基于出生队列研究出生结局与青少年多维度健康结局的纵向关联

Longitudinal associations between birth outcomes and multidimensional health outcomes in adolescents: a birth cohort study

摘要

目的 探讨婴幼儿出生结局与青少年多维度健康结局之间的关联,为提高出生人口质量促进青少年全面健康发展提供科学依据。方法 基于一项孕期微营养素补充的随机对照试验所建立的前瞻性出生队列,关注的出生结局包括出生体重、出生孕周、出生头围、出生身长及其Z值,以及不良出生结局如低出生体重、早产、小于胎龄儿等。基于内化问题得分、外化问题得分、认知得分、肺活量、心率、体质指数、收缩压、舒张压等健康结局指标,采用熵权逼近理想解排序法构建青少年多维度健康综合得分；采用潜在剖面分析将青少年健康模式分为行为问题高风险组、代谢问题高风险组、健康问题低风险组三个类别。采用限制性立方样条探讨婴幼儿出生结局与青少年多维度健康综合得分间可能的非线性关系；并应用多分类Logistic回归模型分析婴幼儿出生结局与青少年多维度分类健康结局的关联,广义线性模型分析婴幼儿出生结局与青少年多维度健康综合得分的关联；所有回归模型均调整了众多混杂因素或协变量。结果 共计纳入研究对象1 767人,其中男孩1 050人(59.42%)。新生儿平均头围(33.20±1.50)cm,出生身长(49.10±2.65)cm,出生体重(3.21±0.41)kg；其中,4.02%的新生儿为早产,3.39%为低出生体重,而小于胎龄儿占比达到13.27%。除出生身长外,其余出生结局指标与青少年多维度健康结局的非线性关联P值均大于0.05。多分类Logistic回归模型发现婴幼儿出生头围每增加1 cm,其在青少年时期发生高风险行为问题的风险将降低12%(95% CI:0.79～0.97)；出生孕周每增加1周,其青少年时期发生高风险行为问题的风险可降低10%(95% CI:0.81～0.99)。出生体重每增加1个标准差,其青少年时期发生代谢问题的风险将增加15%(95% CI:1.03～1.28)。广义线性模型分析发现婴幼儿出生头围每增加1 cm,其在青少年时的多维度健康综合得分将增加0.17分(95% CI:0.01～0.33)。但在调整混杂因素后,不良出生结局与青少年多维度健康结局的关联均无统计学意义。结论 适宜的出生结局有可能降低青少年期发生行为、代谢问题等的风险,为生命历程慢性病共病的生命早期零级预防和制定全生命周期的健康管理策略提供了新的科学依据和防控思路。

Abstract

Objective To investigate the longitudinal associations between infant birth outcomes and multidimensional adolescent health outcomes, aiming to provide scientific evidence for improving birth population quality and promoting comprehensive healthy development in adolescents. Methods Based on a prospective birth cohort embedded within a randomized controlled trial (RCT) of maternal micronutrient supplementation during pregnancy, the study focused on the following birth outcomes: birth weight, gestational age at birth, head circumference, birth length (and their respective z-scores), as well as adverse birth outcomes including low birth weight (LBW), preterm birth, and small for gestational age (SGA). A multidimensional composite score was developed using the entropy-weighted TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) method, incorporating internalizing problems, externalizing problems, cognitive scores, vital capacity, heart rate, body mass index (BMI), systolic blood pressure, and diastolic blood pressure and used latent profile analysis (LPA) which identified three distinct health phenotypes: high-risk behavioral problems group, high-risk metabolic problems group, and low-risk healthy group. We employed restricted cubic splines (RCS) to examine potential nonlinear relationships between infant birth outcomes and the multidimensional adolescent health composite score. Multinomial Logistic regression was employed to analyze the association between birth outcomes and multidimensional adolescent health classifications, while generalized linear models assessed the relationship between birth outcomes and multidimensional health composite scores. All regression models were adjusted for multiple potential confounders/covariates. Results The study recruited 1,767 participants, of whom 1,050 (59.42%) were male. The average neonatal head circumference was (33.20±1.50) cm, birth length was (49.10±2.65) cm, and birth weight was (3.21±0.41) kg. Among them, 4.02% were preterm births, 3.39% had low birth weight, and 13.27% were small for gestational age. With the exception of birth weight, no significant nonlinear associations were observed between the other birth outcomes and multidimensional adolescent health outcomes (all P＞0.05). Multinomial Logistic regression analysis demonstrated that every 1 cm increment in birth head circumference was significantly associated with a 12% decreased risk of high-risk behavioral problems in adolescence (95% CI: 0.79-0.97). Similarly, each additional week of gestational age conferred a 10% reduction in the likelihood of adolescent high-risk behavioral problems (95% CI: 0.81-0.99). In contrast, one standard deviation increase in birth weight showed a significant positive association with metabolic disorders during adolescence, with a 15% elevated risk (95% CI: 1.03-1.28). Generalized linear models showed that 1 cm increase in birth head circumference might improve 0.17 point in the multidimensional health score during adolescence (95% CI: 0.01-0.33). After adjusting for cofounding factors, the association patterns between adverse birth outcomes and multidimensional adolescent health outcomes did not reach statistical significance. Conclusion Optimal birth outcomes may significantly reduce the risk of behavioral and metabolic disorders during adolescence, thereby providing crucial scientific evidence for implementing primordial prevention strategies against early-life origins of chronic disease comorbidities and informing comprehensive life-course health management approaches.

关键词

出生结局 / 青少年健康 / 多维度评价 / 出生队列 / 生命早期

Key words

birth outcome / adolescent health / multidimensional assessment / birth cohort / early life

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基金资助

国家自然科学基金资助项目(82103867)

中央高校基本科研业务费专项资金资助项目(xxj032025066)

陕西省重点研发计划项目(2024SF-YBXM-310)

陕西省创新能力支撑计划项目(2023-CX-PT-47)

陕西省自然科学基础研究计划项目(2024JC-YBMS-760)