title: The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study.
abstract: BACKGROUND
  Large differences exist in size at birth and in rates of impaired fetal growth worldwide. The relative effects of nutrition, disease, the environment, and genetics on these differences are often debated. In clinical practice, various references are often used to assess fetal growth and newborn size across populations and ethnic origins, whereas international standards for assessing growth in infants and children have been established. In the INTERGROWTH-21(st) Project, our aim was to assess fetal growth and newborn size in eight geographically defined urban populations in which the health and nutrition needs of mothers were met and adequate antenatal care was provided.
  
  
  METHODS
  For this study, fetal growth and newborn size were measured in two INTERGROWTH-21(st) component studies using prespecified markers and the same methods, equipment, and selection criteria. In the Fetal Growth Longitudinal Study (FGLS), we studied educated, affluent, healthy women, with adequate nutritional status who were at low risk of intrauterine growth restriction. The primary markers of fetal growth were ultrasound measurements of fetal crown-rump length at less than 14 weeks and 0 days of gestation and fetal head circumference from 14 weeks and 0 days to 40 weeks and 0 days of gestation, and birthlength for newborn size. In the concomitant, population-based Newborn Cross-Sectional Study (NCSS), we measured birthlength in all newborn babies from the eight geographically defined urban populations with the same methods, instruments, and staff as in FGLS. From this large NCSS cohort, we selected an FGLS-like subpopulation to match FGLS with the same eligibility criteria.
  
  
  RESULTS
  Between May 14, 2009, and Aug 2, 2013, we enrolled 4607 women in FGLS and 59 137 women in NCSS. From NCSS, 20 486 (34·6%) women met the FGLS eligibility criteria, and constituted the FGLS-like subpopulation. With variance component analysis, only between 1·9% and 3·5% of the total variability in crown-rump length, fetal head circumference, and newborn birthlength could be attributed to between-site differences. With standardised site effect analysis in 16 gestational age windows from 9 weeks and 0 days of gestation to birth for the three measures (128 comparisons), only one was marginally higher than 0·5 SD of the standardised site difference range. Sensitivity analyses, excluding individual populations in turn from the pooling of all-site centiles across gestational ages, showed no noticeable effect on the 3rd, 50th, and 97th centiles derived from the remaining populations. Our populations were consistent at birth with those in the WHO Multicentre Growth Reference Study (MGRS). The mean birthlength for term newborn babies in that study was 49·5 cm (SD 1·9), which was very similar to that in the FGLS cohort (49·4 cm [1·9]) and the NCSS derived FGLS-like subpopulation (49·3 cm [1·8]).
  
  
  CONCLUSIONS
  Fetal growth and newborn length are similar across diverse geographical settings when mothers' nutritional and health needs are met, and environmental constraints on growth are low. The findings for birthlength are in strong agreement with those of the WHO MGRS. These results provide the conceptual frame to create international standards for growth from conception to newborn baby, which will extend the present infant to childhood WHO MGRS standards.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & 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
authors.affiliation: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Aris T
authors.initials: AT
authors.lastname: Papageorghiou
authors.affiliation: School of Public Health, Peking University, Beijing, China.
authors.forename: Ruyan
authors.initials: R
authors.lastname: Pang
authors.affiliation: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & 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: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Cheikh Ismail
authors.affiliation: 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: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Lambert
authors.affiliation: Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya.
authors.forename: Maria
authors.initials: M
authors.lastname: Carvalho
authors.affiliation: Department of Family and Community Health, Ministry of Health, Muscat, Sultanate of Oman.
authors.forename: Yasmin A
authors.initials: YA
authors.lastname: Jaffer
authors.affiliation: Dipartimento di Scienze Pediatriche e dell'Adolescenza, Cattedra di Neonatologia, 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: Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Doug G
authors.initials: DG
authors.lastname: Altman
authors.affiliation: Nagpur INTERGROWTH-21st Research Centre, Ketkar Hospital, Nagpur, India.
authors.forename: Manorama
authors.initials: M
authors.lastname: Purwar
authors.affiliation: Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, USA.
authors.forename: Ihunnaya O
authors.initials: IO
authors.lastname: Frederick
authors.affiliation: Department of Engineering Science, University of Oxford, Oxford, UK.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Noble
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: Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan; Center for Global Child Health, Hospital for Sick Children, Toronto, Canada.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.affiliation: Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D049628:Body Size; D002508:Cephalometry; D000013:Congenital Abnormalities / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D047109:Fetal Development; D005865:Gestational Age; D057238:Growth Charts; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D011247:Pregnancy; D055815:Young Adult