Longitudinal first-trimester reference charts for crown to rump length and related fetal structures in a...

Early fetal growth is a critical period for human development and of great importance for later life health. Detailed knowledge on normal and abnormal development of first trimester fetal and related structures is limited. This study aimed to construct first-trimester population distribution centiles for weeks of gestation and reference centiles for fetal crown to rump length, and yolk, gestational and amniotic sac between 6 and 13 weeks of gestation.

We used data from 3464 ultrasounds in 1609 pregnant women with information on first day of last menstrual period (LMP) and regular menstrual cycles participating in a population-based cohort study from preconception onwards. Ultrasound assessments were performed in a dedicated research center around 7, 9 and 11 weeks of gestation and included measurements of the crown to rump length, and diameters and volumes of the yolk, amniotic and gestational sac. Using Generalized Additive Modeling for Location, Size and Shape (GAMLSS), distribution and reference centiles were estimated for gestational age, crown to rump length, yolk sac, gestational sac and amniotic sac for the first trimester.

We constructed distribution centiles for pregnancy dating based on first-trimester crown to rump length from 10 to 70 mm. Next, we generated gestational-age-based 5th, 10th, 25th, 50th, 75th, 90th, and 95th reference centiles for crown to rump length, and yolk, gestational and amniotic sac diameter and volume from 6 + 0 to 12 + 6 weeks of gestation. Length and diameter outcomes appeared to follow a nearly linear growth trajectory during this period of gestation. Confidence intervals showed that the centiles were most reliable between 6 + 0 and 12 + 6 weeks gestation.

Using an urban population-based cohort in a high-income, Western country, we calculated descriptive population distribution centiles for LMP-based weeks of gestation, as well as reference charts for crown to rump length, yolk sac, gestational sac and amniotic sac for LMP-based gestational age. The latter are intended for use in clinical and population-based settings. Interpretation of these charts should proceed with the source population and potential bias in mind.