The Generation R Study: design and cohort update until the age of 4 years

  • Vincent W. V. JaddoeEmail author
  • Cornelia M. van Duijn
  • Albert J. van der Heijden
  • Johan P. Mackenbach
  • Henriëtte A. Moll
  • Eric A. P. Steegers
  • Henning Tiemeier
  • Andre G. Uitterlinden
  • Frank C. Verhulst
  • Albert Hofman
Developmental Epidemiology


The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Of all eligible children at birth, 61% participate in the study. In addition, more detailed assessments are conducted in a subgroup of 1,232 pregnant women and their children. Data collection in the prenatal phase and postnatal phase until the age of 4 years includes questionnaires, detailed physical and ultrasound examinations, behavioural observations and biological samples. This paper gives an update of the study design and cohort profile until the children’s age of 4 years. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.


Design Cohort study Child Pregnancy 



The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The authors thank Rachel Bakker and Claudia Kruithof for their assistance in data management. The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and The Netherlands Organization for Health Research and Development (ZonMw).


  1. 1.
    Hofman A, Jaddoe VW, Mackenbach JP, Moll HA, Snijders RF, Steegers EA, et al. Growth, development and health from early fetal life until young adulthood: the Generation R Study. Paediatr Perinat Epidemiol. 2004;18:61–72. doi: 10.1111/j.1365-3016.2003.00521.x.PubMedCrossRefGoogle Scholar
  2. 2.
    Jaddoe VW, Mackenbach JP, Moll HA, Steegers EA, Tiemeier H, Verhulst FC, et al. The Generation R Study: design and cohort profile. Eur J Epidemiol. 2006;21:475–84. doi: 10.1007/s10654-006-9022-0.PubMedCrossRefGoogle Scholar
  3. 3.
    Centre for Research and Statistics. Rotterdam (COS). 2005.
  4. 4.
    Troe EJ, Raat H, Jaddoe VW, Hofman A, Looman CW, Moll HA, et al. Explaining differences in birthweight between ethnic populations. The Generation R Study. BJOG. 2007;114:1557–65. doi: 10.1111/j.1471-0528.2007.01508.x.PubMedCrossRefGoogle Scholar
  5. 5.
    Statistics Netherlands. Standard Onderwijsindeling 2003. Voorburg/Heerlen: Statistics Netherlands; 2004.Google Scholar
  6. 6.
    Statistics Netherlands. Allochtonen in Nederland 2004. Voorburg/Heerlen: Statistics Netherlands; 2004.Google Scholar
  7. 7.
    Silva LM, Steegers EA, Burdorf A, Jaddoe VW, Arends LR, Hofman A, et al. No midpregnancy fall in diastolic blood pressure in women with a low educational level: the Generation R Study. Hypertension. 2008;52:645–51. doi: 10.1161/HYPERTENSIONAHA.108.116632.PubMedCrossRefGoogle Scholar
  8. 8.
    Verburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, et al. New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008;31:388–96. doi: 10.1002/uog.5225.PubMedCrossRefGoogle Scholar
  9. 9.
    Tunon K, Eik-Nes SH, Grottum P. A comparison between ultrasound and a reliable last menstrual period as predictors of the day of delivery in 15,000 examinations. Ultrasound Obstet Gynecol. 1996;8:178–85. doi: 10.1046/j.1469-0705.1996.08030178.x.PubMedCrossRefGoogle Scholar
  10. 10.
    Jaddoe VW, Verburg BO, de Ridder MA, Hofman A, Mackenbach JP, Moll HA, et al. Maternal smoking and fetal growth characteristics in different periods of pregnancy: the Generation R Study. Am J Epidemiol. 2007;165:1207–15. doi: 10.1093/aje/kwm014.PubMedCrossRefGoogle Scholar
  11. 11.
    Roza SJ, Verburg BO, Jaddoe VW, Hofman A, Mackenbach JP, Steegers EA, et al. Effects of maternal smoking in pregnancy on prenatal brain development. The Generation R Study. Eur J NeuroSci. 2007;25:611–7. doi: 10.1111/j.1460-9568.2007.05393.x.PubMedCrossRefGoogle Scholar
  12. 12.
    Verburg BO, Jaddoe VW, Wladimiroff JW, Hofman A, Witteman JC, Steegers EA. Fetal hemodynamic adaptive changes related to intrauterine growth: the Generation R Study. Circulation. 2008;117:649–59. doi: 10.1161/CIRCULATIONAHA.107.709717.PubMedCrossRefGoogle Scholar
  13. 13.
    Verburg BO, Geelhoed JJ, Steegers EA, Hofman A, Moll HA, Witteman JC, et al. Fetal kidney volume and its association with growth and blood flow in fetal life: the Generation R Study. Kidney Int. 2007;72:754–61. doi: 10.1038/ Scholar
  14. 14.
    Jaddoe VW, Bakker R, van Duijn CM, van der Heijden AJ, Lindemans J, Mackenbach JP, et al. The Generation R Study biobank: a resource for epidemiological studies in children and their parents. Eur J Epidemiol. 2007;22:917–23. doi: 10.1007/s10654-007-9209-z.PubMedCrossRefGoogle Scholar
  15. 15.
    Ye X, Pierik FH, Hauser R, Duty S, Angerer J, Park MM, et al. Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, The Netherlands: the Generation R study. Environ Res. 2008;108:260–7. doi: 10.1016/j.envres.2008.07.014.PubMedCrossRefGoogle Scholar
  16. 16.
    Rours GI, Verkooyen RP, Willemse HF, van der Zwaan EA, van Belkum A, de Groot R, et al. Use of pooled urine samples and a utomated DNA isolation to achieve improved sensitivity and cost-effectiveness of large-scale testing for Chlamydia trachomatis in pregnant women. R J Clin Microbiol. 2005;43:4684–90. doi: 10.1128/JCM.43.9.4684-4690.2005.CrossRefGoogle Scholar
  17. 17.
    Stichting Perinatale Registratie Nederland. 2008. (
  18. 18.
    van Batenburg-Eddes T, de Groot L, Arends L, de Vries A, Moll HA, Steegers EA, et al. Does gestational duration within the normal range predict infant neuromotor development? Early Hum Dev. 2008;84:659–65. doi: 10.1016/j.earlhumdev.2008.04.007.PubMedCrossRefGoogle Scholar
  19. 19.
    Burgmeijer RJF, Merkx JAM. Pakket … En hoe pakt het uit: Ouder en Kindzorg tussen wetenschap en praktijk. Nederlands Congres Ouder en Kindzorg. Assen: van Gorcum; 1999.Google Scholar
  20. 20.
    Roza SJ, Steegers EA, Verburg BO, Jaddoe VW, Moll HA, Hofman A, et al. What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems in the general population. Am J Epidemiol. 2008;168:1145–52. doi: 10.1093/aje/kwn233.PubMedCrossRefGoogle Scholar
  21. 21.
    Ay L, Hokken-Koelega AC, Mook-Kanamori DO, Hofman A, Moll HA, Mackenbach JP, et al. Tracking and determinants of subcutaneous fat mass in early childhood: the Generation R Study. Int J Obes. 2008;32:1050–9. doi: 10.1038/ijo.2008.76.CrossRefGoogle Scholar
  22. 22.
    Geelhoed JJ, Verburg BO, Nauta J, Lequin M, Hofman A, Moll HA, et al. Tracking and determinants of kidney size from fetal life until the age of 2 years: the Generation R Study. Am J Kidney Dis. 2008. doi: 10.1053/j.ajkd.2008.07.030.
  23. 23.
    Gabriele C, Asgarali R, Jaddoe VW, Hofman A, Moll HA, Jongste JC. Smoke exposure, airway symptoms and exhaled nitric oxide in infants: the Generation R study. Eur Respir J. 2008;32:307–13. doi: 10.1183/09031936.00132607.PubMedCrossRefGoogle Scholar
  24. 24.
    Labout JA, Duijts L, Arends LR, Jaddoe VW, Hofman A, de Groot R, et al. Factors associated with pneumococcal carriage in healthy dutch infants: the Generation R Study. J Pediatr. 2008;153:771–6. doi: 10.1016/j.jpeds.2008.05.061.PubMedCrossRefGoogle Scholar
  25. 25.
    Lebon A, Labout JA, Verbrugh HA, Jaddoe VW, Hofman A, van Wamel W, et al. Dynamics and determinants of Staphylococcus aureus carriage in infancy: the Generation R Study. J Clin Microbiol. 2008;46:3517–21. doi: 10.1128/JCM.00641-08.PubMedCrossRefGoogle Scholar
  26. 26.
    Duijts L, Bakker-Jonges LE, Labout JA, Jaddoe VW, Hofman A, Steegers EA, et al. Perinatal stress influences lymphocyte subset counts in neonates. The generation R study. Pediatr Res. 2008;63:292–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF- 36). I. Conceptual framework and item selection. Med Care. 1992;30:473–83. doi: 10.1097/00005650-199206000-00002.PubMedCrossRefGoogle Scholar
  28. 28.
    Carver DJ, Chapman CA, Thomas VS, Stadnyk KJ, Rockwood K. Validity and reliability of the medical outcomes study short form-20 questionnaire as a measure of quality of life in elderly people living at home. Age Ageing. 1999;28:169–74. doi: 10.1093/ageing/28.2.169.PubMedCrossRefGoogle Scholar
  29. 29.
    De Brock AJLL, Vermulst AA, Gerris JRM, Abidin RR. Nijmeegse Ouderlijke Stress Index. Lisse. Swets en Zeitlinger b.v.; 1992.Google Scholar
  30. 30.
    Gerris JR, Boxtel DA, Vermulst AA, Janssens JM, van Zuthpen RA, Felling AJ. Parenting in Dutch families. Nijmegen: University of Nijmegen, Institute of Family Studies; 1993.Google Scholar
  31. 31.
    Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry. 1987;150:782–6. doi: 10.1192/bjp.150.6.782.PubMedCrossRefGoogle Scholar
  32. 32.
    Derogatis LR, Melisaratos N. The brief symptom inventory: an introductory report. Psychol Med. 1983;13:595–605.PubMedGoogle Scholar
  33. 33.
    Wardle J, Guthrie CA, Sanderson S, Rapoport LJ. Development of the children’s eating behaviour questionnaire. Child Psychol Psychiatry. 2001;42:963–70. doi: 10.1111/1469-7610.00792.CrossRefGoogle Scholar
  34. 34.
    Raat H, Botterweck AM, Landgraf JM, Hoogeveen WC, Essink-Bot ML. Reliability and validity of the short form of the child health questionnaire for parents (CHQ-PF28) in large random school based and general population samples. J Epidemiol Community Health. 2005;59:75–82. doi: 10.1136/jech.2003.012914.PubMedCrossRefGoogle Scholar
  35. 35.
    Jenkins MA, Clarke JR. Validation of a questionnaire and bronchial hyper- responsiveness against respiratory physician assessment in the diagnosis of asthma. Int J Epidemiol. 1996;25:609–16. doi: 10.1093/ije/25.3.609.PubMedCrossRefGoogle Scholar
  36. 36.
    St James-Roberts I, Halil T. Infant crying patterns in the first year: normal community and clinical findings. J Child Psychol Psychiatry. 1991;32:951–68. doi: 10.1111/j.1469-7610.1991.tb01922.x.PubMedCrossRefGoogle Scholar
  37. 37.
    van der Wal MF, van den Boom DC, Pauw-Plomp H, de Jonge GA. Mothers’ reports of infant crying and soothing in a multicultural population. Arch Dis Child. 1998;79:312–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Gartstein MA, Rothbart MK. Studying infant temperament via the revised infant behavior questionnaire. Infant Behav Dev. 2003;26:64–86. doi: 10.1016/S0163-6383(02)00169-8.CrossRefGoogle Scholar
  39. 39.
    Ireton H, Glascoe FP. Assessing children’s development using parents’ reports. The child development inventory. Clin Pediatr. 1995;34:248–55. doi: 10.1177/000992289503400504.CrossRefGoogle Scholar
  40. 40.
    St James-Roberts I, Wolke D. Differences between maternal and objective ratings of difficult neonatal behavioural style: implications for temperament research and clinical perspectives. J Reprod Infant Psychol. 1983;1:53–60. doi: 10.1080/02646838308403151.CrossRefGoogle Scholar
  41. 41.
    St James-Roberts I, Wolke D. Convergences and discrepancies, among mothers’ and professionals’ assessments of difficult neonatal behaviour. J Child Psychol Psych All Discipl. 1989;29:21–42. doi: 10.1111/j.1469-7610.1988.tb00686.x.CrossRefGoogle Scholar
  42. 42.
    Achenbach TM. Manual for the child behavior checklist/4–18 and 1991 Profile. Burlington: University of Vermont Department of Psychiatry; 1991.Google Scholar
  43. 43.
    Verhulst FC, Van der Ende J, Koot HM. Manual for the CBCL/4–18. Rotterdam: Erasmus Universiteit/Dept of Child and Adolescent Psychiatry, Sophia Children’s Hospital; 1996.Google Scholar
  44. 44.
    Walker LS, Garber SJ, van Slyke DA. Development and validation of the pain response inventory for children. Psychol Assess. 1997;9:392–405. doi: 10.1037/1040-3590.9.4.392.CrossRefGoogle Scholar
  45. 45.
    Fenson L, Dale PS, Reznick JS, Thal D, Bates E, Hartung JP. MacArthur communicative development inventories; user’s guide and technical manual. San Diego: Singular Publishing Group, Inc; 1983.Google Scholar
  46. 46.
    Saudino KJ, Dale PS, Oliver B, Petrill SA, Richardson V, Rutter M, et al. The validity of parent-based assessment of cognitive abilities of 2-year-olds. Br J Dev Psychol. 1998;16:349–63.Google Scholar
  47. 47.
    Isquith PK, Gioia GA, Espy KA. Executive function in preschool children: examination through everyday behavior. Dev Neuropsychol. 2004;26:403–22. doi: 10.1207/s15326942dn2601_3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Vincent W. V. Jaddoe
    • 1
    • 2
    • 3
    Email author
  • Cornelia M. van Duijn
    • 2
  • Albert J. van der Heijden
    • 3
  • Johan P. Mackenbach
    • 4
  • Henriëtte A. Moll
    • 3
  • Eric A. P. Steegers
    • 5
  • Henning Tiemeier
    • 2
    • 6
  • Andre G. Uitterlinden
    • 2
    • 7
  • Frank C. Verhulst
    • 6
  • Albert Hofman
    • 2
  1. 1.The Generation R Study Group (AE006)Erasmus Medical CenterRotterdamThe Netherlands
  2. 2.Department of EpidemiologyErasmus Medical CenterRotterdamThe Netherlands
  3. 3.Department of PaediatricsErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands
  4. 4.Department of Public HealthErasmus Medical CenterRotterdamThe Netherlands
  5. 5.Department of Obstetrics & GynaecologyErasmus Medical CenterRotterdamThe Netherlands
  6. 6.Department of Child & Adolescent PsychiatryErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands
  7. 7.Department of Internal MedicineErasmus Medical CenterRotterdamThe Netherlands

Personalised recommendations