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[围孕期母体同型半胱氨酸与子代出生体重结局:一项前瞻性队列研究]

[Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study].

作者信息

Zhang Y, Chen X T, Yao Q Y, Chen H Y, Li M R, Wang D M, Dou Y L, Peng Y Z, Gu X Y, Yan W L, Huang G Y

机构信息

Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center,Shanghai Key Laboratory of Birth Defects, Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases, Chinese Academy of Medical Sciences, Shanghai 201102, China.

Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai Key Laboratory of Birth Defects, Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases, Chinese Academy of Medical Sciences, Shanghai 201102, China.

出版信息

Zhonghua Er Ke Za Zhi. 2024 Feb 2;62(2):120-128. doi: 10.3760/cma.j.cn112140-20231030-00332.

Abstract

To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 September 2016 to 11 November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (=-2.30, 95% -4.43--0.16, =0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (=-7.39, 95%-11.50--3.21, <0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (=1.05, 95% 1.01-1.08, =0.002). Periconceptional vitamin B was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

摘要

为了量化孕前母亲同型半胱氨酸(HCY)与后代出生体重及小于胎龄儿(SGA)风险之间的关联。在这项前瞻性队列研究中,19984对母婴对来自上海孕前队列;婴儿于2016年9月1日至2022年11月11日出生。使用标准化问卷收集母亲的人口统计学信息、病史、膳食补充剂使用情况以及孕期的母亲并发症,并采集她们的血清样本。基于入组时抽取的血清样本,采用化学发光微粒子免疫分析法测定血清HCY、叶酸和维生素B。出生体重数据从病历中获取。应用多重插补方法处理关键变量中的缺失数据。采用多变量线性回归和泊松回归模型分析孕前母亲HCY浓度与后代出生体重及SGA风险之间的关系。共有9452对母婴在孕前入组,其余10532对在孕早期入组。怀孕年龄大于35岁的母亲比例为9.2%(1832/19984),初产妇比例为76.5%(15283/19984),孕前超重和肥胖比例为14.0%(2804/19984),孕前使用叶酸补充剂的比例为21.4%(4272/19984),孕早期补充叶酸的比例为85.2%(8976/10532);妊娠期糖尿病发生率为6.2%(1245/19984),妊娠期高血压综合征发生率为3.6%(711/19984)。后代出生体重为(3297±468)g,有1962例SGA儿童(9.8%)。孕前适宜胎龄人群的HCY浓度为(7.9±3.2)μmol/L,孕前亚组为(8.3±3.7)μmol/L,孕早期亚组为(7.3±2.4)μmol/L。在调整围产期人口统计学信息、不良妊娠结局、血清叶酸和维生素B等协变量后,孕前母亲HCY升高与后代出生体重降低显著相关(β=-2.30,95%CI -4.43--0.16,P=0.035)。仅孕早期亚组与后代出生体重降低显著相关(β=-7.39,95%CI -11.50--3.21,P<0.001)。未发现孕期HCY与后代SGA风险之间存在关联。然而,孕早期HCY升高与后代SGA风险增加相关(RR=1.05,95%CI 1.01-1.08,P=0.002)。孕前维生素B是HCY与后代出生体重之间关联的中介因素,分别占总体孕前人群、孕前亚组和孕早期亚组其总效应的16.5%、41.2%和5.4%。母亲孕前HCY水平与后代出生体重降低有关,但与SGA风险无关。孕早期亚组母亲HCY升高可能与后代SGA风险增加有关。

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