified as cesarean section. Cesarean deliveries that were performed immediately after the decision to deliver without waiting for at least 6 hours of fasting, which is required for safe anesthesia, were termed emergency cesarean deliveries, while all others were defined as elective cesarean deliveries. The general indications for cesarean delivery were: previous cesarean delivery (129), maternal wish (93), malpresentation (58), fetal distress (20), preeclampsia with severe features (10), placental abruption (8), vaginismus (6), obstructed labor (6), chord prolapse and chord presentation (6), dystocia (5), and placenta previa (3), ordered from most common to least common. Data acquisition All patient demographics, clinical characteristics and neonatal outcomes were obtained from the hospital database and medical records and then compared between the three groups. Because no neonatal death was observed during the study period and the incidence of serious adverse neonatal events in late preterm births is relatively low, we examined composite outcome measures that combine different components of neonatal outcome to draw conclusions. In addition, there were no serious neonatal adverse events, including sepsis, APGAR-5 (Appearance, Pulse, Grimace, Activity, and Respiration scores at fifth minute) scores of < 7, meconium aspiration syndrome, intracranial hemorrhage, and necrotizing enterocolitis. Therefore, the primary neonatal outcomes and measures were defined as composite neonatal outcome (CNO) consisting of any of the following features that may lead to severe neonatal morbidity: APGAR-5 score, admission to the neonatal intensive care unit (NICU), hypoglycemia, hyperbilirubinemia requiring phototherapy, and any of the following components of the composite respiratory outcome (CRO), including transient tachypnea of the newborn, respiratory distress syndrome (RDS), need for mechanical ventilation, and continuous positive airway pressure therapy. Statistical analysis All statistical analyzes were performed using R Statistical Software (version 2021.09.4 + 403.pro3; R Foundation for Statistical Computing, Vienna, Austria). Kolmogrov-Simirnov or Shapiro-Wilk tests were used to determine normality. Descriptive analyzes were performed using means and standard deviations for the normally distributed variable "birthweight". One-way ANOVA was used to compare this parameter between groups. Levene's test was used to assess the homogeneity of variance. For numerical data that were not normally distributed, descriptive analyzes were performed using medians and quartiles (Q1-Q3). Kruskal-Wallis tests were performed to compare these parameters between groups. The Mann-Whitney U test was performed to test the significance of pairwise differences, using the Bonferroni correction to adjust for multiple comparisons. Descriptive analyzes were performed for categorical variables using frequency and percentage. Relationships between categorical variables were analyzed using the chi-square test or Fisher's exact test (if the assumptions of the chi-square test do not apply due to low expected cell counts). Potential factors identified in the univariate analyzes were entered into a binary logistic regression analysis to identify additional independent predictors of CRO and CNO. The Hosmer-Lemeshow goodness-of-fit statistic was used to assess model fit. An overall type I error level of 5% was used to derive statistical significance. A p-value of less than 0.05 was considered a statistically significant result. Results A total of 352 participants (704 newborns) with dichorionic-diamniotic twin pregnancies who had a late preterm delivery were included. Of these, 209 women (418 newborns) did not receive ACT (control group), while 76 (152 newborns) and 67 (134 newborns) women received ACT < 34 0/7 WG and ≥ 34 0/7 WG, respectively. Demographic and clinical characteristics are shown in Table 1 . Maternal age, number of previous miscarriages and cesarean deliveries, history of preterm delivery, and hypertensive disorders in the current pregnancy were similar. The median body mass index, gravidity, and parity of women in group 1 were significantly lower than those in the control group [28.5 (26–32) vs. 30 (27–33), p = 0.01; 2 (1–3) vs. 3 (2–4), p < 0.001, and 1 (0–1) vs. 1 (1–2), p < 0.001, respectively]. An analysis of birth and neonatal characteristics and outcomes is shown in Table 2 . There were no significant differences between the groups with respect to the primary outcomes. An analysis after Bonferroni correction of the neonatal characteristics and early neonatal outcomes of the study groups is shown in Table 3 . Multivariate logistic regression analysis identified gestational age at birth (GAB), female gender, birthweight, and early preterm ACT as independent protective factors predicting CRO [odds ratio (OR) = 0.74, 95% confidence interval (CI) 0.57–0.95, p = 0.01; OR = 0.58, 95% CI 0.38–0.87, p = 0.01; OR = 0.83, 95% CI 0.77–0.90, p < 0.001, and OR = 0.46, 95% CI 0.27–0.81, p < 0.01, respectively], and NICU admission (OR = 0.58, 95% CI 0.47–0.72, p < 0.001; OR = 0.69, 95% CI 0.48–0.98, p = 0.04, OR = 0.85, 95% CI 0.80–0.91, p < 0.001, and OR = 0.56, 95% CI 0.35–0.90, p = 0.01, respectively). On the other hand, GAB, birthweight, and early preterm ACT were also independent protective factors predictive of CNO (OR = 0.66, 95% CI 0.53–0.83, p < 0.001, OR = 0.83, 95% CI 0.78–0.89, p < 0.001, and OR = 0.60, 95% CI 0.37–0.97, p = 0.03, respectively) while GAB and birthweight were the independent protective factors for hypoglycemia in multivariate logistic regression analysis (OR = 0.41, 95% CI 0.19–0.87, p = 0.02, and OR = 0.58, 95% CI 0.47–0.72, p < 0.001, respectively) (Table 4 ). In this context, administration of ACT < 34 WG, each 1-week increase in GAB, female gender, and each 100-gram increase in birthweight provided 2.1-, 1.3-, 1.7-, and 1.2-fold protection against adverse results of CRO; 1.6-, 1.7-, 1.4-, and 1.1-fold protection against admission to the NICU, respectively. In addition, administration of ACT < 34 WG, each 1-week increase in GAB, and each 100-gram increase in birthweight provided 1.8-, 1.5-, and 1.2-fold protection from adverse results of CNO, respectively, whereas each 1-week increase in GAB and each 100-gram increase in birthweight contributed to 2.4- and 1.7-fold protection from hypoglycemia, respectively. Table 1 Demographic and basic clinical characteristics of the participants Variable No ACT (n = 209) < 34 WG ACT (n = 76) ≥ 34 WG ACT (n = 67) Total (n = 352) p Maternal age (years) 29 (26–33) 28 (24–32) 28 (26–33) 29 (26–33) 0.36 BMI (kg/m 2 ) 30 (27–33) a 28.5 (26–32) a 30 (28–33) 30 (27–33) 0.01 * Gravida (number) 3 (2–4) b 2 (1–3) b 2 (1–3) 2 (2–3) < 0.001 * Parity (number) 1 (1–2) c 1 (0–1) c 1 (0–2) 1 (0–2) < 0.001 * Miscarriage (number) 0 (0–1) 0 (0–0) 0 (0–0) 0 (0–0) 0.4 Previous C/S (number) 0 (0-0.25) 0 (0–0) 0 (0–0) 0 (0–0) 0.42 History of previous PTD 15 (7.2) 6 (7.9) 5 (7.5) 26 (7.4) 0.95 Hypertensive disorders 12 (5.7) 7 (9.2) 5 (7.5) 24 (6.8) 0.33 ACT, Antenatal corticosteroid treatment; BMI, Body mass index; C/S, Cesarean section; kg/m 2 , Kilograms per square meter; PTD, Preterm delivery; WG, Weeks’ gestation. Data are expressed as median (Q1-Q3), or number (percentage) where appropriate. A p value of < 0.05 indicates a significant difference. Statistically significant p-values are in bold. Superscripted lowercase letters indicates groups with statistically significant difference, while superscripted asterisk indicates corrected p-values with Bonferroni correction. Table 2 Birth characteristics and early outcomes of newborns Variable No ACT (n:418) < 34 WG ACT (n:152) ≥ 34 WG ACT (n:134) Total (n:704) p GAB (WG) 36 (35.2–36.4) 34.4 (34–35.4) 35.1 (34.5–35.6) 35.4 (34.6–36.2) < 0.001 APGAR-5 score 9 (9–10) 9 (9–10) 10 (9–10) 10 (9 − 0) 0.01 Birthweight (grams) 2419 ± 347.3 2199 ± 321.1 2363 ± 268.4 2361 ± 356.4 < 0.001 Delivery mode Vaginal 12 (1.7) 4 (0.6) 0 (0) 16 (2.3) 0.11 Cesarean 406 (57.7) 148 (21) 134 (19) 688 (97.7) Cesarean delivery Urgent 106 (26.1) 46 (31.1) 28 (20.9) 180 (26.2) 0.151 Elective 300 (73.9) 102 (68.9) 106 (79.1) 508 (73.8) Female gender 221 (52.9) 72 (47.4) 66 (49.3) 359 (51) 0.46 NICU admission 164 (39.2) 78 (51.3) 66 (49.3) 308 (43.8) 0.01 Hypoglycemia 7 (1.7) 11 (7.2) 3 (2.2) 21 (3) 0.003 HRP 87 (20.8) 31 (20.4) 26 (19.4) 144 (20.5) 0.94 CPAP therapy 31 (7.4) 17 (11.2) 4 (3) 52 (7.4) 0.03 TTN 26 (6.2) 5 (3.3) 6 (4.5) 37 (5.3) 0.34 RDS 34 (8.1) 11 (7.2) 6 (4.5) 51 (7.2) 0.36 Need for MV 34 (8.1) 26 (17.1) 19 (14.2) 79 (11.2) 0.005 CRO 97 (23.2) 44 (28.9) 35 (26.1) 176 (25) 0.35 CNO 146 (34.9) 67 (44.1) 55 (41) 268 (38.1) 0.1 ACT, Antenatal corticosteroid treatment; APGAR, Appearance, pulse, grimace, activity, and respiration scores at fifth minute; CNO, Composite neonatal outcome; CPAP, Continuous positive airway pressure; CRO, Composite respiratory outcome; GAB, Gestational age at birth; HRP, Hyperbilirubinemia requiring phototherapy; MV, Mechanical ventilation; NICU, Neonatal intensive care unit; RDS, Respiratory distress syndrome; TTN, Transient tachypnea of the newborn; WG, Weeks’ gestation. Data are expressed as mean ± standard deviation, median (Q1-Q3), or number (percentage) where appropriate. A p value of < 0.05 indicates a significant difference. Statistically significant p-values are in bold. Table 3 Analysis after Bonferroni correction of neonatal characteristics and early neonatal outcomes showing statistically significant differences Variable No ACT (n = 418) < 34 WG ACT (n = 152) ≥ 34 WG ACT (n = 134) No ACT (n = 418) Birthweight < 0.001 0.23 APGAR-5 score 1.0 0.02 Hypoglycemia 0.002 0.71 CPAP therapy 0.2 0.1 Mechanical ventilation 0.003 0.05 NICU admission 0.01 0.04 < 34 WG ACT (n = 152) Birthweight < 0.001 < 0.001 APGAR-5 score 1.0 0.01 Hypoglycemia 0.002 0.09 CPAP therapy 0.2 0.01 Mechanical ventilation 0.003 0.6 NICU admission 0.01 0.72 ≥ 34 WG ACT (n = 134) Birthweight 0.23 < 0.001 APGAR-5 score 0.02 0.01 Hypoglycemia 0.71 0.09 CPAP therapy 0.1 0.01 Mechanical ventilation 0.05 0.6 NICU admission 0.04 0.72 ACT, Antenatal corticosteroid treatment; APGAR-5, Appearance, pulse, grimace, activity, and respiration scores at fifth minute; CPAP, Continuous positive airway pressure; NICU, Neonatal intensive care unit; WG, Weeks’ gestation. P values are given with Bonferroni correction. A p value of < 0.05 indicates a significant difference. Statistically significant p-values are in bold. Table 4 Multivariate logistic regression analysis of neonatal variables for adverse neonatal outcomes Variable CRO CNO Hypoglycemia NICU admission OR (95%CI) p OR (95% CI) p OR (95%CI) p OR (95% CI) p GAB (WG) 0.74 (0.57–0.95) 0.01 0.66 (0.53–0.83) < 0.001 0.41 (0.19–0.87) 0.02 0.58 (0.47–0.72) < 0.001 Female gender 0.58 (0.38–0.87) 0.01 0.69 (0.48–0.99) 0.06 1.12 (0.41–3.03) 0.82 0.69 (0.48–0.98) 0.04 Birthweight (100 grams) 0.83 (0.77–0.90) < 0.001 0.83 (0.78–0.89) < 0.001 0.58 (0.47–0.72) < 0.001 0.85 (0.80–0.91) < 0.001 < 34 WG ACT 0.46 (0.27–0.81) < 0.01 0.60 (0.37–0.97) 0.03 1.08 (0.34–3.38) 0.89 0.56 (0.35–0.90) 0.01 ≥ 34 WG ACT 0.81 (0.50–1.31) 0.38 0.94 (0.61–1.45) 0.78 0.96 (0.27–3.38) 0.94 0.97 (0.65–1.46) 0.89 ACT, Antenatal corticosteroid treatment; CI, Confidence interval; CPAP, Continuous positive airway pressure; CNO, Composite neonatal outcome; CRO, Composite respiratory outcome; GAB, Gestational age at birth; NICU, Neonatal intensive care unit; OR, Odds ratio; WG, Weeks’ gestation. The unit of change in birthweight was given as 100-grams because the effect of a 1-gram change would be extremely small. A p value of < 0.05 indicates a significant difference. Statistically significant p-values are in bold. Discussion The principal findings of the present study were: In women with dichorionic-diamniotic twin pregnancies delivered in the late preterm period, (1) ACT was not significantly associated with a reduction in adverse neonatal complications regardless of the timing of exposure during pregnancy and was significantly associated with an increased rate of neonatal hypoglycemia, particularly in women treated before 34 0/7 WG; (2) Rates of admission to NICU were significantly higher in the corticosteroid-exposed groups regardless of the timing of exposure during pregnancy; (3) Neonatal birthweight was significantly lower in the ACT < 34 0/7 WG group; (4) GAB, birthweight, and early preterm ACT were independent protective factors predicting CRO, CNO, and NICU admission. In recent decades, various factors such as financial security, career priority, and lack of emotional and psychological readiness have discouraged women from becoming mothers at a young age. This trend has led to more and more women trying to become pregnant at an older age, when fertility begins to decline. Therefore, the number of pregnancies conceived using assisted reproductive methods is increasing, and as an inevitable consequence, the number of multiple pregnancies is also gradually increasing worldwide [ 21 – 24 ]. Multiple pregnancies are associated with an increased risk of pregnancy complications, particularly spontaneous abortions, preterm birth, preeclampsia, and maternal hemorrhage [ 21 ]. On the other hand, preterm birth is the leading cause of infant death, and the degree of prematurity is the most important determinant of morbidity and mortality [ 25 ]. Therefore, strategies to predict and prevent preterm birth and treatment approaches to reduce neonatal morbidity and mortality in populations at high risk of preterm birth are essential. In this context, fibronectin and, more commonly, sonographic measurement of cervical length have been used to predict preterm birth in singleton pregnancies [ 26 ]. In a recent study, the combination of sonographic measurement of cervical length and determination of granulocyte elastase in cervical secretions proved to be a useful tool for predicting preterm birth in asymptomatic twin pregnancies [ 27 ]. Administration of corticosteroids to women in whom preterm birth is inevitable is the most important antenatal intervention to reduce adverse neonatal outcomes [ 4 , 28 ]. ACT is recommended between 24 0/7 and 33 6/7 WG and may even be considered between 23 0/7 and 24 0/7 WG in women with an inevitable preterm birth within seven days, including pregnancies with rupture of membranes [ 4 , 7 , 29 ]. Recent data suggest that ACT may be beneficial in women at risk of late preterm delivery [ 28 ]. The risk of neonatal sepsis, chorioamnionitis, or endometritis was not increased, but neonatal hypoglycemia occurred more frequently when ACT was administered in the late preterm period [ 30 ]. On the other hand, there are vulnerable pregnancy populations, including twins and multiple pregnancies, where the effects of ACT have not yet been adequately studied. As there is a need for studies that address the gaps and practice for the use of late preterm ACT in women with dichorionic-diamniotic twins who are at high risk for inevitable late preterm birth, we conducted this article. Furthermore, to our knowledge, this article is the first study to examine the effects of ACT in such pregnancies, comparing whether they were treated before or after 34 0/7 WG. A study conducted by Gyamfi-Bannerman et al. found that late preterm corticosteroid therapy was associated with improved respiratory morbidity in late preterm infants [ 28 ]. In another study by Martinka et al, which was designed as a secondary analysis of an earlier randomized controlled trial in twin pregnancies (Twin Delivery Study) and in which the analysis was restricted to women who had delivered in the late preterm period, the rates of improvement in composite respiratory outcomes were comparable to the corresponding rates in the study by Gyamfi-Bannerman et al. The authors concluded that the benefit-risk ratio of ACT with respect to neonatal respiratory morbidity in twin pregnancies at risk of late preterm delivery is expected to be similar to that in singletons [ 31 , 32 ]. However, this conclusion is limited because it is a theoretically based indirect assumption and the pharmacodynamics of corticosteroids are different in singleton and twin pregnancies. Twins develop in a different environment than singletons and face many difficulties during the intrauterine period, such as competition for maternal nutrients, limited space and smaller placentas or even smaller placental proportions in the case of monochorionicity. In a study by Ben-David et al. similar results were obtained as in our study regarding neonatal outcomes [ 33 ]. However, they compared only the women exposed to ACT during late preterm period with the control group, whereas the comparison in our study was made by dividing the treatment groups according to whether ACT was administered before or ≥ 34 0/7 WG. In addition, a more homogeneous distribution was achieved in our study by excluding diabetic pregnancies and twins other than dichorionic-diamniotic. Corticosteroid treatment is a double-edged sword because, although it reduces the risk of respiratory neonatal morbidity and mortality, steroid-induced maternal hyperglycemia can also lead to other neonatal outcomes, particularly neonatal hypoglycemia, especially in preterm newborns. Since maternal glucose supply is interrupted immediately after birth, the newborn must initiate endogenous glucose production to maintain euglycemia. This adaptation process begins with a decrease in neonatal insulin and an increase in glucagon shortly after birth [ 34 ]. This mechanism may be disrupted in hyperinsulinemic preterm newborns exposed to ACT, and persistent neonatal hypoglycemia can lead to serious consequences [ 35 , 36 ]. Fortunately, maternal hyperglycemia induced by corticosteroids lasts only a few days [ 37 ]. On the other hand, a recent study by Carpenter et al. found an increase in granulocytes and a decrease in lymphocytes in the umbilical cord blood of fetuses whose mothers had received betamethasone treatment during late preterm period [ 38 ]. These alterations in the white blood cells can have negative consequences for the newborn, which tries to adapt to the external environment and fight possible infectious agents after the protective maternal immunity has been extinguished at birth. In our study, neonatal hypoglycemia rates were significantly higher in the ACT < 34 0/7 WG group and were observed more frequently in the ACT ≥ 34 0/7 WG group than in the unexposed group. On the other hand, it should be considered that this result could be closely related to the significantly higher GAB in the control group, in which the protective mechanisms against hypoglycemia function better than in those born at earlier weeks. Mean birthweight was also significantly lower in the ACT < 34 0/7 WG group than in the control group, but there was no significant difference between the ACT ≥ 34 0/7 WG group and the control group. In addition, the rates of NICU admission and need for mechanical ventilation were higher in the ACT < 34 0/7 WG group. Similar to hypoglycemia, all these results could be closely related to the significantly lower GAB in this group. Although the APGAR-5 values in the ACT ≥ 34 0/7 WG group were statistically significantly higher than in the other groups, this result loses significance as the median values are very close to each other and the minimum APGAR-5 score was already seven. In the light of the results of our study, it would be appropriate not to perform ACT in twins diagnosed with preterm labor unless birth is predicted before 34 0/7 WG. Given the known side effects and as yet unknown effects of corticosteroids, it is therefore very important to accurately identify women in whom the risk of preterm birth before 34 0/7 WG is unavoidable [ 39 , 40 ]. The main limitation of our study is its retrospective nature. In addition, intrauterine physiology and pharmacodynamics differ in multiple pregnancies, and the corticosteroid doses in our study, as in many studies, were the same standard doses used in singleton pregnancies. The major strength is that the study was conducted in a large tertiary referral hospital where the same algorithms were used for the diagnosis, management and follow-up of women with twin pregnancies. Conclusions In conclusion, late preterm ACT did not improve neonatal outcomes and was associated with a higher rate of neonatal hypoglycemia in late preterm twins. ACT < 34 0/7 WG, GAB and birthweight are independent protective factors that would predict CRO, CNO and NICU admission, while female gender is the independent protective factor for all factors except CNO. Further prospective randomized controlled trials are needed to better define the need, treatment protocol, dosing, efficacy, safety, and limitations of ACT in women with twin pregnancies at high risk for late preterm delivery. Abbreviations ACT Antenatal corticosteroid treatment APGAR Appearance, pulse, grimace activity and respiration CI Confidence Interval CNO Composite neonatal outcome CRO Composite respiratory outcome LMP Last menstrual period NICU Neonatal intensive care unit OR Odds ratio RDS Respiratory distress syndrome WG Weeks of gestation Declarations Ethics approval and consent to participate The Ethics Committee of University of Health Sciences Etlik Zübeyde Hanım Maternity and Women's Health Education and Research Hospital, Ankara, Turkey (March 16, 2022, 04/31) granted approval of the study and waived obtaining informed consent due to the retrospective nature of the study [41]. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed in the current study are available on request from the corresponding author on reasonable request. Competing Interests The authors have no relevant financial or non-financial interests to declare Funding The authors declare that they have received no funds, grants, or other support during the preparation of this manuscript. Authors’ contributions All authors contributed to the conception and design of the study. MLD participated in the project development, analysis strategy and took the lead in writing the manuscript. KYY contributed to data analysis and writing of the manuscript. SÖ, DK, AK, and ASK contributed to data collection. FBF provided writing assistance. SS and STS contributed to the statistical analysis and interpretation of the results. ŞÇ and YEÜ provided proofreading and language support. This version of the manuscript was submitted to the journal with the explicit consent of all authors. References Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, Wilson EC. Births: final data for 2009. Natl Vital Stat Rep. 2011;60(1):1–70. Moutquin JM. Classification and heterogeneity of preterm birth. BJOG. 2003. 10.1016/s1470-0328(03)00021-1 . Makrydimas G, Sotiriadis A. Prediction of preterm birth in twins. Best Pract Res Clin Obstet Gynaecol. 2014. 10.1016/j.bpobgyn.2013.11.007 . American College of Obstetricians and Gynecologists, & Society for Maternal-Fetal Medicine. Obstetric care consensus 6: periviable birth. Obstet Gynecol. 2017. 10.1097/AOG.0000000000002352 . Kemp MW, Schmidt AF, Jobe AH. Optimizing antenatal corticosteroid therapy. Semin Fetal Neonatal Med. 2019. 10.1016/j.siny.2019.05.003 . Wapner RJ. Antenatal corticosteroids for periviable birth. Semin Perinatol. 2013. 10.1053/j.semperi.2013.06.024 . 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. 10.1002/14651858.CD004454.pub3 . Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004. 10.1542/peds.114.2.372 . Kramer MS, Demissie K, Yang H, Platt RW, Sauvé R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA. 2000. 10.1001/jama.284.7.843 . Gázquez Serrano IM, Arroyos Plana A, Díaz Morales O, Herráiz Perea C, Holgueras Bragado A. Antenatal corticosteroid therapy and late preterm infant morbidity and mortality. Pediatr. 2014. 10.1016/j.anpedi.2014.01.026 . Gyamfi-Bannerman C, Zupancic JAF, Sandoval G, Grobman WA, Blackwell SC, Tita ATN, et al. Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2019. 10.1001/jamapediatrics.2019.0032 . Üstün N, Hocaoğlu M, Turgut A, Arslanoğlu S, Ovalı F. Does antenatal corticosteroid therapy improve neonatal outcomes in late preterm birth? J Matern Fetal Neonatal Med. 2022. 10.1080/14767058.2020.1808614 . Yinon Y, Haas J, Mazaki-Tovi S, Lapidot N, Mazkereth R, Hourvitz A, et al. Should patients with documented fetal lung immaturity after 34 weeks of gestation be treated with steroids? Am J Obstet Gynecol. 2012. 10.1016/j.ajog.2012.06.019 . Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995. 10.1016/0002-9378(95)90222-8 . McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020. 10.1002/14651858.CD004454.pub4 . Spong CY. Defining term pregnancy: recommendations from the Defining Term Pregnancy Workgroup. JAMA. 2013. 10.1001/jama.2013.6235 . American College of Obstetricians and Gynecologists. ACOG Committee Opinion 579. Definition of term pregnancy. Obstet Gynecol. 2013. 10.1097/01.AOG.0000437385.88715.4a . Stewart DL, Barfield WD, Committee On Fetus And Newborn. Updates on an At-Risk Population: Late-Preterm and Early-Term Infants. Pediatrics. 2019. 10.1542/peds.2019-2760 . Salomon LJ, Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T, Kagan KO et al. ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan [published correction appears in Ultrasound Obstet Gynecol. 2013;41(2):240]. Ultrasound Obstet Gynecol. 2013; 10.1002/uog.12342 . Committee on Obstetric Practice. Committee Opinion 713: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol. 2017. 10.1097/AOG.0000000000002237 . Multifetal Gestations. Twin, Triplet, and Higher-Order Multifetal Pregnancies: ACOG Practice Bulletin, Number 231. Obstet Gynecol. 2021. 10.1097/AOG.0000000000004397 . Graham ME, Jelin A, Hoon AH Jr, Floet W, Levey AM, Graham E. Assisted reproductive technology: Short- and long-term outcomes. Dev Med Child Neurol. 2023. 10.1111/dmcn.15332 . Blondel B, Kogan MD, Alexander GR, Dattani N, Kramer MS, Macfarlane A, et al. The impact of the increasing number of multiple births on the rates of preterm birth and low birthweight: an international study. Am J Public Health. 2002. 10.2105/ajph.92.8.1323 . Cheong-See F, Schuit E, Arroyo-Manzano D, Khalil A, Barrett J, Joseph KS, et al. Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis. BMJ. 2016. 10.1136/bmj.i4353 . Harrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med. 2016. 10.1016/j.siny.2015.12.007 . Son M, Miller ES. Predicting preterm birth: Cervical length and fetal fibronectin. Semin Perinatol. 2017. 10.1053/j.semperi.2017.08.002 . Tanaka K, Yamada K, Matsushima M, Izawa T, Furukawa S, Kobayashi Y, et al. Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using cervical length and granulocyte elastase. Taiwan J Obstet Gynecol. 2017. 10.1016/j.tjog.2016.07.014 . Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016. 10.1056/nejmoa1516783 . National Institutes of Health Consensus Development Panel. Antenatal corticosteroids revisited: repeat courses - National Institutes of Health Consensus Development Conference Statement, August 17–18, 2000. Obstet Gynecol. 2001; 10.1016/s0029-7844(01)01410-7 . Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012. 10.1016/j.jpeds.2012.05.022 . Barrett JF, Hannah ME, Hutton EK, Willan AR, Allen AC, Armson BA, et al. A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. N Engl J Med. 2013. 10.1056/nejmoa1214939 . Martinka D, Barrett J, Mei-Dan E, Zaltz A, Melamed N. Respiratory morbidity in late preterm twin infants. Arch Gynecol Obstet. 2019. 10.1007/s00404-019-05191-z . Ben-David A, Zlatkin R, Bookstein-Peretz S, Meyer R, Mazaki-Tovi S, Yinon Y. Does antenatal steroids treatment in twin pregnancies prior to late preterm birth reduce neonatal morbidity? Evidence from a retrospective cohort study. Arch Gynecol Obstet. 2020. 10.1007/s00404-020-05709-w . Kalhan S, Parimi P. Gluconeogenesis in the fetus and neonate. Semin Perinatol. 2000. 10.1053/sp.2000.6360 . Sifianou P, Thanou V, Karga H. Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation. J Pediatr Pharmacol Ther. 2015. 10.5863/1551-6776-20.2.138 . Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, Reijneveld SA, Bos AF. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics. 2012. 10.1542/peds.2012-0079 . Barondiot C, Morel O, Vieux R, Sery GA, Floriot M, Hascoet JM. Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good? Arch Pediatr. 2007. 10.1016/j.arcped.2007.03.025 . Carpenter JR, Jablonski KA, Koncinsky J, Varner MW, Gyamfi-Bannerman C, Joss-Moore LA. Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing. Reprod Sci. 2022. 10.1007/s43032-022-00859-5 . Jobe AH, Goldenberg RL. Antenatal corticosteroids: an assessment of anticipated benefits and potential risks. Am J Obstet Gynecol. 2018. 10.1016/j.ajog.2018.04.007 . Räikkönen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. JAMA. 2020. 10.1001/jama.2020.3937 . Higher Education Institutions Scientific Research and Publication Ethics Directive. (1981) https://www.yok.gov.tr/Sayfalar/Kurumsal/mevzuat/bilimsel-arastirma-ve-etik-yonetmeligi.aspx Accessed 27 December 2021. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 Mar, 2025 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 24 Dec, 2024 Reviews received at journal 19 Dec, 2024 Reviewers agreed at journal 05 Dec, 2024 Reviews received at journal 07 Jul, 2024 Reviewers agreed at journal 28 Jun, 2024 Reviewers invited by journal 28 Jun, 2024 Editor invited by journal 08 May, 2024 Submission checks completed at journal 03 May, 2024 Editor assigned by journal 03 May, 2024 First submitted to journal 01 May, 2024 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. 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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-4355844","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":300181360,"identity":"ecf181c4-2aaf-4348-9209-fe0325e8d012","order_by":0,"name":"Murat Levent 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groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4355844/v1/d32cc007102e553d9a219eed.jpeg"},{"id":79120621,"identity":"98629495-67c7-4322-bd99-a0fecb7b0dc5","added_by":"auto","created_at":"2025-03-24 16:10:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1554790,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4355844/v1/99b66b5a-042d-486b-b713-90c26c6cb57c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"(Is there a place for) antenatal corticosteroid treatment after 34 weeks of gestation in twin pregnancies when late preterm delivery is inevitable","fulltext":[{"header":"Background","content":"\u003cp\u003ePreterm birth, a major cause of neonatal morbidity and mortality, is any live birth before 37 weeks' gestation (WG). Preterm birth and its associated complications are more common in twins. According to the 2006 National Vital Statistics Report on birth data in the United States, 11.1% of singleton pregnancies and 61.9% of multiple pregnancies resulted in preterm birth [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe World Health Organization classifies preterm births as mild or late (34\u0026ndash;37 WG), moderate (32\u0026ndash;34 WG), very (28\u0026ndash;32 WG), and extreme (\u0026lt;\u0026thinsp;28 WG) preterm births [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Late preterm births account for 60% of all live twin births [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Studies on preterm birth have focused mainly on preterm infants born before 34 0/7 WG who are more likely to have severe complications of prematurity. Antenatal corticosteroid treatment (ACT) to induce fetal lung maturity is the most effective intervention to improve perinatal outcomes and has long been offered to women in whom preterm birth before 34 0/7 WG is inevitable [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Despite lower neonatal complication and mortality rates compared with preterm infants born at lower weeks, late preterm infants have a relatively higher risk of morbidity and mortality compared with term infants [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In some studies, ACT was found to be a significant factor in reducing neonatal respiratory complications in the late preterm period, while according to other studies, this reduction was not significant [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, there are no definitive data on the use of late preterm ACT in twin pregnancies where late preterm delivery is inevitable and ACT is not administered before 34 0/7 WG.\u003c/p\u003e \u003cp\u003eResearch is needed in this area to close the gap between knowledge and practice. In addition, there are still many questions about the side effects and benefits of ACT that need to be clarified. The aim of this study was to compare the neonatal outcomes of late preterm-born dichorionic-diamniotic twins who received ACT in the late preterm period or \u0026lt;\u0026thinsp;34 0/7 WG with those who did not.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDesign of the study\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study of women with dichorionic-diamniotic twins who had a late preterm birth between January 1, 2017, and December 31, 2021, at a large reference hospital providing tertiary care and medical training. The Ethics Committee of University of Health Sciences Etlik Lady Z\u0026uuml;beyde Maternity and Women's Health Education and Research Hospital, Ankara, Turkey, approved the conduct, protocol and procedures of the study (16.03.2022-04/31) and waived the requirement for written informed consent for participation due to the retrospective nature of the study. After approval, a retrospective review of the patients' medical records was carried out.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the study population, selection of participants and definitions\u003c/h2\u003e \u003cp\u003eTwins with intrauterine demise of one or both fetuses, twins other than dichorionic-diamniotic, singletons and higher order pregnancies were not included. Pregnancies with fetal factors such as growth restriction, congenital infections, malformations and genetic abnormalities, pregnant women with diabetes, prelabor rupture of membranes, missing data and those who had received more than one course of ACT, including a rescue course, and deliveries within 48 hours after the first dose of the standard ACT regimen were excluded. All pregnant women selected for participation had reassuring fetal well-being of both fetuses at hospital admission, defined as pregnancies with a maximum vertical amniotic pocket of \u0026ge;\u0026thinsp;2 cm and a reactive non-stress test. In addition, women who had reassuring antepartum fetal well-being at the time of hospital admission but required emergency delivery due to non-reassuring intrapartum well-being were included, while patients who had already been diagnosed with antepartum fetal distress at the time of admission were not included. During the five-year period covered by this retrospective study, a total of 69792 (100%) live births were recorded. Of these, 1462 (2.09%) were twins, 1232 (1.76%) were dichorionic-diamniotic twins, of which 580 were born late preterm. According to the inclusion criteria, a total of 352 subjects (704 newborns) were eligible, of whom 76 (152 newborns) received ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG; 67 (134 newborns) received late preterm ACT, and 209 (418 newborns) did not receive ACT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAny live birth between 34 0/7 and 36 6/7 WG is designated as \"late preterm\" by the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the National Center for Health Statistics [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Gestational age was calculated from the first day of the last menstrual period (LMP) and confirmed by sonographic dating. If the two calculations differed by \u0026le;\u0026thinsp;7 days, gestational age was determined based on LMP; otherwise, sonographic dating was used. Sonographic findings that indicated dichorionicity were separate placental masses, different fetal sexes, and the appearance of the intertwin membrane as a \"lambda\" or \"twin-peak\" sign [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eACT was defined as delivery at least 48 hours after the first dose of the standard regimen, which involves the administration of two intramuscular injections of 12 mg betamethasone 24 hours apart. The indication for ACT was anticipated preterm delivery in women less than 37 0/7 WG, who had not yet been treated with antenatal corticosteroids during the current pregnancy. Rescue-dose corticosteroid treatment was defined as the administration of a single repeat course of antenatal corticosteroids in women with \u0026lt;\u0026thinsp;34 0/7 WG who are at risk of preterm delivery within seven days and who had received ACT more than 14 days ago [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe presence of uterine contractions of sufficient frequency, amplitude and duration to cause progressive cervical effacement and/or dilation between 34 0/7 and 36 6/7 WG was defined as late preterm labor. The mode of delivery was classified as either vaginal or cesarean section. If an emergency cesarean section was required to deliver the second twin after vaginal delivery of the first twin, delivery of the first fetus was classified as vaginal delivery, while delivery of the second twin was classified as cesarean section.\u003c/p\u003e \u003cp\u003eCesarean deliveries that were performed immediately after the decision to deliver without waiting for at least 6 hours of fasting, which is required for safe anesthesia, were termed emergency cesarean deliveries, while all others were defined as elective cesarean deliveries. The general indications for cesarean delivery were: previous cesarean delivery (129), maternal wish (93), malpresentation (58), fetal distress (20), preeclampsia with severe features (10), placental abruption (8), vaginismus (6), obstructed labor (6), chord prolapse and chord presentation (6), dystocia (5), and placenta previa (3), ordered from most common to least common.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData acquisition\u003c/h2\u003e \u003cp\u003e All patient demographics, clinical characteristics and neonatal outcomes were obtained from the hospital database and medical records and then compared between the three groups. Because no neonatal death was observed during the study period and the incidence of serious adverse neonatal events in late preterm births is relatively low, we examined composite outcome measures that combine different components of neonatal outcome to draw conclusions. In addition, there were no serious neonatal adverse events, including sepsis, APGAR-5 (Appearance, Pulse, Grimace, Activity, and Respiration scores at fifth minute) scores of \u0026lt;\u0026thinsp;7, meconium aspiration syndrome, intracranial hemorrhage, and necrotizing enterocolitis. Therefore, the primary neonatal outcomes and measures were defined as composite neonatal outcome (CNO) consisting of any of the following features that may lead to severe neonatal morbidity: APGAR-5 score, admission to the neonatal intensive care unit (NICU), hypoglycemia, hyperbilirubinemia requiring phototherapy, and any of the following components of the composite respiratory outcome (CRO), including transient tachypnea of the newborn, respiratory distress syndrome (RDS), need for mechanical ventilation, and continuous positive airway pressure therapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyzes were performed using R Statistical Software (version 2021.09.4\u0026thinsp;+\u0026thinsp;403.pro3; R Foundation for Statistical Computing, Vienna, Austria). Kolmogrov-Simirnov or Shapiro-Wilk tests were used to determine normality. Descriptive analyzes were performed using means and standard deviations for the normally distributed variable \"birthweight\". One-way ANOVA was used to compare this parameter between groups. Levene's test was used to assess the homogeneity of variance. For numerical data that were not normally distributed, descriptive analyzes were performed using medians and quartiles (Q1-Q3). Kruskal-Wallis tests were performed to compare these parameters between groups. The Mann-Whitney U test was performed to test the significance of pairwise differences, using the Bonferroni correction to adjust for multiple comparisons. Descriptive analyzes were performed for categorical variables using frequency and percentage. Relationships between categorical variables were analyzed using the chi-square test or Fisher's exact test (if the assumptions of the chi-square test do not apply due to low expected cell counts). Potential factors identified in the univariate analyzes were entered into a binary logistic regression analysis to identify additional independent predictors of CRO and CNO. The Hosmer-Lemeshow goodness-of-fit statistic was used to assess model fit. An overall type I error level of 5% was used to derive statistical significance. A p-value of less than 0.05 was considered a statistically significant result.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 352 participants (704 newborns) with dichorionic-diamniotic twin pregnancies who had a late preterm delivery were included. Of these, 209 women (418 newborns) did not receive ACT (control group), while 76 (152 newborns) and 67 (134 newborns) women received ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG and \u0026ge;\u0026thinsp;34 0/7 WG, respectively. Demographic and clinical characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Maternal age, number of previous miscarriages and cesarean deliveries, history of preterm delivery, and hypertensive disorders in the current pregnancy were similar. The median body mass index, gravidity, and parity of women in group 1 were significantly lower than those in the control group [28.5 (26\u0026ndash;32) vs. 30 (27\u0026ndash;33), p\u0026thinsp;=\u0026thinsp;0.01; 2 (1\u0026ndash;3) vs. 3 (2\u0026ndash;4), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, and 1 (0\u0026ndash;1) vs. 1 (1\u0026ndash;2), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively]. An analysis of birth and neonatal characteristics and outcomes is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. There were no significant differences between the groups with respect to the primary outcomes. An analysis after Bonferroni correction of the neonatal characteristics and early neonatal outcomes of the study groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Multivariate logistic regression analysis identified gestational age at birth (GAB), female gender, birthweight, and early preterm ACT as independent protective factors predicting CRO [odds ratio (OR)\u0026thinsp;=\u0026thinsp;0.74, 95% confidence interval (CI) 0.57\u0026ndash;0.95, p\u0026thinsp;=\u0026thinsp;0.01; OR\u0026thinsp;=\u0026thinsp;0.58, 95% CI 0.38\u0026ndash;0.87, p\u0026thinsp;=\u0026thinsp;0.01; OR\u0026thinsp;=\u0026thinsp;0.83, 95% CI 0.77\u0026ndash;0.90, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, and OR\u0026thinsp;=\u0026thinsp;0.46, 95% CI 0.27\u0026ndash;0.81, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, respectively], and NICU admission (OR\u0026thinsp;=\u0026thinsp;0.58, 95% CI 0.47\u0026ndash;0.72, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; OR\u0026thinsp;=\u0026thinsp;0.69, 95% CI 0.48\u0026ndash;0.98, p\u0026thinsp;=\u0026thinsp;0.04, OR\u0026thinsp;=\u0026thinsp;0.85, 95% CI 0.80\u0026ndash;0.91, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, and OR\u0026thinsp;=\u0026thinsp;0.56, 95% CI 0.35\u0026ndash;0.90, p\u0026thinsp;=\u0026thinsp;0.01, respectively). On the other hand, GAB, birthweight, and early preterm ACT were also independent protective factors predictive of CNO (OR\u0026thinsp;=\u0026thinsp;0.66, 95% CI 0.53\u0026ndash;0.83, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;0.83, 95% CI 0.78\u0026ndash;0.89, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, and OR\u0026thinsp;=\u0026thinsp;0.60, 95% CI 0.37\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.03, respectively) while GAB and birthweight were the independent protective factors for hypoglycemia in multivariate logistic regression analysis (OR\u0026thinsp;=\u0026thinsp;0.41, 95% CI 0.19\u0026ndash;0.87, p\u0026thinsp;=\u0026thinsp;0.02, and OR\u0026thinsp;=\u0026thinsp;0.58, 95% CI 0.47\u0026ndash;0.72, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In this context, administration of ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 WG, each 1-week increase in GAB, female gender, and each 100-gram increase in birthweight provided 2.1-, 1.3-, 1.7-, and 1.2-fold protection against adverse results of CRO; 1.6-, 1.7-, 1.4-, and 1.1-fold protection against admission to the NICU, respectively. In addition, administration of ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 WG, each 1-week increase in GAB, and each 100-gram increase in birthweight provided 1.8-, 1.5-, and 1.2-fold protection from adverse results of CNO, respectively, whereas each 1-week increase in GAB and each 100-gram increase in birthweight contributed to 2.4- and 1.7-fold protection from hypoglycemia, respectively.\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\u003eDemographic and basic clinical characteristics of the participants\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo ACT\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;34 WG ACT\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;34 WG ACT\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;67)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;352)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal age (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (26\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (24\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (26\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29 (26\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (27\u0026ndash;33)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.5 (26\u0026ndash;32)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (28\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (27\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGravida (number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eParity (number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0\u0026ndash;1)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMiscarriage (number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrevious C/S (number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0-0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of previous PTD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertensive disorders\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eACT, Antenatal corticosteroid treatment; BMI, Body mass index; C/S, Cesarean section; kg/m\u003csup\u003e2\u003c/sup\u003e, Kilograms per square meter; PTD, Preterm delivery; WG, Weeks\u0026rsquo; gestation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are expressed as median (Q1-Q3), or number (percentage) where appropriate. A p value of \u0026lt;\u0026thinsp;0.05 indicates a significant difference. Statistically significant p-values are in bold. Superscripted lowercase letters indicates groups with statistically significant difference, while superscripted asterisk indicates corrected p-values with Bonferroni correction.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eBirth characteristics and early outcomes of newborns\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo ACT\u003c/p\u003e \u003cp\u003e(n:418)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;34 WG ACT\u003c/p\u003e \u003cp\u003e(n:152)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;34 WG ACT\u003c/p\u003e \u003cp\u003e(n:134)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n:704)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGAB (WG)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (35.2\u0026ndash;36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.4 (34\u0026ndash;35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.1 (34.5\u0026ndash;35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.4 (34.6\u0026ndash;36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAPGAR-5 score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (9\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (9\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (9\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (9\u0026thinsp;\u0026minus;\u0026thinsp;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirthweight (grams)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2419\u0026thinsp;\u0026plusmn;\u0026thinsp;347.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2199\u0026thinsp;\u0026plusmn;\u0026thinsp;321.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2363\u0026thinsp;\u0026plusmn;\u0026thinsp;268.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2361\u0026thinsp;\u0026plusmn;\u0026thinsp;356.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDelivery mode\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVaginal\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCesarean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e406 (57.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e134 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e688 (97.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCesarean delivery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUrgent\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (31.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e180 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eElective\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300 (73.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (68.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106 (79.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e508 (73.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale gender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e221 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (49.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e359 (51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNICU admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (49.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e308 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypoglycemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e144 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCPAP therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTTN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRDS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeed for MV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e176 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCNO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146 (34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e268 (38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eACT, Antenatal corticosteroid treatment; APGAR, Appearance, pulse, grimace, activity, and respiration scores at fifth minute; CNO, Composite neonatal outcome; CPAP, Continuous positive airway pressure; CRO, Composite respiratory outcome; GAB, Gestational age at birth; HRP, Hyperbilirubinemia requiring phototherapy; MV, Mechanical ventilation; NICU, Neonatal intensive care unit; RDS, Respiratory distress syndrome; TTN, Transient tachypnea of the newborn; WG, Weeks\u0026rsquo; gestation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (Q1-Q3), or number (percentage) where appropriate. A p value of \u0026lt;\u0026thinsp;0.05 indicates a significant difference. Statistically significant p-values are in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eAnalysis after Bonferroni correction of neonatal characteristics and early neonatal outcomes showing statistically significant differences\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=\"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=\"char\" char=\".\" 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\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo ACT (n\u0026thinsp;=\u0026thinsp;418)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;34 WG ACT (n\u0026thinsp;=\u0026thinsp;152)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;34 WG ACT\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;134)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eNo ACT (n\u0026thinsp;=\u0026thinsp;418)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBirthweight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAPGAR-5 score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHypoglycemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCPAP therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMechanical ventilation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNICU admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;34 WG ACT (n\u0026thinsp;=\u0026thinsp;152)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBirthweight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAPGAR-5 score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHypoglycemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCPAP therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMechanical ventilation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNICU admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;34 WG ACT\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;134)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBirthweight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAPGAR-5 score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHypoglycemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCPAP therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMechanical ventilation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNICU admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eACT, Antenatal corticosteroid treatment; APGAR-5, Appearance, pulse, grimace, activity, and respiration scores at fifth minute; CPAP, Continuous positive airway pressure; NICU, Neonatal intensive care unit; WG, Weeks\u0026rsquo; gestation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eP values are given with Bonferroni correction. A p value of \u0026lt;\u0026thinsp;0.05 indicates a significant difference. Statistically significant p-values are in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic regression analysis of neonatal variables for adverse neonatal outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCRO\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCNO\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eHypoglycemia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eNICU admission\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95%CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eOR (95%CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGAB (WG)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.74 (0.57\u0026ndash;0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.66 (0.53\u0026ndash;0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.41 (0.19\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.58 (0.47\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale gender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.58 (0.38\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69 (0.48\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.12 (0.41\u0026ndash;3.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.69 (0.48\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirthweight (100 grams)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.77\u0026ndash;0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.83 (0.78\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.58 (0.47\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.85 (0.80\u0026ndash;0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;34 WG ACT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.46 (0.27\u0026ndash;0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60 (0.37\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.08 (0.34\u0026ndash;3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.56 (0.35\u0026ndash;0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;34 WG ACT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.81 (0.50\u0026ndash;1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94 (0.61\u0026ndash;1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.96 (0.27\u0026ndash;3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.97 (0.65\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eACT, Antenatal corticosteroid treatment; CI, Confidence interval; CPAP, Continuous positive airway pressure; CNO, Composite neonatal outcome; CRO, Composite respiratory outcome; GAB, Gestational age at birth; NICU, Neonatal intensive care unit; OR, Odds ratio; WG, Weeks\u0026rsquo; gestation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eThe unit of change in birthweight was given as 100-grams because the effect of a 1-gram change would be extremely small. A p value of \u0026lt;\u0026thinsp;0.05 indicates a significant difference. Statistically significant p-values are in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe principal findings of the present study were: In women with dichorionic-diamniotic twin pregnancies delivered in the late preterm period, (1) ACT was not significantly associated with a reduction in adverse neonatal complications regardless of the timing of exposure during pregnancy and was significantly associated with an increased rate of neonatal hypoglycemia, particularly in women treated before 34 0/7 WG; (2) Rates of admission to NICU were significantly higher in the corticosteroid-exposed groups regardless of the timing of exposure during pregnancy; (3) Neonatal birthweight was significantly lower in the ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG group; (4) GAB, birthweight, and early preterm ACT were independent protective factors predicting CRO, CNO, and NICU admission.\u003c/p\u003e \u003cp\u003eIn recent decades, various factors such as financial security, career priority, and lack of emotional and psychological readiness have discouraged women from becoming mothers at a young age. This trend has led to more and more women trying to become pregnant at an older age, when fertility begins to decline. Therefore, the number of pregnancies conceived using assisted reproductive methods is increasing, and as an inevitable consequence, the number of multiple pregnancies is also gradually increasing worldwide [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple pregnancies are associated with an increased risk of pregnancy complications, particularly spontaneous abortions, preterm birth, preeclampsia, and maternal hemorrhage [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. On the other hand, preterm birth is the leading cause of infant death, and the degree of prematurity is the most important determinant of morbidity and mortality [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, strategies to predict and prevent preterm birth and treatment approaches to reduce neonatal morbidity and mortality in populations at high risk of preterm birth are essential. In this context, fibronectin and, more commonly, sonographic measurement of cervical length have been used to predict preterm birth in singleton pregnancies [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In a recent study, the combination of sonographic measurement of cervical length and determination of granulocyte elastase in cervical secretions proved to be a useful tool for predicting preterm birth in asymptomatic twin pregnancies [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdministration of corticosteroids to women in whom preterm birth is inevitable is the most important antenatal intervention to reduce adverse neonatal outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. ACT is recommended between 24 0/7 and 33 6/7 WG and may even be considered between 23 0/7 and 24 0/7 WG in women with an inevitable preterm birth within seven days, including pregnancies with rupture of membranes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Recent data suggest that ACT may be beneficial in women at risk of late preterm delivery [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The risk of neonatal sepsis, chorioamnionitis, or endometritis was not increased, but neonatal hypoglycemia occurred more frequently when ACT was administered in the late preterm period [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn the other hand, there are vulnerable pregnancy populations, including twins and multiple pregnancies, where the effects of ACT have not yet been adequately studied. As there is a need for studies that address the gaps and practice for the use of late preterm ACT in women with dichorionic-diamniotic twins who are at high risk for inevitable late preterm birth, we conducted this article. Furthermore, to our knowledge, this article is the first study to examine the effects of ACT in such pregnancies, comparing whether they were treated before or after 34 0/7 WG. A study conducted by Gyamfi-Bannerman et al. found that late preterm corticosteroid therapy was associated with improved respiratory morbidity in late preterm infants [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In another study by Martinka et al, which was designed as a secondary analysis of an earlier randomized controlled trial in twin pregnancies (Twin Delivery Study) and in which the analysis was restricted to women who had delivered in the late preterm period, the rates of improvement in composite respiratory outcomes were comparable to the corresponding rates in the study by Gyamfi-Bannerman et al. The authors concluded that the benefit-risk ratio of ACT with respect to neonatal respiratory morbidity in twin pregnancies at risk of late preterm delivery is expected to be similar to that in singletons [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, this conclusion is limited because it is a theoretically based indirect assumption and the pharmacodynamics of corticosteroids are different in singleton and twin pregnancies. Twins develop in a different environment than singletons and face many difficulties during the intrauterine period, such as competition for maternal nutrients, limited space and smaller placentas or even smaller placental proportions in the case of monochorionicity.\u003c/p\u003e \u003cp\u003eIn a study by Ben-David et al. similar results were obtained as in our study regarding neonatal outcomes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. However, they compared only the women exposed to ACT during late preterm period with the control group, whereas the comparison in our study was made by dividing the treatment groups according to whether ACT was administered before or \u0026ge;\u0026thinsp;34 0/7 WG. In addition, a more homogeneous distribution was achieved in our study by excluding diabetic pregnancies and twins other than dichorionic-diamniotic. Corticosteroid treatment is a double-edged sword because, although it reduces the risk of respiratory neonatal morbidity and mortality, steroid-induced maternal hyperglycemia can also lead to other neonatal outcomes, particularly neonatal hypoglycemia, especially in preterm newborns. Since maternal glucose supply is interrupted immediately after birth, the newborn must initiate endogenous glucose production to maintain euglycemia. This adaptation process begins with a decrease in neonatal insulin and an increase in glucagon shortly after birth [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This mechanism may be disrupted in hyperinsulinemic preterm newborns exposed to ACT, and persistent neonatal hypoglycemia can lead to serious consequences [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Fortunately, maternal hyperglycemia induced by corticosteroids lasts only a few days [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. On the other hand, a recent study by Carpenter et al. found an increase in granulocytes and a decrease in lymphocytes in the umbilical cord blood of fetuses whose mothers had received betamethasone treatment during late preterm period [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. These alterations in the white blood cells can have negative consequences for the newborn, which tries to adapt to the external environment and fight possible infectious agents after the protective maternal immunity has been extinguished at birth.\u003c/p\u003e \u003cp\u003eIn our study, neonatal hypoglycemia rates were significantly higher in the ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG group and were observed more frequently in the ACT\u0026thinsp;\u0026ge;\u0026thinsp;34 0/7 WG group than in the unexposed group. On the other hand, it should be considered that this result could be closely related to the significantly higher GAB in the control group, in which the protective mechanisms against hypoglycemia function better than in those born at earlier weeks. Mean birthweight was also significantly lower in the ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG group than in the control group, but there was no significant difference between the ACT\u0026thinsp;\u0026ge;\u0026thinsp;34 0/7 WG group and the control group. In addition, the rates of NICU admission and need for mechanical ventilation were higher in the ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG group. Similar to hypoglycemia, all these results could be closely related to the significantly lower GAB in this group. Although the APGAR-5 values in the ACT\u0026thinsp;\u0026ge;\u0026thinsp;34 0/7 WG group were statistically significantly higher than in the other groups, this result loses significance as the median values are very close to each other and the minimum APGAR-5 score was already seven.\u003c/p\u003e \u003cp\u003eIn the light of the results of our study, it would be appropriate not to perform ACT in twins diagnosed with preterm labor unless birth is predicted before 34 0/7 WG. Given the known side effects and as yet unknown effects of corticosteroids, it is therefore very important to accurately identify women in whom the risk of preterm birth before 34 0/7 WG is unavoidable [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The main limitation of our study is its retrospective nature. In addition, intrauterine physiology and pharmacodynamics differ in multiple pregnancies, and the corticosteroid doses in our study, as in many studies, were the same standard doses used in singleton pregnancies. The major strength is that the study was conducted in a large tertiary referral hospital where the same algorithms were used for the diagnosis, management and follow-up of women with twin pregnancies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, late preterm ACT did not improve neonatal outcomes and was associated with a higher rate of neonatal hypoglycemia in late preterm twins. ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 0/7 WG, GAB and birthweight are independent protective factors that would predict CRO, CNO and NICU admission, while female gender is the independent protective factor for all factors except CNO. Further prospective randomized controlled trials are needed to better define the need, treatment protocol, dosing, efficacy, safety, and limitations of ACT in women with twin pregnancies at high risk for late preterm delivery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntenatal corticosteroid treatment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPGAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAppearance, pulse, grimace activity and respiration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComposite neonatal outcome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComposite respiratory outcome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLast menstrual period\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRespiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWeeks of gestation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of University of Health Sciences Etlik Z\u0026uuml;beyde Hanım Maternity and Women\u0026apos;s Health Education and Research Hospital, Ankara, Turkey (March 16, 2022, 04/31) granted approval of the study and waived obtaining informed consent due to the retrospective nature of the study [41].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed in the current study are available on request from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have received no funds, grants, or other support during the preparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the conception and design of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMLD participated in the project development, analysis strategy and took the lead in writing the manuscript. KYY contributed to data analysis and writing of the manuscript. S\u0026Ouml;, DK, AK, and ASK contributed to data collection. FBF provided writing assistance. SS and STS contributed to the statistical analysis and interpretation of the results. Ş\u0026Ccedil; and YE\u0026Uuml; provided proofreading and language support. This version of the manuscript was submitted to the journal with the explicit consent of all authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMartin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, Wilson EC. Births: final data for 2009. Natl Vital Stat Rep. 2011;60(1):1\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoutquin JM. Classification and heterogeneity of preterm birth. BJOG. 2003. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1470-0328(03)00021-1\u003c/span\u003e\u003cspan address=\"10.1016/s1470-0328(03)00021-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakrydimas G, Sotiriadis A. Prediction of preterm birth in twins. Best Pract Res Clin Obstet Gynaecol. 2014. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bpobgyn.2013.11.007\u003c/span\u003e\u003cspan address=\"10.1016/j.bpobgyn.2013.11.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican College of Obstetricians and Gynecologists, \u0026amp; Society for Maternal-Fetal Medicine. Obstetric care consensus 6: periviable birth. Obstet Gynecol. 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0000000000002352\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000002352\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKemp MW, Schmidt AF, Jobe AH. Optimizing antenatal corticosteroid therapy. Semin Fetal Neonatal Med. 2019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.siny.2019.05.003\u003c/span\u003e\u003cspan address=\"10.1016/j.siny.2019.05.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWapner RJ. Antenatal corticosteroids for periviable birth. Semin Perinatol. 2013. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.semperi.2013.06.024\u003c/span\u003e\u003cspan address=\"10.1053/j.semperi.2013.06.024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD004454.pub3\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD004454.pub3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.114.2.372\u003c/span\u003e\u003cspan address=\"10.1542/peds.114.2.372\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKramer MS, Demissie K, Yang H, Platt RW, Sauv\u0026eacute; R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA. 2000. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.284.7.843\u003c/span\u003e\u003cspan address=\"10.1001/jama.284.7.843\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026aacute;zquez Serrano IM, Arroyos Plana A, D\u0026iacute;az Morales O, Herr\u0026aacute;iz Perea C, Holgueras Bragado A. Antenatal corticosteroid therapy and late preterm infant morbidity and mortality. Pediatr. 2014. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.anpedi.2014.01.026\u003c/span\u003e\u003cspan address=\"10.1016/j.anpedi.2014.01.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGyamfi-Bannerman C, Zupancic JAF, Sandoval G, Grobman WA, Blackwell SC, Tita ATN, et al. Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamapediatrics.2019.0032\u003c/span\u003e\u003cspan address=\"10.1001/jamapediatrics.2019.0032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Uuml;st\u0026uuml;n N, Hocaoğlu M, Turgut A, Arslanoğlu S, Ovalı F. Does antenatal corticosteroid therapy improve neonatal outcomes in late preterm birth? J Matern Fetal Neonatal Med. 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/14767058.2020.1808614\u003c/span\u003e\u003cspan address=\"10.1080/14767058.2020.1808614\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYinon Y, Haas J, Mazaki-Tovi S, Lapidot N, Mazkereth R, Hourvitz A, et al. Should patients with documented fetal lung immaturity after 34 weeks of gestation be treated with steroids? Am J Obstet Gynecol. 2012. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajog.2012.06.019\u003c/span\u003e\u003cspan address=\"10.1016/j.ajog.2012.06.019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0002-9378(95)90222-8\u003c/span\u003e\u003cspan address=\"10.1016/0002-9378(95)90222-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD004454.pub4\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD004454.pub4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpong CY. Defining term pregnancy: recommendations from the Defining Term Pregnancy Workgroup. JAMA. 2013. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2013.6235\u003c/span\u003e\u003cspan address=\"10.1001/jama.2013.6235\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican College of Obstetricians and Gynecologists. ACOG Committee Opinion 579. Definition of term pregnancy. Obstet Gynecol. 2013. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/01.AOG.0000437385.88715.4a\u003c/span\u003e\u003cspan address=\"10.1097/01.AOG.0000437385.88715.4a\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStewart DL, Barfield WD, Committee On Fetus And Newborn. Updates on an At-Risk Population: Late-Preterm and Early-Term Infants. Pediatrics. 2019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.2019-2760\u003c/span\u003e\u003cspan address=\"10.1542/peds.2019-2760\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalomon LJ, Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T, Kagan KO et al. ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan [published correction appears in Ultrasound Obstet Gynecol. 2013;41(2):240]. Ultrasound Obstet Gynecol. 2013; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/uog.12342\u003c/span\u003e\u003cspan address=\"10.1002/uog.12342\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCommittee on Obstetric Practice. Committee Opinion 713: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol. 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0000000000002237\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000002237\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMultifetal Gestations. Twin, Triplet, and Higher-Order Multifetal Pregnancies: ACOG Practice Bulletin, Number 231. Obstet Gynecol. 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0000000000004397\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000004397\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraham ME, Jelin A, Hoon AH Jr, Floet W, Levey AM, Graham E. Assisted reproductive technology: Short- and long-term outcomes. Dev Med Child Neurol. 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/dmcn.15332\u003c/span\u003e\u003cspan address=\"10.1111/dmcn.15332\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlondel B, Kogan MD, Alexander GR, Dattani N, Kramer MS, Macfarlane A, et al. The impact of the increasing number of multiple births on the rates of preterm birth and low birthweight: an international study. Am J Public Health. 2002. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2105/ajph.92.8.1323\u003c/span\u003e\u003cspan address=\"10.2105/ajph.92.8.1323\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheong-See F, Schuit E, Arroyo-Manzano D, Khalil A, Barrett J, Joseph KS, et al. Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis. BMJ. 2016. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.i4353\u003c/span\u003e\u003cspan address=\"10.1136/bmj.i4353\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med. 2016. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.siny.2015.12.007\u003c/span\u003e\u003cspan address=\"10.1016/j.siny.2015.12.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSon M, Miller ES. Predicting preterm birth: Cervical length and fetal fibronectin. Semin Perinatol. 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.semperi.2017.08.002\u003c/span\u003e\u003cspan address=\"10.1053/j.semperi.2017.08.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka K, Yamada K, Matsushima M, Izawa T, Furukawa S, Kobayashi Y, et al. Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using cervical length and granulocyte elastase. Taiwan J Obstet Gynecol. 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.tjog.2016.07.014\u003c/span\u003e\u003cspan address=\"10.1016/j.tjog.2016.07.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/nejmoa1516783\u003c/span\u003e\u003cspan address=\"10.1056/nejmoa1516783\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Institutes of Health Consensus Development Panel. Antenatal corticosteroids revisited: repeat courses - National Institutes of Health Consensus Development Conference Statement, August 17\u0026ndash;18, 2000. Obstet Gynecol. 2001; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0029-7844(01)01410-7\u003c/span\u003e\u003cspan address=\"10.1016/s0029-7844(01)01410-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpeds.2012.05.022\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2012.05.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarrett JF, Hannah ME, Hutton EK, Willan AR, Allen AC, Armson BA, et al. A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. N Engl J Med. 2013. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/nejmoa1214939\u003c/span\u003e\u003cspan address=\"10.1056/nejmoa1214939\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartinka D, Barrett J, Mei-Dan E, Zaltz A, Melamed N. Respiratory morbidity in late preterm twin infants. Arch Gynecol Obstet. 2019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-019-05191-z\u003c/span\u003e\u003cspan address=\"10.1007/s00404-019-05191-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBen-David A, Zlatkin R, Bookstein-Peretz S, Meyer R, Mazaki-Tovi S, Yinon Y. Does antenatal steroids treatment in twin pregnancies prior to late preterm birth reduce neonatal morbidity? Evidence from a retrospective cohort study. Arch Gynecol Obstet. 2020. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-020-05709-w\u003c/span\u003e\u003cspan address=\"10.1007/s00404-020-05709-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalhan S, Parimi P. Gluconeogenesis in the fetus and neonate. Semin Perinatol. 2000. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/sp.2000.6360\u003c/span\u003e\u003cspan address=\"10.1053/sp.2000.6360\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSifianou P, Thanou V, Karga H. Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation. J Pediatr Pharmacol Ther. 2015. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5863/1551-6776-20.2.138\u003c/span\u003e\u003cspan address=\"10.5863/1551-6776-20.2.138\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKerstjens JM, Bocca-Tjeertes IF, de Winter AF, Reijneveld SA, Bos AF. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics. 2012. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.2012-0079\u003c/span\u003e\u003cspan address=\"10.1542/peds.2012-0079\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarondiot C, Morel O, Vieux R, Sery GA, Floriot M, Hascoet JM. Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good? Arch Pediatr. 2007. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.arcped.2007.03.025\u003c/span\u003e\u003cspan address=\"10.1016/j.arcped.2007.03.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarpenter JR, Jablonski KA, Koncinsky J, Varner MW, Gyamfi-Bannerman C, Joss-Moore LA. Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing. Reprod Sci. 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s43032-022-00859-5\u003c/span\u003e\u003cspan address=\"10.1007/s43032-022-00859-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJobe AH, Goldenberg RL. Antenatal corticosteroids: an assessment of anticipated benefits and potential risks. Am J Obstet Gynecol. 2018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajog.2018.04.007\u003c/span\u003e\u003cspan address=\"10.1016/j.ajog.2018.04.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026auml;ikk\u0026ouml;nen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. JAMA. 2020. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2020.3937\u003c/span\u003e\u003cspan address=\"10.1001/jama.2020.3937\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHigher Education Institutions Scientific Research and Publication Ethics Directive. (1981) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.yok.gov.tr/Sayfalar/Kurumsal/mevzuat/bilimsel-arastirma-ve-etik-yonetmeligi.aspx\u003c/span\u003e\u003cspan address=\"https://www.yok.gov.tr/Sayfalar/Kurumsal/mevzuat/bilimsel-arastirma-ve-etik-yonetmeligi.aspx\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e Accessed 27 December 2021.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Antenatal corticosteroids, betamethasone, hypoglycemia, late preterm, outcome, twin pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-4355844/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4355844/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTwins are associated with an increased risk of premature birth, a major cause of neonatal morbidity and mortality. Antenatal corticosteroid treatment (ACT) is the main intervention to improve neonatal outcomes in unavoidable preterm births. Our aim was to investigate the association between neonatal outcome and ACT in twin pregnancies with late preterm birth, where the effects of corticosteroids have not been adequately studied.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWomen with dichorionic-diamniotic twins who had a late preterm birth between 2017 and 2021 at a large referral hospital providing tertiary care and medical training were retrospectively analyzed. Women who met the inclusion criteria were divided into three groups: No ACT (n\u0026thinsp;=\u0026thinsp;209), ACT\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks' gestation (n\u0026thinsp;=\u0026thinsp;76) and ACT\u0026thinsp;\u0026ge;\u0026thinsp;34 weeks' gestation (n\u0026thinsp;=\u0026thinsp;67). The groups were compared with regard to adverse neonatal complications. Primary outcome measures were composite respiratory and composite neonatal outcomes. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eComposite respiratory and composite neonatal outcomes which did not differ significantly between groups. Gestational age at birth, birthweight and ACT before 34 weeks' gestation were independent protective factors for composite respiratory outcome, composite neonatal outcome and admission to the neonatal intensive care unit. Female gender was an independent protective factor for both composite respiratory outcome and neonatal intensive care unit admission, while gestational age at birth and birthweight were independent protective factors for hypoglycemia.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eACT at or after 34 weeks' gestation did not improve neonatal outcomes in dichorionic-diamniotic twins born late preterm and was associated with a higher rate of neonatal hypoglycemia than those not treated with corticosteroids.\u003c/p\u003e","manuscriptTitle":"(Is there a place for) antenatal corticosteroid treatment after 34 weeks of gestation in twin pregnancies when late preterm delivery is inevitable","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-13 15:43:07","doi":"10.21203/rs.3.rs-4355844/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-24T08:48:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-19T16:56:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60665295767732313295962733268634433026","date":"2024-12-05T16:57:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-07T19:59:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275941570234225765517525789321266127786","date":"2024-06-28T11:29:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-28T10:36:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-08T12:13:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-04T02:25:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-04T02:25:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2024-05-01T19:53:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"29e1604d-95d9-4e1e-b0e5-8b9dcfe3d9a6","owner":[],"postedDate":"May 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-24T16:05:50+00:00","versionOfRecord":{"articleIdentity":"rs-4355844","link":"https://doi.org/10.1186/s12884-025-07398-2","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2025-03-19 15:57:39","publishedOnDateReadable":"March 19th, 2025"},"versionCreatedAt":"2024-05-13 15:43:07","video":"","vorDoi":"10.1186/s12884-025-07398-2","vorDoiUrl":"https://doi.org/10.1186/s12884-025-07398-2","workflowStages":[]},"version":"v1","identity":"rs-4355844","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4355844","identity":"rs-4355844","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}