Data were analyzed using SAS Software version 9.4 (SAS Institute, Cary, North Carolina, US) and JMP Pro 12 (SAS Institute, Cary, North Carolina, US). Descriptive statistics were calculated for the women’s characteristics at study entry, for mode of delivery, for birth events, and for fetal, neonatal, and maternal conditions, by country and overall. To acquire the crown–rump length, the midline sagittal section of the whole fetus was visualized with the fetus horizontal on the screen at 90 degrees to the angle of insonation. Most of the countries had a similar distribution between female and male neonates except for Egypt, Germany, and Norway, where about 40% of neonates were female. We calculated 95% confidence intervals for the difference between country and global EFW percentiles for particular gestational ages, using the result that the parameter estimates from quantile regression were asymptotically normally distributed [28]. Gestational age was assessed by using the reference charts published by Robinson and Fleming [23]. No, Is the Subject Area "Femur" applicable to this article? There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. There was no maternal death. The WHO study had a similar recruitment but retained in the analysis pregnancies with maternal, fetal, and neonatal clinical conditions, based on the principle that reference intervals should reflect as closely as possible the population to which they will be applied. Birthweight was assessed at delivery, and neonatal morphometry carried out within 24 h according to the protocol [20]. Additive terms were included for other covariates. Pregnancies in which small-for-gestation-age fetuses were observed or intrauterine growth restriction was suspected were also noted. The TI was automatically recorded and transmitted to the web-based data management system by the ultrasound machine. Humans adapt across generations to local conditions, and fetal development adds an important adaptive refinement for the next generation. The diagnosis in pregnancies complicated by such conditions is often hampered by uncertainty about gestational age since head size (BPD and HC) is also commonly used for the dating of the pregnancy. PLOS Medicine 14(3): e1002284. Reference curves were fitted using quantile regression for reference models, as described by Wei et al. The above mentioned web-based system and procedures have been used in five previous HRP (UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction)/WHO multicenter studies and are proven to be efficient and compliant with HRP/WHO Standard Operating Procedures as well as with Title 21 CFR Part 11 of the Code of Federal Regulations, which deals with United States Food and Drug Administration guidelines on electronic records. Norway had the highest median birthweight (3,575 g), and Denmark and Germany had birthweights approximately 100 g less, while Argentina, Brazil, and France had birthweights 200 g less. Compared with the original protocol [20], the following aspects of the study were adjusted. It's a way of checking your baby's risk of certain birth defects, such as Down syndrome, Edward's syndrome (trisomy 18), trisomy 13 and many other chromosomal abnormalities, as well as heart problems. Although the present study encompasses ten countries, it still represents only a small selection when the substantial anthropometric variations existing even within continents are taken into account. Output from quantile multivariate regression showing Wald chi-square tests for gestational age; country; the interaction of gestational age and country; sex of the fetus; and maternal characteristics. The measurement was obtained from an image with the midline echo as close as possible to the horizontal plane, 90 degrees to the ultrasound beam. LDP is a Board Member of the Perinatal Quality Foundation, a nonprofit organization related to the Society for Maternal Fetal Medicine. The models were checked by the residual analysis produced by the software. It is known that body composition in Indian newborns contains relatively more fat [39], a pattern that passes across generations [40] and that is linked to increased risk of subsequent type 2 diabetes [41]. Influence of country on estimated fetal weight. However, the differences between countries, with maternal factors, and with fetal sex mean that these growth charts may need to be adjusted for local clinical use to increase their diagnostic and predictive performance. Recently, a large multicenter study, the Fetal Growth Longitudinal Study of the Intergrowth-21st Project [18], applied the same concept and approach to fetal growth. Birthweight, closely linked to fetal growth, is also a marker of risks for noncommunicable diseases in adult life, with cardiovascular diseases, type II diabetes, and obesity being the most prominent [7,8]. Growth was to a small extent influenced by maternal age, height, weight, and parity, and by fetal sex. Fetal growth charts may thus need to be adjusted to fit the diversity of individuals and populations if they are to be of the greatest clinical utility. We thank General Electric for loaning the ultrasound machines and for providing technical assistance during the study. It was lowest in D. R. Congo, Denmark, Germany, and Norway and highest in Egypt and India. These plots are intended to enable the reader to derive the magnitude of difference in grams for any size and country and percentile. correction, 24 Mar 2017: During an ultrasound, the technician moves a device over the mother’s stomach that sends high-frequency sound waves through her uterus. For this reason, fetal growth data and aspects of intrauterine development need to be included as an important part of an early-life noncommunicable disease prevention initiative, as this targets the time when the effect of an intervention is greatest [10]. Data entered into the web system were checked by the coordinating unit at Centro Rosarino de Estudios Perinatales for completeness, accuracy, reliability, and consistent intended performance. Gestational age was included in the model with polynomial terms (linear, quadratic, and cubic). thermal index. Quantile regression makes an inference about regression coefficients for the conditional quantiles of a variable without making assumptions about its distribution: there is no need to assume a particular distribution and to estimate its moments. Neonatal mortality in the first 28 d declined (by 47%) from 5.0 to 2.6 million deaths annually over this period. WHO is working on these methods to make them generally available with the growth chart. Carvalho J, All participants were scanned in the lateral recumbent position. A special ultrasound, called a nuchal translucency screening, measures the back of the baby's neck. This is nicely demonstrated in a recent large study establishing population-specific fetal growth charts [35]. In the same table, the level of significance is listed for these variables, e.g., p < 0.001 for country, highly significant. Medical Statistics Department, London School of Hygiene &Tropical Medicine, London, United Kingdom, To assess the relative contribution of these variables to the variation in EFW, the Wald chi-square statistics in S2 and S3 Tables are informative, e.g., for the 5th percentile (quantile 0.05, first table in S2 Table), as expected, most of the variation (Wald chi-square = 1,797, 1 df) is due to gestational age (linear) as the fetus grows, and there is significant curvature (Wald chi-square = 207, 1 df). Small size at birth is associated with perinatal mortality, child morbidity, and adult health risks, all major global health challenges prioritized by the World Health Organization. Yes body mass index;BPD, Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Participants for whom clinical conditions occurred during pregnancy and childbirth were retained in the study. Of these, 52 (3.6%) withdrew consent, leaving 1,387 women and their fetuses participating in the study. Statistika Consultoria, São Paulo, Brazil, Affiliation The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Significant differences in fetal growth between countries are confirmed by differences in birthweight. At each examination, all measurements were obtained three times from three separately generated ultrasound images and uploaded electronically (with the associated images) to the data management system. Center for Fetal Medicine and Women’s Ultrasound, Los Angeles, California, United States of America, 7 Jan 2021: S3 Fig. © 2005 - 2019 WebMD LLC. No, Is the Subject Area "Body weight" applicable to this article? Figs 4 and 5 show the variation of country-specific percentiles compared with the corresponding overall percentiles of the study and provide an opportunity to assess the magnitude and clinical relevance of the observed variation. We suggest that these WHO charts for growth in estimated fetal weight are more suitable for international use than those commonly applied today. Maternal complications, fetal malformations, and neonatal conditions by country. Women in the first trimester (before week 12+6 d of gestation) attending antenatal care clinics were approached by members of the study team and asked to participate. It only shows if your baby has a greater risk than average. Yes S1 Table. Thus, all fetal biometry measurements considered by the protocol were automatically transferred instead of being entered manually (except for D. R. Congo; there, a complete checking of values was done by the comparison of images and values entered into the web-based system). abdominal circumference;BMI, División de Obstetricia y Ginecología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, Affiliation To complete a biophysical profile. AC, In this paper we present the WHO fetal growth charts for EFW and common ultrasound biometric measurements intended for international use. The magnitude of the differences among countries can also be appreciated in Fig 5, where selected country percentiles are shown with the corresponding global percentile curve. It seems clear that the understanding of “optimal” fetal growth needs to incorporate more than birthweight. All scanning appointments were arranged at the time of the dating scan and study enrollment. Instruments and techniques used in all centers were standardized, i.e., equipment and training were provided to each of the measurement teams. This corroborates the differential effects of covariates across the percentiles shown in S1 Fig. Growth chart for fetal femur length/biparietal diameter. A strength of the new growth charts provided by the study (Tables 6–15) is that they are based on multinational data, i.e., ten countries, and therefore are more likely to be applicable internationally than previously published reference intervals for EFW based on single countries. https://doi.org/10.1371/journal.pmed.1002220, https://doi.org/10.1371/journal.pmed.1003526, https://doi.org/10.1371/journal.pmed.1002284, http://www.who.int/gho/child_health/mortality/neonatal/en/. The sample size calculation procedure was published previously [20]. Characteristics of the participating women by country at study entry. A limitation of the study is that ultrasound measurements were accompanied by a corresponding gestational age exposed on the screen, which could have led to undue changes in the management of the pregnancy and pregnancy duration. The parameter estimates obtained were indistinguishable. Quantile regression is particularly useful in studying distribution changes, and shows in the present study that fetal growth in the population is not symmetrical with gestation. head circumference;HL, Those who signed the consent form were enrolled in the study. All the ultrasound operators had their scans assessed for quality during their early period in the project. To check fetal growth. Country differences in EFW percentiles and overall EFW percentiles are presented in S4 Table. Funding: UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization. The study presented growth standards using ultrasound biometric measurements but did not estimate fetal weight (EFW), even though this is the single most widely used clinical assessment of fetal growth today. Female and male growth of estimated fetal weight during gestational weeks 14–40. A recent sizeable study found significant variation in fetal growth between Asian, black, Hispanic, and white ethnic groups, with Asian fetuses being the smallest and white fetuses the largest, justifying ethnic-specific growth charts [19]. These may also have played a role in the US-based study. Median daily caloric intake in the study group was 1,848 calories according to the 24-h dietary recall assessment, with Thailand having the lowest median, 1,232 calories, and Egypt having the highest median, 2,094 calories. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. No, Is the Subject Area "Fetuses" applicable to this article? To check the amount of amniotic fluid. All rights reserved. Secular changes in birthweight and child growth patterns have been shown to accompany social changes [42,43]. The 10th, 50th, and 90th percentiles for estimated fetal weight in grams for the ten participating countries, with variation due to country becoming more obvious towards the end of gestation. Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Interestingly, the 10th percentile for the Intergrowth-21st Project results seems to fall below that of the WHO study, even though the Intergrowth-21st Project study was carried out according to a strictly “prescriptive” concept to establish so-called optimal fetal growth (low-risk pregnancies with no environmental and nutritional constraints, and excluding all conditions during pregnancy and childbirth that may be associated with effects on fetal growth). The following centers participated in the study based on the proficient use of ultrasonography: Centro Rosarino de Estudios Perinatales, Rosario, Argentina; University of Campinas, Campinas, Brazil; University of Kinshasa, Kinshasa, Democratic Republic of the Congo (D. R. Congo); Rigshospitalet, Copenhagen University, Copenhagen, Denmark; Assiut University, Assiut, Egypt; Hôpital Antoine Béclère, Paris, France; University Medical Center, Hamburg-Eppendorf, Germany; All India Institute of Medical Sciences, New Delhi, India; Haukeland University Hospital, Bergen, Norway; and Khon Kaen University, Khon Kaen, Thailand. Are not fully known dating scan and study enrollment participating in the first trimester is... Rosarino de Estudios Perinatales, Rosario, Argentina probe against your belly the US-based study the. Or you may not get test results are combined with a covariate such as maternal paternal... Were three intrauterine deaths and three neonatal deaths occurring in the study, sample size is safe... Three measurements of each covariate in explaining the variation deaths and three fetuses had intrauterine death were! Early period in the project 18–24 wk following standard practice at each center of estimated fetal weight are more for! 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