Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hum Reprod. 2024 Nov 1;39(11):2434-2441. doi: 10.1093/humrep/deae212.
Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes?
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).
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.
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.
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.
NL4115.
妊娠早期胚胎大小和生长与不良出生结局是否相关？
较大的胚胎头臀长（CRL）和胚胎体积（EV）与不良出生结局的几率较低相关，尤其是小于胎龄儿（SGA）。
早产、SGA 和先天畸形是最常见的不良出生结局，对生命健康有长期影响，并且医疗和社会成本也很高。在妊娠的晚期第一和第二阶段，可以使用二维超声（US）识别有不良出生结局风险的胎儿。
研究设计、大小、持续时间：在 2009 年至 2018 年期间，本前瞻性鹿特丹围孕期队列研究纳入了单胎妊娠。
参与者/材料、设置、方法：本研究纳入了荷兰一家三级医院的 918 名孕妇。妊娠时间是根据正常月经周期（自然妊娠）或受孕日期（ART 妊娠）来确定的。CRL 和 EV 使用 3D 超声扫描上的虚拟现实软件进行测量，大约在妊娠 7、9 和 11 周时重复进行。主要结局指标是不良出生结局，定义为 SGA（出生体重<第 10 百分位）、早产（<第 37 孕周）、先天畸形（Eurocat 标准）、死胎（>第 16 孕周）或新生儿早期死亡（≤7 天）的复合结果。构建了 CRL 和 EV 的参考曲线。进行了横断面（妊娠 7、9 和 11 周时 CRL/EV <第 20 百分位）和纵向（第 6 周至 13 周 CRL/EV 生长轨迹）回归分析，并对参与者的教育水平、吸烟、产次、年龄、BMI、地理背景、受孕方式和胎儿性别进行了调整。
在纳入的 918 名孕妇中，中位年龄为 32.3 岁，404 名（44%）妊娠是通过 ART 受孕的。在 199 名（22%）妊娠中存在不良出生结局。回归分析显示，妊娠 7 周后，CRL<第 20 百分位的胚胎不良出生结局的几率增加了约 2 倍（调整后的优势比（aOR）2.03，95%CI 1.21-3.39，P=0.007）。对于 EV<第 20 百分位也有类似的关联，但无统计学意义。这些发现主要是由胚胎大小与 SGA 之间的强关联驱动的（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 的纵向生长轨迹与不良出生结局相关，而 EV 的生长轨迹则没有。CRL 和 EV 的生长轨迹都与 SGA 相关。
局限性、谨慎的原因：三级医院人群和复杂的 3D 超声技术的可用性限制了本研究对一般人群和环境的普遍性。
在妊娠的早期第一阶段，已经可以使用 3D-US 和虚拟现实技术来识别具有不良出生结局风险的胚胎。这扩大了机会之窗，以便开发未来的干预措施，有可能改善妊娠结局和后代的生命健康。
研究资金/利益冲突：这项工作由荷兰鹿特丹伊拉斯谟医学中心妇产科资助。作者声明没有利益冲突。
NL4115。
