Graafland Naomi, Rousian Melek, de Zwart Merle L, Steegers-Theunissen Regine P M, Steegers Eric A P, Posthumus Anke G
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Hum Reprod Update. 2025 May 1;31(3):166-182. doi: 10.1093/humupd/dmaf001.
The embryonic period in human development is the foundation of lifelong and even transgenerational health. Although previously believed to be uniform, there is increasing evidence that embryonic growth is influenced by the conditions and modifiable lifestyle factors of parents in the periconception period. In ongoing pregnancies, a delay in growth in the first trimester has been associated with miscarriages, malformations, low birth weight, preterm birth, and small for gestational age at birth. This has stimulated research on factors associated with variations in human embryonic growth. However, there is still no consensus on which parental conditions and modifiable lifestyle factors affect first trimester growth and development and to what extent.
A systematic review was undertaken according to PRISMA guidelines to provide an overview of literature on the associations between parental conditions and lifestyle factors in the periconception period and first trimester growth and development, with an aim to identify existing evidence gaps.
A systematic search of the literature concerning articles on embryonic growth and lifestyle factors published between 1900 and 2024 was performed in six electronic databases. Studies were eligible for inclusion if they reported on the association between periconception parental conditions and/or modifiable lifestyle factors and an in vivo measure of first trimester growth or development (i.e. crown-rump length, embryonic volume and/or Carnegie stage) between 6 + 0 and 13 + 6 weeks gestational age in singleton pregnancies. Parental conditions and modifiable lifestyle factors were defined as ex utero determinants divided into characteristics (age, ethnicity, BMI, blood pressure), lifestyle risk factors (caffeine intake, alcohol consumption, and smoking), nutrition (dietary patterns and food groups), vitamins (vitamin B9/B11, vitamin B12, vitamin D, and supplements), and the ambient environment (air pollution, noise exposure, and neighborhood deprivation). Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the evidence level of the studies included in the review.
A total of 4708 unique records were identified, of which 34 studies were included in the systematic review. The majority of studies investigating smoking and BMI suggested an inverse association with embryonic growth and development, while maternal age, folic acid supplement use, and folate levels were positively associated with embryonic growth and development. Studies on blood pressure, ethnicity, vitamin B12, vitamin D, alcohol consumption, caffeine consumption, and ambient environment were too limited to conclude an association with embryonic growth and development. Reported effect estimates were heterogeneous for all determinants. Based on the GRADE criteria, the quality of evidence for the results of this review was considered low or very low.
Some periconceptional parental conditions and modifiable lifestyle factors are associated with first trimester growth and development and should be considered in clinical preconception care. To advance our understanding and establish strong, high-level evidence-based recommendations, future research should prioritize methodological quality and focus on lifestyle intervention studies.
PROSPERO (ID: CRD42021240618).
人类发育的胚胎期是终身乃至跨代健康的基础。尽管此前认为胚胎生长是一致的，但越来越多的证据表明，胚胎生长会受到受孕前后父母的状况及可改变的生活方式因素的影响。在持续妊娠中，孕早期生长延迟与流产、畸形、低出生体重、早产以及出生时小于胎龄有关。这激发了对与人类胚胎生长变化相关因素的研究。然而，对于哪些父母状况和可改变的生活方式因素会影响孕早期的生长发育以及影响程度如何，仍未达成共识。
根据PRISMA指南进行了一项系统综述，以概述关于受孕前后父母状况和生活方式因素与孕早期生长发育之间关联的文献，旨在找出现有的证据空白。
在六个电子数据库中对1900年至2024年期间发表的有关胚胎生长和生活方式因素的文章进行了系统搜索。如果研究报告了受孕前后父母状况和/或可改变的生活方式因素与单胎妊娠孕龄6 + 0至13 + 6周之间孕早期生长或发育的体内测量指标（即头臀长度、胚胎体积和/或卡内基分期）之间的关联，则这些研究符合纳入条件。父母状况和可改变的生活方式因素被定义为子宫外决定因素，分为特征（年龄、种族、体重指数、血压）、生活方式风险因素（咖啡因摄入量、酒精消费量和吸烟）、营养（饮食模式和食物类别）、维生素（维生素B9/B11、维生素B12、维生素D和补充剂）以及环境（空气污染、噪音暴露和邻里贫困）。使用纽卡斯尔 - 渥太华量表评估纳入研究的偏倚风险。采用推荐分级、评估、制定和评价（GRADE）方法评估综述中纳入研究的证据水平。
共识别出4708条独特记录，其中34项研究纳入了系统综述。大多数调查吸烟和体重指数的研究表明与胚胎生长发育呈负相关，而母亲年龄、叶酸补充剂使用和叶酸水平与胚胎生长发育呈正相关。关于血压、种族、维生素B12、维生素D、酒精消费、咖啡因消费和环境的研究非常有限，无法得出与胚胎生长发育相关的结论。所有决定因素报告的效应估计值均存在异质性。根据GRADE标准，本综述结果的证据质量被认为低或极低。
一些受孕前后的父母状况和可改变的生活方式因素与孕早期生长发育相关，在临床孕前护理中应予以考虑。为了增进我们的理解并建立强有力的、基于高质量证据的建议，未来的研究应优先考虑方法学质量，并专注于生活方式干预研究。
PROSPERO（编号：CRD42021240618）
