Related Experiment Video
Updated: Jun 12, 2025
Author Spotlight: Exploring the Long-Term Health Impacts of Intracytoplasmic Sperm Injection on Offspring
Published on: May 17, 2024
Embryonic size and growth and adverse birth outcomes: the Rotterdam Periconception Cohort
J A Roelants1,2, M J Vermeulen1, S P Willemsen2,3
1Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Insights
Early embryonic size, measured by crown-rump length (CRL) and embryonic volume (EV), is linked to adverse birth outcomes. Smaller embryonic size in the first trimester indicates a higher risk for adverse outcomes, particularly small for gestational age (SGA).
Area of Science:
- Reproductive Medicine and Perinatology
- Medical Imaging and Diagnostics
- Fetal Development and Growth
Background:
- Adverse birth outcomes like preterm birth and small for gestational age (SGA) have significant lifelong health and economic consequences.
- Current methods for identifying at-risk pregnancies using 2D ultrasound are typically applied later in the first or second trimester.
- There is a need for earlier identification of fetal risks to enable timely interventions.
Purpose of the Study:
- To investigate the association between early embryonic size and growth in the first trimester and adverse birth outcomes.
- To determine if embryonic crown-rump length (CRL) and embryonic volume (EV) measurements can predict risks for adverse pregnancy outcomes.
- To establish reference curves for CRL and EV in early pregnancy.
Main Methods:
- A prospective cohort study of 918 singleton pregnancies was conducted between 2009 and 2018.
- Three-dimensional (3D) ultrasound scans with Virtual Reality software were used to measure CRL and EV at 7, 9, and 11 weeks of gestation.
- Adverse birth outcome was defined as a composite of SGA, preterm birth, congenital anomalies, stillbirth, or early neonatal mortality. Regression analyses were adjusted for multiple covariates.
Main Results:
- Embryos with a CRL below the 20th percentile at 7 weeks of gestation had approximately double the odds of an adverse birth outcome (aOR 2.03).
- Smaller embryonic size (CRL and EV) and slower growth trajectories were significantly associated with an increased risk of SGA.
- Longitudinal growth trajectories of CRL, but not EV, were associated with overall adverse birth outcomes.
Conclusions:
- Early first-trimester embryonic size, particularly CRL, is a significant predictor of adverse birth outcomes, especially SGA.
- Three-dimensional ultrasound and Virtual Reality enable early identification of at-risk embryos, expanding the window for potential interventions.
- These findings could lead to improved pregnancy outcomes and lifelong offspring health.
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.
