STUDY QUESTION What is the association between first trimester maternal tryptophan (TRP) metabolites and embryonic and fetal growth? SUMMARY ANSWER Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for-gestational age (SGA), while higher kynurenine (KYN) concentrations are associated with a reduced risk of SGA. WHAT IS KNOWN ALREADY The maternal TRP metabolism is involved in many critical processes for embryonic and fetal growth, including immune modulation and regulation of vascular tone. Disturbances in TRP metabolism are associated with adverse maternal and fetal outcomes. STUDY DESIGN, SIZE, DURATION This study was embedded within the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective observational cohort conducted at a tertiary hospital from November 2010 onwards. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1115 women were included before 11 weeks of gestation between November 2010 and December 2020. Maternal serum samples were collected between 7 and 11 weeks of gestation, and TRP metabolites (TRP, KYN, 5-HTP, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid) were determined using a validated liquid chromatography (tandem) mass spectrometry method. Serial 3D ultrasound scans were performed at 7, 9, and 11 weeks of gestation to accurately assess features of embryonic growth, including crown–rump length (CRL) and embryonic volume (EV) offline using virtual reality systems. Fetal growth parameters were retrieved from medical records and standardized according to Dutch reference curves. Mixed models were used to assess associations between maternal TRP metabolites and CRL and EV trajectories. Linear and logistic regression models were utilized to investigate associations with estimated fetal weight (EFW) and birthweight, and with SGA, respectively. All analyses were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Maternal 5-HTP concentrations and the maternal 5-HTP/TRP ratio were inversely associated with embryonic growth (5-HTP, √CRL: β = –0.015, 95% CI = –0.028 to –0.001; 5-HTP 3√EV: β = –0.009, 95% CI = –0.016 to –0.003). An increased maternal 5-HTP/TRP ratio was also associated with lower EFW and birthweight, and with an increased risk of SGA (odds ratio (OR) = 1.006, 95% CI = 1.00–1.013). In contrast, higher maternal KYN concentrations were associated with a reduced risk of SGA in the unadjusted models (OR = 0.548, 95% CI = 0.320–0.921). LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out because of the observational design of this study. Moreover, this study was conducted in a single tertiary hospital, which assures high internal validity but may limit external validity. WIDER IMPLICATIONS OF THE FINDINGS The novel finding that maternal 5-HTP concentrations are associated with a smaller embryo and fetus implies that disturbances of the maternal serotonin pathway in the first trimester of pregnancy are potentially involved in the pathophysiology of fetal growth restriction. The association between higher maternal KYN concentrations and a reduced risk of SGA substantiate the evidence that the KYN pathway has an important role in fetal growth. More research is needed to delve deeper into the potential role of the maternal TRP metabolism during the periconception period and pregnancy outcome for mother and offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Department of Obstetrics and Gynecology and the Department of Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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妊娠早期母体色氨酸代谢与胚胎和胎儿生长：鹿特丹围孕期队列（预测研究）

研究问题 妊娠早期母体色氨酸 (TRP) 代谢物与胚胎和胎儿生长之间有何关联？摘要答案 较高的 5-羟色氨酸 (5-HTP) 浓度与胚胎生长和胎儿生长减缓以及小于胎龄 (SGA) 的风险增加相关，而较高的犬尿氨酸 (KYN) 浓度与较低的风险相关SGA 的。已知信息 母体 TRP 代谢参与胚胎和胎儿生长的许多关键过程，包括免疫调节和血管张力调节。 TRP 代谢紊乱与不良的母婴结局相关。研究设计、规模、持续时间 这项研究被纳入鹿特丹围孕期队列（预测研究）中，这是一个从 2010 年 11 月起在一家三级医院持续进行的前瞻性观察队列。参与者/材料、背景、方法 2010 年 11 月至 2020 年 12 月期间，共有 1115 名妊娠 11 周前的妇女被纳入研究。在妊娠 7 周至 11 周之间收集母体血清样本，并收集 TRP 代谢物（TRP、KYN、5-HTP）。 、5-羟基色胺和 5-羟基吲哚乙酸）使用经过验证的液相色谱（串联）质谱方法进行测定。在妊娠第 7、9 和 11 周进行连续 3D 超声扫描，以使用虚拟现实系统离线准确评估胚胎生长特征，包括冠臀长度 (CRL) 和胚胎体积 (EV)。从病历中检索胎儿生长参数并根据荷兰参考曲线进行标准化。混合模型用于评估母体 TRP 代谢物与 CRL 和 EV 轨迹之间的关联。利用线性和逻辑回归模型分别研究与估计胎儿体重 (EFW) 和出生体重以及与 SGA 的关联。所有分析均针对潜在的混杂因素进行了调整。主要结果和机会的作用 母体 5-HTP 浓度和母体 5-HTP/TRP 比率与胚胎生长呈负相关（5-HTP，√CRL：β = –0.015，95% CI = –0.028 至 –0.001； 5-HTP 3√EV：β = –0.009，95% CI = –0.016 至 –0.003)。母亲 5-HTP/TRP 比率升高还与 EFW 和出生体重降低以及 SGA 风险增加相关（比值比 (OR) = 1.006，95% CI = 1.00–1.013）。相比之下，在未调整的模型中，较高的母亲 KYN 浓度与 SGA 风险降低相关（OR = 0.548，95% CI = 0.320–0.921）。局限性、注意原因 由于本研究的观察设计，不能排除残留混杂因素。此外，这项研究是在一家三级医院进行的，这保证了较高的内部效度，但可能会限制外部效度。研究结果的更广泛意义这一新发现表明，母体 5-HTP 浓度与较小的胚胎和胎儿有关，这意味着妊娠前三个月母体血清素途径的紊乱可能与胎儿生长受限的病理生理学有关。较高的母体 KYN 浓度与降低的 SGA 风险之间的关联证实了 KYN 通路在胎儿生长中具有重要作用的证据。需要更多的研究来更深入地研究母体 TRP 代谢在围孕期以及母亲和后代妊娠结局中的潜在作用。研究资助/竞争利益 本研究由荷兰鹿特丹大学医学中心伊拉斯谟医学中心妇产科和临床化学系资助。作者没有需要披露的竞争利益。试用注册号 不适用。