{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:01:59Z","timestamp":1790874119697,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Macrosomia, a critical perinatal complication, is closely linked to maternal obesity and gestational diabetes mellitus (GDM). However, the extent to which GDM status modifies the association between pre-pregnancy body mass index (BMI) and macrosomia, particularly across demographic subgroups, remains poorly understood. This study aimed to quantify glycemic status-specific risk thresholds and explore subgroup interactions in a large prospective cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective cohort study, 34,031 women initiating antenatal care before 14\u202fweeks of gestation were enrolled at a tertiary hospital in Central China (2013\u20132019). Participants were stratified by GDM status and pre-pregnancy BMI categories. Multivariable logistic regression, restricted cubic spline (RCS) models, and interaction analyses evaluated associations between BMI and macrosomia (birth weight \u2265 4,000\u202fg), adjusting for sociodemographic, behavioral, and clinical covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Macrosomia incidence was markedly higher in GDM (6.2%) vs. non-GDM pregnancies (3.6%). Adjusted models revealed a steeper dose\u2013response gradient in GDM: each 1-unit BMI increase conferred 24% higher odds (aOR: 1.24 [95% CI 1.20, 1.28]) in GDM vs. 13% (aOR: 1.13 [1.11, 1.15]) in non-GDM. Obesity amplified risk 6.80-fold (aOR: 6.80 [4.02, 11.51]) in GDM vs. 4.70-fold (aOR: 4.70 [3.12, 7.10]) in non-GDM. RCS models identified nonlinear trajectories in both GDM and non-GDM pregnancies (reference level: 22.94\u202fkg\/m<jats:sup>2<\/jats:sup> for GDM and 25.10\u202fkg\/m<jats:sup>2<\/jats:sup> for non-GDM). Significant interactions were observed in GDM pregnancies, and the association between pre-pregnancy BMI values and macrosomia was stronger in women &amp;lt; 35\u202fyears (aOR: 1.29 vs. \u226535\u202fyears, aOR: 1.15), primigravida (aOR: 1.61 vs. multigravida, aOR: 1.18), primiparous (aOR: 1.36 vs. multiparous, aOR: 1.18), and female infants (aOR: 1.29 vs. male, aOR: 1.20). In non-GDM pregnancies, only parity (primiparous, aOR: 1.08 vs. multiparous, aOR: 1.19) and gravidity (primigravida, aOR: 1.05 vs. multigravida, aOR: 1.19) modified the pre-pregnancy BMI-macrosomia relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GDM status modifies pre-pregnancy BMI-associated macrosomia risks, with distinct thresholds and subgroup vulnerabilities. These findings necessitate glycemic status-specific clinical guidelines and precision interventions targeting high-risk subgroups. Universal preconception weight optimization remains pivotal for non-GDM populations. This study underscores the urgency of integrating metabolic and demographic heterogeneity into perinatal care to mitigate the dual epidemics of overweight\/obesity and GDM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1633088","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T04:10:37Z","timestamp":1750997437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pre-pregnancy body mass index and risk of macrosomia: glycemic status-specific thresholds and subgroup interactions in a prospective cohort"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuhang","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabi","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1080\/00016340801899289","article-title":"The macrosomic fetus: a challenge in current obstetrics","volume":"87","author":"Henriksen","year":"2008","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/uog.20279","article-title":"Maternal and neonatal complications of fetal macrosomia: systematic review and meta-analysis","volume":"54","author":"Beta","year":"2019","journal-title":"Ultrasound Obstet Gynecol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/ijo.2009.131","article-title":"Fetal macrosomia and adolescence obesity: results from a longitudinal cohort study","volume":"33","author":"Wang","year":"2009","journal-title":"Int J Obes"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0301-2115(03)00154-4","article-title":"Risk factors for macrosomia and its clinical consequences: a study of 350, 311 pregnancies","volume":"111","author":"Jolly","year":"2003","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/uog.20278","article-title":"Maternal and neonatal complications of fetal macrosomia: cohort study","volume":"54","author":"Beta","year":"2019","journal-title":"Ultrasound Obstet Gynecol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3389\/fphar.2015.00103","article-title":"Health economic modeling to assess short-term costs of maternal overweight, gestational diabetes, and related macrosomia a pilot evaluation","volume":"6","author":"Lenoir-Wijnkoop","year":"2015","journal-title":"Front Pharmacol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/S0140-6736(12)61605-5","article-title":"Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey","volume":"381","author":"Koyanagi","year":"2013","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12916-021-02046-w","article-title":"Differential effect of pre-pregnancy low BMI on fetal macrosomia: a population-based cohort study","volume":"19","author":"Li","year":"2021","journal-title":"BMC Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1111\/obr.12455","article-title":"Association between perinatal outcomes and maternal pre-pregnancy body mass index","volume":"17","author":"Liu","year":"2016","journal-title":"Obes Rev"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.3390\/nu14163347","article-title":"Gestational diabetes mellitus and high triglyceride levels mediate the association between pre-pregnancy overweight\/obesity and macrosomia: a prospective cohort study in Central China","volume":"14","author":"Song","year":"2022","journal-title":"Nutrients"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.ajog.2007.10.796","article-title":"Impact of maternal body mass index on neonate birthweight and body composition","volume":"198","author":"Hull","year":"2008","journal-title":"Am J Obstet Gynecol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1530\/REP-10-0088","article-title":"Obesity, insulin resistance, and pregnancy outcome","volume":"140","author":"Catalano","year":"2010","journal-title":"Reproduction"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.diabres.2019.06.014","article-title":"Interactive effects of prepregnancy overweight and gestational diabetes on macrosomia and large for gestational age: a population-based prospective cohort in Tianjin, China","volume":"154","author":"Yang","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"123207","DOI":"10.1016\/j.lfs.2024.123207","article-title":"Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: the role of EGFR signaling and placental syncytiotrophoblast","volume":"359","author":"Xu","year":"2024","journal-title":"Life Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e067946","DOI":"10.1136\/bmj-2021-067946","article-title":"Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis","volume":"377","author":"Ye","year":"2022","journal-title":"BMJ"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e26763","DOI":"10.7759\/cureus.26763","article-title":"Fetal macrosomia among non-diabetic women: our experience in a developing country","volume":"14","author":"Shafqat","year":"2022","journal-title":"Cureus"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/S0140-6736(18)30313-1","article-title":"Intervention strategies to improve nutrition and health behaviours before conception","volume":"391","author":"Barker","year":"2018","journal-title":"Lancet"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/OGX.0000000000001261","article-title":"Antenatal care: a comparative review of guidelines","volume":"79","author":"Boureka","year":"2024","journal-title":"Obstet Gynecol Surv"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"101637","DOI":"10.1016\/j.eclinm.2022.101637","article-title":"Development, validation and clinical utility of a risk prediction model for adverse pregnancy outcomes in women with gestational diabetes: the PeRSonal GDM model","volume":"52","author":"Cooray","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e001931","DOI":"10.1136\/bmjpo-2023-001931","article-title":"Maternal anaemia during early pregnancy and the risk of neonatal outcomes: a prospective cohort study in Central China","volume":"8","author":"Chen","year":"2024","journal-title":"BMJ Paediatr Open"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/01.aog.0000425667.10377.60","article-title":"ACOG Committee opinion no. 549: obesity in pregnancy","volume":"121","year":"2013","journal-title":"OBGYN"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1111\/1471-0528.14599","article-title":"WHO recommendations on antenatal care for a positive pregnancy experience-going beyond survival","volume":"124","author":"Tun\u00e7alp","year":"2017","journal-title":"BJOG"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1080\/01443610400007828","article-title":"Mode of delivery and birth outcomes of macrosomic infants","volume":"24","author":"Boulet","year":"2004","journal-title":"J Obstet Gynaecol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00404-017-4573-8","article-title":"Maternal pre-pregnancy obesity and the risk of macrosomia: a meta-analysis","volume":"297","author":"Dai","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1016\/j.wombi.2017.06.003","article-title":"Maternal pre-pregnancy body mass index, gestational weight gain influence birth weight","volume":"31","author":"Zhao","year":"2018","journal-title":"Women Birth"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1080\/14767058.2016.1252746","article-title":"Risk factors and outcomes of macrosomia in China: a multicentric survey based on birth data","volume":"30","author":"Wang","year":"2017","journal-title":"J Matern Fetal Neonatal Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"4231","DOI":"10.1210\/jc.2002-020311","article-title":"Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways","volume":"87","author":"Ramsay","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.3390\/biom5043142","article-title":"Immune mechanisms linking obesity and preeclampsia","volume":"5","author":"Spradley","year":"2015","journal-title":"Biomol Ther"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1146\/annurev-immunol-031210-101322","article-title":"Inflammatory mechanisms in obesity","volume":"29","author":"Gregor","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.3390\/nu14051072","article-title":"Pre-pregnancy body mass index and risk of macrosomia and large for gestational age births with gestational diabetes mellitus as a mediator: a prospective cohort study in Central China","volume":"14","author":"Song","year":"2022","journal-title":"Nutrients"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1159\/000295710","article-title":"Insulin resistance, a link between maternal overweight and fetal macrosomia in nondiabetic pregnancies","volume":"74","author":"Ahlsson","year":"2010","journal-title":"Horm Res Paediatr"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1186\/s12884-023-05657-8","article-title":"Associations of maternal pre-pregnancy BMI and gestational weight gain with the risks of adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus","volume":"23","author":"Ke","year":"2023","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3109\/00016348909021017","article-title":"Uterine size, parity and umbilical cord length","volume":"68","author":"S\u00f8rnes","year":"1989","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1046\/j.1365-3016.11.s1.7.x","article-title":"Does changing paternity contribute to the risk of intrauterine growth retardation?","volume":"11","author":"Krulewitch","year":"1997","journal-title":"Paediatr Perinat Epidemiol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1097\/CM9.0000000000002077","article-title":"Prevalence and characteristics of macrosomia in the first and subsequent pregnancy: a multi-center retrospective study","volume":"135","author":"Juan","year":"2022","journal-title":"Chin Med J"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejogrb.2020.06.004","article-title":"Pre-pregnancy maternal obesity, macrosomia, and risk of stillbirth: a population-based study","volume":"252","author":"Ikedionwu","year":"2020","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.placenta.2021.01.024","article-title":"The impact of advanced maternal age on pregnancy and offspring health: a mechanistic role for placental angiogenic growth mediators","volume":"106","author":"Biagioni","year":"2021","journal-title":"Placenta"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.2337\/dc11-0728","article-title":"Determinants of body fat in infants of women with gestational diabetes mellitus differ with fetal sex","volume":"34","author":"Lingwood","year":"2011","journal-title":"Diabetes Care"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.2337\/dc07-1485","article-title":"Fetal programming of type 2 diabetes: is sex important?","volume":"30","author":"Yajnik","year":"2007","journal-title":"Diabetes Care"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2458-9-421","article-title":"Accuracy and usefulness of BMI measures based on self-reported weight and height: findings from the NHANES & NHIS 2001-2006","volume":"9","author":"Stommel","year":"2009","journal-title":"BMC Public Health"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1633088\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T04:10:38Z","timestamp":1750997438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1633088\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":40,"alternative-id":["10.3389\/fnut.2025.1633088"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1633088","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]},"article-number":"1633088"}}