STUDY QUESTION Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? SUMMARY ANSWER The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and negatively with tryptophan, while higher hair cortisol concentrations are associated with reduced first-trimester growth without mediation of tryptophan. WHAT IS KNOWN ALREADY A high degree of maternal vulnerability during the periconception period is associated with impaired first-trimester growth and pregnancy complications, with consequences for long-term health of the child and future life course. However, due to the challenges of early identification of vulnerable women, the uptake of periconception care is low in this target group. STUDY DESIGN, SIZE, DURATION Between June 2022 and June 2023, this study was conducted in a sub-cohort of 160 pregnant women participating in the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective tertiary hospital-based cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS One hundred and thirty-two women with ongoing pregnancies and available stress biomarker data were included in the analysis. Data on periconceptional social, lifestyle, and medical risk factors were collected via self-administered questionnaires, and these factors were used for the development of a composite maternal vulnerability risk score. Stress biomarkers, including stress hormones (hair cortisol and cortisone) and inflammatory and oxidative stress biomarkers (C-reactive protein, total homocysteine, and tryptophan metabolites) were determined in the first trimester of pregnancy. First-trimester growth was assessed by crown–rump length (CRL) and embryonic volume (EV) measurements at 7, 9, and 11 weeks gestation by making use of an artificial intelligence algorithm and virtual reality techniques using 3D ultrasound data sets. The associations between the maternal vulnerability risk score and stress biomarkers were identified using linear regression models, and between stress hormones and CRL- and EV-trajectories using mixed models. A mediation analysis was performed to assess the contribution of tryptophan. All associations were adjusted for potential confounders, which were identified using a data-driven approach. Several sensitivity analyses were performed to check the robustness of the findings. MAIN RESULTS AND THE ROLE OF CHANCE The maternal vulnerability risk score was positively associated with concentrations of hair cortisol and cortisone (pg/mg) (β = 0.366, 95% CI = 0.010–0.722; β = 0.897, 95% CI = 0.102–1.691, respectively), and negatively with tryptophan concentrations (µmol/L) (β = –1.637, 95% CI = –2.693 to –0.582). No associations revealed for C-reactive protein and total homocysteine. Higher hair cortisol concentrations were associated with reduced EV-trajectories (3√EV: β = –0.010, 95% CI = –0.017 to –0.002), while no associations were found with CRL-trajectories. Mediation by tryptophan was not shown. LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out, and the external validity may be limited due to the study’s single-center observational design in a tertiary hospital. WIDER IMPLICATIONS OF THE FINDINGS There is mounting evidence that a high degree of maternal vulnerability negatively affects maternal and perinatal health, and that of the future life course. The results of our study emphasize the need to identify highly vulnerable women as early as possible, at least before conception. Our findings suggest that the chronic stress response and alterations of the maternal tryptophan metabolism are involved in maternal vulnerability, affecting first-trimester growth, with potential impact on the long-term health of the offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Departments of Obstetrics and Gynecology and Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Junior Award granted by the De Snoo—van ’t Hoogerhuijs Foundation in March 2022. There are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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产妇脆弱性对压力生物标志物和孕早期生长的影响：鹿特丹围孕期队列（预测研究）


研究问题 母体的脆弱程度是否与应激生物标志物（应激激素、C 反应蛋白、色氨酸代谢物和一碳代谢物）呈正相关，长期暴露于应激激素是否会减慢妊娠早期的生长？摘要答案 产妇脆弱性风险评分与头发皮质醇和可的松浓度呈正相关，与色氨酸呈负相关，而较高的头发皮质醇浓度与没有色氨酸介导的孕早期生长减少相关。众所周知，孕期母亲在围孕期的高度脆弱性与孕早期生长受损和妊娠并发症有关，对孩子的长期健康和未来的生命历程产生影响。然而，由于早期识别弱势妇女的挑战，该目标群体对围孕期保健的接受率较低。研究设计、规模、持续时间 在 2022 年 6 月至 2023 年 6 月期间，这项研究是在参与鹿特丹围孕期队列（预测研究）的 160 名孕妇的子队列中进行的，这是一个正在进行的前瞻性三级医院队列。参与者/材料、地点、方法 分析包括 132 名持续怀孕的妇女和可用的压力生物标志物数据。通过自填问卷收集有关围孕期社会、生活方式和医疗危险因素的数据，并将这些因素用于开发综合孕产妇脆弱性风险评分。 在妊娠早期测定应激生物标志物，包括应激激素 （头发皮质醇和可的松） 以及炎症和氧化应激生物标志物 （C 反应蛋白、总同型半胱氨酸和色氨酸代谢物）。利用人工智能算法和使用 3D 超声数据集的虚拟现实技术，通过在妊娠 7 、 9 和 11 周时测量冠臀长度 （CRL） 和胚胎体积 （EV） 来评估孕早期的生长。使用线性回归模型确定产妇脆弱性风险评分与压力生物标志物之间的关联，使用混合模型确定压力激素与 CRL 和 EV 轨迹之间的关联。进行中介分析以评估色氨酸的贡献。所有关联都针对潜在的混杂因素进行了调整，这些混杂因素是使用数据驱动的方法确定的。进行了几次敏感性分析以检查结果的稳健性。主要结果和机会的作用 产妇脆弱性风险评分与头发皮质醇和可的松浓度 （pg/mg） 呈正相关 （β = 0.366,95% CI = 0.010–0.722;β = 0.897,95% CI = 0.102–1.691），与色氨酸浓度 （μmol/L） 呈负相关 （β = –1.637,95% CI = –2.693 至 –0.582）。未发现 C 反应蛋白和总同型半胱氨酸的关联。较高的头发皮质醇浓度与 EV 轨迹减少相关 （3√EV： β = –0.010,95% CI = –0.017 至 –0.002），而未发现与 CRL 轨迹相关。未显示色氨酸的介理。 局限性，谨慎的原因 不能排除残余混杂，并且由于该研究在三级医院的单中心观察设计，外部有效性可能会受到限制。研究结果的更广泛意义 越来越多的证据表明，孕产妇的高度脆弱性对孕产妇和围产期健康以及未来生命历程的负面影响。我们的研究结果强调需要尽早识别高度脆弱的女性，至少在受孕之前。我们的研究结果表明，慢性应激反应和母体色氨酸代谢的改变与母体脆弱性有关，影响孕早期的生长，对后代的长期健康有潜在影响。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 MC 妇产科和临床化学系以及 De Snoo—van 't Hoogerhuijs 基金会于 2022 年 3 月授予的初级奖资助。没有利益冲突。试验注册号 N/A。