title: International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.
abstract: BACKGROUND
  In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses.
  
  
  METHODS
  The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study.
  
  
  RESULTS
  We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth.
  
  
  CONCLUSIONS
  We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Aris T
authors.initials: AT
authors.lastname: Papageorghiou
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK; Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Ohuma
authors.affiliation: Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.affiliation: Università degli Studi di Torino, Torino, Italy.
authors.forename: Tullia
authors.initials: T
authors.lastname: Todros
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Cheikh  Ismail
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Lambert
authors.affiliation: Department of Family and Community Health, Ministry of Health, Muscat, Oman.
authors.forename: Yasmin A
authors.initials: YA
authors.lastname: Jaffer
authors.affiliation: Università degli Studi di Torino, Torino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertino
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Gravett
authors.affiliation: Nagpur INTERGROWTH-21(st) Research Centre, Ketkar Hospital, Nagpur, India.
authors.forename: Manorama
authors.initials: M
authors.lastname: Purwar
authors.affiliation: Department of Engineering Science, University of Oxford, Oxford, UK.
authors.forename: J Alison
authors.initials: JA
authors.lastname: Noble
authors.affiliation: School of Public Health, Peking University, Beijing, China.
authors.forename: Ruyan
authors.initials: R
authors.lastname: Pang
authors.affiliation: Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
authors.forename: Cesar G
authors.initials: CG
authors.lastname: Victora
authors.affiliation: Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil; Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas, Pelotas, RS, Brazil.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Barros
authors.affiliation: Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya.
authors.forename: Maria
authors.initials: M
authors.lastname: Carvalho
authors.affiliation: Department of Obstetrics and Fetal Medicine, Hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France.
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Salomon
authors.affiliation: Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan; Center for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kennedy
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK. Electronic address: jose.villar@obs-gyn.ox.ac.uk.
authors.forename: José
authors.initials: J
authors.lastname: Villar
mesh_terms: D000005:Abdomen / Q000196:embryology / Q000502:physiology; D000293:Adolescent; D000328:Adult; D002508:Cephalometry / Q000379:methods; D005260:Female; D005269:Femur / Q000196:embryology; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D008423:Maternal Age; D011247:Pregnancy; D011446:Prospective Studies; D012015:Reference Standards; D016216:Ultrasonography, Prenatal / Q000592:standards; D014504:Urban Health; D055815:Young Adult