围孕期母体补充剂摄入与人类胚胎的生长、发育和出生结果的研究

STUDY QUESTION

研究问题

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population?

在高危人群中，与单用叶酸（FA）相比，围孕期使用含叶酸的复合微量营养素补充剂（MMS）是否会促进胚胎生长、发育和增加出生体重？

SUMMARY ANSWER

主要回答

Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA.

与使用FA的女性相比，摄入MMS的女性在孕早期胚胎形态发育方面无显著差异，但可以提升孕早期胚胎生长轨迹，并减少新生儿中小于胎龄儿（SGA），体重低于第三百分位（<P3）的发生。

WHAT IS KNOWN ALREADY

已知信息

Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA.

在普通人群中，孕妇围孕期摄入叶酸与胚胎和胎儿生长的增加以及神经管缺陷、其他先天性畸形、低出生体重和SGA风险降低相关。

STUDY DESIGN, SIZE, DURATION

研究设计、规模、持续时间

A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020.

本研究为在三级医院进行的一项前瞻性队列研究（鹿特丹围孕期队列），研究时间为2010年1月至2020年12月。

PARTICIPANTS/MATERIALS, SETTING, METHODS

研究对象/材料、场景、方法

We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires.

本研究纳入了来自鹿特丹围孕期队列的1076名女性，这些女性在孕10周前入组，并随访至分娩。通过测量顶臀长（CRL）和胚胎体积（EV）来评估胚胎发育情况，并使用纵向三维超声扫描和虚拟现实技术，根据卡内基分期来描述胚胎形态。分娩结果从医疗记录中提取。一般特征和营养补充剂的使用情况则从研究问卷中获取。

MAIN RESULTS AND THE ROLE OF CHANCE

主要结果与偶然性作用

This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012–0.090, EV: β = 0.022, 95% CI 0.002–0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA.

本研究表明，与单用FA的孕妇相比，使用MMS的孕妇的胚胎生长轨迹有所提升（调整后模型，CRL：β= 0.052，95% CI 0.012-0.090，EV：β=0.022，95% CI 0.002-0.042）。此外，与使用叶酸的孕妇相比，使用复合微量营养素的孕妇分娩的新生儿为小于胎龄儿（SGA，< p3）的风险降低了45%（调整后OR= 0.546，95% CI 0.308，0.969）。然而，在使用MMS或FA的孕妇之间，胚胎形态发育（卡内基阶段）和流产的发生并无显著差异。

LIMITATIONS, REASONS FOR CAUTION

局限性及需谨慎的理由

Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS.

由于MMS的成分和剂量不同，目前尚不清楚是哪种特定的微量营养素、组合或剂量可以提升胚胎生长轨迹，降低小于胎龄儿（SGA）风险。同时也很难区分FA单独或作为MMS成分使用，其效果有何不同。

WIDER IMPLICATIONS OF THE FINDINGS

研究发现的更广泛意义

Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended.

本研究结果强调了围孕期母体补充MMS作为一种预防胚胎发育迟缓和SGA的潜在干预措施的重要性。因此，我们建议存在微量元素摄入不足风险的女性在围孕期补充MMS。然而，高剂量和复合微量营养素可能产生的有害副作用，我们必须保持警惕，因此需要研究最佳的成分组合和剂量，并建议进行严密的监测。

参考文献：

N Schenkelaars, S Schoenmakers, M Rousian, S P Willemsen, M M Faas, R P M Steegers-Theunissen, Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort, Human Reproduction, Volume 39, Issue 9, September 2024, Pages 1925–1933, https://doi.org/10.1093/humrep/deae168