Establishment and clinical application of fetal growth charts: A retrospective observational study in Wuhan China

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We attempted to establish the best evaluation method of fetal growth curve suitable for Chinese children, and evaluate the impact of this chart and other charts used for a long time in a Chinese population, such as Hadlock chart, and to compare their ability to predict newborn small for gestational age (SGA). Methods For this retrospective observational study, we reviewed ultrasound data from all pregnant women (n = 29286) who gave birth in Tongji Hospital between 2007 and 2022. A fractional polynomial regression model was applied to generate Wuhan fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Wuhan charts and published charts were quantified by calculating the Z-score. Results 33982 scans of fetal biometry contributed by 29286 pregnancies with reliable gestational age were analyzed. With Hadlock references (< 3rd centile), the proportions of small heads and short femurs were 8.23% and 11.98% in late gestation respectively. With AC < 10th centile, all these references were poor at predicting neonatal SGA and short femur. Conclusions Applying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA and short femurs. A curve that is more suitable for Chinese fetus is urgently needed. Growth chart Birth weight Biometry Fetal growth reference Ultrasound measurement Hadlock charts China Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction The fetal growth curve is a quantitative standard for intrauterine fetal growth and development, which is of great significance for monitoring fetal growth status, early detection of abnormalities, and guiding clinical treatment. [ 1 ] Optimal fetal growth is considered as a fundamental foundation for long-term health, while the abnormal growth may have an impact on increased disease risk throughout the entire life cycle. Fetal growth deviation is associated with adverse pregnancy outcomes. Infants with small birth weight (SGA, birth weight 90%) may have higher chance of short-term and long-term adverse health outcomes, such as fetal, infant and child mortality, reproductive disorders and chronic diseases late in life. [ 2 ] Using fetal growth curve to measure fetal biometry through ultrasound examination can reflect the normal fetal growth status at different gestational weeks. Clinicians can track fetal growth and development during pregnancy, which helps to evaluate whether the fetus has abnormal growth and development, to better predict high-risk pregnancy, and to develop individualized treatment plans. [ 3 ] Although appropriate fetal growth is important for humans, there is currently no intrauterine standard based on ultrasound measurements of fetal growth among the Chinese population. Birth weight is determined by genetic, intrauterine and environmental influences. Traditionally, the assessment of fetal growth is conducted by comparing the estimated fetal weight with population-based standards. [ 4 ] At present, there are several important issues affecting the standards used for ultrasound, and one of the main is differences is the racial/ethnic and national differences in the recruited women. Second major issue is that complications of pregnancy and fetus (such as congenital abnormalities and stillbirth) are excluded from NICHD research and INTERGROWTH because of the intention to set up standards; NICHD defines exclusion criteria including preterm birth < 37 weeks of pregnancy and karyotype abnormalities, both of which are not excluded from INTERGROWTH, and fetuses with complications are not excluded from WHO standards. [ 3 , 5 ] Thirdly, different national standards use different statistical analysis methods to simulate the fetal growth trajectory and calculate the corresponding percentile, and there is no unified standards. [ 6 ] In addition, it is found that fetal growth is largely influenced by race and nationality; Therefore, if the international reference or standard is directly used in Chinese clinical practice without strict evaluation, it will be risky. At present, the fetal growth curve in China is formulated based on the standards of other countries in Europe, America or Asia. These standards may not apply to the Chinese population, and long-term use of these standards may lead to misdiagnosis and missed diagnosis of the fetal growth. This study aims to evaluate the impact of using long-term Hadlock reference and other fetal growth references in the Chinese population, and compare their ability to predict neonatal SGA. 2. Methods 2.1 Ethics approval The study was approved by the ethics committee of Wuhan Tongji Hospital and the need for informed consent was waived. 2.2 Data source and study population For this retrospective observational study, we reviewed all examinations of women with singleton pregnancy booked for prenatal visit at Wuhan Tongji Hospital between 2007and 2022. Our center mainly provides ultrasound examinations to both low-risk and high-risk pregnant women who lived in Wuhan. A search of the database was performed to identify the scans performed on singleton pregnancies (January 2007 and October 2022), of which each woman contributed 1 to 8 ultrasound examinations. All these data were collected and checked by two investigators. In our center, after the dating scan of crown-rump length (CRL), women were offered routine scans at 16 to 18, 20 to 24, 28 to 32, and 36 to 40 weeks, unless they were suspected of having high risk pregnancy. The following information was collected: parents information including age, weight, height, body mass index (BMI), education background, family history; pregnancy information including parity, gravidity; fetal birth information including sex, date of birth, birth weight, birth-length, Apgar score, head circumference and leg length of newborn. Inclusion criteria were: (1) both parents are Chinese; (2) singleton pregnancy; (3) difference in gestational age (GA) according to LMP and CRL measurement in the first trimester 7 days (based on Hadlock formula[7]); (4) scans at GA between 14 + 0 and 40 + 6 weeks. Exclusion criteria were: (1) pregnancies without first-trimester dating based on CRL; (2) fetuses with severe congenital malformations and chromosomal abnormalities; (3) the mother suffers from pregnancy induced hypertension, gestational diabetes/diabetes, SLE and other diseases that lead to abnormal fetal growth; (4)measured value − 5 and + 5 standard deviation (SD). 2.3 Fetal ultrasonic measurements In our center, all sonographers were required to undergo extensive ultrasound scanning training for at least 6 months. All scans of fetal biometry were performed transabdominally by standard ultrasound machines(GE Voluson E8 [GE Healthcare, Zipf, Austria]) equipped with the high-resolution curvilinear transabdominal probe. All biometric measurements (HC, BPD, AC, and FL) were taken as to the following techniques. Fetal head measurements were takenin the axial plane at the level where the continuous midline echo was broken by the cavum septi pellucidi in the anterior third and both thalami could be seen symmetrically. It was required that the calvaria appeared smooth and symmetrical bilaterally. Fetal skull BPD was measured from the outer edge of the proximal calvarial wall to the inner edge of the distal calvarial wall (outer–inner; BPDoi). Fetal HC was measured by fitting a computer-generated ellipse to include the outer edges of the calvarial margins of the fetal skull. AC was measured on a transverse circular plane of the fetal abdomen at the level where the spine, descending aorta, anterior third of the umbilical vein, and stomach bubble could be seen in the same plane. The FL was measured from the greater trochanter to the lateral condyle, with both ends visible and at a horizontal angle < 45°. [8,9] During the third trimester, particular care was taken not to include the epiphysis. Strict quality control was performed regularly. Five studies were selected for our comparison, Intergrowth (IG)-21st, National Institute of Child Health and Human Development (NICHD), World Health Organization (WHO), Hadlock, and Hong Kong. 2.4 Statistical analyses Various statistical methods for constructing fetal growth charts have been suggested, including models of quantile regression.[10] After describing the patterns of growth in our population, we quantitatively compared them with other populations from five charts (IG-21st, NICHD, WHO, Hadlock, and Hong Kong) using the Z-score method, as recommended by Zhao et al.[11] Z-score for each fetal parameter was calculated using the formula: Z-score = (XGA MGA)/SDGA, where XGA is the fitted reference value at a known GA from other studies, MGA is the fitted mean value calculated from our reference equations at this GA, and SDGA is the fitted SD at the same GA from our population. If the difference between curves and ours is very small, the Z-score for the 3rd, 50th, or 97th centile curves should be close to 1.88, 0, and 1.88, respectively. Z-scores below 1.88 indicate that the lower limiting value of other curves is lower than ours.[12] We evaluated the impact of applying these published charts in Wuhan, by calculating the proportions of fetuses below the 3rd centile of these charts. We compared the ability of predicting SGA by AC < 10th centile between our chart and other charts. Neonatal SGA was defined as weight at birth < 10th centile in our population at a gestation-specific GA. Sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were next performed to measure the discriminatory abilities of these charts for SGA. Statistical analyses were performed using SPSS (version 26; IBM, Armonk, NY, USA) and Python 3.9 (version 3.9; PSF, DE, USA). Continuous variables were summarized as mean ± SD or median, and categorical variables by number and percentage. 3. Results 3.1 Baseline characteristics From 2007 to 2022, we identified 29286 live-birth singleton pregnancies with a total of 47355 ultrasound scans (HC, BPD, AC, and FL) during the second or third trimester [Figure 1 ] from our database. A total of 2494 (5.27%) scans were excluded from the analysis due to the absence of first trimester dating based on CRL length. Among the 45,826 (43.05%) remaining pregnancies, 10879 (22.97%) were excluded for at least one of the following reasons: the absolute value of the difference between GA based on LMP and CRL was > 7 days; GA 40 + 0 weeks; fetal biometry measurements were below 5 SD or above 5 SD; and fetuses with severe congenital malformations and chromosomal abnormalities; and pregnancies with hypertension, gestational diabetes/diabetes, SLE and other diseases. Finally, 33982 (71.76%) scans that had a reliable GA that was corroborated by the first-trimester ultrasound were included in the current analysis. The median number of ultrasound scans in all pregnancies was three (range 1–8). The demographic characteristics and perinatal events of pregnancies from Wuhan are presented. The mean maternal age, height, weight, and BMI were 30.2 ± 5.7 years, 162.5 ± 7.1 cm, 58.4 ± 10.2 kg, and 21.6 ± 4.6 kg/m2, respectively. The mean birth weight and birth length were 3105.7 ± 591.9 g and 4.9 ± 2.3 cm, respectively. In our study cohort, 4.8% of pregnancies resulted in a preterm birth (defined as < 37 weeks of gestation), 1.2% were low birthweight (defined as full-term [≥ 37weeks] birthweight < 2500 g), and 52.3%were males. 3.2 Construction of Wuhan fetal growth curves and comparisons with the curve from other populations The comparisons of the fitted curves between Wuhan and other populations are presented in Fig. 2 – 5 . For HC, three centiles of Wuhan curve performed similar to the curves of the IG-21st, Hong Kong, WHO and NICHD Asian groups but differed from the Hadlock curves [Figure 2 ]. The 3rd centile of the Hadlock curve was lower than ours in the early second trimester and clearly higher after 32 weeks. The BPD curves of Wuhan population were similar to those of the IG-21st, NICHD Asian and Hong Kong groups but considerably lower than Hadlock curve throughout the middle and late gestation. The 3rd and 97th centile curves for the BPD of Hadlock were not plotted as data were not available in the original publication. For AC, although the 50th centile of the five charts were similar to ours, the 3rd or 97th centiles were lower than ours in the early second trimester and clearly lower after 32 weeks. The largest difference was observed in the FL measurements. For FL, Wuhan curves performed very close to the curves of IG-21st, Hong Kong, WHO and NICHD Asian groups but differed from the Hadlock curves. The 97rd centile of the Hadlock curve was higher than ours and all three centiles of Hadlock were higher than ours after 30 weeks. Z-scores were then used to quantify the differences in fetal biometric measurements between the Wuhan population and those of five previously published populations across different GAs [Figure 6 ]. The differences in AC, BPD, FL and HC between the 3rd centiles of Wuhan curve were beyond ± 1 SD before 24 weeks and within ± 1 SD after 24 weeks. Conversely, AC, HC, FL Z-scores of Hadlock tended to progressively increase with increased GA, with the difference approaching − 1 SD at 14 weeks and + 1 SD at 40 weeks. The results of this part further support the inferiority of the Hadlock. 3.3 Impact of adopting published curves in a Chinese population To assess the impact of adopting published references in the Wuhan population, we compared their ability to identify fetal growth restriction by calculating the proportion of individual biometry measurements below the 3rd centile. The IG-21st, NICHD and Hong Kong identified a proportion of HCs below the 3rd centile closer to the expected value of 3% than the Hadlock charts. At 34 to 40 weeks, the proportions for small head fetuses (< 3rd centile) were 1.46%, 2.25%, and 1.65%, and for short femur were 1.91%, 1.41%, and 1.95%, using IG-21st, NICHD and Hong Kong references, respectively. Of note, Hadlock chart overestimated small HCs and short femur fetuses in late gestation, reporting 10.4% HCs and 11.98% of short femur fetuses below the 3rd centile at 34 to 40 weeks. 3.4 Comparisons of the performance of different curves in predicting biometry measurements The sensitivity and AUC of Wuhan chart and other charts for the prediction of SGA and short femur at birth increased with pregnancy proceeding [Figure 7 ]. The sensitivity and AUC of Hadlock chart in FL predicts are higher than those of other charts, while the sensitivity and AUC of Wuhan chart in HC and AC predicts are highest before 34 weeks, however after 34 weeks the sensitivity and AUC of the Hadlock chart is highest, followed by the Wuhan chart. 4 Discussion In recent years, fetal growth restriction (SGA) has become a hot topic in the fetal medicine. It is important to assess fetal size to determine the presence of SGA during prenatal examination. However, the recognition ability for SGA and FL by the most common evaluation indicator Hadlock's is not satisfactory. This large-scale validation study, which includes approximately 32000 ultrasound scans, also indicates that the full-term use of the Hadlock reference curve has poor ability to identify fetal dwarfism, insufficient diagnosis of SGA in the early stages of pregnancy, and over diagnosis in the late stages of pregnancy. For example, in our database, an additional 3.6% (6.6% -3.0%) and 5.9% (8.9% -3.0%) of pregnancies were misclassified as short femur and small head at 34 to 40 weeks, respectively, which may require further unnecessary investigation and increase parental expense and anxiety. Hadlock, as a short diameter method, aims to evaluate fetal size by measuring multiple indicators such as head circumference, abdominal circumference, and femoral length. [ 13 ] However, the Hadlock method is not as accurate in identifying SGA and FL. A French study of over 14,000 singleton births showed that Hadlock's sensitivity in identifying SGA was less than 50%. [ 14 ] This indicates that it can only correctly recognize about half of SGA fetuses. This is mainly because the SD (standard deviation) in the Hadlock method usually adopts a constant value, and this can lead to individual fetal growth not fitting in line with the actual situation. There are also racial differences, which are inconsistent with the results of other countries. For example, studies in Peru and South Korea have found that the error of the Hadlock method may be significant, and in many cases, systematic corrections are needed to obtain more accurate prediction results. [ 15 , 16 ] Some studies also indicate that the Hadlock method is not entirely applicable to the Chinese population. [ 5 , 17 ] The results of a nationwide cross-sectional study show that IG-21st standard is more suitable for fat free bioassay than other reference standards, especially HC, but not for fat bioassay, such as abdominal circumference. [ 18 ] The proportion of AC below the third Percentile is only 1%. This discovery has also received research support from European countries such as France, Greece, the Netherlands, Norway, Italy, and the United States. [19–21] Clearly, Socioeconomic status is the main determinant of fat based growth. We established growth curves for neonatal weight, head circumference, body length, and abdominal circumference using various statistical methods based on cross-sectional and retrospective data. We found that there are significant differences and characteristics in indicators such as newborn height and weight in China compared to other standard curves (such as WHO). At the same time, there are also certain differences in the growth curves among different regions and seasons. Compared with other fetal growth curves, our results have the following advantages: First, we excluded Complications of pregnancy and fetal factors, such as congenital abnormalities and stillbirth, to ensure the accuracy and reliability of the data. At the same time, we used large-scale data collection and statistical analysis to conduct detailed research on the entire pregnancy cycle with broad coverage, in order to obtain more accurate growth curves. Secondly, compared with other similar studies, our sample has a more diversified population structure, including people from different regions, races, ages, education levels and socioeconomic status. This diversity not only reflects the differences and diverse characteristics of health status in different regions, but also provides more accurate reference standards for various populations. In this way, our research results can be promoted and applied for Chinese population. Finally, our research results are not just a fetal growth curve table, but a research platform that contains a large amount of medical information. In addition to providing standard growth curves, it is also possible to conduct in-depth discussions on the impact of different factors on fetal development, providing better guidance and treatment plans for medical institutions and doctors. We believe that this platform will have a positive impact on the development of infant and child health care. However, we also acknowledge several limitations. Firstly, this is a retrospective study of analysis, without real-time tracking and monitoring, there may be a small amount of bias. Secondly, our study is a single center study, though we have made great effort to consider the diversity of sample sources, we still cannot fully cover the entire fetal population in the country. Thirdly, we did not conduct validation analysis, which is what we need to do in the next step. In the future, we plan to conduct more sample collection, utilize new analytical methods and cross center collaboration to establish more accurate and reliable Chinese fetal growth curves. As a populous country, China has billions of newborns every year, but we do not have a Chinese fetal growth curve. Our research shows that those other’s growth curves currently used may not necessarily be suitable for our national population, and long-term use of these references can lead to misdiagnosis of fetal dwarfism, which will have serious consequences and significant impact. We suggest establishing a multicenter fetal growth curve standard that is more suitable for the Chinese population, and adopting this standard will greatly reduce the diagnosis of fetal dwarfism. In conclusion, our study demonstrated that the Hadlock references had an higher rate of overdiagnosis of fetal smallness in the second and third trimester and could lead to serious misdiagnosis for fetal smallness in late gestation, potentially resulting in an unnecessary invasive examination, or unappropriate interventions such induction of labor. We suggest a more suitable standard for Chinese infants In China, a country with a large population, we suggest a more suitable standard for Chinese infants and if it was to beis adopted properly, overdiagnosis of fetal short stature may be greatly reduced. Declarations Funding None. Conflicts of interest None. Authors' contributions Nan Yu and Wei Li performed the data analyses and wrote the manuscript; Ling Feng and Yihong Yang contributed significantly to analysis and manuscript preparation; Jianli Wu helped perform the analysis with constructive discussions. Jin Li and Liang Wang performed the data analysis and formal analysis. 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CRL: Crown-rump length\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/d646068e1a1491e67d69d100.png"},{"id":58307607,"identity":"3dda0165-28b3-40cd-b3bb-18969fe44dd8","added_by":"auto","created_at":"2024-06-13 18:43:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":142514,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of fitted 3rd, 50th, and 97th centile curves of HC between Wuhan fetal growth curve (red dashed curves) and other curves (blue solid curves).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/328ee68b03279cbd8755b2d0.png"},{"id":58307603,"identity":"57744ff1-0eb6-4905-aef4-546087d4dad8","added_by":"auto","created_at":"2024-06-13 18:43:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":126494,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of fitted 3rd, 50th, and 97th centile curves of BPD between Wuhan fetal growth curve (red dashed curves) and other curves (blue solid curves).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/048124119d0cb0f38f3a4138.png"},{"id":58307601,"identity":"954df0a8-f29d-448a-b017-3471fa0e3aca","added_by":"auto","created_at":"2024-06-13 18:43:58","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":145109,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of fitted 3rd, 50th, and 97th centile curves of AC between Wuhan fetal growth curve (red dashed curves) and other curves (blue solid curves).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/e289a90df4f1b96962c7f071.png"},{"id":58308909,"identity":"bb04b17e-d308-464c-9f34-72d8f4577464","added_by":"auto","created_at":"2024-06-13 18:51:58","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":139139,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of fitted 3rd, 50th, and 97th centile curves of FL between Wuhan fetal growth curve (red dashed curves) and other curves (blue solid curves).\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/bf4165b5c2c38fdb8824c439.png"},{"id":58307605,"identity":"25882694-d5e6-4355-b7b0-7b36d68d2c78","added_by":"auto","created_at":"2024-06-13 18:43:58","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":106721,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of our new equations with references from Intergrowth-21st, NICHD, WHO, Hadlock, and Hong Kong curves for HC, BPD, AC, and FL. The dotted lines represent the expected Z-scores for the 3rd centiles (horizontal line in the middle) or ± 0.5 SD or ± 1 SD, calculated from our population.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/ed419eee6bc9eb27f525ca8d.png"},{"id":58307602,"identity":"304855a4-189a-4626-bf50-e2a918c620bc","added_by":"auto","created_at":"2024-06-13 18:43:58","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":775263,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity (A) and AUC (B) using the BPD, HC, AC and FL cutoff below the 10th centile to detect SGA and short femur (\u0026lt;10th centile) at birth increased as pregnancy.\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/ff192ffd549bd5f760a3216e.jpeg"},{"id":59263080,"identity":"66779941-e3cc-4515-a888-8eaaf315ad02","added_by":"auto","created_at":"2024-06-28 10:16:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1805722,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4480562/v1/406c4ec0-424f-43e9-8831-c1cec0f9a52a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Establishment and clinical application of fetal growth charts: A retrospective observational study in Wuhan China","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe fetal growth curve is a quantitative standard for intrauterine fetal growth and development, which is of great significance for monitoring fetal growth status, early detection of abnormalities, and guiding clinical treatment.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e Optimal fetal growth is considered as a fundamental foundation for long-term health, while the abnormal growth may have an impact on increased disease risk throughout the entire life cycle. Fetal growth deviation is associated with adverse pregnancy outcomes. Infants with small birth weight (SGA, birth weight\u0026thinsp;\u0026lt;\u0026thinsp;10%) or large birth weight (LGA, birth weight\u0026thinsp;\u0026gt;\u0026thinsp;90%) may have higher chance of short-term and long-term adverse health outcomes, such as fetal, infant and child mortality, reproductive disorders and chronic diseases late in life.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Using fetal growth curve to measure fetal biometry through ultrasound examination can reflect the normal fetal growth status at different gestational weeks. Clinicians can track fetal growth and development during pregnancy, which helps to evaluate whether the fetus has abnormal growth and development, to better predict high-risk pregnancy, and to develop individualized treatment plans. \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough appropriate fetal growth is important for humans, there is currently no intrauterine standard based on ultrasound measurements of fetal growth among the Chinese population. Birth weight is determined by genetic, intrauterine and environmental influences. Traditionally, the assessment of fetal growth is conducted by comparing the estimated fetal weight with population-based standards.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e At present, there are several important issues affecting the standards used for ultrasound, and one of the main is differences is the racial/ethnic and national differences in the recruited women. Second major issue is that complications of pregnancy and fetus (such as congenital abnormalities and stillbirth) are excluded from NICHD research and INTERGROWTH because of the intention to set up standards; NICHD defines exclusion criteria including preterm birth\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks of pregnancy and karyotype abnormalities, both of which are not excluded from INTERGROWTH, and fetuses with complications are not excluded from WHO standards.\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e Thirdly, different national standards use different statistical analysis methods to simulate the fetal growth trajectory and calculate the corresponding percentile, and there is no unified standards.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e In addition, it is found that fetal growth is largely influenced by race and nationality; Therefore, if the international reference or standard is directly used in Chinese clinical practice without strict evaluation, it will be risky. At present, the fetal growth curve in China is formulated based on the standards of other countries in Europe, America or Asia. These standards may not apply to the Chinese population, and long-term use of these standards may lead to misdiagnosis and missed diagnosis of the fetal growth.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the impact of using long-term Hadlock reference and other fetal growth references in the Chinese population, and compare their ability to predict neonatal SGA.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e2.1 Ethics approval\u003c/h2\u003e\nThe study was approved by the ethics committee of Wuhan Tongji Hospital and the need for informed consent was waived.\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2 Data source and study population\u003c/h2\u003e\nFor this retrospective observational study, we reviewed all examinations of women with singleton pregnancy booked for prenatal visit at Wuhan Tongji Hospital between 2007and 2022. Our center mainly provides ultrasound examinations to both low-risk and high-risk pregnant women who lived in Wuhan.\u003cbr /\u003eA search of the database was performed to identify the scans performed on singleton pregnancies (January 2007 and October 2022), of which each woman contributed 1 to 8 ultrasound examinations. All these data were collected and checked by two investigators. In our center, after the dating scan of crown-rump length (CRL), women were offered routine scans at 16 to 18, 20 to 24, 28 to 32, and 36 to 40 weeks, unless they were suspected of having high risk pregnancy. The following information was collected: parents information including age, weight, height, body mass index (BMI), education background, family history; pregnancy information including parity, gravidity; fetal birth information including sex, date of birth, birth weight, birth-length, Apgar score, head circumference and leg length of newborn. Inclusion criteria were: (1) both parents are Chinese; (2) singleton pregnancy; (3) difference in gestational age (GA) according to LMP and CRL measurement in the first trimester 7 days (based on Hadlock formula[7]); (4) scans at GA between 14\u0026thinsp;+\u0026thinsp;0 and 40\u0026thinsp;+\u0026thinsp;6 weeks. Exclusion criteria were: (1) pregnancies without first-trimester dating based on CRL; (2) fetuses with severe congenital malformations and chromosomal abnormalities; (3) the mother suffers from pregnancy induced hypertension, gestational diabetes/diabetes, SLE and other diseases that lead to abnormal fetal growth; (4)measured value \u0026minus;\u0026thinsp;5 and +\u0026thinsp;5 standard deviation (SD).\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003e2.3 Fetal ultrasonic measurements\u003c/h2\u003e\n\u003cp\u003eIn our center, all sonographers were required to undergo extensive ultrasound scanning training for at least 6 months. All scans of fetal biometry were performed transabdominally by standard ultrasound machines(GE Voluson E8 [GE Healthcare, Zipf, Austria]) equipped with the high-resolution curvilinear transabdominal probe. All biometric measurements (HC, BPD, AC, and FL) were taken as to the following techniques. Fetal head measurements were takenin the axial plane at the level where the continuous midline echo was broken by the cavum septi pellucidi in the anterior third and both thalami could be seen symmetrically. It was required that the calvaria appeared smooth and symmetrical bilaterally. Fetal skull BPD was measured from the outer edge of the proximal calvarial wall to the inner edge of the distal calvarial wall (outer\u0026ndash;inner; BPDoi). Fetal HC was measured by fitting a computer-generated ellipse to include the outer edges of the calvarial margins of the fetal skull. AC was measured on a transverse circular plane of the fetal abdomen at the level where the spine, descending aorta, anterior third of the umbilical vein, and stomach bubble could be seen in the same plane. The FL was measured from the greater trochanter to the lateral condyle, with both ends visible and at a horizontal angle\u0026thinsp;\u0026lt;\u0026thinsp;45\u0026deg;. [8,9] During the third trimester, particular care was taken not to include the epiphysis. Strict quality control was performed regularly. Five studies were selected for our comparison, Intergrowth (IG)-21st, National Institute of Child Health and Human Development (NICHD), World Health Organization (WHO), Hadlock, and Hong Kong.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003e2.4 Statistical analyses\u003c/h2\u003e\n\u003cp\u003eVarious statistical methods for constructing fetal growth charts have been suggested, including models of quantile regression.[10] After describing the patterns of growth in our population, we quantitatively compared them with other populations from five charts (IG-21st, NICHD, WHO, Hadlock, and Hong Kong) using the Z-score method, as recommended by Zhao et al.[11] Z-score for each fetal parameter was calculated using the formula: Z-score = (XGA MGA)/SDGA, where XGA is the fitted reference value at a known GA from other studies, MGA is the fitted mean value calculated from our reference equations at this GA, and SDGA is the fitted SD at the same GA from our population. If the difference between curves and ours is very small, the Z-score for the 3rd, 50th, or 97th centile curves should be close to 1.88, 0, and 1.88, respectively. Z-scores below 1.88 indicate that the lower limiting value of other curves is lower than ours.[12] We evaluated the impact of applying these published charts in Wuhan, by calculating the proportions of fetuses below the 3rd centile of these charts. We compared the ability of predicting SGA by AC\u0026thinsp;\u0026lt;\u0026thinsp;10th centile between our chart and other charts. Neonatal SGA was defined as weight at birth\u0026thinsp;\u0026lt;\u0026thinsp;10th centile in our population at a gestation-specific GA. Sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were next performed to measure the discriminatory abilities of these charts for SGA.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS (version 26; IBM, Armonk, NY, USA) and Python 3.9 (version 3.9; PSF, DE, USA). Continuous variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median, and categorical variables by number and percentage.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Baseline characteristics\u003c/h2\u003e \u003cp\u003eFrom 2007 to 2022, we identified 29286 live-birth singleton pregnancies with a total of 47355 ultrasound scans (HC, BPD, AC, and FL) during the second or third trimester [Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e] from our database. A total of 2494 (5.27%) scans were excluded from the analysis due to the absence of first trimester dating based on CRL length. Among the 45,826 (43.05%) remaining pregnancies, 10879 (22.97%) were excluded for at least one of the following reasons: the absolute value of the difference between GA based on LMP and CRL was \u0026gt;\u0026thinsp;7 days; GA\u0026thinsp;\u0026lt;\u0026thinsp;14\u0026thinsp;+\u0026thinsp;0 weeks or \u0026gt;\u0026thinsp;40\u0026thinsp;+\u0026thinsp;0 weeks; fetal biometry measurements were below 5 SD or above 5 SD; and fetuses with severe congenital malformations and chromosomal abnormalities; and pregnancies with hypertension, gestational diabetes/diabetes, SLE and other diseases. Finally, 33982 (71.76%) scans that had a reliable GA that was corroborated by the first-trimester ultrasound were included in the current analysis. The median number of ultrasound scans in all pregnancies was three (range 1\u0026ndash;8).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe demographic characteristics and perinatal events of pregnancies from Wuhan are presented. The mean maternal age, height, weight, and BMI were 30.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 years, 162.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1 cm, 58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 kg, and 21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6 kg/m2, respectively. The mean birth weight and birth length were 3105.7\u0026thinsp;\u0026plusmn;\u0026thinsp;591.9 g and 4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 cm, respectively. In our study cohort, 4.8% of pregnancies resulted in a preterm birth (defined as \u0026lt;\u0026thinsp;37 weeks of gestation), 1.2% were low birthweight (defined as full-term [\u0026ge;\u0026thinsp;37weeks] birthweight\u0026thinsp;\u0026lt;\u0026thinsp;2500 g), and 52.3%were males.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Construction of Wuhan fetal growth curves and comparisons with the curve from other populations\u003c/h2\u003e \u003cp\u003eThe comparisons of the fitted curves between Wuhan and other populations are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e5\u003c/span\u003e. For HC, three centiles of Wuhan curve performed similar to the curves of the IG-21st, Hong Kong, WHO and NICHD Asian groups but differed from the Hadlock curves [Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. The 3rd centile of the Hadlock curve was lower than ours in the early second trimester and clearly higher after 32 weeks. The BPD curves of Wuhan population were similar to those of the IG-21st, NICHD Asian and Hong Kong groups but considerably lower than Hadlock curve throughout the middle and late gestation. The 3rd and 97th centile curves for the BPD of Hadlock were not plotted as data were not available in the original publication. For AC, although the 50th centile of the five charts were similar to ours, the 3rd or 97th centiles were lower than ours in the early second trimester and clearly lower after 32 weeks. The largest difference was observed in the FL measurements. For FL, Wuhan curves performed very close to the curves of IG-21st, Hong Kong, WHO and NICHD Asian groups but differed from the Hadlock curves. The 97rd centile of the Hadlock curve was higher than ours and all three centiles of Hadlock were higher than ours after 30 weeks.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eZ-scores were then used to quantify the differences in fetal biometric measurements between the Wuhan population and those of five previously published populations across different GAs [Figure \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e]. The differences in AC, BPD, FL and HC between the 3rd centiles of Wuhan curve were beyond \u0026plusmn;\u0026thinsp;1 SD before 24 weeks and within \u0026plusmn;\u0026thinsp;1 SD after 24 weeks. Conversely, AC, HC, FL Z-scores of Hadlock tended to progressively increase with increased GA, with the difference approaching \u0026minus;\u0026thinsp;1 SD at 14 weeks and +\u0026thinsp;1 SD at 40 weeks. The results of this part further support the inferiority of the Hadlock.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Impact of adopting published curves in a Chinese population\u003c/h2\u003e \u003cp\u003eTo assess the impact of adopting published references in the Wuhan population, we compared their ability to identify fetal growth restriction by calculating the proportion of individual biometry measurements below the 3rd centile. The IG-21st, NICHD and Hong Kong identified a proportion of HCs below the 3rd centile closer to the expected value of 3% than the Hadlock charts. At 34 to 40 weeks, the proportions for small head fetuses (\u0026lt;\u0026thinsp;3rd centile) were 1.46%, 2.25%, and 1.65%, and for short femur were 1.91%, 1.41%, and 1.95%, using IG-21st, NICHD and Hong Kong references, respectively. Of note, Hadlock chart overestimated small HCs and short femur fetuses in late gestation, reporting 10.4% HCs and 11.98% of short femur fetuses below the 3rd centile at 34 to 40 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Comparisons of the performance of different curves in predicting biometry measurements\u003c/h2\u003e \u003cp\u003eThe sensitivity and AUC of Wuhan chart and other charts for the prediction of SGA and short femur at birth increased with pregnancy proceeding [Figure \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e]. The sensitivity and AUC of Hadlock chart in FL predicts are higher than those of other charts, while the sensitivity and AUC of Wuhan chart in HC and AC predicts are highest before 34 weeks, however after 34 weeks the sensitivity and AUC of the Hadlock chart is highest, followed by the Wuhan chart.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn recent years, fetal growth restriction (SGA) has become a hot topic in the fetal medicine. It is important to assess fetal size to determine the presence of SGA during prenatal examination. However, the recognition ability for SGA and FL by the most common evaluation indicator Hadlock's is not satisfactory. This large-scale validation study, which includes approximately 32000 ultrasound scans, also indicates that the full-term use of the Hadlock reference curve has poor ability to identify fetal dwarfism, insufficient diagnosis of SGA in the early stages of pregnancy, and over diagnosis in the late stages of pregnancy. For example, in our database, an additional 3.6% (6.6% -3.0%) and 5.9% (8.9% -3.0%) of pregnancies were misclassified as short femur and small head at 34 to 40 weeks, respectively, which may require further unnecessary investigation and increase parental expense and anxiety.\u003c/p\u003e \u003cp\u003eHadlock, as a short diameter method, aims to evaluate fetal size by measuring multiple indicators such as head circumference, abdominal circumference, and femoral length.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e However, the Hadlock method is not as accurate in identifying SGA and FL. A French study of over 14,000 singleton births showed that Hadlock's sensitivity in identifying SGA was less than 50%.\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e This indicates that it can only correctly recognize about half of SGA fetuses. This is mainly because the SD (standard deviation) in the Hadlock method usually adopts a constant value, and this can lead to individual fetal growth not fitting in line with the actual situation. There are also racial differences, which are inconsistent with the results of other countries. For example, studies in Peru and South Korea have found that the error of the Hadlock method may be significant, and in many cases, systematic corrections are needed to obtain more accurate prediction results. \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e Some studies also indicate that the Hadlock method is not entirely applicable to the Chinese population. \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e The results of a nationwide cross-sectional study show that IG-21st standard is more suitable for fat free bioassay than other reference standards, especially HC, but not for fat bioassay, such as abdominal circumference. \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e The proportion of AC below the third Percentile is only 1%. This discovery has also received research support from European countries such as France, Greece, the Netherlands, Norway, Italy, and the United States. \u003csup\u003e[19\u0026ndash;21]\u003c/sup\u003e Clearly, Socioeconomic status is the main determinant of fat based growth.\u003c/p\u003e \u003cp\u003eWe established growth curves for neonatal weight, head circumference, body length, and abdominal circumference using various statistical methods based on cross-sectional and retrospective data. We found that there are significant differences and characteristics in indicators such as newborn height and weight in China compared to other standard curves (such as WHO). At the same time, there are also certain differences in the growth curves among different regions and seasons. Compared with other fetal growth curves, our results have the following advantages: First, we excluded Complications of pregnancy and fetal factors, such as congenital abnormalities and stillbirth, to ensure the accuracy and reliability of the data. At the same time, we used large-scale data collection and statistical analysis to conduct detailed research on the entire pregnancy cycle with broad coverage, in order to obtain more accurate growth curves. Secondly, compared with other similar studies, our sample has a more diversified population structure, including people from different regions, races, ages, education levels and socioeconomic status. This diversity not only reflects the differences and diverse characteristics of health status in different regions, but also provides more accurate reference standards for various populations. In this way, our research results can be promoted and applied for Chinese population. Finally, our research results are not just a fetal growth curve table, but a research platform that contains a large amount of medical information. In addition to providing standard growth curves, it is also possible to conduct in-depth discussions on the impact of different factors on fetal development, providing better guidance and treatment plans for medical institutions and doctors. We believe that this platform will have a positive impact on the development of infant and child health care.\u003c/p\u003e \u003cp\u003eHowever, we also acknowledge several limitations. Firstly, this is a retrospective study of analysis, without real-time tracking and monitoring, there may be a small amount of bias. Secondly, our study is a single center study, though we have made great effort to consider the diversity of sample sources, we still cannot fully cover the entire fetal population in the country. Thirdly, we did not conduct validation analysis, which is what we need to do in the next step. In the future, we plan to conduct more sample collection, utilize new analytical methods and cross center collaboration to establish more accurate and reliable Chinese fetal growth curves.\u003c/p\u003e \u003cp\u003eAs a populous country, China has billions of newborns every year, but we do not have a Chinese fetal growth curve. Our research shows that those other\u0026rsquo;s growth curves currently used may not necessarily be suitable for our national population, and long-term use of these references can lead to misdiagnosis of fetal dwarfism, which will have serious consequences and significant impact. We suggest establishing a multicenter fetal growth curve standard that is more suitable for the Chinese population, and adopting this standard will greatly reduce the diagnosis of fetal dwarfism.\u003c/p\u003e \u003cp\u003eIn conclusion, our study demonstrated that the Hadlock references had an higher rate of overdiagnosis of fetal smallness in the second and third trimester and could lead to serious misdiagnosis for fetal smallness in late gestation, potentially resulting in an unnecessary invasive examination, or unappropriate interventions such induction of labor. We suggest a more suitable standard for Chinese infants In China, a country with a large population, we suggest a more suitable standard for Chinese infants and if it was to beis adopted properly, overdiagnosis of fetal short stature may be greatly reduced.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNan Yu and Wei Li performed the data analyses and wrote the manuscript;\u0026nbsp;Ling Feng and Yihong Yang\u0026nbsp;contributed significantly to analysis and manuscript preparation;\u0026nbsp;Jianli Wu\u0026nbsp;helped perform the analysis with constructive discussions.\u0026nbsp;Jin Li and Liang Wang\u0026nbsp;performed the data analysis and formal analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the support of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of supporting data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be made available on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBlue NR, Mele L, Grobman WA, Bailit JL, Wapner RJ, Thorp JM Jr, Caritis SN, Prasad M, Tita ATN, Saade GR, Rouse DJ, Blackwell SC, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Predictive performance of newborn small for gestational age by a United States intrauterine vs birthweight-derived standard for short-term neonatal morbidity and mortality. Am J Obstet Gynecol MFM. 2022;4(3):100599.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiossi G, Pedroza C, Costantine MM, Truong VTT, Gargano G, Saade GR. Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies. Ultrasound Obstet Gynecol. 2017;50(2):156\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKiserud T, Benachi A, Hecher K, Perez RG, Carvalho J, Piaggio G, Platt LD. The World Health Organization fetal growth charts: concept, findings, interpretation, and application. Am J Obstet Gynecol. 2018;218(2S):S619\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlexander GR, Kogan MD, Himes JH. 1994\u0026ndash;1996 U.S. singleton birth weight percentiles for gestational age by race, Hispanic origin, and gender. Matern Child Health J. 1999;3(4):225\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuck Louis GM, Grewal J, Albert PS, Sciscione A, Wing DA, Grobman WA, Newman RB, Wapner R, D'Alton ME, Skupski D, Nageotte MP, Ranzini AC, Owen J, Chien EK, Craigo S, Hediger ML, Kim S, Zhang C, Grantz KL. Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies. Am J Obstet Gynecol. 2015;213(4):449.e1-449.e41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrantz KL, Hediger ML, Liu D, Buck Louis GM. Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study. Am J Obstet Gynecol. 2018;218(2S):S641-S655.e28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5\u0026ndash;18 weeks) with high-resolution real-time US. Radiology. 1992;182(2):501\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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;32:1507\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeung TN, Pang MW, Daljit SS, Leung TY, Poon CF, Wong SM, Lau TK. Fetal biometry in ethnic Chinese: biparietal diameter, head circumference, abdominal circumference and femur length. Ultrasound Obstet Gynecol. 2008;31(3):321\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKiserud T, Piaggio G, Carroli G, Widmer M, Carvalho J, Neerup Jensen L, Giordano D, Cecatti JG, Abdel Aleem H, Talegawkar SA, Benachi A, Diemert A, Tshefu Kitoto A, Thinkhamrop J, Lumbiganon P, Tabor A, Kriplani A, Gonzalez Perez R, Hecher K, Hanson MA, G\u0026uuml;lmezoglu AM, Platt LD. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight. PLoS Med. 2017;14(1):e1002220.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalomon LJ, Duyme M, Crequat J, Brodaty G, Talmant C, Fries N, Althuser M. French fetal biometry: reference equations and comparison with other charts. Ultrasound Obstet Gynecol. 2006;28(2):193\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao J, Yuan Y, Tao J, Chen C, Wu X, Liao Y, Wu L, Zeng Q, Chen Y, Wang K, Li X, Liu Z, Zhou J, Zhou Y, Li S, Zhu J. Which fetal growth charts should be used? A retrospective observational study in China. Chin Med J (Engl). 2022;135(16):1969\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlue NR, Beddow ME, Savabi M, Katukuri VR, Chao CR. Comparing the Hadlock fetal growth standard to the Eunice Kennedy Shriver National Institute of Child Health and Human Development racial/ethnic standard for the prediction of neonatal morbidity and small for gestational age. Am J Obstet Gynecol. 2018;219(5):474.e1-474.e12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonier I, Blondel B, Ego A, Kaminiski M, Goffinet F, Zeitlin J. Poor effectiveness of antenatal detection of fetal growth restriction and consequences for obstetric management and neonatal outcomes: a French national study. BJOG. 2015;122(4):518\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerialdi M, Caulfield LE, Zavaleta N, Figueroa A, Costigan KA, Dominici F, Dipietro JA. Fetal growth in Peru: comparisons with international fetal size charts and implications for fetal growth assessment. Ultrasound Obstet Gynecol. 2005;26(2):123\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwon JY, Park IY, Wie JH, Choe S, Kim CJ, Shin JC. Fetal biometry in the Korean population: reference charts and comparison with charts from other populations. Prenat Diagn. 2014;34(10):927\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng YKY, Lu J, Leung TY, et al. Prospective assessment of INTERGROWTH-21st and World Health Organization estimated fetal weight reference curves. Ultrasound Obstet Gynecol. 2018;51(6):792\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNwabuobi C, Odibo L, Camisasca-Lopina H, Leavitt K, Tuuli M, Odibo AO. Comparing INTERGROWTH-21st Century and Hadlock growth standards to predict small for gestational age and short-term neonatal outcomes. J Matern Fetal Neonatal Med. 2020;33(11):1906\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStirnemann JJ, Fries N, Bessis R, Fontanges M, Mangione R, Salomon LJ. Implementing the INTERGROWTH-21st fetal growth standards in France: a 'flash study' of the College Fran\u0026ccedil;ais d'Echographie Foetale (CFEF). Ultrasound Obstet Gynecol. 2017;49(4):487\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhandari N, Bahl R, Taneja S, de Onis M, Bhan MK, Hua X, Shen M, Reddy UM, Buck Louis G, Souza JP, G\u0026uuml;lmezoglu AM et al. Growth performance of affluent Indian children is similar to that in developed countries. Bull World Health Organ. Comparison of the INTERGROWTH-21st, National Institute of Child Health and Human Development, and WHO fetal growth standards. Int J Gynaecol Obstet 2018; 143:156\u0026ndash;163.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Growth chart, Birth weight, Biometry, Fetal growth reference, Ultrasound measurement, Hadlock charts, China","lastPublishedDoi":"10.21203/rs.3.rs-4480562/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4480562/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOptimal fetal growth is recognized as a basic foundation for long-term health, while aberrations in growth may have implications for disease risk across the lifespan. We attempted to establish the best evaluation method of fetal growth curve suitable for Chinese children, and evaluate the impact of this chart and other charts used for a long time in a Chinese population, such as Hadlock chart, and to compare their ability to predict newborn small for gestational age (SGA).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFor this retrospective observational study, we reviewed ultrasound data from all pregnant women (n\u0026thinsp;=\u0026thinsp;29286) who gave birth in Tongji Hospital between 2007 and 2022. A fractional polynomial regression model was applied to generate Wuhan fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Wuhan charts and published charts were quantified by calculating the Z-score.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e33982 scans of fetal biometry contributed by 29286 pregnancies with reliable gestational age were analyzed. With Hadlock references (\u0026lt;\u0026thinsp;3rd centile), the proportions of small heads and short femurs were 8.23% and 11.98% in late gestation respectively. With AC\u0026thinsp;\u0026lt;\u0026thinsp;10th centile, all these references were poor at predicting neonatal SGA and short femur.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eApplying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA and short femurs. A curve that is more suitable for Chinese fetus is urgently needed.\u003c/p\u003e","manuscriptTitle":"Establishment and clinical application of fetal growth charts: A retrospective observational study in Wuhan China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-13 18:43:52","doi":"10.21203/rs.3.rs-4480562/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4f780e3-c2f7-49f2-8883-c06303cc2aff","owner":[],"postedDate":"June 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-20T12:23:38+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-13 18:43:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4480562","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4480562","identity":"rs-4480562","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}