Effectiveness of a lifestyle intervention for pregnant women with abnormal glucose metabolism in early pregnancy (EAGM): protocol for a multicentre, open-labelled, two-arm, pragmatic randomised controlled trial - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice BMC Pregnancy Childbirth . 2026 Mar 9;26:410. doi: 10.1186/s12884-026-08908-6 Search in PMC Search in PubMed View in NLM Catalog Add to search Effectiveness of a lifestyle intervention for pregnant women with abnormal glucose metabolism in early pregnancy (EAGM): protocol for a multicentre, open-labelled, two-arm, pragmatic randomised controlled trial Lingyi Kong Lingyi Kong 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Lingyi Kong 1, 2, # , Lixia Shen Lixia Shen 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Lixia Shen 1, 2, # , Lepei Xie Lepei Xie 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Lepei Xie 1, 2 , Zhaolei Li Zhaolei Li 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Zhaolei Li 1, 2 , Caixia Zhu Caixia Zhu 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Caixia Zhu 1, 2 , Shaofeng Zhang Shaofeng Zhang 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Shaofeng Zhang 1, 2 , Yihong Huang Yihong Huang 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Yihong Huang 1, 2 , Zilian Wang Zilian Wang 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Zilian Wang 1, 2, ✉ , Haitian Chen Haitian Chen 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China Find articles by Haitian Chen 1, 2, ✉ Author information Article notes Copyright and License information 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China ✉ Corresponding author. # Contributed equally. Received 2025 Oct 2; Accepted 2026 Mar 2; Collection date 2026. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ . PMC Copyright notice PMCID: PMC13081433 PMID: 41796294 Abstract Introduction Universal screening for hyperglycaemia in women without pregestational diabetes in China has led to a significant rise in the detection of abnormal glucose metabolism in early pregnancy (EAGM), defined as elevated fasting blood glucose (FPG, 5.1–6.9 mmol/L or 92–124 mg/dL) and/or haemoglobin A1c (HbA1c, 5.7%-6.4% or 41–47 mmol/mol) levels in the first trimester (< 14 weeks' gestation). EAGM is correlated with adverse pregnancy outcomes. However, whether early treatment can improve maternal and neonatal outcomes remains unclear. Methods We present a protocol (V1.0, date August 15, 2024) for the EAGM trial, which is a multicentre, open-labelled, two-arm, pragmatic randomised controlled trial in China. Eligible pregnancies with EAGM will be recruited from 17 hospitals. Participants (N = 3430) will be randomly allocated in a 1:1 ratio to the intervention group or the control group. The intervention group will begin early lifestyle intervention combined with routine prenatal care from < 15 weeks' gestation, while the control group will receive routine prenatal care alone. All participants will undergo an oral glucose tolerance test at 24–28 weeks' gestation, and whether to continue the intervention will depend on the test result. The primary outcome is a composite neonatal outcome of large-for-gestational-age and preterm birth at < 37 weeks' gestation. Discussion The EAGM trial is the first large-scale randomised controlled trial in China designed to evaluate the effectiveness of early lifestyle intervention for pregnant women with EAGM, identified by elevated HbA1c and/or FPG before 14 weeks' gestation. The findings are anticipated to provide high-quality evidence to guide future screening strategies and clinical management of early hyperglycaemia in pregnancy. Trial registration ClinicalTrials.gov: NCT06767722 . Registered 10 January 2025. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-026-08908-6. Keywords: Early Pregnancy, Fasting Plasma Glucose, Haemoglobin A1c, Lifestyle Intervention, Pregnancy Outcomes Background The increasing prevalence of hyperglycaemia in pregnancy has emerged as a critical public health challenge in perinatal healthcare in China. In current clinical practice, glucose screening is routinely performed during the first prenatal visit for women without pregestational diabetes. The widespread use of screening has resulted in a significant increase in the detection of abnormal glucose metabolism in early pregnancy (EAGM), defined as elevated fasting blood glucose (FPG, 5.1–6.9 mmol/L or 92–124 mg/dL) and/or haemoglobin A1c (HbA1c, 5.7%−6.4% or 41–47 mmol/mol) levels in the first trimester (< 14 weeks' gestation) below diagnostic thresholds for diabetes. Previous evidence indicates that both elevated FPG and HbA1c are correlated with gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, large-for-gestational-age (LGA) infants, macrosomia, primary caesarean delivery, preterm birth, and neonatal distress [ 1 – 6 ]. Our multicenter retrospective cohort study also demonstrated that, after adjustment for potential confounders, women with EAGM had significantly higher risks of GDM (adjusted odds ratio [aOR] 3.85, 95% confidential interval [CI] 3.51–4.20), gestational hypertension (aOR 1.42, 95%CI 1.20–1.67), macrosomia (aOR 1.43, 95%CI 1.19–1.73), and preterm birth (aOR 1.30, 95%CI 1.11–1.52) compared to those with normoglycaemia [ 7 ]. These complications, particularly GDM, are independently associated with long-term cardiometabolic risks for both mothers and their offspring [ 8 ]. Whether early screening and intervention for women with EAGM can improve maternal and neonatal outcomes remains unclear. A systematic review examined randomised controlled trials comparing early (< 20 weeks' gestation) versus routine (≥ 20 weeks' gestation) screening for hyperglycaemia in pregnancy to assess the effects of early screening and treatment on pregnancy outcomes [ 9 ]. The findings suggested that early screening (primarily using HbA1c) and subsequent intervention significantly reduced the risk of LGA infants with a relative risk (RR) of 0.29 (95% CI 0.09–0.90), favouring early assessment in pregnancy. The main limitation of this meta-analysis was the heterogeneity of the trial design, including screening strategies, methods, and diagnostic criteria. Another limitation was the small sample sizes of the included trials. More recently, the TOBOGM trial investigated whether immediate treatment of early GDM (identified by a 75 g oral glucose tolerance test [OGTT] using WHO 2013 criteria) before 20 weeks' gestation improved pregnancy outcomes in women with risk factors [ 10 ]. The intervention followed standard GDM management, with three primary outcomes assessed, including a composite of adverse neonatal outcomes, pregnancy-related hypertension, and neonatal lean body mass. The results showed a modestly lower incidence of a composite of adverse neonatal outcomes in the intervention group than the control group, while no significant differences were observed for the other two primary outcomes. Moreover, subgroup analyses suggested the possibility of a greater effect of the intervention on the composite adverse neonatal outcome among the women who underwent OGTT at less than 14 weeks' gestation than among those who underwent OGTT at ≥ 14 weeks' gestation. The TOBOGM trial has indicated the potential for improved neonatal outcomes through the management of women with early hyperglycaemia identified before 14 weeks' gestation. It should be noted that OGTT is still not recommended as routine screening in early pregnancy. Thus, there is still a need to determine whether early treatment for pregnant women with mild hyperglycaemia using alternative testing and diagnostic criteria, such as FPG and HbA1c, and with screening in all women, improves pregnancy outcomes. Existing evidence has not evaluated universal first-trimester screening, and no studies have specifically focused on Asian populations. Given the possibility of ethnic variations in EAGM and its relationship with pregnancy outcomes, a large, randomised trial is warranted in China to assess the impact of lifestyle intervention for the prevention of adverse maternal and neonatal outcomes in women with EAGM. Based on the existing evidence, in this trial, we define pregnant women with HbA1c 5.7%−6.4% and/or FPG 5.1–6.9 mmol/L before 14 weeks of gestation as EAGM, aiming to identify those at higher risk of adverse pregnancy and neonatal outcomes. We note that some organizations, such as the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the American College of Obstetricians and Gynecologists identify this group of women as early GDM [ 11 ]. However, we use the term EAGM instead of early GDM, as our focus is on reducing the risk of adverse maternal and neonatal outcomes associated with hyperglycaemia in pregnancy. We hypothesised that, for women with EAGM in the first trimester, early lifestyle intervention combined with routine prenatal care would lead to a reduction in the incidence of adverse composite neonatal outcomes, compared to routine prenatal care alone. The findings could provide high-quality evidence to inform management strategies for EAGM and support the integration of early glucose screening into standard prenatal care. Moreover, this trial may help to mitigate the public health burden associated with hyperglycaemia-related adverse outcomes in mothers and their offspring. The primary objective of the EAGM trial is to assess whether the application of a lifestyle intervention, in addition to routine prenatal care, is superior to routine prenatal care alone for preventing LGA or preterm birth in babies born to pregnant women with EAGM. The secondary objectives are to estimate the difference between groups concerning other important maternal and neonatal outcomes, and to evaluate the cost-effectiveness of early lifestyle intervention in women with EAGM. Methods Trial design and setting A multicentre, parallel-group, open-label, pragmatic, randomised controlled trial will be conducted to evaluate the effect of early lifestyle intervention in women with EAGM. This study will be conducted in 17 hospitals across China. The recruitment was initiated on April 16, 2025, and the trial is expected to be completed by June 2027. Eligibility criteria Pregnant women will be invited to participate in this study if they meet the following inclusion criteria: (1) Over 18 years of age; (2) Singleton pregnancies; (3) An abnormal glucose metabolism determined by a blood test performed prior to 14 weeks' gestation, defined as FPG 5.1–6.9 mmol/L and/or HbA1c 5.7–6.4%; (4) Able to provide informed consent. Exclusion criteria: (1) Pregestational diabetes (diagnosed as diabetes mellitus before pregnancy, or FPG ≥ 7.0 mmol/L or HbA1c ≥ 6.5% at the first prenatal visit), impaired fasting glucose, or impaired glucose tolerance diagnosed before pregnancy. (2) Plan for termination of pregnancy due to foetal anomaly identified at the first trimester scan. (3) Use of medications known to interfere with glucose metabolism (e.g., corticosteroids, antipsychotic drugs) at the time of randomisation. (4) Any other physical (serious medical conditions such as cancer, organ failure, epilepsy, paraplegia, disability) or psychological condition (e.g., learning difficulties, serious mental illness) that is likely to interfere with the conduct of the trial according to evaluation by the trial monitoring group. (5) Women currently with hyperemesis gravidarum leading to dehydration or requiring hospitalisation. Intervention Participants randomised to the intervention group will receive lifestyle intervention in addition to routine prenatal care. The intervention strategy aligns with the standard GDM care for women diagnosed with GDM at 24–28 weeks' gestation, but it is implemented earlier at 11–14 weeks' gestation for women diagnosed with EAGM. In our trial, the intervention will consist of one initial educational session followed by five follow-up sessions every four weeks. The face-to-face educational session will be conducted by qualified dieticians, nurses, or obstetricians, which consists of education about hyperglycaemia, advice on lifestyle intervention, instructions on self-monitoring of blood glucose (SMBG), and medical therapy. The contents of the education session are consistent with local guidelines or practice, and details are shown in Supplementary Material. Participants in the intervention group will initiate SMBG along with lifestyle intervention after attending the educational session. Participants will perform SMBG with finger sticks using calibrated devices. The optimal target of blood glucose includes fasting glucose 3.3–5.3 mmol/L, one-hour postprandial glucose < 7.8 mmol/L, and two-hour postprandial glucose ≤ 6.7 mmol/L [ 12 ]. Initially, participants are required to perform the four-time SMBG (fasting and two-hour postprandial) for three consecutive days. If the optimal target is reached, the SMBG frequency can be reduced to four times daily for at least one day a week. All the results of SMBG, diet, and physical activity will be recorded on telehealth applications or a paper sheet. Insulin therapy will be considered when target glucose levels cannot be consistently achieved through dietary therapy and exercise. Participants who need insulin therapy will be admitted to the hospital, where obstetricians and physicians will assess their conditions and decide whether to initiate insulin therapy. Participants who are already receiving insulin therapy at the time of the OGTT at 24–28 weeks will continue therapy regardless of the 75 g OGTT test result. The trial flowchart is shown in Fig. 1 . Fig. 1. Open in a new tab Flowchart of EAGM trial design. Abbreviations: FPG: Fasting plasma glucose; HbA1c: Haemoglobin A1c; EAGM: Early abnormal glucose metabolism; GDM: Gestational diabetes mellitu s ; OGTT: 75 g Oral glucose tolerance test The follow-up sessions will be conducted in person, via telephone, or Wechat by a trained research assistant, which include review of SMBG records, dietary and physical activity feedback, and reinforcement for adherence to SMBG and lifestyle intervention goals. The research assistant will provide support to address any potential barriers and challenges as needed. The timeline of participants is summarized in Fig. 2 . Fig. 2. Open in a new tab Participant Timeline for EAGM trial design. Abbreviations: HbA1c: Haemoglobin A1c; FPG: Fasting plasma glucose; CRF: Case report form Participants in the intervention group will also follow routine prenatal care in addition to the treatment before the OGTT test taken between 24 and 28 weeks' gestation. The frequency of prenatal visits will be the same as the control group and can be increased if the participant has suboptimal glycaemic control or other medical or obstetric conditions according to obstetricians' decisions. Following the OGTT test between 24 and 28 weeks' gestation, whether to continue the intervention depends on the OGTT results. Participants diagnosed with GDM or overt diabetes will continue lifestyle intervention and SMBG in addition to routine prenatal care, while those with normal OGTT test results will discontinue intervention and follow the routine prenatal care, but they will still be advised to maintain a healthy lifestyle. Comparison Participants in the control group will receive routine prenatal care following Chinese clinical guidelines [ 12 ]. Routine prenatal care between 14 and 28 weeks' gestation will include: (1) Prenatal visit once every 4 weeks, the frequency of which can be increased according to obstetricians' decisions if the participant has other medical or obstetric conditions; (2) Weight and blood pressure measurement during each prenatal visit; (3) Routine anomaly scan at 20–24 weeks' gestation; (4) 75 g OGTT test at 24–28 weeks' gestation. Routine prenatal care from 28 weeks' gestation for participants with negative OGTT results will include: (1) Prenatal visits once biweekly from 28 to 35 weeks' gestation and once weekly from 36 weeks' gestation to delivery. The frequency can be increased according to obstetricians' decisions if the participant has other medical or obstetric conditions; (2) Weight and blood pressure measurement during each prenatal visit; (3) Routine ultrasound scans at 30–32 weeks and 36–37 weeks' gestation. Routine prenatal care from 28 weeks' gestation for participants diagnosed with GDM or overt diabetes will include: (1) Follow routine prenatal care as described in women with normal blood glucose level; (2) Initiate lifestyle intervention and SMBG as per local guidelines. Participants in the intervention group will utilise a dedicated telehealth application to log dietary intake, exercise frequency/duration, and SMBG results. Researchers will monitor adherence through the application's backend system and provide timely feedback by sending messages to remind participants to submit their records promptly or sending tailored health advice if any intervention is deemed inappropriate. Outcomes The primary outcome will be a composite of LGA (neonatal birthweight > 90th percentile for the same gestational age and sex using a normal range derived from the Chinese population [ 13 ]) and preterm birth (delivery at < 37 weeks' gestation). Secondary outcome The key second outcome will be pregnancy-related hypertensive disorders according to the International Society for the Study of Hypertension in Pregnancy criteria [ 14 ], including gestational hypertension, preeclampsia, and eclampsia. Other maternal outcomes will be diagnosis of GDM (according to IADPSG criteria [ 11 ]), prescription of hypoglycaemic drugs, preeclampsia requiring delivery before 37 weeks' gestation, total gestational weight gain (kg), mode of delivery (vaginal birth, assisted vaginal birth, elective pre-labour Caesarean section, emergency pre-labour Caesarean section, emergency Caesarean section in labour), maternal hypoglycaemia (number of glucose measurements < 3.3 mmol/L), severe maternal hypoglycaemia (symptomatic hypoglycaemia such as faint, fatigue or shiver, which needs urgent help). Other neonatal outcomes will be any of the components of primary outcome including LGA or preterm birth, macrosomia (birthweight ≥ 4000 g), neonatal birthweight (g), small-for-gestational-age (SGA) (neonatal birthweight < 10th percentile for the same gestational age and sex using a normal range derived from the Chinese population [ 13 ]), gestational age at birth, preterm birth at < 34 weeks' gestation, Apgar score at 1 min and 5 min after birth, neonatal hypoglycaemia (blood glucose level < 2.6 mmol/L [ 15 ]), admission to neonatal wards or intensive care unit (including principal recorded indication for admission, and length of stay in neonatal wards or intensive care unit), miscarriage (foetal loss < 24 weeks' gestation), stillbirth (foetal loss ≥ 24 weeks' gestation), termination of pregnancy, early neonatal death (from birth up to 7 days after birth), late neonatal death (between 7 and up to 28 days from birth). All the outcomes mentioned above will be collected up to primary hospital discharge, or 28 days after the estimated date of delivery, whichever is sooner. Adverse events Adverse Events AE associated with lifestyle interventions are infrequently observed in pregnancy studies, with SGA infants representing the primary reported occurrence, which was already captured within our trial endpoints. While insulin therapy may be required for a minority of participants, its safety is well-established. Our AE monitoring will focus specifically on events with probable intervention-related causality, including maternal and neonatal hypoglycaemia, which will be systematically recorded in the electronic case report forms. Sample size The sample size calculations are driven by the primary outcome (neonatal composite of LGA or preterm birth). A control group event rate for the primary outcome is assumed to be 24% based on local retrospective data. To test a 4.8% absolute risk reduction on the composite outcomes, a sample size of 3086 women will have 90% power to detect a relative risk reduction of 20%, with a 5% two-sided significance level. Allowing for up to 10% loss to follow-up would require a total sample size of approximately 3430 women, 1715 women per group. A 4.8% target difference is reasonable given this is the same size of difference observed in meta-analysis [ 16 ] (4.9%) and large-scale randomised trial [ 10 ] (5.6%). Based on local data, the proportion of women in the target population expected to have EAGM is around 8.4%. Assuming a recruitment rate of 75%, we need to screen 54,445 singleton pregnancies. Recruitment Eligible women will be contacted via telephone by a trained research team member to assess participation interest. Willing participants will receive further information provided by the research team with full knowledge of the trial via telephone or face-to-face. If the woman wishes to participate and confirms eligibility, electronic informed consent will be obtained. The participant data will be entered into a customised bespoke web-based database integrated with an electronic data capture (EDC) system via DAP Software (Beijing) ( www.nextedc.cn ). Randomisation Following consent, the research team member will randomise participants in a 1:1 allocation ratio based on a computer-generated random sequence using a central randomisation system. Randomisation is stratified by pre-pregnancy body mass index (BMI) (≥ 24.0 versus < 24.0 kg/m 2 ) and maternal age (≥ 35 versus < 35 years old) using permuted block randomisation to ensure balanced allocation. Blinding Given the behavioural nature of the lifestyle intervention, this open-label trial does not mask participants, healthcare providers, and outcome assessors. All data analysts will remain blinded to allocation unless unblinding is required by the data monitoring committee (DMC) for specific analyses or data validation purposes. Data collection and management All trial data will be stored and archived in accordance with China's Guidelines for Planning and Reporting of Drug Clinical Trial Data Management and Statistical Analysis (2016, No. 113) and Good Clinical Practice standards (GCP, 2020, No. 57). During enrolment, demographic data will be collected based on memories and the first prenatal examination, including general information, medical history, family history, obstetric history, blood pressure, and weight at the first prenatal examination. Laboratory results will include FBG, HbA1c in the first trimester, OGTT results during 24–28 weeks' gestation. On every follow-up visit, information on medicine usage, AE, and hospitalisation since the last visit will be collected. If an ultrasound is performed between two visits, the result will be recorded by the researchers. Data on pregnancy outcomes will be collected from the hospital maternity records. All study data, including demographic characteristics, laboratory results, follow-up visit information, and pregnancy outcomes, will be entered into the EDC system by trained researchers. Statistical methods The primary comparison groups will be composed of those randomised to lifestyle intervention plus routine prenatal care versus those randomised to routine prenatal care. The data analysis will primarily be based on the intention-to-treat principle, whereby participants will be analysed according to their original randomisation group regardless of subsequent compliance or protocol deviations. For each outcome measure, we will present appropriate summary statistics by treatment group, accompanied by point estimates and their corresponding 95% CI. Binary outcomes, including both primary and secondary outcomes, will be analysed using log-binomial regression models to derive adjusted risk ratios and risk differences with 95% CI, adjusting for relevant variables. The p-value associated with the intervention group parameter from the relative risk estimation model will be reported. Continuous outcomes will be analysed through linear regression models if the outcome is sufficiently normally distributed (or where data can be suitably transformed), with results expressed as mean differences and 95% CI. For skewed continuous variables, unadjusted median differences with 95% CI will be presented. Regarding the key secondary outcome of pregnancy-related hypertensive disorders, we will incorporate a conditional hierarchical approach to hypothesis testing to ensure appropriate control for the overall rate of type I error. Superiority testing for this outcome will only be conducted if the primary outcome demonstrates statistically significant differences. In such cases, we will consider the secondary outcome to show superiority if either the p-value from the model is ≤ 0.05 or the 95% CI for the effect estimate excludes the null value. Monitoring An independent DMC has been established to periodically evaluate trial progress, safety data, and critical efficacy outcomes, advising the sponsor on trial continuation, modification, or termination. All data analyses will be reviewed by the DMC, which will convene at least annually as stipulated in its charter, unless circumstances necessitate schedule modification. Emergency meetings may be called should safety concerns arise. While no interim analyses are planned, the DMC retains the authority to recommend trial discontinuation should any concerns regarding participant safety emerge. The Trial Management Group (TMG) will oversee all aspects of trial conduct through a combination of on-site and central monitoring strategies. Monthly TMG meetings will ensure protocol compliance and facilitate timely interventions to protect both participant welfare and trial integrity. The DMC and the TMG will report to the trial steering committee, which is responsible for providing overall trial oversight through annual meetings and additional sessions as trial requirements dictate. Patient and public involvement During the trial, we will take a flexible approach, such as individual interviews or targeted consultations, to gather feedback from women with EAGM or a history of GDM. This input is intended to refine recruitment strategies and materials, improve data collection tools, and develop strategies to enhance participant recruitment and adherence. Throughout the study, we will also collect information on the usability of the telehealth application and the perceived burden of follow-up procedures. All feedback will contribute to the improvement of the intervention and follow-up processes. Discussion This trial will evaluate the effectiveness of an early lifestyle intervention for women with EAGM, which combines dietary therapy, physical activity, weight management, and SMBG from the first trimester, compared with routine prenatal care alone for preventing EAGM-related adverse outcomes. Meanwhile, this trial will evaluate the cost-effectiveness of early lifestyle intervention in women with EAGM. To our knowledge, the EAGM trial is the first large-scale, multicentre randomised controlled trial focusing on EAGM management in China. We respond to the globally rising prevalence of hyperglycaemia by focusing on the population with EAGM before standard diagnostic timing. Through early lifestyle intervention, we aim to reduce the risk of subsequent adverse maternal and neonatal outcomes. Our findings will not only address a critical evidence gap but also provide vital evidence to inform future screening and intervention strategies for women with EAGM. The universal screening approach and lifestyle intervention implemented in this Chinese population enhance the generalisability of our results to other healthcare settings, including low- and middle-income countries. Major guidelines present different strategies for screening hyperglycaemia in early pregnancy. The American Diabetes Association (ADA) recommends screening before 15 weeks using FPG or HbA1c to identify overt diabetes [ 17 ]. The IADPSG advocates universal screening with FPG, HbA1c, or random plasma glucose in populations with high type 2 diabetes prevalence [ 11 ]. The Chinese guideline supports universal FPG screening at the first prenatal visit [ 18 ]. Although overt diabetes is consistently defined as FPG ≥ 7.0 mmol/L or HbA1c ≥ 6.5%, diagnostic thresholds for EAGM vary across guidelines [ 12 ]. Studies involving Chinese populations have linked FPG ≥ 5.1 mmol/L to adverse outcomes such as macrosomia, hypertensive disorders, and preterm birth [ 19 – 22 ]. For HbA1c, while IADPSG and ADA recommend a risk threshold of 5.9%−6.4% based largely on Caucasian populations [ 3 , 23 ], studies in South-Central Asians indicate that values ≥ 5.7% may increase the risk of macrosomia and preeclampsia, suggesting ethnic variations in optimal cut-offs [ 4 , 24 ]. Data specific to East Asian populations remain limited. We defined our primary outcome as a composite neonatal measure encompassing LGA and preterm birth because they are among the most frequent adverse outcomes associated with EAGM and both can be objectively assessed. In conclusion, this trial is among the first large-scale randomised controlled investigations in China to evaluate the benefits of early lifestyle intervention for pregnant women identified with EAGM (defined by elevated HbA1c and/or FPG) before 14 weeks' gestation. By focusing specifically on an Asian population, this trial addresses a significant evidence gap regarding ethnic variations in glycaemic thresholds and their association with adverse pregnancy outcomes. The findings are anticipated to provide high-quality evidence to guide future screening strategies and clinical management of early hyperglycaemia in pregnancy. Supplementary Information Supplementary Material 1. (28.8KB, docx) Supplementary Material 2. (24.4KB, docx) Acknowledgements We are grateful to Professor KK Cheng, Professor Katie Morries, Professor Louise J Jackson, Mr Lee Middleton, Dr Kumarendran Balachandran, Dr Lin Hu, and Dr Fangzhou Xu (University of Birmingham, UK) for their valuable suggestions and discussions. Abbreviations EAGM Early abnormal glucose metabolism FPG Fasting plasma glucose HbA1c Haemoglobin A1c LGA Large-for-gestational-age GDM Gestational diabetes mellitus aOR Adjusted odds ratio CI Confidential Interval RR Relative risk OGTT 75G Oral glucose tolerance test IADPSG International Association of Diabetes and Pregnancy Study Groups SMBG Self-monitoring of blood glucose GWG Gestational weight gain SGA Small-for-gestational-age AE Adverse Event EDC Electronic Data Capture DMC Data Monitoring Committee TMG Trial Management Group ADA American Diabetes Association Author’s contributions LS and HC were responsible for the study conception and design. LS and LK were responsible for the drafting of the manuscript. LX, ZL, CZ, SZ and YH were responsible for methodology and manuscript preparation. LS, LK and HC made critical revisions to the paper for important intellectual content. HC and ZW supervised the study. All authors read and approved the final manuscript. Funding The EAGM trial is funded by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0532100), Major clinical projects of Guangzhou Municipality (2024P-ZD12), and Sun Yat-Sen University Clinical Research 5010 Program (2022004). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of this protocol manuscript for publication. Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate Ethical approval for the study was obtained from the Clinical Research and Laboratory Animal Ethics Committee, The First Affiliated Hospital of Sun Yat-sen University ([2024]645). The study is registered at ClinicalTrials.gov. Electronic informed consent will be obtained from each participant before performing any trial-related activities by the researchers. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Footnotes Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Lingyi Kong and Lixia Shen contributed equally to this paper as co-first authors. Contributor Information Zilian Wang, Email: [email protected]. Haitian Chen, Email: [email protected]. References 1. Wei YM, Liu XY, Shou C, Liu XH, Meng WY, Wang ZL, et al. 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