Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements

Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements Yixiu Zhang, Hua Meng, Yuxin Jiang, Zhonghui Xu, Yunshu Ouyang, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-451255/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 8 You are reading this latest preprint version Abstract Background: To develop an ultrasonographic dating formula for predicting gestational age (GA) based on fetal crown–rump length (CRL) in a Chinese population, evaluate its systematic prediction error and compare it with existing formulae. Methods: This was a prospective cross-sectional study of spontaneously conceived singleton pregnancies among women with a regular menstrual cycle in the preceding year. Ultrasound examinations were performed at 11–14 weeks according to the date of the last menstrual cycle. The CRL was measured three times for each fetus, and the mean was used to derive the best-fit fractional polynomial regression model for estimation of GA in relation to CRL. For each fetus, the GA was compared with the GA calculated using six established dating formulae based on CRL measurements. The means of the differences between estimated and menstrual age were calculated for each formula. All the women were followed up routinely until the birth of the fetus. Results: Of the 4710 subjects recruited, the mean and standard deviation values of CRL changed linearly with GA. The corresponding regression equation and its correlation coefficient (R 2 ) was GA = 59.361513 + 0.461425 ´ CRL (R 2 = 0.8028). The mean difference between estimated and menstrual age was 0.22 days (95% confidence interval 0.05–0.21), lower than that of the six existing CRL dating formulae. Conclusions: We have derived a CRL-based dating formula suitable for naturally conceived pregnancies for GA between 11+0 and 13+6 weeks. The formula has no systematic prediction error, comparing favorably with the existing published dating formulae. Maternal & Fetal Medicine Sexual & Reproductive Medicine crown–rump length gestational age growth and development ultrasound Figures Figure 1 Background During pregnancy, accurate evaluation of gestational age (GA) is essential for predicting the delivery date and measuring neonatal maturity [ 1 – 3 ]. For the overall population, GA estimation can be used to assess the proportion of small-for-GA and premature infants accurately [ 4 ]. GA is often calculated from the date of the last menstrual period (LMP), but the LMP date is unreliable in some pregnant women [ 5 ]. In the past 30 years, many formulae have been published on the use of ultrasound measurements to estimate GA for naturally conceived fetuses and those derived from assisted reproductive technology (ART). Clinically, ultrasound parameters, such as crown–rump length (CRL) or biparietal diameter, are often used to predict GA, and are widely used in the first trimester [ 6 – 7 ]. During the first 9–13 weeks of gestation, GA can be calculated accurately from the CRL, because the linear growth rate in this measure is very rapid with a low standard deviation (SD). However, in the second and third trimesters, the CRL measured by ultrasonography is not available or no longer accurate, leading to inaccurate estimations of GA [ 8 ]. Many studies have reported formulae for estimating GA using the CRL [ 9 – 13 ], but there has been heterogeneity in the study designs, statistical methods, presentation of results and other aspects [ 14 ]. In addition, some formulae have been designed for the calculation of GA before 12 weeks of gestation, and become inaccurate if extended beyond this period [ 10 ]. Moreover, some authors have proposed the potential impacts of ethnicity on CRL. Most previously published CRL dating formulae were based on Western populations. but no large-scale prospective ultrasound evaluation data in the first trimester have been published for fetuses in the mainland of China. Methods This study was approved by the Ethics Committee of Peking Union Medical College Hospital and other relevant hospitals. All pregnant women participating in this study signed informed consent forms. All methods were carried out in accordance with relevant guidelines and regulations. Design This was a prospective, cross-sectional, multi-center study conducted in 14 tertiary hospitals in the mainland of China from 2008 to 2015. The study was conducted by the Chinese Fetal Growth and Prenatal Screening Consortium, which is a large-scale project about fetal growth and prenatal anomaly screening and diagnosis [ 15 ]. The study included pregnant Chinese women in their first trimester. Maternal, paternal, socioeconomic, and pregnancy characteristics were self-reported prospectively by questionnaire. The GA was calculated from the LMP, and ultrasound examinations were performed at the 11 + 0 to 13 + 6 weeks of gestation. The ultrasound examinations were arranged specifically for this study, and each woman was examined only once during the first trimester. All of them underwent continuous ultrasound follow-up during the second and third trimester, and were hospitalized for delivery. Follow-up results were obtained mainly by case review or telephone follow-up records. Data collection Ethnically Chinese woman, whose husband was also ethnically Chinese, were recuited when they were first documented at our prenatal diagnosis center. Spontaneously conceived singleton pregnancies were included for low-risk women with good nutritional status, and regular menstrual cycles of 28–30 days in the 12 months before pregnancy, were included. Exclusion criteria were applied as follows: an unclear LMP; irregular menstrual cycles; maternal diseases that might affect fetal growth (e.g., diabetes mellitus, renal or immunological diseases); multiple pregnancies; severe complications of pregnancy (such as pre-eclampsia, pregnancy-induced hypertension, gestational diabetes, or late pregnancy hemorrhage); spontaneous abortions; fetal deaths; congenital malformations; chromosomal abnormalities; or neonatal deaths. No fetuses were excluded because of abnormal biometry or birth weight. Commercial available ultrasound equipment (GE Healthcare Voluson E8, GE Healthcare Voluson 730, and Philips IU22) were used with curvilinear transabdominal sector probes (C5-2, C6-3 and V7-3, respectively). All sonographers received rigorous standardized training [ 15 , 16 ]. CRL measurement followed the guidelines of the Fetal Medicine Foundation [ 17 ]. The central sagittal section of the fetus was selected for each CRL measurement. The fetal body was flexed naturally, the top of the head and the sacral tail were displayed clearly, and the trunk showed a full sagittal section of the spine. The image was enlarged to display the fetal body, which occupied two-thirds to three-quarters of the screen. The cursor was placed on the image of the outer edge of the skin on the top of the fetal head to the outer edge of the sacrococcygeal skin, avoiding the limbs and yolk sac. Each CRL was measured three times, and the mean value was used for analysis. Analysis of data The original data are displayed as a scatter diagram of GA versus CRL (Fig. 1 ) [ 18 ]. A simple fractional polynomial regression model was derived to establish the regression formula and an optimal mean prediction formula was selected based on the correlation coefficient R 2 . Among the published GA prediction formulae, papers with similar sample sizes and high quality were selected for comparison [ 10 ]. The mean of the difference between the GA predicted by these established CRL formulae and that estimated from the LMP were calculated to evaluate the systematic prediction error. The 95% confidence interval (CI) and quartile intervals of these differences were calculated to reflect the random prediction error [ 19 ]. All statistical analyses were performed using SAS 9.4 software (SAS Institute Inc., Cary, NC, USA); P < 0.05 was considered statistically significant, and unless otherwise stated data are shown as the mean ± standard deviation (SD). Results In total, 4710 pregnant women were included in the study, with a mean maternal age of 29.4 ± 3.7 years (range 18.2–47.5) and a mean maternal BMI of 20.5 ± 2.6 kg/m 2 . There were 4527 women with Han ethnicity (96.11%) and 183 from minority ethnic groups (3.89%); 4255 primiparas (90.34%), and 455 multiparas (9.66%). The mean GA for ultrasound examinations was 88.7 ± 4.5 days, and the mean CRL was 63.48 ± 8.70 mm. A total of 1892 patients (40.17%) with natural deliveries, and 2818 patients (59.83%) with cesarean section deliveries were followed up. There were 2430 male fetuses (51.59%) and 2280 female fetuses (48.41%). Normal neonates were followed up until 1 month after birth, and all physical pediatric examination results were normal. Figure 1 shows the raw data, which demonstrated a significant linear relationship between GA and CRL. The corresponding best-fit equation for the estimation of GA was selected as follows: GA = 59.361513 + 0.461425 ⋅ CRL (R 2 = 0.8028). Table 1 shows the differences in the results between this study and previous ones. The systematic prediction error using our own formula in this study population was 0.12 days (95% CI 0.05–0.21 days). The formulae from Sahota et al. [ 10 ], Hadlock et al. [ 6 ], and Papageorghiou et al . [ 13 ] resulted in systematic errors of 0.28, 0.62 and 0.14 days, respectively. The formulae from Robinson et al. [ 7 ], Verburg et al. [ 12 ] and McKenna et al. [ 9 ], resulted in negative systematic errors of − 0.79 days, − 0.26 days and − 0.99 days, respectively. In terms of random error, the quartile interval of the difference between the predicted and actual GA in this study was 3.01 days, lower than those in the previous six studies described above. Table 1 Difference between predicted and actual gestational age (GA) in days. Formula for estimating GA based on CRL Systemetic prediction error (95% CI) a Median difference between predicted and actual GA (upper and lower quartiles). b Random prediction error (interquartile distance). b Our study 59.361513 + 0.461425×CRL 0.12 (0.05,0.21) 0.12 (− 1.48,1.53) 3.01 Papageorghiou et al. [13] 40.9041+(3.21585×CRL 0.5 ) + 0.348956×CRL 0.14 (0.04,0.23) 0.14 (− 1.64,1.73) 3.37 Verburg et al. [12] exp (1.4653 + 0.001737 × CRL + 0.2313 × log(CRL) −0.26 (− 0.34,−0.16) −0.26 (− 1.86,1.20) 3.06 Sahota et al. [10] 26.643 + 7.822×CRL 0.5 0.28 (0.20,0.38) 0.28 (− 1.32,1.78) 3.10 Hadlock et al. [6] 7×(exp(1.684969 + 0.315646×(CRL/10) -0.049306×((CRL/10) 2 ) + 0.004057×((CRL/10) 3 ) − 0.000120456×((CRL/10) 4 ))) 0.62 (0.55,0.70) 0.62 (− 1.05,2.19) 3.24 Robinsin et al. [7] 8.052 x (CRL 0.5 ) + 23.73 −0.79 (− 0.87,−0.71) −0.79 (− 2.43,0.74) 3.17 McKennan et al. [9] 32.61967 + 2.62975× CRL − 0.42399 × log(CRL) × CRL −0.99 (− 1.07,−0.91) −0.99 (− 2.56,0.50) 3.06 a The difference between the actual and predicted GA estimated by our formula showed a skewed distribution, so the median is used to represent the overall prediction error. b For the same reason, in these columns error is expressed as the interquartile distance. Discussion Main findings There has been great heterogeneity in the study design, statistical analysis and presentation of results in reported formulae for calculating GA [ 14 ]. Some of the studies included nonselected or low-risk pregnant women, but most of them did not use adequate quality control standards. In other studies, retrospective analyses were used to obtain data from clinical workstations, with a high risk of bias. The purpose of our study was to establish a formula for calculating GA for naturally conceived fetuses at 11–14 weeks of gestation in the mainland of China. Unified enrollment standards, clinical procedures, data collection procedures and strict quality control procedures were used, so that the examination results could be promoted widely. All data in this study were measured specifically for the purpose of this study, and were obtained from a prospective study rather than a retrospective clinical database. According to the study design recommended by Altman et al. [ 20 ], low-risk pregnant women with a naturally conceived singleton pregnancy, and a clear LMP date were selected, and each fetus was measured only once during pregnancy. All pregnant women were followed up until the birth of the fetus, and data were excluded only when the fetus presented with congenital malformations or intrauterine death, to avoid generating an abnormal database. In this study, GA was calculated according to the first day of the LMP. We selected only pregnant women who had records of regular menstrual cycles of 28–30 days for at least 1 year before pregnancy. They had not taken ovulation-inducing or contraceptives drugs or other estrogenic hormones for at least 6 months before pregnancy. Other methods used previously to calculate the GA have included the date of oocyte collection in ART cycles, serum human chorionic gonadotropin levels, elevated luteinizing hormone levels, the timing of embryo transfer in ART cycles, ultrasound detection of follicular rupture, cervical mucus morphology, basal body temperature increases, and the date of sexual intercourse. Some studies have used the GA of fetuses produced by in vitro fertilization (IVF) as a gold standard. However, fetuses produced through IVF cannot be identical biologically to naturally conceived ones because there might be differences between the dates of ovulation and conception. IVF-derived fetuses might also have growth difference during the first trimester. The biological characteristics of pregnant women following ART might be different from low-risk women with natural conceptions. Therefore, we believe that the application of formulae for evaluating GA derived from ART-conceived fetuses to naturally conceived fetuses is probably invalid. The formula for calculating GA obtained in this study was based on univariate linear regression analysis, similar to that of McKennan et al. [ 9 ]. Systematic prediction errors and random prediction errors were used to evaluate the differences in formulae for estimating GA between this study and others. Sladkevicius et al. [ 21 ] summarized 21 CRL-based dating formulae, among which three were selected from naturally conceived fetuses with relatively large sample sizes, including the studies by Robinson et al. [ 7 ] in 1975, Hadlock et al. [ 6 ] in 1991 and von Kaisenberg et al. [ 11 ] in 2002. However, Sahota et al. [ 10 ] pointed out that there was actually no formula for calculating GA in the study by von Kaisenberg et al. [ 11 ], which was incorrectly derived by Sladkevicius et al. [ 21 ] based on a size estimation formula. Napolitano et al. [ 14 ] carried out a systematic analysis on formulae for calculating GA, and four studies with scores higher than 18 points (29-point maximum) were selected: Sahota et al. [ 10 ], Verburg et al. [ 12 ], Robinson et al. [ 7 ], and McKennan et al [ 9 ]. In 2014, Papageorghiou et al. [ 13 ] proposed a “worldwide” CRL-based dating formula from data of 4321 fetuses. The results of our study was compared with the above six studies [ 6 , 7 , 9 , 10 , 12 , 13 ] and our formula lay in the middle of them. Three studies overestimated the GA, and three underestimated it, compared with our study. Our results were very consistent with the recent high-quality studies, such as those by Papageorghiou et al. [ 13 ], Sahota et al. [ 10 ] and Verburg et al. [ 12 ]. The prediction differences were + 0.14, + 0.28 and − 0.26 days, respectively. However, the results of this study had relatively large differences from some relatively old papers, such as those of Robinson et al. [ 7 ] and Hadlock et al. [ 6 ], which might be related to the poor resolution of the instruments used in their studies. We believe that there is no clinically significant difference in CRL-based GA formulae derived from Chinese and non-Chinese fetuses [ 10 , 14 ]. At the same time, this suggests that fetal growth and development are similar between different populations when methodological standards are high and appropriate selection is made. Strengths and limitations It should be noted that one disadvantage of estimating GA by measuring fetal CRL alone using ultrasound is the unknown biological variation of this measure during the first trimester of pregnancy. Therefore, we recommend collecting all information (including LMP and assessing its reliability) from pregnant women at their first visit in the first trimester [ 22 ]. When the GA calculated by measuring CRL by ultrasound and that from LMP are basically consistent, the GA can be calculated according to the date of the LMP. However, when the timing of the LMP is very accurate and reliable, and there is a big difference from the GA calculated by CRL, clinics should suspect that the fetus might have pathological abnormalities causing disorders of growth and development, which need to be further monitored and diagnosed [ 23 , 24 ]. At the same time, calculated variabilities in the GA, such as SD values or percentiles, should be explained to pregnant women as estimated prediction error. Conclusions A formula for calculating GA among Chinese fetuses based on CRL at 10–15 weeks of gestation with no significant systematic error was obtained in this study. It is highly consistent with formulae for calculating GA obtained from other high-quality studies published in recent years. Abbreviations GA: gestational age; LMP: last menstrual period; CRL: crown–rump length. Declarations Acknowledgments We thank all of the participating women and staff in the Chinese Fetal Growth and Prenatal Screening Consortium. This study could not have been accomplished without their enthusiasm and cooperation. Authors’ contributions HM, YXJ conceived the idea, wrote the protocol, submitted the ethics approval form.FD primarily analysed the data. YXZ analysed parts of the data and drafted the final manuscript for submission. ZHX, YSOY, SLL, QC, QQW, RL, TR, ALC, XLC, TZY, PC, HNX, HL, QD, MY, XY, JL, JWT, KS, HL checked the patient and got the data. All authors have read and approved the manuscript Funding This work was supported by the Chinese 11th Five-Year National Science & technology support program under Grant 2006BAI05A04, Chinese 12th Five-Year National Science & technology support program under Grant 2014BAI06B05 and National Natural Science Foundation of China under Grant 81901745. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the Ethics Committee of Peking Union Medical College Hospital and other relevant hospitals. All pregnant women participating in this study signed informed consent forms. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Miller J, Turan S, Baschat AA. Fetal growth restriction. Semin Perinatol. 2008;32(4): 274-80. Taipale P, Hiilesmaa V. Predicting delivery date by ultrasound and last menstrual period in early gestation. Obstet Gynecol. 2001;97(2):189-94. Ananth CV. Menstrual versus clinical estimate of gestational age dating in the United States: temporal trends and variability in indices of perinatal outcomes. Paediatr Perinat Epidemiol. 2007;21 Suppl 2:22-30. Callaghan WM, Dietz PM. Differences in birth weight for gestational age distributions according to the measures used to assign gestational age. Am J Epidemiol. 2010;171(7):826-36. Lynch CD, Zhang J. The research implications of the selection of a gestational age estimation method. Paediatr Perinat Epidemiol. 2007;21 Suppl 2:86-96. Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5-18 weeks) with high-resolution real-time US. Radiology. 1992;182(2):501-5. Robinson HP, Fleming JE. A critical evaluation of sonar "crown-rump length" measurements. Br J Obstet Gynaecol. 1975;82(9):702-10. Kalish RB, Thaler HT, Chasen ST, Gupta M, Berman SJ, Rosenwaks Z, et al. First- and second-trimester ultrasound assessment of gestational age. Am J Obstet Gynecol. 2004;191(3):975-8. McLennan AC, Schluter PJ. Construction of modern Australian first trimester ultrasound dating and growth charts. J Med Imaging Radiat Oncol. 2008;52(5):471-9. Sahota DS, Leung TY, Leung TN, Chan OK, Lau TK. Fetal crown-rump length and estimation of gestational age in an ethnic Chinese population. Ultrasound Obstet Gynecol. 2009;33(2):157-60. von Kaisenberg CS, Fritzer E, Kühling H, Jonat W. Fetal transabdominal biometry at 11-14 weeks of gestation. Ultrasound Obstet Gynecol. 2002;20(6):564-74. Verburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, et al. New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008;31(4):388-96. Papageorghiou AT, Kennedy SH, Salomon LJ, Ohuma EO, Cheikh Ismail L, Barros FC, et al. International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy. Ultrasound Obstet Gynecol. 2014;44(6):641-8. Napolitano R, Dhami J, Ohuma EO, Ioannou C, Conde-Agudelo A, Kennedy SH, Villar J, Papageorghiou AT. Pregnancy dating by fetal crown-rump length: a systematic review of charts. BJOG. 2014;121(5):556-65. Zhang Y, Meng H, Jiang Y, Xu Z, Ouyang Y, Li S, et al. Chinese fetal biometry: reference equations and comparison with charts from other populations. J Matern Fetal Neonatal Med. 2019;32(9):1507-1515. Ioannou C, Sarris I, Hoch L, Salomon LJ, Papageorghiou AT; International Fetal and Newborn Growth Consortium for the 21st Century. Standardisation of crown-rump length measurement. BJOG. 2013;120 Suppl 2:38-41. Sarris I, Ioannou C, Ohuma EO, Altman DG, Hoch L, Cosgrove C, et al. Standardisation and quality control of ultrasound measurements taken in the INTERGROWTH-21st Project. BJOG. 2013;120 Suppl 2:33-7. Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol. 2004;191(1):45-67. Ohuma EO, Papageorghiou AT, Villar J, Altman DG. Estimation of gestational age in early pregnancy from crown-rump length when gestational age range is truncated: the case study of the INTERGROWTH-21st Project. BMC Med Res Methodol. 2013; 13:151. Altman DG, Chitty LS. New charts for ultrasound dating of pregnancy. Ultrasound Obstet Gynecol. 1997;10(3):174-91. Sladkevicius P, Saltvedt S, Almström H, Kublickas M, Grunewald C, Valentin L. Ultrasound dating at 12-14 weeks of gestation. A prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies. Ultrasound Obstet Gynecol. 2005;26(5):504-11. Salomon LJ. Early fetal growth: concepts and pitfalls. Ultrasound Obstet Gynecol. 2010;35(4):385-9. Mukri F, Bourne T, Bottomley C, Schoeb C, Kirk E, Papageorghiou AT. Evidence of early first-trimester growth restriction in pregnancies that subsequently end in miscarriage. BJOG. 2008;115(10):1273-8. Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early-pregnancy origins of low birth weight. Nature. 2002;417(6892):916. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major revision 24 May, 2021 Reviews received at journal 22 May, 2021 Reviewers agreed at journal 12 May, 2021 Reviewers invited by journal 12 May, 2021 Editor assigned by journal 10 May, 2021 Editor invited by journal 10 May, 2021 Submission checks completed at journal 10 May, 2021 First submitted to journal 22 Apr, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-451255","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":26142740,"identity":"d6dec6b3-e145-4f25-9e76-0b7c645dd1c5","order_by":0,"name":"Yixiu Zhang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yixiu","middleName":"","lastName":"Zhang","suffix":""},{"id":26142743,"identity":"62c07609-550e-44ee-8462-97c8c2ab5eff","order_by":1,"name":"Hua Meng","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Meng","suffix":""},{"id":26142745,"identity":"e2472420-37e9-4692-a08b-e00bc9355efb","order_by":2,"name":"Yuxin Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBACxmYogw2EEiok5ORJ0/LgjIWxYQMJNrIxPmyrSGQ4QEAZczvzs4df2w4n9kn3mD1InCeRwNjA/PDRDbwOYzM3lm07bMwmcyzdIHGbRB47A5uxcQ5+v5hJS7YdlmOTSD4mAdRSzNjAwyaNXwv7N5AWHjaJxDaJxDkSiQ0HCGrhMZP8CLelgTgtZdIM59KN2STS0iQSjkkYGzYT8Ith//Ftkj/KrBPnz8gxk/xRUycnz9788DFeLQ3AgOZlQxZixqMcBEDJg/HHHwKqRsEoGAWjYGQDAH7uRMm8QNBnAAAAAElFTkSuQmCC","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yuxin","middleName":"","lastName":"Jiang","suffix":""},{"id":26142748,"identity":"1a99e5e1-1402-4e48-a16c-5b4de5411dd6","order_by":3,"name":"Zhonghui Xu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhonghui","middleName":"","lastName":"Xu","suffix":""},{"id":26142749,"identity":"39e6c52b-93e0-4312-a7dc-dacc39d8e7f6","order_by":4,"name":"Yunshu Ouyang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yunshu","middleName":"","lastName":"Ouyang","suffix":""},{"id":26142753,"identity":"a59be2d9-c389-4e97-b594-0c1f2336402e","order_by":5,"name":"Shengli Li","email":"","orcid":"","institution":"Shenzhen Maternity and Child Healthcare Hospital Affiliated to Nanfang Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shengli","middleName":"","lastName":"Li","suffix":""},{"id":26142758,"identity":"3c392d6e-8bf2-4769-91df-de5b400c4364","order_by":6,"name":"Qian Chen","email":"","orcid":"","institution":"Peking University First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Chen","suffix":""},{"id":26142761,"identity":"97f38021-ead1-49e9-97a2-a522034c667c","order_by":7,"name":"Qingqing Wu","email":"","orcid":"","institution":"Capital Medical University Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qingqing","middleName":"","lastName":"Wu","suffix":""},{"id":26142765,"identity":"3d97a760-945c-4337-919a-7402ad2c4878","order_by":8,"name":"Rui Li","email":"","orcid":"","institution":"Southwest Hospital of the Third Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Li","suffix":""},{"id":26142768,"identity":"d786c2fd-6617-4ab8-9c47-92a7fa4e0bc8","order_by":9,"name":"Tong Ru","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, Nanjing University Medical School","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Ru","suffix":""},{"id":26142769,"identity":"7e8a3934-ad53-4b3d-a1db-537ffb669b60","order_by":10,"name":"Ailu Cai","email":"","orcid":"","institution":"Shengjing Hospital of China Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ailu","middleName":"","lastName":"Cai","suffix":""},{"id":26142770,"identity":"61de1dc7-0c98-492c-bacb-5ec84bb93f05","order_by":11,"name":"Xinlin Chen","email":"","orcid":"","institution":"Hubei Maternal and Child Health Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xinlin","middleName":"","lastName":"Chen","suffix":""},{"id":26142772,"identity":"4a18c0ff-fe7b-4b72-ac35-de379ddf26e2","order_by":12,"name":"Taizhu Yang","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Taizhu","middleName":"","lastName":"Yang","suffix":""},{"id":26142774,"identity":"449e5322-cead-4516-9632-654b6e455cfd","order_by":13,"name":"Ping Chen","email":"","orcid":"","institution":"Shanghai First Maternity and Infant Health Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Chen","suffix":""},{"id":26142776,"identity":"5bf31ca2-396d-4a25-a509-c110d6829cdf","order_by":14,"name":"Hongning Xie","email":"","orcid":"","institution":"First Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongning","middleName":"","lastName":"Xie","suffix":""},{"id":26142778,"identity":"f1576910-4d3e-474b-9e4a-7dc62d7ecb8f","order_by":15,"name":"Hong Lu","email":"","orcid":"","institution":"Women's Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Lu","suffix":""},{"id":26142779,"identity":"802f7fde-b6b3-4823-b710-c54db9bd6cdc","order_by":16,"name":"Qing Dai","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Dai","suffix":""},{"id":26142780,"identity":"107161d8-5188-477b-bcda-d6558d0d95e1","order_by":17,"name":"Fen Dong","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences, China-Japan Friendship Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fen","middleName":"","lastName":"Dong","suffix":""},{"id":26142781,"identity":"f73b0cbd-efc3-47ae-b771-5cdea51883f7","order_by":18,"name":"Meng Yang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Meng","middleName":"","lastName":"Yang","suffix":""},{"id":26142782,"identity":"a7dee830-652a-4c9a-ba8c-db6a977854b4","order_by":19,"name":"Xiao Yang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Yang","suffix":""},{"id":26142783,"identity":"35585111-a1b5-4ed6-afce-f0fb5a003707","order_by":20,"name":"Jia Lu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Lu","suffix":""},{"id":26142784,"identity":"f4c3079a-6bda-495d-804b-ccc1e81320ca","order_by":21,"name":"Jiawei Tian","email":"","orcid":"","institution":"The 2nd Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiawei","middleName":"","lastName":"Tian","suffix":""},{"id":26142785,"identity":"b257b469-e2df-421b-9457-f6d962477fee","order_by":22,"name":"Kun Sun","email":"","orcid":"","institution":"Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Sun","suffix":""},{"id":26142787,"identity":"62e5661d-b79d-4b3e-8773-c87312a9bc57","order_by":23,"name":"Hui Li","email":"","orcid":"","institution":"Shengjing Hospital of China Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2021-04-22 14:00:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-451255/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-451255/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":9040689,"identity":"2cf4580e-7332-4b7b-9bb2-5b3956bfd452","added_by":"auto","created_at":"2021-05-11 13:17:15","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":275837,"visible":true,"origin":"","legend":"Scatter plot of gestational age (GA) versus crown–rump length (CRL) in 4710 Chinese fetuses.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-451255/v1/8a9669dfbf698711d219c469.jpg"},{"id":13692686,"identity":"55696ed6-3298-4993-8dc3-788c111bb682","added_by":"auto","created_at":"2021-09-17 12:44:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":465047,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-451255/v1/835c9300-7fd5-48e3-8e41-bf0c72c5af8b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements","fulltext":[{"header":"Background","content":"\u003cp\u003eDuring pregnancy, accurate evaluation of gestational age (GA) is essential for predicting the delivery date and measuring neonatal maturity [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. For the overall population, GA estimation can be used to assess the proportion of small-for-GA and premature infants accurately [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. GA is often calculated from the date of the last menstrual period (LMP), but the LMP date is unreliable in some pregnant women [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. In the past 30 years, many formulae have been published on the use of ultrasound measurements to estimate GA for naturally conceived fetuses and those derived from assisted reproductive technology (ART). Clinically, ultrasound parameters, such as crown\u0026ndash;rump length (CRL) or biparietal diameter, are often used to predict GA, and are widely used in the first trimester [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. During the first 9\u0026ndash;13 weeks of gestation, GA can be calculated accurately from the CRL, because the linear growth rate in this measure is very rapid with a low standard deviation (SD). However, in the second and third trimesters, the CRL measured by ultrasonography is not available or no longer accurate, leading to inaccurate estimations of GA [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Many studies have reported formulae for estimating GA using the CRL [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e], but there has been heterogeneity in the study designs, statistical methods, presentation of results and other aspects [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. In addition, some formulae have been designed for the calculation of GA before 12 weeks of gestation, and become inaccurate if extended beyond this period [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, some authors have proposed the potential impacts of ethnicity on CRL. Most previously published CRL dating formulae were based on Western populations. but no large-scale prospective ultrasound evaluation data in the first trimester have been published for fetuses in the mainland of China.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Peking Union Medical College Hospital and other relevant hospitals. All pregnant women participating in this study signed informed consent forms. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section3\"\u003e\n\u003cp\u003e\u003cstrong\u003eDesign\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a prospective, cross-sectional, multi-center study conducted in 14 tertiary hospitals in the mainland of China from 2008 to 2015. The study was conducted by the Chinese Fetal Growth and Prenatal Screening Consortium, which is a large-scale project about fetal growth and prenatal anomaly screening and diagnosis [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. The study included pregnant Chinese women in their first trimester. Maternal, paternal, socioeconomic, and pregnancy characteristics were self-reported prospectively by questionnaire. The GA was calculated from the LMP, and ultrasound examinations were performed at the 11\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e to 13\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks of gestation. The ultrasound examinations were arranged specifically for this study, and each woman was examined only once during the first trimester. All of them underwent continuous ultrasound follow-up during the second and third trimester, and were hospitalized for delivery. Follow-up results were obtained mainly by case review or telephone follow-up records.\u003c/p\u003e\n\u003cdiv id=\"Sec4\" class=\"Section4\"\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthnically Chinese woman, whose husband was also ethnically Chinese, were recuited when they were first documented at our prenatal diagnosis center. Spontaneously conceived singleton pregnancies were included for low-risk women with good nutritional status, and regular menstrual cycles of 28\u0026ndash;30 days in the 12 months before pregnancy, were included.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were applied as follows: an unclear LMP; irregular menstrual cycles; maternal diseases that might affect fetal growth (e.g., diabetes mellitus, renal or immunological diseases); multiple pregnancies; severe complications of pregnancy (such as pre-eclampsia, pregnancy-induced hypertension, gestational diabetes, or late pregnancy hemorrhage); spontaneous abortions; fetal deaths; congenital malformations; chromosomal abnormalities; or neonatal deaths. No fetuses were excluded because of abnormal biometry or birth weight.\u003c/p\u003e\n\u003cp\u003eCommercial available ultrasound equipment (GE Healthcare Voluson E8, GE Healthcare Voluson 730, and Philips IU22) were used with curvilinear transabdominal sector probes (C5-2, C6-3 and V7-3, respectively). All sonographers received rigorous standardized training [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. CRL measurement followed the guidelines of the Fetal Medicine Foundation [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. The central sagittal section of the fetus was selected for each CRL measurement. The fetal body was flexed naturally, the top of the head and the sacral tail were displayed clearly, and the trunk showed a full sagittal section of the spine. The image was enlarged to display the fetal body, which occupied two-thirds to three-quarters of the screen. The cursor was placed on the image of the outer edge of the skin on the top of the fetal head to the outer edge of the sacrococcygeal skin, avoiding the limbs and yolk sac. Each CRL was measured three times, and the mean value was used for analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis of data\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003cp\u003eThe original data are displayed as a scatter diagram of GA versus CRL (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. A simple fractional polynomial regression model was derived to establish the regression formula and an optimal mean prediction formula was selected based on the correlation coefficient R\u003csup\u003e2\u003c/sup\u003e. Among the published GA prediction formulae, papers with similar sample sizes and high quality were selected for comparison [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. The mean of the difference between the GA predicted by these established CRL formulae and that estimated from the LMP were calculated to evaluate the systematic prediction error. The 95% confidence interval (CI) and quartile intervals of these differences were calculated to reflect the random prediction error [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. All statistical analyses were performed using SAS 9.4 software (SAS Institute Inc., Cary, NC, USA); \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant, and unless otherwise stated data are shown as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, 4710 pregnant women were included in the study, with a mean maternal age of 29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 years (range 18.2\u0026ndash;47.5) and a mean maternal BMI of 20.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 kg/m\u003csup\u003e2\u003c/sup\u003e. There were 4527 women with Han ethnicity (96.11%) and 183 from minority ethnic groups (3.89%); 4255 primiparas (90.34%), and 455 multiparas (9.66%). The mean GA for ultrasound examinations was 88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 days, and the mean CRL was 63.48\u0026thinsp;\u0026plusmn;\u0026thinsp;8.70 mm. A total of 1892 patients (40.17%) with natural deliveries, and 2818 patients (59.83%) with cesarean section deliveries were followed up. There were 2430 male fetuses (51.59%) and 2280 female fetuses (48.41%). Normal neonates were followed up until 1 month after birth, and all physical pediatric examination results were normal.\u003c/p\u003e\n\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the raw data, which demonstrated a significant linear relationship between GA and CRL. The corresponding best-fit equation for the estimation of GA was selected as follows: GA\u0026thinsp;=\u0026thinsp;59.361513\u0026thinsp;+\u0026thinsp;0.461425 \u0026sdot; CRL (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.8028). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the differences in the results between this study and previous ones. The systematic prediction error using our own formula in this study population was 0.12 days (95% CI 0.05\u0026ndash;0.21 days). The formulae from Sahota \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e], Hadlock \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], and Papageorghiou \u003cem\u003eet al\u003c/em\u003e. [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] resulted in systematic errors of 0.28, 0.62 and 0.14 days, respectively. The formulae from Robinson \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e], Verburg \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e] and McKenna \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e], resulted in negative systematic errors of \u0026minus;\u0026thinsp;0.79 days, \u0026minus;\u0026thinsp;0.26 days and \u0026minus;\u0026thinsp;0.99 days, respectively. In terms of random error, the quartile interval of the difference between the predicted and actual GA in this study was 3.01 days, lower than those in the previous six studies described above.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDifference between predicted and actual gestational age (GA) in days.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFormula for estimating GA based on CRL\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSystemetic prediction error (95% CI)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMedian difference between predicted and actual GA (upper and lower quartiles).\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRandom prediction error (interquartile distance).\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOur study\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.361513\u0026thinsp;+\u0026thinsp;0.461425\u0026times;CRL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.12 (0.05,0.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e0.12 (\u0026minus;\u0026thinsp;1.48,1.53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePapageorghiou et al.\u003csup\u003e[13]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.9041+(3.21585\u0026times;CRL\u003csup\u003e0.5\u003c/sup\u003e)\u0026thinsp;+\u0026thinsp;0.348956\u0026times;CRL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.14 (0.04,0.23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e0.14 (\u0026minus;\u0026thinsp;1.64,1.73)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.37\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVerburg et al.\u003csup\u003e[12]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eexp (1.4653\u0026thinsp;+\u0026thinsp;0.001737 \u0026times; CRL\u0026thinsp;+\u0026thinsp;0.2313 \u0026times; log(CRL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026minus;0.26 (\u0026minus;\u0026thinsp;0.34,\u0026minus;0.16)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e\u0026minus;0.26 (\u0026minus;\u0026thinsp;1.86,1.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.06\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSahota et al.\u003csup\u003e[10]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.643\u0026thinsp;+\u0026thinsp;7.822\u0026times;CRL\u003csup\u003e0.5\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.28 (0.20,0.38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e0.28 (\u0026minus;\u0026thinsp;1.32,1.78)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.10\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHadlock et al.\u003csup\u003e[6]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u0026times;(exp(1.684969\u0026thinsp;+\u0026thinsp;0.315646\u0026times;(CRL/10)\u003c/p\u003e\n\u003cp\u003e-0.049306\u0026times;((CRL/10)\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;+\u0026thinsp;0.004057\u0026times;((CRL/10)\u003csup\u003e3\u003c/sup\u003e)\u0026thinsp;\u0026minus;\u0026thinsp;0.000120456\u0026times;((CRL/10)\u003csup\u003e4\u003c/sup\u003e)))\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.62 (0.55,0.70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e0.62 (\u0026minus;\u0026thinsp;1.05,2.19)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.24\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRobinsin et al.\u003csup\u003e[7]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.052 x (CRL\u003csup\u003e0.5\u003c/sup\u003e)\u0026thinsp;+\u0026thinsp;23.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026minus;0.79 (\u0026minus;\u0026thinsp;0.87,\u0026minus;0.71)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e\u0026minus;0.79 (\u0026minus;\u0026thinsp;2.43,0.74)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.17\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMcKennan et al.\u003csup\u003e[9]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.61967\u0026thinsp;+\u0026thinsp;2.62975\u0026times; CRL \u0026minus;\u0026thinsp;0.42399 \u0026times; log(CRL) \u0026times; CRL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026minus;0.99 (\u0026minus;\u0026thinsp;1.07,\u0026minus;0.91)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026minus;\"\u003e\n\u003cp\u003e\u0026minus;0.99 (\u0026minus;\u0026thinsp;2.56,0.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.06\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003eThe difference between the actual and predicted GA estimated by our formula showed a skewed distribution, so the median is used to represent the overall prediction error.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u003cstrong\u003eb\u003c/strong\u003e\u003c/sup\u003eFor the same reason, in these columns error is expressed as the interquartile distance.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003e\u003cspan class=\"BoldItalic\"\u003eMain findings\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere has been great heterogeneity in the study design, statistical analysis and presentation of results in reported formulae for calculating GA [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Some of the studies included nonselected or low-risk pregnant women, but most of them did not use adequate quality control standards. In other studies, retrospective analyses were used to obtain data from clinical workstations, with a high risk of bias. The purpose of our study was to establish a formula for calculating GA for naturally conceived fetuses at 11\u0026ndash;14 weeks of gestation in the mainland of China. Unified enrollment standards, clinical procedures, data collection procedures and strict quality control procedures were used, so that the examination results could be promoted widely. All data in this study were measured specifically for the purpose of this study, and were obtained from a prospective study rather than a retrospective clinical database. According to the study design recommended by Altman et al. [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e], low-risk pregnant women with a naturally conceived singleton pregnancy, and a clear LMP date were selected, and each fetus was measured only once during pregnancy. All pregnant women were followed up until the birth of the fetus, and data were excluded only when the fetus presented with congenital malformations or intrauterine death, to avoid generating an abnormal database.\u003c/p\u003e\n\u003cp\u003eIn this study, GA was calculated according to the first day of the LMP. We selected only pregnant women who had records of regular menstrual cycles of 28\u0026ndash;30 days for at least 1 year before pregnancy. They had not taken ovulation-inducing or contraceptives drugs or other estrogenic hormones for at least 6 months before pregnancy. Other methods used previously to calculate the GA have included the date of oocyte collection in ART cycles, serum human chorionic gonadotropin levels, elevated luteinizing hormone levels, the timing of embryo transfer in ART cycles, ultrasound detection of follicular rupture, cervical mucus morphology, basal body temperature increases, and the date of sexual intercourse. Some studies have used the GA of fetuses produced by in vitro fertilization (IVF) as a gold standard. However, fetuses produced through IVF cannot be identical biologically to naturally conceived ones because there might be differences between the dates of ovulation and conception. IVF-derived fetuses might also have growth difference during the first trimester. The biological characteristics of pregnant women following ART might be different from low-risk women with natural conceptions. Therefore, we believe that the application of formulae for evaluating GA derived from ART-conceived fetuses to naturally conceived fetuses is probably invalid.\u003c/p\u003e\n\u003cp\u003eThe formula for calculating GA obtained in this study was based on univariate linear regression analysis, similar to that of McKennan \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Systematic prediction errors and random prediction errors were used to evaluate the differences in formulae for estimating GA between this study and others. Sladkevicius \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e] summarized 21 CRL-based dating formulae, among which three were selected from naturally conceived fetuses with relatively large sample sizes, including the studies by Robinson \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e] in 1975, Hadlock \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] in 1991 and von Kaisenberg \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e] in 2002. However, Sahota et al. [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e] pointed out that there was actually no formula for calculating GA in the study by von Kaisenberg \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e], which was incorrectly derived by Sladkevicius \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e] based on a size estimation formula. Napolitano \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e] carried out a systematic analysis on formulae for calculating GA, and four studies with scores higher than 18 points (29-point maximum) were selected: Sahota \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e], Verburg \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e], Robinson \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e], and McKennan \u003cem\u003eet al\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. In 2014, Papageorghiou \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] proposed a \u0026ldquo;worldwide\u0026rdquo; CRL-based dating formula from data of 4321 fetuses. The results of our study was compared with the above six studies [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] and our formula lay in the middle of them. Three studies overestimated the GA, and three underestimated it, compared with our study. Our results were very consistent with the recent high-quality studies, such as those by Papageorghiou \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e], Sahota \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e] and Verburg \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. The prediction differences were +\u0026thinsp;0.14, +\u0026thinsp;0.28 and \u0026minus;\u0026thinsp;0.26 days, respectively. However, the results of this study had relatively large differences from some relatively old papers, such as those of Robinson \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e] and Hadlock \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], which might be related to the poor resolution of the instruments used in their studies. We believe that there is no clinically significant difference in CRL-based GA formulae derived from Chinese and non-Chinese fetuses [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. At the same time, this suggests that fetal growth and development are similar between different populations when methodological standards are high and appropriate selection is made.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan class=\"BoldItalic\"\u003eStrengths and limitations\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt should be noted that one disadvantage of estimating GA by measuring fetal CRL alone using ultrasound is the unknown biological variation of this measure during the first trimester of pregnancy. Therefore, we recommend collecting all information (including LMP and assessing its reliability) from pregnant women at their first visit in the first trimester [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]. When the GA calculated by measuring CRL by ultrasound and that from LMP are basically consistent, the GA can be calculated according to the date of the LMP. However, when the timing of the LMP is very accurate and reliable, and there is a big difference from the GA calculated by CRL, clinics should suspect that the fetus might have pathological abnormalities causing disorders of growth and development, which need to be further monitored and diagnosed [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. At the same time, calculated variabilities in the GA, such as SD values or percentiles, should be explained to pregnant women as estimated prediction error.\u003c/p\u003e"},{"header":"Conclusions","content":" \u003cp\u003eA formula for calculating GA among Chinese fetuses based on CRL at 10\u0026ndash;15 weeks of gestation with no significant systematic error was obtained in this study. It is highly consistent with formulae for calculating GA obtained from other high-quality studies published in recent years.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eGA: gestational age; LMP: last menstrual period; CRL: crown\u0026ndash;rump length.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all of the participating women and staff in the Chinese Fetal Growth and Prenatal Screening Consortium. This study could not have been accomplished without their enthusiasm and cooperation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHM, YXJ conceived the idea, wrote the protocol, submitted the ethics approval form.FD primarily analysed the data. YXZ analysed parts of the data and drafted the final manuscript for submission. ZHX, YSOY, SLL, QC, QQW, RL, TR, ALC, XLC, TZY, PC, HNX, HL, QD, MY, XY, JL, JWT, KS, HL checked the patient and got the data. All authors have read and approved the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Chinese 11th Five-Year National Science \u0026amp; technology support program under Grant 2006BAI05A04, Chinese 12th Five-Year National Science \u0026amp; technology support program under Grant 2014BAI06B05 and National Natural Science Foundation of China under Grant 81901745.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Peking Union Medical College Hospital and other relevant hospitals. All pregnant women participating in this study signed informed consent forms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMiller J, Turan S, Baschat AA. Fetal growth restriction. Semin Perinatol. 2008;32(4): 274-80.\u003c/li\u003e\n\u003cli\u003eTaipale P, Hiilesmaa V. Predicting delivery date by ultrasound and last menstrual period in early gestation. Obstet Gynecol. 2001;97(2):189-94.\u003c/li\u003e\n\u003cli\u003eAnanth CV. Menstrual versus clinical estimate of gestational age dating in the United States: temporal trends and variability in indices of perinatal outcomes. Paediatr Perinat Epidemiol. 2007;21 Suppl 2:22-30.\u003c/li\u003e\n\u003cli\u003eCallaghan WM, Dietz PM. Differences in birth weight for gestational age distributions according to the measures used to assign gestational age. Am J Epidemiol. 2010;171(7):826-36.\u003c/li\u003e\n\u003cli\u003eLynch CD, Zhang J. The research implications of the selection of a gestational age estimation method. Paediatr Perinat Epidemiol. 2007;21 Suppl 2:86-96.\u003c/li\u003e\n\u003cli\u003eHadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5-18 weeks) with high-resolution real-time US. Radiology. 1992;182(2):501-5.\u003c/li\u003e\n\u003cli\u003eRobinson HP, Fleming JE. A critical evaluation of sonar \"crown-rump length\" measurements. Br J Obstet Gynaecol. 1975;82(9):702-10.\u003c/li\u003e\n\u003cli\u003eKalish RB, Thaler HT, Chasen ST, Gupta M, Berman SJ, Rosenwaks Z, et al. First- and second-trimester ultrasound assessment of gestational age. Am J Obstet Gynecol. 2004;191(3):975-8.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eMcLennan AC, Schluter PJ. Construction of modern Australian first trimester ultrasound dating and growth charts. J Med Imaging Radiat Oncol. 2008;52(5):471-9.\u003c/li\u003e\n\u003cli\u003eSahota DS, Leung TY, Leung TN, Chan OK, Lau TK. Fetal crown-rump length and estimation of gestational age in an ethnic Chinese population. Ultrasound Obstet Gynecol. 2009;33(2):157-60.\u003c/li\u003e\n\u003cli\u003evon Kaisenberg CS, Fritzer E, K\u0026uuml;hling H, Jonat W. Fetal transabdominal biometry at 11-14 weeks of gestation. Ultrasound Obstet Gynecol. 2002;20(6):564-74.\u003c/li\u003e\n\u003cli\u003eVerburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, et al. New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008;31(4):388-96.\u003c/li\u003e\n\u003cli\u003ePapageorghiou AT, Kennedy SH, Salomon LJ, Ohuma EO, Cheikh Ismail L, Barros FC, et al. International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy. Ultrasound Obstet Gynecol. 2014;44(6):641-8.\u003c/li\u003e\n\u003cli\u003eNapolitano R, Dhami J, Ohuma EO, Ioannou C, Conde-Agudelo A, Kennedy SH, Villar J, Papageorghiou AT. Pregnancy dating by fetal crown-rump length: a systematic review of charts. BJOG. 2014;121(5):556-65.\u003c/li\u003e\n\u003cli\u003eZhang Y, Meng H, Jiang Y, Xu Z, Ouyang Y, Li S, et al. Chinese fetal biometry: reference equations and comparison with charts from other populations. J Matern Fetal Neonatal Med. 2019;32(9):1507-1515.\u003c/li\u003e\n\u003cli\u003eIoannou C, Sarris I, Hoch L, Salomon LJ, Papageorghiou AT; International Fetal and Newborn Growth Consortium for the 21st Century. Standardisation of crown-rump length measurement. BJOG. 2013;120 Suppl 2:38-41.\u003c/li\u003e\n\u003cli\u003eSarris I, Ioannou C, Ohuma EO, Altman DG, Hoch L, Cosgrove C, et al. Standardisation and quality control of ultrasound measurements taken in the INTERGROWTH-21st Project. BJOG. 2013;120 Suppl 2:33-7.\u003c/li\u003e\n\u003cli\u003eNicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol. 2004;191(1):45-67.\u003c/li\u003e\n\u003cli\u003eOhuma EO, Papageorghiou AT, Villar J, Altman DG. Estimation of gestational age in early pregnancy from crown-rump length when gestational age range is truncated: the case study of the INTERGROWTH-21st Project. BMC Med Res Methodol. 2013; 13:151.\u003c/li\u003e\n\u003cli\u003eAltman DG, Chitty LS. New charts for ultrasound dating of pregnancy. Ultrasound Obstet Gynecol. 1997;10(3):174-91.\u003c/li\u003e\n\u003cli\u003eSladkevicius P, Saltvedt S, Almstr\u0026ouml;m H, Kublickas M, Grunewald C, Valentin L. Ultrasound dating at 12-14 weeks of gestation. A prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies. Ultrasound Obstet Gynecol. 2005;26(5):504-11.\u003c/li\u003e\n\u003cli\u003eSalomon LJ. Early fetal growth: concepts and pitfalls. Ultrasound Obstet Gynecol. 2010;35(4):385-9.\u003c/li\u003e\n\u003cli\u003eMukri F, Bourne T, Bottomley C, Schoeb C, Kirk E, Papageorghiou AT. Evidence of early first-trimester growth restriction in pregnancies that subsequently end in miscarriage. BJOG. 2008;115(10):1273-8.\u003c/li\u003e\n\u003cli\u003eSmith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early-pregnancy origins of low birth weight. Nature. 2002;417(6892):916.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"crown–rump length, gestational age, growth and development, ultrasound","lastPublishedDoi":"10.21203/rs.3.rs-451255/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-451255/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e To develop an ultrasonographic dating formula for predicting gestational age (GA) based on fetal crown–rump length (CRL) in a Chinese population, evaluate its systematic prediction error and compare it with existing formulae.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This was a prospective cross-sectional study of spontaneously conceived singleton pregnancies among women with a regular menstrual cycle in the preceding year. Ultrasound examinations were performed at 11–14 weeks according to the date of the last menstrual cycle. The CRL was measured three times for each fetus, and the mean was used to derive the best-fit fractional polynomial regression model for estimation of GA in relation to CRL. For each fetus, the GA was compared with the GA calculated using six established dating formulae based on CRL measurements. The means of the differences between estimated and menstrual age were calculated for each formula. All the women were followed up routinely until the birth of the fetus. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of the 4710 subjects recruited, the mean and standard deviation values of CRL changed linearly with GA. The corresponding regression equation and its correlation coefficient (R\u003csup\u003e2\u003c/sup\u003e) was GA = 59.361513 + 0.461425 ´ CRL (R\u003csup\u003e2\u003c/sup\u003e = 0.8028). The mean difference between estimated and menstrual age was 0.22 days (95% confidence interval 0.05–0.21), lower than that of the six existing CRL dating formulae.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e We have derived a CRL-based dating formula suitable for naturally conceived pregnancies for GA between 11+0 and 13+6 weeks. The formula has no systematic prediction error, comparing favorably with the existing published dating formulae.\u003c/p\u003e","manuscriptTitle":"Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-05-11 13:17:08","doi":"10.21203/rs.3.rs-451255/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-05-24T06:17:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-05-23T03:46:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"fdc7387c-0793-403b-b1d2-c64481924cb2","date":"2021-05-13T02:51:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-05-12T14:42:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-05-10T11:36:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-05-10T10:04:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-05-10T09:27:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2021-04-22T13:55:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"397bf6b5-6d6f-4cad-9945-bc9fdee05518","owner":[],"postedDate":"May 11th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":4241781,"name":"Maternal \u0026 Fetal Medicine"},{"id":4241782,"name":"Sexual \u0026 Reproductive Medicine"}],"tags":[],"updatedAt":"2021-05-24T06:29:05+00:00","versionOfRecord":[],"versionCreatedAt":"2021-05-11 13:17:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-451255","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-451255","identity":"rs-451255","version":["v1"]},"buildId":"369fNeqWncA4NS6XSWjrt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}