Antenatal Corticosteroids in Diabetic Pregnancies and Outcomes of Very Preterm Infants: a National Multicenter Cohort Study

Antenatal Corticosteroids in Diabetic Pregnancies and Outcomes of Very Preterm Infants: a National Multicenter Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Antenatal Corticosteroids in Diabetic Pregnancies and Outcomes of Very Preterm Infants: a National Multicenter Cohort Study Xiaoping Lei, Lile Zou, Mengya Sun, Juan Du, Siyuan Jiang, Yujie Han, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7107543/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Nov, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted 7 You are reading this latest preprint version Abstract Background Antenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 24 + 0 and 33 + 6 weeks. Due to their significant benefit for the majority of pregnant women, an European guideline also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies. Methods The Chinese Neonatal Network (CHNN), a national multicenter study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. A total of 4337 VPIs born to diabetic mothers enrolled in the present study: 3605 VPIs were exposed to ACS and 732 were not. The outcomes were mortality and severe morbidity in hospital. Logistic regression models were employed to calculate the odds ratio (OR) and its 95% confidence interval (CI) to estimate the associations between ACS and these outcomes. Stratification and sensitivity analyses were conducted to test the robustness of the results in different population. Findings: ACS was associated with a lower risk in the combined outcome (death or any severe morbidity) (adjusted OR [aOR] 0.66, 95%CI: 0.54–0.79), death (aOR 0.55, 95%CI 0.41–0.73), and bronchopulmonary dysplasia (aOR 0.69, 95%CI 0.55–0.85). However, a significantly higher risk of maternal chorioamnionitis (aOR 2.09, 95%CI 1.61–2.72) was observed in the ACS group. Similar results were observed in stratification and sensitivity analyses. Conclusions ACS is associated with lower mortality and reduced morbidity in VPIs born to diabetic mothers. Diabetes Antenatal Corticosteroids Neonatal Outcome Very Preterm Infant Figures Figure 1 Figure 2 What is Known – What is New Previous studies have suggested that antenatal administration of corticosteroids to pregnancies at risk of early preterm delivery can reduce adverse neonatal outcomes, including death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and other short-term complications and may even improve long-term neurological outcomes. Antenatal corticosteroids (ACS) have been widely recommended as standard practice in the management of pregnancies at high risk of preterm delivery between 24 +0 and up to 33 +6 weeks. For lacking supporting data, most recommendations regarding ACS do not extend to pregnant women with diabetes who are at risk for preterm delivery. However, an European guideline states that maternal diabetes is not a contraindication for the use of ACS due to their proven benefits for most pregnant women. To the best of our knowledge, our study represents the first investigation on this specific population. In this data analysis from 79 Neonatal Intensive Care Units in China, the use of ACS in diabetic pregnancies was associated with lower risks of mortality, bronchopulmonary dysplasia, low Apgar scores, the need for advanced resuscitation at delivery, respiratory distress syndrome, and the need for invasive ventilation. Our findings provide evidence of the benefits associated with ACS in reducing neonatal mortality and morbidity in diabetic pregnancies, contributing to the limited body of evidence from this specific population. Introduction Since the 1970s, increasing strong evidence has suggested that antenatal administration of corticosteroids to pregnancies at risk of early preterm delivery can reduce adverse neonatal outcomes, including death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and other short-term complications, 1-5 and may even improve long-term neurological outcomes. 2,6-7 Currently, antenatal corticosteroids (ACS) are widely recommended as standard practice in the management of pregnancies at high risk of preterm delivery between 24 +0 and up to 33 +6 weeks. 8-9 However, most recommendations regarding ACS do not extend to pregnant women with diabetes who are at risk for preterm delivery, due to a lack of supporting data. In most randomized controlled trials (RCTs) studying ACS, researchers have restricted participation to non-diabetic pregnant women. 10-12 Consequently, the results of these studies may not be applicable to pregnant women with diabetes. Although some RCTs did not exclude diabetic mothers, the small sample size in these studies also limited the ability to conduct stratified analyses in this specific population. 2-4 Several observational studies 13-16 and a meta-analysis 17 suggested that ACS might not reduce neonatal morbidity in diabetic mothers with late preterm delivery. So far, there is no evidence from diabetic mothers with high risk of early preterm delivery. Moreover, ACS administration can increase the risks of maternal hyperglycemia and neonatal hypoglycemia, which could complicate blood glucose control in pregnant women with diabetes and potentially elevate the risk of adverse neurodevelopmental outcomes in their offspring. 18-20 The Society for Maternal-Fetal Medicine has advised against the use of late preterm corticosteroids in pregnant patients with pregestational diabetes due to the heightened risk of severe neonatal hypoglycemia. 9 However, pregnant women with diabetes may be at a higher risk of preterm birth compared to those without pregnancy complications. Excluding them from clinical trials has not prevented the consideration of ACS therapy in clinical practice. Indeed, despite the lack of solid evidence from this specific population and the substantial benefits observed in existing studies from the general pregnant population, the latest European guidelines also recommend that maternal diabetes mellitus is not a contraindication to the use of ACS. 21 This multicenter observational study aims to investigate whether the administration of ACS in women with diabetes during pregnancy is associated with improved neonatal outcomes in very preterm infants (VPIs). Methods Study Design The present study is a national multicenter cohort study. The Chinese Neonatal Network (CHNN) is an ongoing prospective cohort study that concentrates on VPIs with a gestational age (GA) below 32 weeks or very low birth weight (VLBW) infants weighing less than 1500g in neonatal intensive care units (NICUs) throughout China. Commencing January 1, 2019, CHNN has developed and preserved a standardized clinical database across 79 NICUs. Participants From January 1st, 2019, to December 31st, 2021, there were 31,915 VPIs or VLBW infants admitted to the NICUs participating in the CHNN. We excluded infants born to non-diabetic mothers (n = 25,952). To minimize selection bias, we also excluded 671 infants who were transferred to CHNN after 24 hours of birth. Additionally, 29 infants with significant chromosomal or structural abnormalities and 552 infants with a GA greater than 32 weeks at birth were excluded from the study. After removing cases with missing data for gender or birth weight (n = 7), the eligible study population was reduced to 4707 VPIs. We then further excluded 144 VPIs due to missing data on ACS use or because corticosteroids were administered for reasons other than ACS. Moreover, 223 VPIs who were transferred out of CHNN or discharged against medical advice were excluded. The final study population consisted of 3605 VPIs exposed to ACS and 732 VPIs without exposure (Figure 1). Exposure and Outcomes ACS are administered to pregnancies at high risk of preterm delivery as a prophylactic measure to improve neonatal outcomes. The two used corticosteroids in this setting are betamethasone and dexamethasone. Betamethasone is given as 12 mg administered intramuscularly in two separate doses, 24 hours apart. Dexamethasone, on the other hand, is administered as 6 mg intramuscularly, typically in four divided doses, with each dose given 12 hours apart. The regimens for ACS administration in the current study include: 1. A partial course of ACS: The delivery occurs after the mother has received only part of the intended full course of corticosteroids. 2. A complete course of ACS ≤ 7 days: The full course of corticosteroids was administered within 7 days before delivery. 3. A complete course of ACS > 7 days: The full course of corticosteroids being administered more than 7 days prior to delivery. 4. Repeat courses of ACS: The mother received multiple courses of corticosteroids during pregnancy, due to ongoing risks of preterm delivery. The primary outcome of this study is composited mortality or any of severe morbidity in hospital. The components of the primary outcome were also analyzed separately, including mortality in hospital, BPD, surgical NEC, and intraventricular hemorrhage (IVH) > II grade or periventricular leukomalacia (PVL). The mortality in CHNN dataset included deaths that occurred both in the hospital and after discharge against medical advice (DAMA). 23 BPD was diagnosed when VPIs required positive pressure support, supplemental oxygen with a fraction of inspired oxygen exceeding 0.21, and failed the oxygen reduction test. 24 The secondary outcomes included: 1. RDS. 2. Need for mechanical ventilation (MV). 3. Low Apgar score, defined as a 1-minute Apgar score ≤ 3 or a 5-minute Apgar score ≤ 7. 4. Treated retinopathy of prematurity (ROP). 5. Early onset sepsis, confirmed by positive culture. 6. Maternal chorioamnionitis, specifically histologic chorioamnionitis. Covariates The maternal and neonatal baseline characteristics included maternal age at delivery, gravidity, parity, mode and site of delivery, infant gender, GA, birth weight (BW), and caffeine therapy. The factors related to preterm births are also used as covariates, including multiple births, the use of assisted reproductive technology, abortion history, hypertensive disorders of pregnancy (including chronic hypertension, gestational hypertension, preeclampsia, or eclampsia), chorioamnionitis, premature rupture of membranes (PROM), and intrauterine growth restriction (IUGR). Statistical analysis Maternal and infant characteristics were compared between VPIs with and without exposure to ACS. Frequencies (percentages) or means with standard deviations (SDs) were reported. The t-test or Wilcoxon rank-sum test was used to compare differences in baseline characteristics. In the first step, the outcomes were compared between VPIs with and without exposure to ACS. A univariate logistic regression model was used to estimate crude odds ratios (ORs) with 95% confidence intervals (CIs) for each outcome. A multivariate logistic regression model was employed to adjust for potential covariates. A series of stratified analyses were conducted to test whether different associations existed in different subgroups, including stratification by course of ACS (a partial course, a single complete course ≤ 7 days, a single complete course > 7 days, or repeat courses prior to birth), GA (< 28, 28 - 29 +6 , or 30 - 31 +6 gestation weeks), BW ( 1500g), number of births (singleton or multiple birth), and infant gender (male or female). As an observational study, we conducted several sensitivity analyses to test the robustness of the results. Firstly, propensity score matching (PSM) was performed to balance the maternal and fetal factors between the two groups. The propensity score was derived using a multivariable logistic regression based on those maternal and fetal factors in the adjusted model. Each VPI without exposure to ACS was matched to two VPIs with exposure, based on the propensity score, using the greedy nearest-neighbor matching algorithm without replacement and a caliper of 0.10 SD of the logit of the propensity score. A conditional logistic regression model was used to explore the associations between ACS and outcomes in the matched subjects, using PSM [25]. Secondly, since only 5% (208) of VPIs were born to mothers with pre-pregnancy diabetes, we could not perform stratification analysis by diabetic types. A sensitivity analysis was conducted in VPIs born to mothers with gestational diabetes mellitus. Thirdly, as a cohort study, the information about ACS administration was obtained from both obstetric records and self-reports of the parents. To avoid recall bias, a sensitivity analysis was also conducted in inborn VPIs, whose ACS data only came from obstetric records. In this population, it also avoided selection bias to some extent. All analyses were performed using SAS, version 9.4 (SAS Institute), with a two-sided significance level set at P = 0.05. Role of the funding source The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Results Compared to mothers who did not receive ACS, those who did had notably lower cesarean section rates, albeit with higher occurrences of inborn deliveries, multiple births, utilization of artificial reproductive technology, and premature rupture of membranes (refer to Table 1). However, no discernible differences were observed in other maternal characteristics, as well as infant gender, GA, BW, or intrauterine growth restriction (IUGR) between the two groups (refer to Table 1). Table 2 showed that, compared to VPIs born to mothers without ACS exposure, VPIs with ACS exposure had lower risks of primary outcome (adjusted OR [aOR] 0.66, 95% CI 0.54 to 0.79), death (aOR 0.55, 95% CI 0.41 to 0.73), severe BPD (aOR 0.69, 95% CI 0.55 to 0.85), low Apgar score (aOR 0.76, 95% CI 0.61 to 0.96), RDS (aOR 0.79, 95% CI 0.66 to 0.94), or the need for invasive ventilation (aOR 0.62, 95% CI 0.52 to 0.73). ACS administration had no significant associations with surgical NEC (aOR 0.57, 95% CI 0.32 to 1.02), grades 3-4 IVH or PVL (aOR 0.85, 95% CI 0.59 to 1.22), treated ROP (aOR 1.62, 95% CI 0.91 to 2.90), or early-onset sepsis (aOR 0.72, 95% CI 0.39 to 1.32) in the VPIs. However, a higher risk of maternal chorioamnionitis was associated with ACS exposure (aOR 2.09, 95% CI 1.61 to 2.72). The findings for the primary outcome were consistent across various stratified analyses based on the course of ACS (aORs of 0.64 [95% CI 0.48 to 0.86], 0.60 [95% CI 0.48 to 0.75], 0.72 [95% CI 0.59 to 0.90], and 0.66 [95% CI 0.49 to 0.88] for a partial course, a single complete course ≤ 7 days, a single complete course > 7 days, and repeat courses prior to birth, respectively) (refer to Figure 2 and eTable 1). These consistent results were also observed in the number of births (aORs of 0.65 [95% CI 0.52 to 0.82] and 0.67 [95% CI 0.47 to 0.96] for singleton and multiple VPIs, respectively) (refer to Figure 2 and eTable 2), GA (aORs of 0.69 [95% CI 0.46 to 1.04], 0.64 [95% CI 0.47 to 0.88], and 0.63 [95% CI 0.47 to 0.86] for GA < 28 weeks, 28 - 29 +6 weeks, and 30 - 31 +6 weeks, respectively) (refer to Figure 2 and eTable 3), BW (aORs of 0.68 [95% CI 0.52 to 0.89], 0.55 [95% CI 0.38 to 0.80], and 0.68 [95% CI 0.45 to 1.04] for BW 1500g, respectively) (refer to Figure 2 and eTable 4), and infant gender (aORs of 0.74 [95% CI 0.57 to 0.96] and 0.56 [95% CI 0.42 to 0.74] for male and female VPIs, respectively) (refer to Figure 2 and eTable 5). Furthermore, despite exceptions resulting from disparity in grades 3-4 IVH or PVL in stratification analysis by number of births (aORs of 0.60 [95% CI 0.40 to 0.90] and 2.93 [95% CI 1.02 to 8.40] for singleton and multiple birth, respectively, refer to eTable 2), consistent results were observed in the components of the primary and secondary outcomes across each subgroup (refer to eTables 1-5). Several sensitive analyses also yielded highly consistent results in the primary outcome in populations matched by propensity score (aOR 0.63, 95% CI 0.51 to 0.77) (refer to eTable 6), VPIs born to mothers with gestational diabetes mellitus (aOR 0.64, 95% CI 0.53 to 0.78) (refer to eTable 7), or inborn VPIs (aOR 0.65, 95% CI 0.52 to 0.81) (refer to eTable 8). Discussion In this cohort study, we discovered that the administration of ACS to pregnant women with diabetes who are at risk of very preterm birth, is associated with a reduction in neonatal mortality and severe morbidity in the hospital. However, it was also associated with an increased incidence of maternal chorioamnionitis. These clinical benefits to newborns were also observed in stratified analyses across most subgroups and sensitive analyses within different populations. ACS treatment for pregnancies has been shown to improve preterm neonatal outcomes by reducing neonatal mortality and respiratory morbidity in previous studies. Consistent with these results from non-diabetic pregnancies, 1-5 our findings indicate that a 34% reduction in mortality or severe morbidity in the hospital is associated with the administration of ACS to diabetic mothers with a high likelihood of preterm birth. Based on a large amount of solid evidence from RCTs, ACS has been widely recommended as the standard practice in the management of pregnancies with a high risk of preterm delivery. 8,9,21 However, due to a lack of supporting data from diabetic pregnancies, most of the current recommendations on ACS have not been extended to this specific population. To the best of our knowledge, only four observational studies have focused on the associations between the use of ACS in diabetic pregnancies and neonatal outcomes in late-preterm infants, and no improved neonatal outcomes were observed in infants who were exposed to ACS. 13-17 Even so, the newest European guidelines are also based on a single observational study that shows the beneficial effect of ACS in diabetic pregnancies appears to be similar to the non-diabetic population before 34 weeks, 26 and recommended that maternal diabetes is not a contraindication to the use of ACS. 21 Our findings provide evidence regarding the beneficial effects of ACS in reducing neonatal mortality and morbidity in women with diabetes during pregnancy, and expand the limited body of evidence from this specific population. In addition, based on a series of consistent results from stratification analyses, our findings also provide evidence for various courses of ACS use in diabetic pregnancies with other specific conditions. On the other hand, even though ACS has huge advantages for premature offspring, some studies have found that it can also increase the risks of long-term outcomes, including serious infection in the first 12 months in very preterm births. 27 However, a meta-analysis reported that the long-term adverse outcomes of ACS exposure were only observed in late-preterm and term offspring, whereas better neurocognitive and/or psychological outcomes were observed in very preterm births 28 Actually, these studies on the long-term outcomes of ACS could only be conducted in surviving offspring, and they might be biased by the competing risk of early death. In the present study, the findings seem to indicate that the most important benefit is the reduction of mortality. Although no long-term outcomes could be obtained from the present study, the reduction of mortality might balance any long-term adverse outcomes, such as serious infection. Several concerns about ACS administration were the side effects, including potential risk of infection for both mothers and fetuses. In our study, the use of ACS was associated with an increased risk of maternal chorioamnionitis. This finding is inconsistent with previous studies, which reported no increased risk of chorioamnionitis in pregnant women who received ACS. 1,3 As an observational study, this association may not represent a true causality, and chorioamnionitis may be more likely a maternal complication that precedes ACS exposure. Previous studies have reported that a higher incidence of chorioamnionitis was observed after receiving multiple courses of ACS 29 or with a longer interval to birth. 30 In the present study, it seems that there was no significant increased risk of chorioamnionitis in diabetic mothers with repeated ACS exposure or longer interval to birth, and the partial course group had the highest incidence. Furthermore, although a higher risk of maternal chorioamnionitis was observed in the ACS exposure group, there was no increased risk of neonatal EOS. Another concern about ACS administration is glycemic disorders, including higher risks of maternal hyperglycemia 31 and neonatal hypoglycemia. 18 Unfortunately, due to missing data, our studies cannot estimate whether maternal hyperglycemia and neonatal hypoglycemia existed after ACS exposure. Several other limitations exist in the present study. The observational study design only allows for association, not causal inferences. RCTs are needed to confirm these findings. Second, the types of ACS administration in individuals are unknown, and we cannot analyze the differences between the two drugs. However, previous studies found similar benefits for betamethasone and dexamethasone on neonatal outcomes 32-33 and survival without neurosensory disability at two years of age. 34-35 Meta-analyses also concluded that both dexamethasone and betamethasone are equally effective in preventing most neonatal outcomes, neonatal death, RDS, BPD, and IVH, etc. 35-36 Therefore, it may not affect the association between ACS and improved neonatal outcomes in our population. Third, even though the characteristics of the population were well collected, thus allowing multivariable modeling, ACS-exposed and non-exposed pregnancies may have differed in some characteristics that were not measured, and residual confounding cannot be ruled out. For example, subjects came from NICUs, and the information on ACS use was collected from the Hospital Information System. Recall bias may exist in outborn VPIs. We used inborn infants as the study population to conduct the sensitivity analysis and got similar outcomes (eTable 7). This gives us some confidence in the reliability of our results. Another bias may come from the selection of study subjects. Our population came from a NICU-based cohort rather than a birth cohort from the overall population. We did not get data on stillbirths or abortions after ACS administration. However, a previous RCT study reported that ACS did not increase fetal loss before delivery. 3 In addition, when stratified by ACS course, the partial course group also showed lower risks of neonatal adverse outcomes. Fetal death in this subgroup may not be underestimated and may have biased the results less. In conclusion, ACS was associated with significantly reduced mortality and morbidity in VPIs born to mothers with diabetes, but with an increased risk of maternal chorioamnionitis. Further RCTs and follow-up studies are needed to confirm the benefits of administering ACS to diabetic pregnancies. Declarations The authors have declared no conflicts of interest. Data sharing statement The data used and/or analyzed during the current study are available from the corresponding author on reasonable request. Author contributions Dr Lei had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Lei, Dong, and Zhou. Acquisition of data: Zhou. Analysis, or interpretation of data: Lei. Drafting of the manuscript: Lei, Zou, and Sun. Critical review of the manuscript for important intellectual content: All authors. Statistical analysis: Lei. Administrative, technical, or material support: Zhou. Study supervision : Dong, Zhou, and Lee. Funding: This work was supported by the National Key Research and Development Program of China (2021YFC2701800, 2021YFC2701801); Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan No. 21Y21900800, Canadian Institutes of Health Research (CTP87518) and the National Natural Science Foundation of China (82371710 for Wenbin Dong). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Declaration of interests: The authors have declared no conflicts of interest. Data sharing statement: The data used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval The study was conducted following the Declaration of Helsinki and was approved by the Research Ethics Committee of the Children's Hospital of Fudan University (Approval No. 2018-296). A waiver of consent was universally granted due to the utilization of deidentified patient data. The research adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies. Acknowledgments We thank the data abstractors from the Chinese Neonatal Network. We thank all the staff at the Chinese Neonatal Network coordinating center for providing organizational support (Lin Yuan, PhD; Tongling Yang, RN; Hao Yuan, RN; Li Wang, RN; Yulan Lu, PhD; Jie Yang, PhD). Group Information of the Chinese Neonatal Network: Chairmen: Shoo K. Lee, MBBS, Mount Sinai Hospital, University of Toronto; Chao Chen, MD, Children’s Hospital of Fudan University. Vice-Chairmen: Lizhong Du, MD, Children's Hospital of Zhejiang University School of Medicine; Wenhao Zhou, Children’s Hospital of Fudan University. Site principle investigators of the Chinese Neonatal Network: Children’s Hospital of Fudan University: Yun Cao, MD; The Third Affiliated Hospital of Zhengzhou University: Xiuyong Chen, MD; Guangzhou Women and Children’s Medical Center: Huayan Zhang, MD; Tianjin Obstetrics & Gynecology Hospital: Xiuying Tian, MD; Gansu Provincial Maternity and Child Care Hospital: Jingyun Shi, MD; Northwest Women's and Children's Hospital: Zhankui Li, MD; Shenzhen Maternity and Child Health Care Hospital: Chuanzhong Yang, MD; Guizhou Women and Children’s Hospital: Ling Liu, MD; Suzhou Municipal Hospital affiliated to Nanjing Medical University: Zuming Yang, MD; Shengjing Hospital of China Medical University: Jianhua Fu, MD; Children’s Hospital of Shanxi: Yong Ji, MD; Quanzhou Women and Children’s Hospital: Dongmei Chen, MD; Fujian Women and Children’s Medical Center: Changyi YANG, MD; Children’s Hospital of Nanjing Medical University: Rui Chen , MD; Hunan Children’s Hospital: Xiaoming Peng, MD; Qingdao Women and Children’s Hospital: Ruobing Shan, MD; Nanjing Maternity and Child Health Care Hospital: Shuping Han, MD; The First Bethune Hospital of Jilin University: Hui Wu, MD; The First Affiliated Hospital of Anhui Medical University: Lili WANG, MD; Women and Children's Hospital of Guangxi Zhuang Autonomous Region: Qiufen Wei, MD; The First Affiliated Hospital of Xinjiang Medical University: Mingxia Li, MD; Foshan Women and Children’s Hospital: Yiheng Dai, MD; The Affiliated Hospital of Qingdao University: Hong Jiang, MD; Henan Children’s Hospital: Wenqing Kang, MD; Children’s Hospital of Shanghai: Xiaohui Gong, MD; Chongqing Health Care Center for Women and Children: Xiaoyun Zhong, MD; Children’s Hospital of Chongqing Medical University: Yuan Shi, MD; Wuxi Maternity and Child Healthcare Hospital: Shanyu Jiang, MD; Children's Hospital of Soochow University: Bing Sun, MD; People's Hospital of Xinjiang Uygur Autonomous Region: Long Li, MD; Yuying Children's Hospital Affiliated to Wenzhou Medical University: Zhenlang Lin, MD; Shanghai First Maternity and Infant Hospital: Jiangqin Liu, MD; Anhui Provincial Hospital: Jiahua PAN, MD; Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine: Hongping Xia, MD; Qilu Children’s Hospital of Shandong University: Xiaoying Li, MD; The First Affiliated Hospital of Zhengzhou University: Falin Xu, MD; General Hospital of Ningxia Medical University: Yinping Qiu, MD; Hebei Children’s Hospital: Li Ma, MD; Hainan Women and Children’s Hospital: Ling Yang, MD; The second Xiangya hospital of Central South University: Xiaori He, MD; Ningbo Women&Children Hospital: Yanhong Li, MD; Xiamen Children’s Hospital: Deyi Zhuang, MD; Shaanxi Provincial People’s Hospital: Qin Zhang, MD; The Affiliated Hospital of Southwest Medical University: Wenbin Dong, MD; Shanghai Children’s Medical Center affiliated to Shanghai Jiaotong University School of Medicine: Jianhua Sun, MD; First Affiliated Hospital of Kunming Medical University: Kun Liang, MD; Changzhou Maternal and Children Health Care Hospital: Huaiyan Wang, MD; Shenzhen Children’s Hospital: Jinxing Feng, MD; Jiangxi Provincial Children’s Hospital: Liping Chen, MD; Xiamen Maternity and Child Health Care Hospital: Xinzhu Lin, MD; Zhuhai Center for Maternal and Child Health Care: Chunming Jiang, MD; Guangdong Women and Children's Hospital: Chuan Nie, MD; Wuhan Chidren's Hospital: Linkong Zeng, MD; Beijing Children's Hospital of Capital Medical University: Mingyan Hei, MD; Maternal and Children Hospital of Shaoxing: Hongdan Zhu, MD; The First People's Hospital of Yunnan Province: Hongying MI, MD; Dehong people's Hospital of Yunnan Province: Zhaoqing Yin, MD; First Affiliated Hospital of Xian Jiaotong University: Hongxia Song, MD; Inner Mongolia maternal and child health care hospital: Hongyun Wang, MD; Dalian Municipal Women and Children’s Medical Center: Dong Li, MD; Lianyungang Maternal and Children Health Hospital: Yan Gao , MD; Children's Hospital Affiliated to Capital Institute of Pediatrics: Yajuan Wang, MD; Anhui Children's Hoospital: Liying Dai, MD; Fuzhou Children’s Hospital of Fujian Province: Liyan ZHANG, MD; Kunming Children's Hospital: Yangfang Li, MD; Shenzhen Hospital of Hongkong University: Qianshen Zhang, MD; Peking Union Medical College Hospital: Guofang Ding, MD; Obstetrics & Gynecology Hospital of Fudan University : Jimei Wang, MD; The Affiliated Hospital of Guizhou Medical University: Xiaoxia Chen, MD; Qinghai Women and Children Hospital: Zhen Wang, MD; The International Peace Maternity & Child Health Hospital of China welfare institute: Zheng Tang, MD; Children's Hospital of Zhejiang University: Xiaolu Ma, MD; Inner Mongolia People's Hospital: Xiaomei Zhang, MD; Xiamen Humanity Hospital: Xiaolan Zhang, MD; Shanghai General Hospital: Fang Wu, MD; The First People's Hospital of Yinchuan: Yanxiang Chen, MD; The Third Hospital of Nanchang: Ying Wu, MD; Advisor: Joseph Ting, MBBS; University of Alberta. References 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 Dec 25;12(12):CD004454. doi: 10.1002/14651858.CD004454.pub4. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics . 1972 Oct;50(4):515-25. PMID: 4561295. WHO ACTION Trials Collaborators; Oladapo OT, Vogel JP, et al. Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries. N Engl J Med . 2020 Dec 24;383(26):2514-2525. doi: 10.1056/NEJMoa2022398. Walters AGB, Lin L, Crowther CA, Gamble GD, Dalziel SR, Harding JE. Betamethasone for Preterm Birth: Auckland Steroid Trial Full Results and New Insights 50 Years on. J Pediatr . 2023 Apr;255:80-88.e5. doi: 10.1016/j.jpeds.2022.10.028. Abbasalizadeh F, Pouya K, Zakeri R, Asgari-Arbat R, Abbasalizadeh S, Parnianfard N. Prenatal Administration of Betamethasone and Neonatal Respiratory Distress Syndrome in Multifetal Pregnancies: A Randomized Controlled Trial. Curr Clin Pharmacol . 2020;15(2):164-169. doi: 10.2174/1574884714666191007154936. Salokorpi T, Sajaniemi N, Hällback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta Paediatr . 1997 Mar;86(3):294-8. doi: 10.1111/j.1651-2227.1997.tb08893.x. Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental Outcome After a Single Course of Antenatal Steroids in Children Born Preterm: A Systematic Review and Meta-analysis. Obstet Gynecol . 2015 Jun;125(6):1385-1396. doi: 10.1097/AOG.0000000000000748. Committee on Obstetric Practice. Committee Opinion No. 713: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol . 2017 Aug;130(2):e102-e109. doi: 10.1097/AOG.0000000000002237. Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected] ; Reddy UM, Deshmukh U, Dude A, Harper L, Osmundson SS. Society for Maternal-Fetal Medicine Consult Series #58: Use of antenatal corticosteroids for individuals at risk for late preterm delivery: Replaces SMFM Statement #4, Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery, August 2016. Am J Obstet Gynecol . 2021 Nov;225(5):B36-B42. doi: 10.1016/j.ajog.2021.07.023. Garite TJ, Rumney PJ, Briggs GG, et al. A randomized placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24-28 weeks gestation. American Journal of Obstetrics and Gynecology 1992;166:646-51. Balci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest . 2010;70(2):95-9. doi: 10.1159/000295898. Gamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. Br J Obstet Gynaecol . 1989 Apr;96(4):401-10. doi: 10.1111/j.1471-0528.1989.tb02413.x. PMID: 2665800. Özkan S, Dereli ML, Kurt D, et al. The use of late preterm antenatal corticosteroids in women with gestational diabetes : a puzzle worth solving. BMC Pregnancy Childbirth . 2024 Apr 18;24(1):286. doi: 10.1186/s12884-024-06510-2. Krispin E, Hochberg A, Chen R, Wiznitzer A, Hadar E, Borovich A. Neonatal outcome in gestational-diabetic mothers treated with antenatal corticosteroids delivering at the late preterm and term. Arch Gynecol Obstet . 2018 Oct;298(4):689-695. doi: 10.1007/s00404-018-4848-8. Cassimatis IR, Battarbee AN, Allshouse AA, et al. Neonatal outcomes associated with late preterm betamethasone administration in women with pregestational diabetes. Pediatr Neonatol . 2020 Dec;61(6):645-646. doi: 10.1016/j.pedneo.2020.07.002. Li X, Zhang J, Hao Q, Du Y, Cheng X. The effect of time interval between antenatal corticosteroid administration and delivery on outcomes in late preterm neonates born to mothers with diabetes: a retrospective cohort study. Front Pediatr . 2023 Aug 25;11:1239977. doi: 10.3389/fped.2023.1239977. Saito K, Nishimura E, Ota E, et al. Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review. BMJ Open . 2023 Sep 22;13(9):e065070. doi: 10.1136/bmjopen-2022-065070. Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, Reijneveld SA, Bos AF. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics . 2012 Aug;130(2):e265-72. doi: 10.1542/peds.2012-0079. Räikkönen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. JAMA . 2020 May 19;323(19):1924-1933. doi: 10.1001/jama.2020.3937. Wapner RJ, Sorokin Y, Mele L, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med . 2007 Sep 20;357(12):1190-8. doi: 10.1056/NEJMoa071453. PMID: 17881751. Daskalakis G, Pergialiotis V, Domellöf M, et al. European guidelines on perinatal care: corticosteroids for women at risk of preterm birth. J Matern Fetal Neonatal Med . 2023 Dec;36(1):2160628. doi: 10.1080/14767058.2022.2160628. Hei M, Li X, Shi Y, et al. Chinese Neonatal Network: a national protocol for collaborative research and quality improvement in neonatal care. BMJ Open . 2022 May 2;12(5):e051175. doi: 10.1136/bmjopen-2021-051175. Xiu W, Bai R, Gu X, et al. Discharge against medical advice among infants with 24-31 weeks' gestation admitted to Chinese neonatal intensive care units: A multicenter cohort study. Front Pediatr . 2022 Aug 16;10:943244. doi: 10.3389/fped.2022.943244. Higgins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr . 2018 Jun;197:300-308. doi: 10.1016/j.jpeds.2018.01.043. Kane LT, Fang T, Galetta MS, et al. Propensity Score Matching: A Statistical Method. Clin Spine Surg . 2020 Apr;33(3):120-122. doi: 10.1097/BSD.0000000000000932. Battarbee AN, Sandoval G, Grobman WA, et al. Antenatal Corticosteroids and Preterm Neonatal Morbidity and Mortality among Women with and without Diabetes in Pregnancy. Am J Perinatol . 2022 Jan;39(1):67-74. doi: 10.1055/s-0040-1714391. Yao TC, Chang SM, Wu CS, et al. Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study. BMJ . 2023 Aug 2;382:e075835. doi: 10.1136/bmj-2023-075835. Ninan K, Liyanage SK, Murphy KE, Asztalos EV, McDonald SD. Evaluation of Long-term Outcomes Associated With Preterm Exposure to Antenatal Corticosteroids: A Systematic Review and Meta-analysis. JAMA Pediatr . 2022 Jun 1;176(6):e220483. doi: 10.1001/jamapediatrics.2022.0483. Vermillion ST, Soper DE, Newman RB. Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy. Am J Obstet Gynecol . 2000 Oct;183(4):810-4. doi: 10.1067/mob.2000.108838. McDougall ARA, Aboud L, Lavin T, et al. Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic review. EClinicalMedicine . 2023 Mar 24;58:101916. doi: 10.1016/j.eclinm.2023.101916. Jolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. Diabetes Res Clin Pract . 2016 Aug;118:98-104. doi: 10.1016/j.diabres.2016.06.005. Hofer OJ, Harding JE, Tran T, Crowther CA. Maternal and infant morbidity following administration of repeat dexamethasone or betamethasone prior to preterm birth: A secondary analysis of the ASTEROID Trial. PLoS One . 2022 Feb 22;17(2):e0263927. doi: 10.1371/journal.pone.0263927. Elimian A, Garry D, Figueroa R, Spitzer A, Wiencek V, Quirk JG. Antenatal betamethasone compared with dexamethasone (betacode trial): a randomized controlled trial. Obstet Gynecol . 2007 Jul;110(1):26-30. doi: 10.1097/01.AOG.0000268281.36788.81. Crowther CA, Ashwood P, Andersen CC, et al. Maternal intramuscular dexamethasone versus betamethasone before preterm birth (ASTEROID): a multicentre, double-blind, randomised controlled trial. Lancet Child Adolesc Health . 2019 Nov;3(11):769-780. doi: 10.1016/S2352-4642(19)30292-5. Brownfoot FC, Crowther CA, Middleton P. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev . 2008 Oct 8;(4):CD006764. doi: 10.1002/14651858.CD006764.pub2. Ciapponi A, Klein K, Colaci D, et al. Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis. Am J Obstet Gynecol MFM . 2021 May;3(3):100312. doi: 10.1016/j.ajogmf.2021.100312. Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files 6.supplementaldata.docx 3.tables.docx Cite Share Download PDF Status: Published Journal Publication published 08 Nov, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 03 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 13 Sep, 2025 Reviewers invited by journal 22 Jul, 2025 Editor assigned by journal 14 Jul, 2025 Submission checks completed at journal 14 Jul, 2025 First submitted to journal 12 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7107543","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":489102434,"identity":"bcba3830-133b-4313-a1d8-7e1d57726008","order_by":0,"name":"Xiaoping Lei","email":"data:image/png;base64,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","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiaoping","middleName":"","lastName":"Lei","suffix":""},{"id":489102435,"identity":"410d55e7-ffae-42c6-8a03-97205d246e66","order_by":1,"name":"Lile Zou","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lile","middleName":"","lastName":"Zou","suffix":""},{"id":489102436,"identity":"fdd0ae54-4743-4bd6-a977-59d3c56f2391","order_by":2,"name":"Mengya Sun","email":"","orcid":"","institution":"University，16 Jiangsu Road， Qingdao","correspondingAuthor":false,"prefix":"","firstName":"Mengya","middleName":"","lastName":"Sun","suffix":""},{"id":489102437,"identity":"c1c1273b-82fb-498b-88ae-1514792e6c4b","order_by":3,"name":"Juan Du","email":"","orcid":"","institution":"Capital Medical University, National Center for Children's Health","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Du","suffix":""},{"id":489102438,"identity":"c6b87807-5d8f-4307-b253-e8f223d53740","order_by":4,"name":"Siyuan Jiang","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Siyuan","middleName":"","lastName":"Jiang","suffix":""},{"id":489102439,"identity":"c3ba07a0-c6fe-4e8a-af62-11a53dc482ac","order_by":5,"name":"Yujie Han","email":"","orcid":"","institution":"Qilu Children's Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yujie","middleName":"","lastName":"Han","suffix":""},{"id":489102440,"identity":"7174fea4-cff6-4aea-a9bf-d45594314567","order_by":6,"name":"Dan Zhao","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region，Nanning","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Zhao","suffix":""},{"id":489102441,"identity":"d7694439-2626-4e54-9ac4-3a9eafcd06fc","order_by":7,"name":"Pei Lu","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Pei","middleName":"","lastName":"Lu","suffix":""},{"id":489102442,"identity":"75630991-7253-4524-801f-f3be4d86e0b2","order_by":8,"name":"Wei Shi","email":"","orcid":"","institution":"The Children's Hospital Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Shi","suffix":""},{"id":489102443,"identity":"f3474741-d42c-4bb5-bc63-e8773d3366b7","order_by":9,"name":"Jie Yang","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Yang","suffix":""},{"id":489102444,"identity":"0e76adda-e646-4b9c-9593-1c299256582b","order_by":10,"name":"Jianguo Zhou","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jianguo","middleName":"","lastName":"Zhou","suffix":""},{"id":489102445,"identity":"d507096e-7d07-45bc-b3c2-5f14c82ff9fb","order_by":11,"name":"Liyuan Hu","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Liyuan","middleName":"","lastName":"Hu","suffix":""},{"id":489102446,"identity":"fbb34d85-fb36-41bc-81c4-77eaa91e529a","order_by":12,"name":"Yun Cao","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Cao","suffix":""},{"id":489102447,"identity":"f4c6eb67-b68b-4602-9d55-cdad5e74e1d6","order_by":13,"name":"Mingyan Hei","email":"","orcid":"","institution":"Capital Medical University, National Center for Children's Health","correspondingAuthor":false,"prefix":"","firstName":"Mingyan","middleName":"","lastName":"Hei","suffix":""},{"id":489102448,"identity":"38891163-6505-45d1-a628-06986a34f9b3","order_by":14,"name":"Lizhong Du","email":"","orcid":"","institution":"The Children's Hospital Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lizhong","middleName":"","lastName":"Du","suffix":""},{"id":489102449,"identity":"744f012a-19d6-4e53-82f1-d37db19a49cd","order_by":15,"name":"Wenbin Dong","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenbin","middleName":"","lastName":"Dong","suffix":""},{"id":489102450,"identity":"a0604253-7c55-4d16-b57f-2d6caad16315","order_by":16,"name":"Wenhao Zhou","email":"","orcid":"","institution":"Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Wenhao","middleName":"","lastName":"Zhou","suffix":""},{"id":489102451,"identity":"e988f13a-80b4-4b63-b7de-d5f4b6223388","order_by":17,"name":"Shoo Kim Lee","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Shoo","middleName":"Kim","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-07-12 10:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7107543/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7107543/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-025-06606-7","type":"published","date":"2025-11-08T15:57:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87553026,"identity":"ecac08ad-466c-452c-ab51-3d4f7392bf28","added_by":"auto","created_at":"2025-07-25 06:34:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":109955,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7107543/v1/33e303a18c385a1bda2aea0d.png"},{"id":87553028,"identity":"e19a4cd0-d009-4f28-958f-6e1fd39e0ba5","added_by":"auto","created_at":"2025-07-25 06:34:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":236663,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7107543/v1/b7d74c0c1e2ccc18827ab2a6.png"},{"id":95564052,"identity":"37985d99-18e0-405f-bd08-864a97490687","added_by":"auto","created_at":"2025-11-10 16:07:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":649747,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7107543/v1/ef862971-8592-4a06-8463-666be8ce29bd.pdf"},{"id":87554485,"identity":"68d530bf-87d6-4e32-beca-384250d31345","added_by":"auto","created_at":"2025-07-25 06:42:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":93502,"visible":true,"origin":"","legend":"","description":"","filename":"6.supplementaldata.docx","url":"https://assets-eu.researchsquare.com/files/rs-7107543/v1/ee3c681754a812ccf8f7e503.docx"},{"id":87552263,"identity":"e23ecb10-4617-4750-84ba-609a6c51975b","added_by":"auto","created_at":"2025-07-25 06:26:54","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":23767,"visible":true,"origin":"","legend":"","description":"","filename":"3.tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7107543/v1/22663a7a61fc791f739d279c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antenatal Corticosteroids in Diabetic Pregnancies and Outcomes of Very Preterm Infants: a National Multicenter Cohort Study","fulltext":[{"header":"What is Known – What is New","content":"\u003cp\u003ePrevious studies have suggested that antenatal administration of corticosteroids to pregnancies at risk of early preterm delivery can reduce adverse neonatal outcomes, including death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and other short-term complications and may even improve long-term neurological outcomes. Antenatal corticosteroids (ACS) have been widely recommended as standard practice in the management of pregnancies at high risk of preterm delivery between 24\u003csup\u003e+0\u003c/sup\u003e and up to 33\u003csup\u003e+6\u003c/sup\u003e weeks. For lacking supporting data, most recommendations regarding ACS do not extend to pregnant women with diabetes who are at risk for preterm delivery. However, an European guideline states that maternal diabetes is not a contraindication for the use of ACS due to their proven benefits for most pregnant women. To the best of our knowledge, our study represents the first investigation on this specific population.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this data analysis from 79 Neonatal Intensive Care Units in China, the use of ACS in diabetic pregnancies was associated with lower risks of mortality, bronchopulmonary dysplasia, low Apgar scores, the need for advanced resuscitation at delivery, respiratory distress syndrome, and the need for invasive ventilation. Our findings provide evidence of the benefits associated with ACS in reducing neonatal mortality and morbidity in diabetic pregnancies, contributing to the limited body of evidence from this specific population.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSince the 1970s, increasing strong evidence has suggested that antenatal administration of corticosteroids to pregnancies at risk of early preterm delivery can reduce adverse neonatal outcomes, including death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and other short-term complications,\u003csup\u003e1-5\u0026nbsp;\u003c/sup\u003eand may even improve long-term neurological outcomes.\u003csup\u003e2,6-7\u003c/sup\u003e Currently, antenatal corticosteroids (ACS) are widely recommended as standard practice in the management of pregnancies at high risk of preterm delivery between 24\u003csup\u003e+0\u003c/sup\u003e and up to 33\u003csup\u003e+6\u003c/sup\u003e weeks.\u003csup\u003e8-9\u003c/sup\u003e However, most recommendations regarding ACS do not extend to pregnant women with diabetes who are at risk for preterm delivery, due to a lack of supporting data.\u003c/p\u003e\n\u003cp\u003eIn most randomized controlled trials (RCTs) studying ACS, researchers have restricted participation to non-diabetic pregnant women.\u003csup\u003e10-12\u003c/sup\u003e Consequently, the results of these studies may not be applicable to pregnant women with diabetes. Although some RCTs did not exclude diabetic mothers, the small sample size in these studies also limited the ability to conduct stratified analyses in this specific population.\u003csup\u003e2-4\u0026nbsp;\u003c/sup\u003eSeveral observational studies\u003csup\u003e13-16\u003c/sup\u003e and a meta-analysis\u003csup\u003e17\u003c/sup\u003e suggested that ACS might not reduce neonatal morbidity in diabetic mothers with late preterm delivery. So far, there is no evidence from diabetic mothers with high risk of early preterm delivery. Moreover, ACS administration can increase the risks of maternal hyperglycemia and neonatal hypoglycemia, which could complicate blood glucose control in pregnant women with diabetes and potentially elevate the risk of adverse neurodevelopmental outcomes in their offspring.\u003csup\u003e18-20\u003c/sup\u003e The Society for Maternal-Fetal Medicine has advised against the use of late preterm corticosteroids in pregnant patients with pregestational diabetes due to the heightened risk of severe neonatal hypoglycemia.\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eHowever, pregnant women with diabetes may be at a higher risk of preterm birth compared to those without pregnancy complications. Excluding them from clinical trials has not prevented the consideration of ACS therapy in clinical practice. Indeed, despite the lack of solid evidence from this specific population and the substantial benefits observed in existing studies from the general pregnant population, the latest European guidelines also recommend that maternal diabetes mellitus is not a contraindication to the use of ACS.\u003csup\u003e21\u003c/sup\u003e This multicenter observational study aims to investigate whether the administration of ACS in women with diabetes during pregnancy is associated with improved neonatal outcomes in very preterm infants (VPIs).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy Design\u003c/p\u003e\n\u003cp\u003eThe present study is a national multicenter cohort study. The Chinese Neonatal Network (CHNN) is an ongoing prospective cohort study that concentrates on VPIs with a gestational age (GA) below 32 weeks or very low birth weight (VLBW) infants weighing less than 1500g in neonatal intensive care units (NICUs) throughout China. Commencing January 1, 2019, CHNN has developed and preserved a standardized clinical database across 79 NICUs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants\u003c/p\u003e\n\u003cp\u003eFrom January 1st, 2019, to December 31st, 2021, there were 31,915 VPIs or VLBW infants admitted to the NICUs participating in the CHNN. We excluded infants born to non-diabetic mothers (n = 25,952). To minimize selection bias, we also excluded 671 infants who were transferred to CHNN after 24 hours of birth. Additionally, 29 infants with significant chromosomal or structural abnormalities and 552 infants with a GA greater than 32 weeks at birth were excluded from the study.\u003c/p\u003e\n\u003cp\u003eAfter removing cases with missing data for gender or birth weight (n = 7), the eligible study population was reduced to 4707 VPIs. We then further excluded 144 VPIs due to missing data on ACS use or because corticosteroids were administered for reasons other than ACS. Moreover, 223 VPIs who were transferred out of CHNN or discharged against medical advice were excluded. The final study population consisted of 3605 VPIs exposed to ACS and 732 VPIs without exposure (Figure 1).\u003c/p\u003e\n\u003cp\u003eExposure and Outcomes\u003c/p\u003e\n\u003cp\u003eACS are administered to pregnancies at high risk of preterm delivery as a prophylactic measure to improve neonatal outcomes. The two used corticosteroids in this setting are betamethasone and dexamethasone. Betamethasone is given as 12 mg administered intramuscularly in two separate doses, 24 hours apart. Dexamethasone, on the other hand, is administered as 6 mg intramuscularly, typically in four divided doses, with each dose given 12 hours apart.\u003c/p\u003e\n\u003cp\u003eThe regimens for ACS administration in the current study include:\u003c/p\u003e\n\u003cp\u003e1. A partial course of ACS: The delivery occurs after the mother has received only part of the intended full course of corticosteroids.\u003c/p\u003e\n\u003cp\u003e2. A complete course of ACS \u0026le; 7 days: The full course of corticosteroids was administered within 7 days before delivery.\u003c/p\u003e\n\u003cp\u003e3. A complete course of ACS \u0026gt; 7 days: The full course of corticosteroids being administered more than 7 days prior to delivery.\u003c/p\u003e\n\u003cp\u003e4. Repeat courses of ACS: The mother received multiple courses of corticosteroids during pregnancy, due to ongoing risks of preterm delivery.\u003c/p\u003e\n\u003cp\u003eThe primary outcome of this study is composited mortality or any of severe morbidity in hospital. The components of the primary outcome were also analyzed separately, including mortality in hospital, BPD, surgical NEC,\u0026nbsp;and\u0026nbsp;intraventricular hemorrhage (IVH) \u0026gt; II grade or periventricular leukomalacia (PVL). The mortality in CHNN dataset included deaths that occurred both in the hospital and after discharge against medical advice (DAMA).\u003csup\u003e23\u003c/sup\u003e BPD was diagnosed when VPIs required positive pressure support, supplemental oxygen with a fraction of inspired oxygen exceeding 0.21, and failed the oxygen reduction test.\u003csup\u003e24\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes included:\u003c/p\u003e\n\u003cp\u003e1. RDS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Need for mechanical ventilation (MV).\u003c/p\u003e\n\u003cp\u003e3. Low Apgar score, defined as a 1-minute Apgar score \u0026le; 3 or a 5-minute Apgar score \u0026le; 7.\u003c/p\u003e\n\u003cp\u003e4. Treated retinopathy of prematurity (ROP).\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp;Early onset sepsis, confirmed by positive culture.\u003c/p\u003e\n\u003cp\u003e6. Maternal chorioamnionitis, specifically histologic chorioamnionitis.\u003c/p\u003e\n\u003cp\u003eCovariates\u003c/p\u003e\n\u003cp\u003eThe maternal and neonatal baseline characteristics included maternal age at delivery, gravidity, parity, mode and site of delivery, infant gender, GA, birth weight (BW), and caffeine therapy. The factors related to preterm births are also used as covariates, including multiple births, the use of assisted reproductive technology, abortion history, hypertensive disorders of pregnancy (including chronic hypertension, gestational hypertension, preeclampsia, or eclampsia), chorioamnionitis, premature rupture of membranes (PROM), and intrauterine growth restriction (IUGR).\u003c/p\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eMaternal and infant characteristics were compared between VPIs with and without exposure to ACS. Frequencies (percentages) or means with standard deviations (SDs) were reported. The t-test or Wilcoxon rank-sum test was used to compare differences in baseline characteristics.\u003c/p\u003e\n\u003cp\u003eIn the first step, the outcomes were compared between VPIs with and without exposure to ACS. A univariate logistic regression model was used to estimate crude odds ratios (ORs) with 95% confidence intervals (CIs) for each outcome. A multivariate logistic regression model was employed to adjust for potential covariates.\u003c/p\u003e\n\u003cp\u003eA series of stratified analyses were conducted to test whether different associations existed in different subgroups, including stratification by course of ACS (a partial course, a single complete course \u0026le; 7 days, a single complete course \u0026gt; 7 days, or repeat courses prior to birth), GA (\u0026lt; 28, 28 - 29\u003csup\u003e+6\u003c/sup\u003e, or 30 - 31\u003csup\u003e+6\u003c/sup\u003e gestation weeks), BW (\u0026lt; 1250g, 1250 - 1500g, \u0026gt; 1500g), number of births (singleton or multiple birth), and infant gender (male or female).\u003c/p\u003e\n\u003cp\u003eAs an observational study, we conducted several sensitivity analyses to test the robustness of the results. Firstly, propensity score matching (PSM) was performed to balance the maternal and fetal factors between the two groups. The propensity score was derived using a multivariable logistic regression based on those maternal and fetal factors in the adjusted model. Each VPI without exposure to ACS was matched to two VPIs with exposure, based on the propensity score, using the greedy nearest-neighbor matching algorithm without replacement and a caliper of 0.10 SD of the logit of the propensity score. A conditional logistic regression model was used to explore the associations between ACS and outcomes in the matched subjects, using PSM [25]. Secondly, since only 5% (208) of VPIs were born to mothers with pre-pregnancy diabetes, we could not perform stratification analysis by diabetic types. A sensitivity analysis was conducted in VPIs born to mothers with gestational diabetes mellitus. Thirdly, as a cohort study, the information about ACS administration was obtained from both obstetric records and self-reports of the parents. To avoid recall bias, a sensitivity analysis was also conducted in inborn VPIs, whose ACS data only came from obstetric records. In this population, it also avoided selection bias to some extent.\u003c/p\u003e\n\u003cp\u003eAll analyses were performed using SAS, version 9.4 (SAS Institute), with a two-sided significance level set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\n\u003cp\u003eRole of the funding source\u003c/p\u003e\n\u003cp\u003eThe funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCompared to mothers who did not receive ACS, those who did had notably lower cesarean section rates, albeit with higher occurrences of inborn deliveries, multiple births, utilization of artificial reproductive technology, and premature rupture of membranes (refer to Table 1). However, no discernible differences were observed in other maternal characteristics, as well as infant gender, GA, BW, or intrauterine growth restriction (IUGR) between the two groups (refer to Table 1).\u003c/p\u003e\n\u003cp\u003eTable 2 showed that, compared to VPIs born to mothers without ACS exposure, VPIs with ACS exposure had lower risks of primary outcome (adjusted OR [aOR] 0.66, 95% CI 0.54 to 0.79), death (aOR 0.55, 95% CI 0.41 to 0.73), severe BPD (aOR 0.69, 95% CI 0.55 to 0.85), low Apgar score (aOR 0.76, 95% CI 0.61 to 0.96), RDS (aOR 0.79, 95% CI 0.66 to 0.94), or the need for invasive ventilation (aOR 0.62, 95% CI 0.52 to 0.73). ACS administration had no significant associations with surgical NEC (aOR 0.57, 95% CI 0.32 to 1.02), grades 3-4 IVH or PVL (aOR 0.85, 95% CI 0.59 to 1.22), treated ROP (aOR 1.62, 95% CI 0.91 to 2.90), or early-onset sepsis (aOR 0.72, 95% CI 0.39 to 1.32) in the VPIs. However, a higher risk of maternal chorioamnionitis was associated with ACS exposure (aOR 2.09, 95% CI 1.61 to 2.72).\u003c/p\u003e\n\u003cp\u003eThe findings for the primary outcome were consistent across various stratified analyses based on the course of ACS (aORs of 0.64 [95% CI 0.48 to 0.86], 0.60 [95% CI 0.48 to 0.75], 0.72 [95% CI 0.59 to 0.90], and 0.66 [95% CI 0.49 to 0.88] for a partial course, a single complete course \u0026le; 7 days, a single complete course \u0026gt; 7 days, and repeat courses prior to birth, respectively) (refer to Figure 2 and eTable 1). These consistent results were also observed in the number of births (aORs of 0.65 [95% CI 0.52 to 0.82] and 0.67 [95% CI 0.47 to 0.96] for singleton and multiple VPIs, respectively) (refer to Figure 2 and eTable 2), GA (aORs of 0.69 [95% CI 0.46 to 1.04], 0.64 [95% CI 0.47 to 0.88], and 0.63 [95% CI 0.47 to 0.86] for GA \u0026lt; 28 weeks, 28 - 29\u003csup\u003e+6\u003c/sup\u003e weeks, and 30 - 31\u003csup\u003e+6\u003c/sup\u003e weeks, respectively) (refer to Figure 2 and eTable 3), BW (aORs of 0.68 [95% CI 0.52 to 0.89], 0.55 [95% CI 0.38 to 0.80], and 0.68 [95% CI 0.45 to 1.04] for BW \u0026lt; 1250g, 1250 - 1500g, and \u0026gt; 1500g, respectively) (refer to Figure 2 and eTable 4), and infant gender (aORs of 0.74 [95% CI 0.57 to 0.96] and 0.56 [95% CI 0.42 to 0.74] for male and female VPIs, respectively) (refer to Figure 2 and eTable 5). Furthermore, despite exceptions resulting from disparity in grades 3-4 IVH or PVL in stratification analysis by number of births (aORs of 0.60 [95% CI 0.40 to 0.90] and 2.93 [95% CI 1.02 to 8.40] for singleton and multiple birth, respectively, refer to eTable 2), consistent results were observed in the components of the primary and secondary outcomes across each subgroup (refer to eTables 1-5).\u003c/p\u003e\n\u003cp\u003eSeveral sensitive analyses also yielded highly consistent results in the primary outcome in populations matched by propensity score (aOR 0.63, 95% CI 0.51 to 0.77) (refer to eTable 6), VPIs born to mothers with gestational diabetes mellitus (aOR 0.64, 95% CI 0.53 to 0.78) (refer to eTable 7), or inborn VPIs (aOR 0.65, 95% CI 0.52 to 0.81) (refer to eTable 8).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cohort study, we discovered that the administration of ACS to pregnant women with diabetes who are at risk of very preterm birth, is associated with a reduction in neonatal mortality and severe morbidity in the hospital. However, it was also associated with an increased incidence of maternal chorioamnionitis. These clinical benefits to newborns were also observed in stratified analyses across most subgroups and sensitive analyses within different populations.\u003c/p\u003e\n\u003cp\u003eACS treatment for pregnancies has been shown to improve preterm neonatal outcomes by reducing neonatal mortality and respiratory morbidity in previous studies. Consistent with these results from non-diabetic pregnancies,\u003csup\u003e1-5\u003c/sup\u003e our findings indicate that a 34% reduction in mortality or severe morbidity in the hospital is associated with the administration of ACS to diabetic mothers with a high likelihood of preterm birth. Based on a large amount of solid evidence from RCTs, ACS has been widely recommended as the standard practice in the management of pregnancies with a high risk of preterm delivery.\u003csup\u003e8,9,21\u003c/sup\u003e However, due to a lack of supporting data from diabetic pregnancies, most of the current recommendations on ACS have not been extended to this specific population. To the best of our knowledge, only four observational studies have focused on the associations between the use of ACS in diabetic pregnancies and neonatal outcomes in late-preterm infants, and no improved neonatal outcomes were observed in infants who were exposed to ACS.\u003csup\u003e13-17\u003c/sup\u003e Even so, the newest European guidelines are also based on a single observational study that shows the beneficial effect of ACS in diabetic pregnancies appears to be similar to the non-diabetic population before 34 weeks,\u003csup\u003e26\u003c/sup\u003e and recommended that maternal diabetes is not a contraindication to the use of ACS.\u003csup\u003e21\u003c/sup\u003e Our findings provide evidence regarding the beneficial effects of ACS in reducing neonatal mortality and morbidity in women with diabetes during pregnancy, and expand the limited body of evidence from this specific population. In addition, based on a series of consistent results from stratification analyses, our findings also provide evidence for various courses of ACS use in diabetic pregnancies with other specific conditions. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn the other hand, even though ACS has huge advantages for premature offspring, some studies have found that it can also increase the risks of long-term outcomes, including serious infection in the first 12 months in very preterm births.\u003csup\u003e27\u003c/sup\u003e However, a meta-analysis reported that the long-term adverse outcomes of ACS exposure were only observed in late-preterm and term offspring, whereas better neurocognitive and/or psychological outcomes were observed in very preterm births\u003csup\u003e28\u003c/sup\u003e Actually, these studies on the long-term outcomes of ACS could only be conducted in surviving offspring, and they might be biased by the competing risk of early death. In the present study, the findings seem to indicate that the most important benefit is the reduction of mortality. Although no long-term outcomes could be obtained from the present study, the reduction of mortality might balance any long-term adverse outcomes, such as serious infection.\u003c/p\u003e\n\u003cp\u003eSeveral concerns about ACS administration were the side effects, including potential risk of infection for both mothers and fetuses. In our study, the use of ACS was associated with an increased risk of maternal chorioamnionitis. This finding is inconsistent with previous studies, which reported no increased risk of chorioamnionitis in pregnant women who received ACS.\u003csup\u003e1,3\u003c/sup\u003e As an observational study, this association may not represent a true causality, and chorioamnionitis may be more likely a maternal complication that precedes ACS exposure. Previous studies have reported that a higher incidence of chorioamnionitis was observed after receiving multiple courses of ACS\u003csup\u003e29\u003c/sup\u003e or with a longer interval to birth.\u003csup\u003e30\u003c/sup\u003e In the present study, it seems that there was no significant increased risk of chorioamnionitis in diabetic mothers with repeated ACS exposure or longer interval to birth, and the partial course group had the highest incidence. Furthermore, although a higher risk of maternal chorioamnionitis was observed in the ACS exposure group, there was no increased risk of neonatal EOS. Another concern about ACS administration is glycemic disorders, including higher risks of maternal hyperglycemia\u003csup\u003e31\u003c/sup\u003e and neonatal hypoglycemia.\u003csup\u003e18\u003c/sup\u003e Unfortunately, due to missing data, our studies cannot estimate whether maternal hyperglycemia and neonatal hypoglycemia existed after ACS exposure. Several other limitations exist in the present study. The observational study design only allows for association, not causal inferences. RCTs are needed to confirm these findings. Second, the types of ACS administration in individuals are unknown, and we cannot analyze the differences between the two drugs. However, previous studies found similar benefits for betamethasone and dexamethasone on neonatal outcomes\u003csup\u003e32-33\u003c/sup\u003e and survival without neurosensory disability at two years of age.\u003csup\u003e34-35\u003c/sup\u003e Meta-analyses also concluded that both dexamethasone and betamethasone are equally effective in preventing most neonatal outcomes, neonatal death, RDS, BPD, and IVH, etc.\u003csup\u003e35-36\u003c/sup\u003e Therefore, it may not affect the association between ACS and improved neonatal outcomes in our population.\u003c/p\u003e\n\u003cp\u003eThird, even though the characteristics of the population were well collected, thus allowing multivariable modeling, ACS-exposed and non-exposed pregnancies may have differed in some characteristics that were not measured, and residual confounding cannot be ruled out. For example, subjects came from NICUs, and the information on ACS use was collected from the Hospital Information System. Recall bias may exist in outborn VPIs. We used inborn infants as the study population to conduct the sensitivity analysis and got similar outcomes (eTable 7). This gives us some confidence in the reliability of our results. Another bias may come from the selection of study subjects. Our population came from a NICU-based cohort rather than a birth cohort from the overall population. We did not get data on stillbirths or abortions after ACS administration. However, a previous RCT study reported that ACS did not increase fetal loss before delivery.\u003csup\u003e3\u003c/sup\u003e In addition, when stratified by ACS course, the partial course group also showed lower risks of neonatal adverse outcomes. Fetal death in this subgroup may not be underestimated and may have biased the results less.\u003c/p\u003e\n\u003cp\u003eIn conclusion, ACS was associated with significantly reduced mortality and morbidity in VPIs born to mothers with diabetes, but with an increased risk of maternal chorioamnionitis. Further RCTs and follow-up studies are needed to confirm the benefits of administering ACS to diabetic pregnancies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors have declared no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eData sharing statement\u003c/p\u003e\n\u003cp\u003eThe data used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eDr Lei had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003eStudy concept and design: Lei, Dong, and Zhou.\u003c/p\u003e\n\u003cp\u003eAcquisition of data: Zhou.\u003c/p\u003e\n\u003cp\u003eAnalysis, or interpretation of data: Lei.\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: Lei, Zou, and Sun.\u003c/p\u003e\n\u003cp\u003eCritical review of the manuscript for important intellectual content: All authors.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: Lei.\u003c/p\u003e\n\u003cp\u003eAdministrative, technical, or material support: Zhou.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStudy supervision\u003c/em\u003e: Dong, Zhou, and Lee.\u003c/p\u003e\n\n\u003cp\u003eFunding: This work was supported by the National Key Research and Development Program of China (2021YFC2701800, 2021YFC2701801); Shanghai Science and Technology Commission\u0026apos;s Scientific and Technological Innovation Action Plan No. 21Y21900800, Canadian Institutes of Health Research (CTP87518) and the National Natural Science Foundation of China (82371710 for Wenbin Dong). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. \u003c/p\u003e\n\n\u003cp\u003eDeclaration of interests: The authors have declared no conflicts of interest.\u003c/p\u003e\n\n\u003cp\u003eData sharing statement: The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\n\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThe study was conducted following the Declaration of Helsinki and was approved by the Research Ethics Committee of the Children\u0026apos;s Hospital of Fudan University (Approval No. 2018-296). A waiver of consent was universally granted due to the utilization of deidentified patient data.\u003c/p\u003e\n\u003cp\u003eThe research adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies.\u003c/p\u003e\n\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eWe thank the data abstractors from the Chinese Neonatal Network. We thank all the staff at the Chinese Neonatal Network coordinating center for providing organizational support (Lin Yuan, PhD; Tongling Yang, RN; Hao Yuan, RN; Li Wang, RN; Yulan Lu, PhD; Jie Yang, PhD). \u003c/p\u003e\n\u003cp\u003eGroup Information of the Chinese Neonatal Network: Chairmen: Shoo K. Lee, MBBS, Mount Sinai Hospital, University of Toronto; Chao Chen, MD, Children\u0026rsquo;s Hospital of Fudan University. Vice-Chairmen: Lizhong Du, MD, Children\u0026apos;s Hospital of Zhejiang University School of Medicine; Wenhao Zhou, Children\u0026rsquo;s Hospital of Fudan University. \u003c/p\u003e\n\u003cp\u003eSite principle investigators of the Chinese Neonatal Network: Children\u0026rsquo;s Hospital of Fudan University: Yun Cao, MD; The Third Affiliated Hospital of Zhengzhou University: Xiuyong Chen, MD; Guangzhou Women and Children\u0026rsquo;s Medical Center: Huayan Zhang, MD; Tianjin Obstetrics \u0026amp; Gynecology Hospital: Xiuying Tian, MD; Gansu Provincial Maternity and Child Care Hospital: Jingyun Shi, MD; Northwest Women\u0026apos;s and Children\u0026apos;s Hospital: Zhankui Li, MD; Shenzhen Maternity and Child Health Care Hospital: Chuanzhong Yang, MD; Guizhou Women and Children\u0026rsquo;s Hospital: Ling Liu, MD; Suzhou Municipal Hospital affiliated to Nanjing Medical University: Zuming Yang, MD; Shengjing Hospital of China Medical University: Jianhua Fu, MD; Children\u0026rsquo;s Hospital of Shanxi: Yong Ji, MD; Quanzhou Women and Children\u0026rsquo;s Hospital: Dongmei Chen, MD; Fujian Women and Children\u0026rsquo;s Medical Center: Changyi YANG, MD; Children\u0026rsquo;s Hospital of Nanjing Medical University: Rui Chen , MD; Hunan Children\u0026rsquo;s Hospital: Xiaoming Peng, MD; Qingdao Women and Children\u0026rsquo;s Hospital: Ruobing Shan, MD; Nanjing Maternity and Child Health Care Hospital: Shuping Han, MD; The First Bethune Hospital of Jilin University: Hui Wu, MD; The First Affiliated Hospital of Anhui Medical University: Lili WANG, MD; Women and Children\u0026apos;s Hospital of Guangxi Zhuang Autonomous Region: Qiufen Wei, MD; The First Affiliated Hospital of Xinjiang Medical University: Mingxia Li, MD; Foshan Women and Children\u0026rsquo;s Hospital: Yiheng Dai, MD; The Affiliated Hospital of Qingdao University: Hong Jiang, MD; Henan Children\u0026rsquo;s Hospital: Wenqing Kang, MD; Children\u0026rsquo;s Hospital of Shanghai: Xiaohui Gong, MD; Chongqing Health Care Center for Women and Children: Xiaoyun Zhong, MD; Children\u0026rsquo;s Hospital of Chongqing Medical University: Yuan Shi, MD; Wuxi Maternity and Child Healthcare Hospital: Shanyu Jiang, MD; Children\u0026apos;s Hospital of Soochow University: Bing Sun, MD; People\u0026apos;s Hospital of Xinjiang Uygur Autonomous Region: Long Li, MD; Yuying Children\u0026apos;s Hospital Affiliated to Wenzhou Medical University: Zhenlang Lin, MD; Shanghai First Maternity and Infant Hospital: Jiangqin Liu, MD; Anhui Provincial Hospital: Jiahua PAN, MD; Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine: Hongping Xia, MD; Qilu Children\u0026rsquo;s Hospital of Shandong University: Xiaoying Li, MD; The First Affiliated Hospital of Zhengzhou University: Falin Xu, MD; General Hospital of Ningxia Medical University: Yinping Qiu, MD; Hebei Children\u0026rsquo;s Hospital: Li Ma, MD; Hainan Women and Children\u0026rsquo;s Hospital: Ling Yang, MD; The second Xiangya hospital of Central South University: Xiaori He, MD; Ningbo Women\u0026amp;Children Hospital: Yanhong Li, MD; Xiamen Children\u0026rsquo;s Hospital: Deyi Zhuang, MD; Shaanxi Provincial People\u0026rsquo;s Hospital: Qin Zhang, MD; The Affiliated Hospital of Southwest Medical University: Wenbin Dong, MD; Shanghai Children\u0026rsquo;s Medical Center affiliated to Shanghai Jiaotong University School of Medicine: Jianhua Sun, MD; First Affiliated Hospital of Kunming Medical University: Kun Liang, MD; Changzhou Maternal and Children Health Care Hospital: Huaiyan Wang, MD; Shenzhen Children\u0026rsquo;s Hospital: Jinxing Feng, MD; Jiangxi Provincial Children\u0026rsquo;s Hospital: Liping Chen, MD; Xiamen Maternity and Child Health Care Hospital: Xinzhu Lin, MD; Zhuhai Center for Maternal and Child Health Care: Chunming Jiang, MD; Guangdong Women and Children\u0026apos;s Hospital: Chuan Nie, MD; Wuhan Chidren\u0026apos;s Hospital: Linkong Zeng, MD; Beijing Children\u0026apos;s Hospital of Capital Medical University: Mingyan Hei, MD; Maternal and Children Hospital of Shaoxing: Hongdan Zhu, MD; The First People\u0026apos;s Hospital of Yunnan Province: Hongying MI, MD; Dehong people\u0026apos;s Hospital of Yunnan Province: Zhaoqing Yin, MD; First Affiliated Hospital of Xian Jiaotong University: Hongxia Song, MD; Inner Mongolia maternal and child health care hospital: Hongyun Wang, MD; Dalian Municipal Women and Children\u0026rsquo;s Medical Center: Dong Li, MD; Lianyungang Maternal and Children Health Hospital: Yan Gao , MD; Children\u0026apos;s Hospital Affiliated to Capital Institute of Pediatrics: Yajuan Wang, MD; Anhui Children\u0026apos;s Hoospital: Liying Dai, MD; Fuzhou Children\u0026rsquo;s Hospital of Fujian Province: Liyan ZHANG, MD; Kunming Children\u0026apos;s Hospital: Yangfang Li, MD; Shenzhen Hospital of Hongkong University: Qianshen Zhang, MD; Peking Union Medical College Hospital: Guofang Ding, MD; Obstetrics \u0026amp; Gynecology Hospital of Fudan University : Jimei Wang, MD; The Affiliated Hospital of Guizhou Medical University: Xiaoxia Chen, MD; Qinghai Women and Children Hospital: Zhen Wang, MD; The International Peace Maternity \u0026amp; Child Health Hospital of China welfare institute: Zheng Tang, MD; Children\u0026apos;s Hospital of Zhejiang University: Xiaolu Ma, MD; Inner Mongolia People\u0026apos;s Hospital: Xiaomei Zhang, MD; Xiamen Humanity Hospital: Xiaolan Zhang, MD; Shanghai General Hospital: Fang Wu, MD; The First People\u0026apos;s Hospital of Yinchuan: Yanxiang Chen, MD; The Third Hospital of Nanchang: Ying Wu, MD; Advisor: Joseph Ting, MBBS; University of Alberta.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003e\u003cem\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 Dec 25;12(12):CD004454. doi: 10.1002/14651858.CD004454.pub4.\u003c/em\u003e\u003c/li\u003e\n\u003cli\u003e\u003cem\u003eLiggins GC, Howie RN. A controlled trial\u003c/em\u003e of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. \u003cem\u003ePediatrics\u003c/em\u003e. 1972 Oct;50(4):515-25. PMID: 4561295.\u003c/li\u003e\n\u003cli\u003eWHO ACTION Trials Collaborators; Oladapo OT, Vogel JP, et al. Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries. \u003cem\u003eN Engl J Med\u003c/em\u003e. 2020 Dec 24;383(26):2514-2525. doi: 10.1056/NEJMoa2022398.\u003c/li\u003e\n\u003cli\u003eWalters AGB, Lin L, Crowther CA, Gamble GD, Dalziel SR, Harding JE. Betamethasone for Preterm Birth: Auckland Steroid Trial Full Results and New Insights 50 Years on. \u003cem\u003eJ Pediatr\u003c/em\u003e. 2023 Apr;255:80-88.e5. doi: 10.1016/j.jpeds.2022.10.028.\u003c/li\u003e\n\u003cli\u003eAbbasalizadeh F, Pouya K, Zakeri R, Asgari-Arbat R, Abbasalizadeh S, Parnianfard N. Prenatal Administration of Betamethasone and Neonatal Respiratory Distress Syndrome in Multifetal Pregnancies: A Randomized Controlled Trial. \u003cem\u003eCurr Clin Pharmacol\u003c/em\u003e. 2020;15(2):164-169. doi: 10.2174/1574884714666191007154936.\u003c/li\u003e\n\u003cli\u003eSalokorpi T, Sajaniemi N, H\u0026auml;llback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. \u003cem\u003eActa Paediatr\u003c/em\u003e. 1997 Mar;86(3):294-8. doi: 10.1111/j.1651-2227.1997.tb08893.x.\u003c/li\u003e\n\u003cli\u003eSotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental Outcome After a Single Course of Antenatal Steroids in Children Born Preterm: A Systematic Review and Meta-analysis. \u003cem\u003eObstet Gynecol\u003c/em\u003e. 2015 Jun;125(6):1385-1396. doi: 10.1097/AOG.0000000000000748.\u003c/li\u003e\n\u003cli\u003eCommittee on Obstetric Practice. Committee Opinion No. 713: Antenatal Corticosteroid Therapy for Fetal Maturation. \u003cem\u003eObstet Gynecol\u003c/em\u003e. 2017 Aug;130(2):e102-e109. doi: 10.1097/AOG.0000000000002237.\u003c/li\u003e\n\u003cli\u003eSociety for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected]; Reddy UM, Deshmukh U, Dude A, Harper L, Osmundson SS. Society for Maternal-Fetal Medicine Consult Series #58: Use of antenatal corticosteroids for individuals at risk for late preterm delivery: Replaces SMFM Statement #4, Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery, August 2016. \u003cem\u003eAm J Obstet Gynecol\u003c/em\u003e. 2021 Nov;225(5):B36-B42. doi: 10.1016/j.ajog.2021.07.023.\u003c/li\u003e\n\u003cli\u003eGarite TJ, Rumney PJ, Briggs GG, et al. A randomized placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24-28 weeks gestation. \u003cem\u003eAmerican Journal of Obstetrics and Gynecology\u003c/em\u003e 1992;166:646-51. \u003c/li\u003e\n\u003cli\u003eBalci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. \u003cem\u003eGynecol Obstet Invest\u003c/em\u003e. 2010;70(2):95-9. doi: 10.1159/000295898.\u003c/li\u003e\n\u003cli\u003eGamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. \u003cem\u003eBr J Obstet Gynaecol\u003c/em\u003e. 1989 Apr;96(4):401-10. doi: 10.1111/j.1471-0528.1989.tb02413.x. PMID: 2665800.\u003c/li\u003e\n\u003cli\u003e\u0026Ouml;zkan S, Dereli ML, Kurt D, et al. The use of late preterm antenatal corticosteroids in women with gestational diabetes : a puzzle worth solving. \u003cem\u003eBMC Pregnancy Childbirth\u003c/em\u003e. 2024 Apr 18;24(1):286. doi: 10.1186/s12884-024-06510-2.\u003c/li\u003e\n\u003cli\u003eKrispin E, Hochberg A, Chen R, Wiznitzer A, Hadar E, Borovich A. Neonatal outcome in gestational-diabetic mothers treated with antenatal corticosteroids delivering at the late preterm and term. \u003cem\u003eArch Gynecol Obstet\u003c/em\u003e. 2018 Oct;298(4):689-695. doi: 10.1007/s00404-018-4848-8.\u003c/li\u003e\n\u003cli\u003eCassimatis IR, Battarbee AN, Allshouse AA, et al. Neonatal outcomes associated with late preterm betamethasone administration in women with pregestational diabetes. \u003cem\u003ePediatr Neonatol\u003c/em\u003e. 2020 Dec;61(6):645-646. doi: 10.1016/j.pedneo.2020.07.002.\u003c/li\u003e\n\u003cli\u003eLi X, Zhang J, Hao Q, Du Y, Cheng X. The effect of time interval between antenatal corticosteroid administration and delivery on outcomes in late preterm neonates born to mothers with diabetes: a retrospective cohort study. \u003cem\u003eFront Pediatr\u003c/em\u003e. 2023 Aug 25;11:1239977. doi: 10.3389/fped.2023.1239977.\u003c/li\u003e\n\u003cli\u003eSaito K, Nishimura E, Ota E, et al. Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review. \u003cem\u003eBMJ Open\u003c/em\u003e. 2023 Sep 22;13(9):e065070. doi: 10.1136/bmjopen-2022-065070.\u003c/li\u003e\n\u003cli\u003eKerstjens JM, Bocca-Tjeertes IF, de Winter AF, Reijneveld SA, Bos AF. Neonatal morbidities and developmental delay in moderately preterm-born children. \u003cem\u003ePediatrics\u003c/em\u003e. 2012 Aug;130(2):e265-72. doi: 10.1542/peds.2012-0079.\u003c/li\u003e\n\u003cli\u003eR\u0026auml;ikk\u0026ouml;nen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. \u003cem\u003eJAMA\u003c/em\u003e. 2020 May 19;323(19):1924-1933. doi: 10.1001/jama.2020.3937.\u003c/li\u003e\n\u003cli\u003eWapner RJ, Sorokin Y, Mele L, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. \u003cem\u003eN Engl J Med\u003c/em\u003e. 2007 Sep 20;357(12):1190-8. doi: 10.1056/NEJMoa071453. PMID: 17881751.\u003c/li\u003e\n\u003cli\u003eDaskalakis G, Pergialiotis V, Domell\u0026ouml;f M, et al. European guidelines on perinatal care: corticosteroids for women at risk of preterm birth. \u003cem\u003eJ Matern Fetal Neonatal Med\u003c/em\u003e. 2023 Dec;36(1):2160628. doi: 10.1080/14767058.2022.2160628.\u003c/li\u003e\n\u003cli\u003eHei M, Li X, Shi Y, et al. Chinese Neonatal Network: a national protocol for collaborative research and quality improvement in neonatal care. \u003cem\u003eBMJ Open\u003c/em\u003e. 2022 May 2;12(5):e051175. doi: 10.1136/bmjopen-2021-051175.\u003c/li\u003e\n\u003cli\u003eXiu W, Bai R, Gu X, et al. Discharge against medical advice among infants with 24-31 weeks\u0026apos; gestation admitted to Chinese neonatal intensive care units: A multicenter cohort study. \u003cem\u003eFront Pediatr\u003c/em\u003e. 2022 Aug 16;10:943244. doi: 10.3389/fped.2022.943244.\u003c/li\u003e\n\u003cli\u003eHiggins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. \u003cem\u003eJ Pediatr\u003c/em\u003e. 2018 Jun;197:300-308. doi: 10.1016/j.jpeds.2018.01.043.\u003c/li\u003e\n\u003cli\u003eKane LT, Fang T, Galetta MS, et al. Propensity Score Matching: A Statistical Method. \u003cem\u003eClin Spine Surg\u003c/em\u003e. 2020 Apr;33(3):120-122. doi: 10.1097/BSD.0000000000000932.\u003c/li\u003e\n\u003cli\u003eBattarbee AN, Sandoval G, Grobman WA, et al. Antenatal Corticosteroids and Preterm Neonatal Morbidity and Mortality among Women with and without Diabetes in Pregnancy. \u003cem\u003eAm J Perinatol\u003c/em\u003e. 2022 Jan;39(1):67-74. doi: 10.1055/s-0040-1714391.\u003c/li\u003e\n\u003cli\u003eYao TC, Chang SM, Wu CS, et al. Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study. \u003cem\u003eBMJ\u003c/em\u003e. 2023 Aug 2;382:e075835. doi: 10.1136/bmj-2023-075835.\u003c/li\u003e\n\u003cli\u003eNinan K, Liyanage SK, Murphy KE, Asztalos EV, McDonald SD. Evaluation of Long-term Outcomes Associated With Preterm Exposure to Antenatal Corticosteroids: A Systematic Review and Meta-analysis. \u003cem\u003eJAMA Pediatr\u003c/em\u003e. 2022 Jun 1;176(6):e220483. doi: 10.1001/jamapediatrics.2022.0483.\u003c/li\u003e\n\u003cli\u003eVermillion ST, Soper DE, Newman RB. Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy. \u003cem\u003eAm J Obstet Gynecol\u003c/em\u003e. 2000 Oct;183(4):810-4. doi: 10.1067/mob.2000.108838.\u003c/li\u003e\n\u003cli\u003eMcDougall ARA, Aboud L, Lavin T, et al. Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic review. \u003cem\u003eEClinicalMedicine\u003c/em\u003e. 2023 Mar 24;58:101916. doi: 10.1016/j.eclinm.2023.101916.\u003c/li\u003e\n\u003cli\u003eJolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. \u003cem\u003eDiabetes Res Clin Pract\u003c/em\u003e. 2016 Aug;118:98-104. doi: 10.1016/j.diabres.2016.06.005.\u003c/li\u003e\n\u003cli\u003eHofer OJ, Harding JE, Tran T, Crowther CA. Maternal and infant morbidity following administration of repeat dexamethasone or betamethasone prior to preterm birth: A secondary analysis of the ASTEROID Trial. \u003cem\u003ePLoS One\u003c/em\u003e. 2022 Feb 22;17(2):e0263927. doi: 10.1371/journal.pone.0263927.\u003c/li\u003e\n\u003cli\u003eElimian A, Garry D, Figueroa R, Spitzer A, Wiencek V, Quirk JG. Antenatal betamethasone compared with dexamethasone (betacode trial): a randomized controlled trial. \u003cem\u003eObstet Gynecol\u003c/em\u003e. 2007 Jul;110(1):26-30. doi: 10.1097/01.AOG.0000268281.36788.81.\u003c/li\u003e\n\u003cli\u003eCrowther CA, Ashwood P, Andersen CC, et al. Maternal intramuscular dexamethasone versus betamethasone before preterm birth (ASTEROID): a multicentre, double-blind, randomised controlled trial. \u003cem\u003eLancet Child Adolesc Health\u003c/em\u003e. 2019 Nov;3(11):769-780. doi: 10.1016/S2352-4642(19)30292-5.\u003c/li\u003e\n\u003cli\u003eBrownfoot FC, Crowther CA, Middleton P. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e. 2008 Oct 8;(4):CD006764. doi: 10.1002/14651858.CD006764.pub2.\u003c/li\u003e\n\u003cli\u003eCiapponi A, Klein K, Colaci D, et al. Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis. \u003cem\u003eAm J Obstet Gynecol MFM\u003c/em\u003e. 2021 May;3(3):100312. doi: 10.1016/j.ajogmf.2021.100312.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\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":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Diabetes, Antenatal Corticosteroids, Neonatal Outcome, Very Preterm Infant","lastPublishedDoi":"10.21203/rs.3.rs-7107543/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7107543/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAntenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 24\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e and 33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks. Due to their significant benefit for the majority of pregnant women, an European guideline also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe Chinese Neonatal Network (CHNN), a national multicenter study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. A total of 4337 VPIs born to diabetic mothers enrolled in the present study: 3605 VPIs were exposed to ACS and 732 were not. The outcomes were mortality and severe morbidity in hospital. Logistic regression models were employed to calculate the odds ratio (OR) and its 95% confidence interval (CI) to estimate the associations between ACS and these outcomes. Stratification and sensitivity analyses were conducted to test the robustness of the results in different population.\u003c/p\u003e\u003ch2\u003eFindings:\u003c/h2\u003e\u003cp\u003eACS was associated with a lower risk in the combined outcome (death or any severe morbidity) (adjusted OR [aOR] 0.66, 95%CI: 0.54\u0026ndash;0.79), death (aOR 0.55, 95%CI 0.41\u0026ndash;0.73), and bronchopulmonary dysplasia (aOR 0.69, 95%CI 0.55\u0026ndash;0.85). However, a significantly higher risk of maternal chorioamnionitis (aOR 2.09, 95%CI 1.61\u0026ndash;2.72) was observed in the ACS group. Similar results were observed in stratification and sensitivity analyses.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eACS is associated with lower mortality and reduced morbidity in VPIs born to diabetic mothers.\u003c/p\u003e","manuscriptTitle":"Antenatal Corticosteroids in Diabetic Pregnancies and Outcomes of Very Preterm Infants: a National Multicenter Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-25 06:26:50","doi":"10.21203/rs.3.rs-7107543/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-03T16:46:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T11:15:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165097584968900103608141173141232757693","date":"2025-09-14T03:40:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-22T10:07:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-15T00:57:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-15T00:57:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-07-12T10:28:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"df133813-d4db-4589-9e99-014d8fce6708","owner":[],"postedDate":"July 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:02:02+00:00","versionOfRecord":{"articleIdentity":"rs-7107543","link":"https://doi.org/10.1007/s00431-025-06606-7","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2025-11-08 15:57:42","publishedOnDateReadable":"November 8th, 2025"},"versionCreatedAt":"2025-07-25 06:26:50","video":"","vorDoi":"10.1007/s00431-025-06606-7","vorDoiUrl":"https://doi.org/10.1007/s00431-025-06606-7","workflowStages":[]},"version":"v1","identity":"rs-7107543","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7107543","identity":"rs-7107543","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}