Effect of human embryonic morphological development on fetal growth parameters: the Rotterdam Periconceptional Cohort (Predict Study)

Research question: Is embryonic morphological development according to the Carnegie stages associated with pregnancy outcome? Design: In a tertiary hospital-based cohort, 182 singleton non-malformed pregnancies were selected. Serial transvaginal three-dimensional ultrasound (3D-US) scans were carried out between 6+0 and 10+2 gestational weeks. Embryonic development was annotated according to the morphological criteria of the Carnegie classification using a virtual reality system. Second-trimester biparietal diameter, head circumference, abdominal circumference and femur length measurements were retrieved from medical records. Z-scores were calculated for mid-pregnancy estimated fetal weight (EFW) and newborn birth weight. Associations between longitudinal Carnegie stages and fetal growth parameters were investigated using linear mixed models, with subgroup analysis based on fetal gender. Results: A total of 576 first-trimester 3D-US scans were analysed (median of three scans per pregnancy). Embryonic development was positively associated with EFW z-score (β = 0.69; 95% CI 0.51 to 0.86; P < 0.001), biparietal diameter and femur length, but not with head circumference, abdominal circumference and birth weight z-score. After stratification for fetal gender, positive associations for both males and females were confirmed between embryonic development and EFW z-scores. Moreover, opposite gender-specific associations were detected between embryonic development and birth weight z-scores (males: β = 0.37; 95% CI 0.04 to 0.70; P < 0.05; females: β = -0.36; 95% CI -0.62 to -0.10; P < 0.01). Conclusions: Human embryonic development according to the Carnegie stages is associated with fetal growth parameters with gender-specificity of birth weight. These results emphasize the importance of the first-trimester of pregnancy, raising the morphological staging of the embryo as a new methodology for early risk assessment and improvement of subsequent fetal growth parameters.