We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012–3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.

我们建立了有效的早孕期预测模型，用于预测小于胎龄 (SGA) 和胎儿生长受限 (FGR)，且不存在先兆子痫 (PE)，无论疾病发作的孕龄如何[早期 FGR 发生在 32 孕周之前] 32 孕周后发生的周或晚期 FGR]。这项回顾性研究针对 2012 年 11 月至 2020 年 3 月期间的单胎白人妊娠 (n = 6440) 进行。最后，6440 名孕妇中的 4469 名拥有自在捷克共和国布拉格母婴护理研究所分娩以来的完整医疗记录。该研究纳入了所有诊断为 SGA 的病例（n = 37) 或无 PE 的 FGR (n = 82)，以及 80 名选择的正常妊娠。四种 microRNA（miR-1-3p、miR-20a-5p、miR-146a-5p 和 miR-181a-5p）以 10.0% 的假阳性率 (FPR) 识别出 75.68% 的 SGA 病例。八种 microRNA（miR-1-3p、miR-20a-5p、miR-20b-5p、miR-126-3p、miR-130b-3p、miR-146a-5p、miR-181a-5p 和 miR-499a- 5p）在 10.0% FPR 下识别出 83.80% 的 SGA 病例。通过实施母亲临床特征[母亲年龄和BMI、通过辅助生殖技术（ART）进行不孕症治疗、早孕期PE和/或FGR筛查以及自发性早产，进一步改进了基于microRNA的SGA预测模型。 FMF算法]。然后，在使用 4 个 microRNA 和 8 个 microRNA 生物标志物的情况下，FPR 为 10.0% 时，分别有 81.08% 和 89.19% 的妊娠发生 SGA。与 SGA 相比，基于有限数量的母亲临床特征（母亲年龄和 BMI、ART 不孕症治疗和 4 个 microRNA）的 SGA 简化预测模型并没有提高 SGA 的检出率（10.0% FPR 时为 70.27% SGA 病例）仅基于 4 或 8 个 microRNA 生物标志物的表达谱的 SGA 预测模型。仅识别出 7 个 microRNA（miR-16-5p、miR-20a-5p、miR-145-5p、miR-146a-5p、miR-181a-5p、miR-342-3p 和 miR-574-3p） 42.68 % FGR 病例的 FPR 为 10.0%（AUC 0.725）。然而，仅 10 个 microRNA 的组合（miR-16-5p、miR-20a-5p、miR-100-5p、miR-143-3p、miR-145-5p、miR-146a-5p、miR-181a-5p 、miR-195-5p、miR-342-3p 和 miR-574-3p）达到了更高的辨别能力（AUC 0.774）。它在 FPR 为 10.0% 时确定了 40.24% 的 FGR 病例。基于 microRNA 的 FGR 任何亚型的预测模型通过实施母亲临床特征 [母亲年龄和 BMI、ART 不孕治疗、产次（未产）、前次妊娠中 SGA 或 FGR 的发生情况以及任何自身免疫性疾病的发生，以及慢性高血压的存在]。然后，在使用 7 个 microRNA 生物标志物或 10 个 microRNA 生物标志物的情况下，在 10.0% FPR 的情况下，确定了 64.63% 和 65.85% 的妊娠将发生 FGR。当上述变量旁边的其他临床变量（例如妊娠早期筛查 PE 和/或 FGR 以及自发性早产（均通过 FMF 算法））添加到 FGR 的预测模型中时，检测能力甚至增加到 74.39% 的病例FPR 为 10.0% 时为 78.05%。