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中国循证儿科杂志

中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (6): 413-419.DOI: 10.3969/j.issn.1673-5501.2024.06.002

• 论著 • 上一篇    下一篇

孕前血清叶酸浓度与妊娠期高血压疾病的关联分析：前瞻性队列研究

张羿1，彭远舟1，陈逍天1，姚沁玙2，陈红燕2，李梦茹2，王定美2，窦亚兰1，顾晓妍1，黄国英2，严卫丽1   

  1. 1 国家儿童医学中心，复旦大学附属儿科医院临床流行病研究室&临床试验中心，上海市出生缺陷防治重点实验室，中国医学科学院小儿遗传相关心血管疾病早期防控创新单元上海，201102；2 国家儿童医学中心, 复旦大学附属儿科医院心血管中心上海市出生缺陷防治重点实验室 中国医学科学院小儿遗传相关心血管疾病早期防控创新单元上海，201102
  • 收稿日期:2024-11-09 修回日期:2024-12-22 出版日期:2024-12-25 发布日期:2024-12-25
  • 通讯作者: 严卫丽

The association between prepregnancy serum folate concentration and hypertensive disorders of pregnancy: A prospective cohort study

ZHANG Yi1, PENG Yuanzhou1, CHEN Xiaotian1, YAO Qinyu2, CHEN Hongyan2, LI Mengru2, WANG Dingmei2, DOU Yalan2, GU Xiaoyan2, HUANG Guoying2, YAN Weili2   

  1. 1 Department of Clinical Epidemiology and Clinical Trial Unit, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, National Children's Medical Center, Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002) of Chinese Academy of Medical sciences, Shanghai 201102, China; 2 Pediatric Heart Center, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, National Children's Medical Center, Research Unit of Early Intervention of Genetically Related childhood Cardiovascular Diseases (2018RU002) of Chinese Academy of Medical sciences, Shanghai 201102,China
  • Received:2024-11-09 Revised:2024-12-22 Online:2024-12-25 Published:2024-12-25
  • Contact: YAN Weili

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摘要： 背景妊娠期高血压疾病（HDP）是引发孕产妇不良妊娠结局以及新生儿死亡的关键因素之一。目前，关于围孕期叶酸补充能否有效预防HDP还有争议，这凸显了深入探究叶酸内暴露与HDP关系的必要性。本研究将探索量化孕前血清叶酸（SF）水平与HDP风险之间的关联，旨在为制定针对性的一级预防和干预策略提供坚实的科学依据。 目的探讨孕前SF浓度与HDP风险的关联, 为一级预防及干预策略提供科学依据。 设计前瞻性队列研究。 方法研究对象来自上海市孕前亲子队列人群中（SPCC）2016年3月16日至2023年12月31日纳入的备孕女性并完成孕期随访的对象。主要结局为HDP, 包括妊娠高血压(GH)和子前期(PE), 基于产前医疗记录诊断。SF和血清同型半胱氨酸（HCY）采用化学发光微粒子免疫法检测。孕前个人社会人口学信息、孕产史和叶酸补充剂的使用通过调查问卷收集。首先采用Poisson回归模型分析孕前SF浓度与HDP发生风险之间的关系, 再采用限制性立方样条回归探索二者之间的非线性关系, 最后根据孕前体质指数(BMI)的分类进行亚组分析。调整的协变量包括是否初产妇、怀孕年龄(岁)、孕前BMI(kg·m-2)、围孕期是否饮酒、主动或被动吸烟暴露、围孕期是否服用叶酸补充剂、孕前血样采集至末次月经的间隔时间(月)以及HCY。 主要结局指标孕前SF浓度与HDP的关系。 结果SPCC中研究期间孕前共纳入备孕女性22 488人, 排除未怀孕(6 056人)、流产(774人)以及缺乏基线叶酸浓度(955人)的对象, 最终14 703人进入分析。该人群中1 218人(8.3%)年龄＞35岁, 84.2%为初产妇, 12.0%为孕前超重和肥胖, 22.5%自我报告孕前使用过叶酸补充剂。孕期发生HDP 587人(4.0%), 其中GH 555人(3.8%), PE 32人(0.2%)。总人群孕前SF浓度为（10.2±4.5）ng·mL-1, 其中非HDP组和HDP组分别为（10.2±4.5）ng·mL-1和（9.6±4.4）ng·mL-1。调整协变量后, 孕前SF浓度每升高1 ng·mL-1与HDP平均发病率降低3%有显著关联(RR=0.97, 95%CI: 0.95~0.99, P=0.008), 且二者之间非线性关系不显著(P=0.475)。当SF＞13.5 ng·mL-1时HDP风险下降的人群归因风险度为19.2%并有统计学意义((95%CI：2.4%~32.8%, P=0.022)。 结论孕前保持SF浓度处于高浓度与HDP风险降低有显著关联。

关键词: 孕前血清叶酸, 妊娠期高血压疾病, 前瞻性队列研究, 一级预防

Abstract: Background Hypertensive disorders of pregnancy (HDP) are one of the key factors leading to adverse pregnancy outcomes and neonatal mortality. Currently, there is controversy over whether perinatal folic acid supplementation can effectively prevent HDP, highlighting the necessity of further investigating the relationship between folate exposure and HDP. Our study aimed to quantify associations between preconception serum folate (SF) levels and HDP risk, providing scientific evidence for primary prevention and intervention strategies. Objective To explore the association between preconception SF levels and HDP risk, and provide scientific evidence for primary prevention and intervention strategies. DesignProspective cohort study. MethodsParticipant women were from the Shanghai Preconception Cohort (SPCC) enrolled before pregnancy from March 16, 2016, to December 31, 2023, and completed follow-up during pregnancy. The primary outcomes were HDP, including gestational hypertension (GH) and preeclampsia (PE) confirmed based on medical records. SF and serum homocysteine (HCY) levels were measured using a chemiluminescent microparticle immunoassay. Pre-pregnancy personal sociodemographic information, obstetric history, and use of folic acid supplements were collected through questionnaires. We used Poisson regression models to assess the relationship between SF levels and the risk of HDP, and to calculate the population attributable risk fraction for corresponding SF levels. Next, we conducted restricted cubic spline regression to test potential non-linear relationships and subgroup analysis was performed according to the pre-pregnancy BMI classifications. Adjusted covariates included primipara, age at pregnancy (years), pre-pregnancy BMI, alcohol consumption during the periconceptional period, active or passive smoking, use of folic acid supplements during the periconceptional period, the interval between pre-pregnancy blood sample collection and the last menstrual period, and HCY levels. Main outcome measures Associations between preconception SF levels and risk of HDP. ResultsThe study included a total of 22, 488 women preparing for pregnancy from the SPCC cohort. After excluding those who did not become pregnant (n=6, 056), experienced a miscarriage(n=774), or did not have baseline folic acid data(n=955), 14, 703 individuals were included in the analysis. At baseline, 1, 218 women (8.3%) were over 35 years old before pregnancy, 12, 382 women (84.2%) were first-time mothers, 1, 768 women (12.0%) were overweight or obese before pregnancy, and 3, 310 women (22.5%) used folic acid supplements before pregnancy. During follow-up, 587 women (4.0%) were diagnosed with HDP, including 555 with GH (3.8%) and 32 with PE (0.2%). The overall SF concentration was 10.2±4.5 ng·mL-1, with the non-HDP group at 10.2±4.5 ng·mL-1 and the HDP group at 9.6±4.4 ng·mL-1. After adjusting for covariates, each 1 ng·mL-1 increase in preconception SF levels was significantly associated with a 3% reduction in the average incidence of HDP (RR=0.97, 95%CI: 0.95-0.99, P=0.008), with no significant non-linear relationship observed between the two (P=0.475). When SF levels exceeded 13.5 ng·mL-1, the population attributable risk for HDP reduction was 19.2%, which was statistically significant (95%CI: 2.4%-32.8%, P=0.022). ConclusionHigher preconception SF levels are significantly associated with a reduced risk of HDP.

Key words: Pre-pregnancy serum folate, Hypertensive disorders in pregnancy, Prospective cohort study, Primary prevention