孕早中期体质量指数轨迹与早产之间的因果多中介分析^*

Causal Multiple Mediation Analysis of the Association Between Early and Mid-Pregnancy Body Mass Index Trajectories and Preterm Birth

摘要

目的 探讨孕早中期体质量指数（body mass index, BMI）轨迹与早产的关联，并探究妊娠期糖尿病（gestational diabetes mellitus, GDM）与炎症因子的中介作用，为早产预防和早期干预提供参考依据。方法 采用前瞻性队列研究，选取2018–2021年于重庆市妇幼保健院分娩的孕产妇1 221例。采用组基轨迹模型构建孕早中期BMI轨迹，logistic回归分析及因果中介分析探讨GDM、炎症因子在孕早中期BMI轨迹与早产之间的中介作用。结果 共识别出三条BMI轨迹：模式一（48.98%）、模式二（38.41%）和模式三（12.61%）。模式二与模式一轨迹形状相似，但整体水平介于模式一与模式三之间；模式三孕早期处于肥胖水平，随妊娠进展BMI略有下降，孕中期趋稳后小幅回升。在调整协变量后，模式三的早产风险是模式一的3.1倍〔比值比（odds ratio, OR）=3.10，95%置信区间（confidence interval, CI）：1.59～6.06〕。白细胞计数和单核细胞百分比在模式三与早产之间的中介效应具有统计学意义，消除比例分别为0.5%和5.1%。未发现GDM的中介作用。结论 孕早中期BMI较高的孕产妇早产的发生风险显著增加，且白细胞计数和单核细胞百分比在其中起中介作用，未发现GDM的中介作用。

Abstract

Objective To investigate the associations between body mass index (BMI) trajectories in early and mid-pregnancy and preterm birth, to examine the mediating effects of gestational diabetes mellitus (GDM) and inflammatory markers, and to provide evidence for early prevention and intervention of preterm birth. Methods A prospective cohort study was conducted and 1 221 pregnant women who delivered babies at Chongqing Maternal and Child Health Hospital between 2018 to 2021 were included. Group-based trajectory modeling was used to identify BMI trajectories in early and mid-pregnancy. Logistic regression and causal mediation analyses were performed to evaluate the mediating effects of GDM and inflammatory factors in the associations between BMI trajectories and preterm birth. Results Three BMI trajectories were identified, and the participants were categorized accordingly into Group 1 (48.98%), Group 2 (38.41%), and Group 3 (12.61%). Group 2 demonstrated a trajectory similar in shape to that of Group 1, with an overall level between those of Group 1 and Group 3. Participants in Group 3 were in the obese range in early pregnancy, with their BMI decreasing slightly along with the progression of pregnancy and stabilizing and then rising slightly in mid-pregnancy. After adjusting for confounders, Group 3 showed higher risks of preterm birth, which were 3.1 times those of Group 1 (odds ratio [OR] = 3.10, 95% CI: 1.59-6.06). Additionally, white blood cell count and monocyte percentage significantly mediated this association, with proportion eliminated of 0.5% and 5.1%, respectively. No mediating effect of GDM was observed. Conclusion Pregnant women with higher BMI during early and mid-pregnancy exhibit a significantly increased risk of preterm birth. White blood cell count and monocyte percentage may serve as key inflammatory mediators linking this association while the mediating effect of GDM is not found.

关键词

体质量变化轨迹 / 妊娠期糖尿病 / 炎症 / 早产

Key words

Body-mass trajectory / Gestational diabetes mellitus / Inflammation / Premature birth

参考文献

[1] World Health Organization. Born too soon: decade of action on preterm birth. Geneva: World Health Organization, 2023.

[2] 中华医学会妇产科学分会产科学组 . 早产临床防治指南(2024版). 中华妇产科杂志, 2024, 59(4): 257-269. doi: 10.3760/cma.j.cn112141-20231119-00208.

[3] Subgroup of Obstetrics, Society of Obstetrics and Gynecology, Chinese Medical Association. Clinical guidelines for the prevention and treatment of preterm birth (2024 edition). Chinese Journal of Obstetrics and Gynecology, 2024, 59(4): 257-269. doi: 10.3760/cma.j.cn112141-20231119-00208.

[4] 吴天晨, 李驿馨, 石慧峰, 等. 2017年至2022年中国早产流行病学特征及变化趋势. 中华围产医学杂志, 2025, 28(2): 126-133. doi: 10.3760/cma.j.cn113903-20240905-00612.

[5] WU T C, LI Y X, SHI H F, et al. Epidemiological characteristics and changing trends of preterm birth in China from 2017 to 2022. Chinese Journal of Perinatal Medicine, 2025, 28(2): 126-133. doi: 10.3760/cma.j.cn113903-20240905-00612.

[6] 林利霞. 孕期增重模式与出生结局及婴幼儿体格发育的关联及血脂的中介作用. 武汉: 华中科技大学, 2023. doi: 10.27157/d.cnki.ghzku.2023.003607.

[7] LIN L X. Association of gestational weight gain patterns with birth outcomes and infant physical development and the mediating role of blood lipids. Wuhan: Huazhong University of Science and Technology, 2023. doi: 10.27157/d.cnki.ghzku.2023.003607.

[8] 石英杰. 我国早产流行现状及影响因素的前瞻性队列研究. 北京: 北京协和医学院, 2021. doi: 10.27648/d.cnki.gzxhu.2021.000639.

[9] SHI Y J. Prevalence and influencing factors of preterm birth in China: a prospective cohort study. Beijing: Peking Union Medical College, 2021. doi: 10.27648/d.cnki.gzxhu.2021.000639.

[10] 杨雅琴, 李佳慧, 赵莉萍, 等. 自发性早产预测的研究进展. 中国生育健康杂志, 2023, 34(5): 492-497. doi: 10.12114/j.issn.1004-8189.2023.05.017.

[11] YANG Y Q, LI J H, ZHAO L P, et al. Research progress in the prediction of spontaneous preterm birth. Chinese Journal of Reproductive Health, 2023, 34(5): 492-497. doi: 10.12114/j.issn.1004-8189.2023.05.017.

[12] MEYER D M, STECHER L, BREI C, et al. Mid-pregnancy weight gain is associated with offspring adiposity outcomes in early childhood. Pediatr Res, 2021, 90(2): 390-396. doi: 10.1038/s41390-020-01202-x.

[13] 宫可心, 李海滟, 余夏妍, 等. 孕早中期增重速率与妊娠期糖尿病风险的队列研究. 卫生研究, 2023, 52(5): 726-731. doi: 10.19813/j.cnki.weishengyanjiu.2023.05.007.

[14] GONG K X, LI H Y, YU X Y, et al. Gestational weight gain rate in the first and second trimesters and risk of gestational diabetes mellitus: a cohort study. Journal of Hygiene Research, 2023, 52(5): 726-731. doi: 10.19813/j.cnki.weishengyanjiu.2023.05.007.

[15] 谢双华, 阴赪宏. 免疫炎症指数与早产的关系研究进展. 中国医刊, 2024, 59(12): 1281-1283. doi: 10.3969/j.issn.1008-1070.2024.12.002.

[16] XIE S H, YIN C H. Research progress on the relationship between immune-inflammatory index and preterm birth. Chinese Journal of Medicine, 2024, 59(12): 1281-1283. doi: 10.3969/j.issn.1008-1070.2024.12.002.

[17] LI G, XING Y, WANG G, et al. Does recurrent gestational diabetes mellitus increase the risk of preterm birth? A population-based cohort study. Diabetes Res Clin Pract, 2023, 199: 110628. doi: 10.1016/j.diabres.2023.110628.

[18] HUANG S, GUO Y, XU X, et al. Gestational diabetes complicated with preterm birth: a retrospective cohort study. BMC Pregnancy Childbirth, 2024, 24(1): 631. doi: 10.1186/s12884-024-06810-7.

[19] PREDA A, ILIESCU D G, COMĂNESCU A, et al. Gestational diabetes and preterm birth: what do we know? our experience and mini-review of the literature. J Clin Med, 2023, 12(14): 4572. doi: 10.3390/jcm12144572.

[20] 中华医学会妇产科学分会产科学组, 中华医学会围产医学分会, 中国妇幼保健协会妊娠合并糖尿病专业委员会. 妊娠期高血糖诊治指南(2022)[第一部分]. 中华妇产科杂志, 2022, 57(1): 3-12. doi: 10.3760/cma.j.cn112141-20210917-00528.

[21] Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association; Chinese Society of Perinatal Medicine, Chinese Medical Association; Commitee of Pregnancy with Diabetes Mellitus, China Maternal and Child Health Association. Guideline of diagnosis and treatment of hyperglycemia in pregnancy (2022) [Part one]. Chin J Obstet Gynecol, 2022, 57(1): 3-12. doi: 10.3760/cma.j.cn112141-20210917-00528.

[22] 中华医学会妇产科学分会产科学组, 中华医学会围产医学分会, 中国妇幼保健协会妊娠合并糖尿病专业委员会 . 妊娠期高血糖诊治指南(2022)[第二部分]. 中华妇产科杂志, 2022, 57(2): 81-90. doi: 10.3760/cma.j.cn112141-20210917-00529.

[23] Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association; Chinese Society of Perinatal Medicine, Chinese Medical Association; Commitee of Pregnancy with Diabetes Mellitus, China Maternal and Child Health Association. Guideline of diagnosis and treatment of hyperglycemia in pregnancy (2022) [Part two]. Chin J Obstet Gynecol, 2022, 57(2): 81-90. doi: 10.3760/cma.j.cn112141-20210917-00529.

[24] MORALES-MUÑOZ I, MARWAHA S, UPTHEGROVE R, et al. Role of inflammation in short sleep duration across childhood and psychosis in young adulthood. JAMA Psychiatry, 2024, 81(8): 825-833. doi: 10.1001/jamapsychiatry.2024.0796.

[25] Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies Press, 2009.

[26] YU Y, LIEW Z, WANG A, et al. Mediating roles of preterm birth and restricted fetal growth in the relationship between maternal education and infant mortality: a Danish population-based cohort study. PLoS Med, 2019, 16(6): e1002831. doi: 10.1371/journal.pmed.1002831.

[27] 张佳妮, 柳吉羱, 毛赤慧, 等. 妊娠期糖尿病诊疗现状与进展-美国糖尿病学会《糖尿病诊疗标准(2025)》相关内容浅析. 四川大学学报(医学版), 2025, 56(3): 627-632. doi: 10.12182/20250560101.

[28] ZHANG J N, LIU J Y, MAO C H, et al. Current status and progress in the diagnosis and treatment of gestational diabetes mellitus: a brief analysis of the relevant contents of the American Diabetes Association's "Standards of Medical Care in Diabetes (2025)". J Sichuan Univ (Med Sci), 2025, 56(3): 627-632. doi: 10.12182/20250560101.

[29] GUO T, ZHENG S, CHEN T, et al. The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study. EClinicalMedicine, 2024, 69: 102486. doi: 10.1016/j.eclinm.2024.102486.

[30] WANG J, ZHENG Y, WANG Y, et al. BMI trajectory of rapid and excessive weight gain during adulthood is associated with bone loss: a cross-sectional study from NHANES 2005-2018. J Transl Med, 2023, 21(1): 536. doi: 10.1186/s12967-023-04397-9.

[31] VANDERWEELE T J. A unification of mediation and interaction: a 4-Way decomposition. Epidemiology, 2014, 25(5): 749-761. doi: 10.1097/EDE.0000000000000121.

[32] VANDERWEELE T J. Policy-relevant proportions for direct effects. Epidemiology, 2013, 24(1): 175-176. doi: 10.1097/EDE.0000000000000067.

[33] SHI B Y, CHOIRAT C, COULL B A, et al. CMAverse: a suite of functions for reproducible causal mediation analyses. Epidemiology, 2021, 32(5): e20-e22. doi: 10.1097/EDE.0000000000001378.

[34] 陈玉铃. 孕早中期体重增加与妊娠期糖尿病发病率及分娩结局的相关性分析. 广州: 广州医科大学, 2023.

[35] CHEN Y L. Correlation analysis of weight gain in the first and second trimesters of pregnancy with the incidence of gestational diabetes mellitus and delivery outcomes. Guangzhou: Guangzhou Medical University, 2023.

[36] LIN L, HUANG Y, CHEN L, et al. Gestational weight trajectory and risk of adverse pregnancy outcomes among women with gestational diabetes mellitus: a retrospective cohort study. Matern Child Nutr, 2024, 20(3): e13645. doi: 10.1111/mcn.13645.

[37] 张丹丹, 谈迪心, 王斌, 等. 孕期增重与早产关联的流行病学分析. 中华流行病学杂志, 2016, 37(7): 1012-1016. doi: 10.3760/cma.j.issn.0254-6450.2016.07.021.

[38] ZHANG D D, TAN D X, WANG B, et al. Epidemiological analysis of the association between gestational weight gain and preterm birth. Chinese Journal of Epidemiology, 2016, 37(7): 1012-1016. doi: 10.3760/cma.j.issn.0254-6450.2016.07.021.

[39] CARNERO A M, MEJIA C R, GARCIA P J. Rate of gestational weight gain, pre-pregnancy body mass index and preterm birth subtypes: a retrospective cohort study from Peru. BJOG, 2012, 119: 924-935. doi: 10.1111/j.1471-0528.2012.03345.x.

[40] ARVIZU M, WANG S, MITSUNAMI M, et al. BMI status and weight trajectories across females' reproductive years and risk of adverse pregnancy outcomes: a prospective cohort study. Am J Clin Nutr, 2024, 120(1): 225-231. doi: 10.1016/j.ajcnut.2024.04.034.

[41] LI H, MIAO C, XU L, et al. Maternal pre-pregnancy body mass index, gestational weight gain trajectory, and risk of adverse perinatal outcomes. Int J Gynaecol Obstet, 2022, 157(3): 723-732. doi: 10.1002/ijgo.13922.

[42] 魏丹, 周永红, 郭瑜, 等. 早产与炎症反应相关机制的研究进展. 中国医刊, 2024, 59(5): 485-488. doi: 10.3969/j.issn.1008-1070.2024.05.006.

[43] WEI D, ZHOU Y H, GUO Y, et al. Research progress on the mechanism of preterm birth related to inflammatory response. Chinese Journal of Medicine, 2024, 59(5): 485-488. doi: 10.3969/j.issn.1008-1070.2024.05.006.

[44] LIU K, CHEN Y, TONG J, et al. Association of maternal obesity with preterm birth phenotype and mediation effects of gestational diabetes mellitus and preeclampsia: a prospective cohort study. BMC Pregnancy Childbirth, 2022, 22(1): 459. doi: 10.1186/s12884-022-04780-2.

[45] WAHID H H, ANAHAR F N, ISAHAK N H, et al. Role of platelet activating factor as a mediator of inflammatory diseases and preterm delivery. Am J Pathol, 2024, 194(6): 862-878. doi: 10.1016/j.ajpath.2024.02.011.

[46] HU H, FENG P, YU Q, et al. The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neononal birth weight. J Diabetes, 2022, 14(1): 26-33. doi: 10.1111/1753-0407.13233.

[47] LI H, XIANG Z, LI H, et al. Mediating effects of maternal blood lipids and glucose on the relationship between pre-pregnancy body mass index and newborn birth weight in women with gestational diabetes mellitus. BMC Pregnancy Childbirth, 2025, 25(1): 1322. doi: 10.1186/s12884-025-08264-x.

基金资助

*国家自然科学基金重点支持项目(U20A20411)