STUDY QUESTION Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER Larger embryonic crown–rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants’ educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21—3.39, P = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16–4.09), P = 0.02; 9-week EV: aOR 2.09 (1.10—3.97, P = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NL4115.

中文翻译：

---

胚胎大小和生长以及不良出生结局：鹿特丹围孕期队列


研究问题 怀孕前三个月的早期胚胎大小和生长是否与不良分娩结局有关？摘要答案 较大的胚胎冠-臀部长度 （CRL） 和胚胎体积 （EV） 与不良出生结局的几率较低有关，尤其是小于胎龄儿 （SGA）。已知的早产、SGA 和先天性异常是最普遍的不良分娩结果，会对终身健康造成影响，并产生高昂的医疗和社会成本。在妊娠早期和中期，可以使用 2 维超声检查 （US） 识别有不良分娩结局风险的胎儿。研究设计、规模、持续时间 2009 年至 2018 年间，单胎妊娠被纳入这个正在进行的前瞻性鹿特丹围孕期队列。参与者/材料、设置、方法 本研究包括来自荷兰一家三级医院的 918 名孕妇。妊娠日期基于规律的月经周期（自然妊娠）或受孕日期（ART 妊娠）。使用虚拟现实软件在 3 维 （3D） 超声扫描上测量 CRL 和 EV，在妊娠 7 、 9 和 11 周左右重复进行。主要结局指标是不良出生结局，定义为 SGA （出生体重 <第 10 个百分位数）、早产 （<妊娠第 37 周）、先天性异常 （Eurocat 标准）、死产 （>妊娠第 16 周） 或早期新生儿死亡率 （≤7 天出生）。构建了 CRL 和 EV 的参考曲线。 进行横断面 （CRL/EV <妊娠 7 、 9 和 11 周时的第 20 个百分位数）和纵向 （CRL/EV 生长轨迹在第 6 周和第 13 周之间）回归分析，并调整参与者的教育水平、吸烟、产次、年龄、BMI、地理背景、受孕方式和胎儿性别。主要结果和机会的作用 在纳入的 918 名孕妇中，中位年龄为 32.3 岁，404 例 （44%） 妊娠是通过 ART 受孕的。在 199 例 （22%） 妊娠中，存在不良分娩结局。回归分析显示，在妊娠 7 周以后，CRL <20th percentile 的胚胎不良分娩结局的几率增加 ∼2 倍（调整比值比 （aOR） 2.03,95% CI 1.21—3.39，P = 0.007）。EV <20th percentile 也发现了类似的关联，但无统计学意义。这些发现主要是由胚胎大小与 SGA 之间的强相关性驱动的 （例如 7 周 CRL：aOR 2.18 （1.16-4.09），P = 0.02;9 周 EV：aOR 2.09 （1.10—3.97，P = 0.02）。CRL 的纵向生长轨迹与 EV 的纵向生长轨迹无关，与不良出生结局相关。CRL 和 EV 增长轨迹都与 SGA 相关。局限性，谨慎理由 三级医院的人群和复杂的 3D 超声技术的可用性限制了这项研究对一般人群和环境的普遍性。研究结果的更广泛意义 在怀孕的前三个月早期，就可以通过使用 3D-US 和虚拟现实来识别不良分娩结果风险增加的胚胎。 这扩大了机会之窗，使未来干预措施的开发成为可能，以潜在地改善妊娠结局和后代在其生命过程中的健康。研究资金/竞争利益 这项工作由荷兰鹿特丹大学医学中心伊拉斯谟 MC 妇产科资助。作者声明没有利益冲突。试验注册号 NL4115。