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This article has been cited by other articles in PMC. Abstract Objectives There are no international standards for relating fetal crown—rump length CRL to gestational age GA , and most existing charts have considerable methodological limitations. GA was calculated on the basis of a certain last menstrual period, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding 2 months. CRL was measured using strict protocols and quality-control measures.
All women were followed up throughout pregnancy until delivery and hospital discharge. Cases of neonatal and fetal death, severe pregnancy complications and congenital abnormalities were excluded from the study. GA estimation is carried out according to the two equations: Conclusions We have produced international prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the first trimester that can be used throughout the world.
At a population level, GA estimation is required to determine rates of small-for-gestational-age fetuses and preterm birth accurately in order to allocate resources appropriately 4 , 5. GA has traditionally been calculated from the first day of the last menstrual period LMP.
However, in a proportion of pregnancies, depending on the locality, the LMP is unknown or the information is unreliable 6 , 7. Between 9 and 13 weeks' gestation, linear growth evaluated by CRL is rapid and the SD is rather small, which means that GA can be estimated accurately.
In later pregnancy, head circumference is typically used for dating, as CRL can no longer be measured owing to curling of the growing fetus; however, variation is greater, which results in less accurate estimation of GA 9. For this reason, first-trimester ultrasound estimation of GA is recommended in clinical practice 8. Various studies have been conducted to derive CRL reference charts for the estimation of GA, mostly in single institutions or geographical locations.
A review of their methodological quality has shown several limitations including highly heterogeneous study designs and approaches to statistical analysis and reporting This could be achieved by first selecting pregnant women at low risk for fetal growth impairment, living in environments with minimal exposure to factors that have an adverse effect on growth.
From such populations, women at low risk of adverse pregnancy outcomes who deliver healthy newborns without congenital malformations would then be identified 11 — Our aim in this study was to generate CRL data according to GA using an optimal study design and prescriptive approach in order to develop international, population-based standards for early fetal linear size estimation and ultrasound dating of pregnancy in the first trimester that can be used throughout the world.
Briefly, we recruited women from the selected populations with no clinically relevant obstetric or gynecological history, who met the entry criteria of optimal health, nutrition, education and socioeconomic status to create a group of affluent, clinically healthy women who were at low risk of intrauterine growth restriction and preterm birth. The women, who were all well-educated and living in urban areas, reported the date and certainty of their LMP at their first antenatal clinic visit in response to specific questions.
However, as the first contact with the study often occurred at several different clinics in the geographical area, it was considered acceptable to use other, locally available, machines for the CRL measurement at the first antenatal visit only, provided that they were evaluated and approved by the study team. All 39 ultrasonographers at the eight study sites underwent rigorous training and standardization specifically for CRL measurement The ultrasonographers were only certified to measure CRL in the study if they demonstrated adequate knowledge of the study protocol and the quality of the images submitted for review was satisfactory CRL was measured once using strict techniques and imaging criteria Statistical methods The sample size was based principally on the precision and accuracy of a single centile and regression-based reference limits 19 , We have shown that with a sample of , we would obtain a precision of 0.
Further details on the precision obtained at the 5th or 10th centile by sample size ranging from to are provided in a previous publication We determined a mean target sample of women per site, after excluding complicated pregnancies and those lost to follow-up We also excluded mothers diagnosed with catastrophic or very severe medical conditions, those with severe unanticipated pregnancy-related conditions requiring hospital admission and those identified during pregnancy who no longer fulfilled all the entry criteria.
The statistical methods used are described in detail elsewhere We applied fractional polynomial models to the data by fitting separate models to the mean and SD of GA to account for increases in variance with greater CRL and gestation 23 , Using equations of the mean and SD one can easily compute any desired centile using the relationship: In our analysis, all three statistical approaches gave very similar results, and we opted for the one simulation for small and large CRL that had the best fit at both the upper and lower limits of GA.
Fitted curves 3rd, 50th and 97th centiles from different models were assessed visually for a good fit and by comparing the deviances from each model. Goodness of fit was assessed by a scatter plot of the distribution of residuals in Z-scores by CRL and also by counting the number of observations below the 3rd and above the 97th centiles.
Assessment of increasing variability with gestation, and smooth changes of both mean and SD across GA, were undertaken as part of the fractional polynomial approach. All the women were closely followed up throughout pregnancy by the study team until delivery and discharge from hospital. A total of women had live singleton births in the absence of severe maternal conditions or congenital abnormalities detected by ultrasound or at birth.