Original Investigation
Pathogenesis and Treatment of Kidney Disease
Tracking and Determinants of Kidney Size From Fetal Life Until the Age of 2 Years: The Generation R Study

https://doi.org/10.1053/j.ajkd.2008.07.030Get rights and content

Background

An adverse fetal environment may lead to smaller kidneys and subsequently kidney disease and hypertension in adulthood. The aims of this study are to examine whether kidney size tracks from fetal life to childhood and whether maternal and fetal characteristics are associated with kidney size at the age of 2 years.

Study Design

Prospective cohort study from fetal life onward.

Setting & Participants

The study was conducted in a group of 688 infants in Rotterdam, The Netherlands. Entry criteria were singleton, noncomplicated pregnancies, and Dutch ethnicity.

Predictors

The maternal characteristics age, height, and prepregnancy weight were measured in early pregnancy. Fetal growth, head circumference, abdominal circumference, femur length and estimated fetal weight, and placental characteristics were assessed in the second and third trimesters.

Outcomes & Measurements

Kidney size, defined as length, width, depth, and volume, was measured in the third trimester of pregnancy and at postnatal ages 6 and 24 months.

Results

Overall median gestational age was 40.3 weeks (95% range, 36.0 to 42.3 weeks), and mean birth weight was 3,536 ± 524 (SD) g. Children tended to remain in the lowest and highest quartiles of kidney volume from the third trimester to the age of 2 years (odds ratio, 2.05; 95% confidence interval, 1.38 to 3.06; odds ratio, 3.29; 95% confidence interval, 2.22 to 4.87, respectively). Maternal height and prepregnancy weight were associated positively with kidney volume at the age of 2 years. Third-trimester fetal head circumference, abdominal circumference, and estimated weight and postnatal length were associated positively with kidney volume at the age of 2 years. Preferential fetal blood flow to the brain was associated with smaller kidneys.

Limitations

Kidney measurements successfully performed in only 86% of children.

Conclusions

Small kidney size in fetal life tends to persist in early childhood. Maternal anthropometrics and fetal biometrics and blood flow patterns are associated with kidney size in childhood. Follow-up studies are needed to examine whether these variations in kidney size are related to kidney function and blood pressure in later life.

Section snippets

Design

This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood in Rotterdam, The Netherlands.21, 22 Assessments in pregnancy included physical examinations, fetal ultrasounds, biological samples, and questionnaires and were planned 3 times in pregnancy to collect information about fetal growth and its main determinants. More detailed assessments of fetal and postnatal growth and development are conducted in a subgroup, the

Results

The percentage of boys was 51% (Table 1). Overall median age of infants at their 6-month visit was 6.3 months (95% range, 5.4 to 8.1 months), and at their 2-year visit, 25.1 months (95% range, 23.6 to 28.2 months). We defined small for gestational age (SGA) as children with birth weight less than −2 SDs for gestational age. In total, only 15 children in our study group fulfilled this criterion for SGA. Furthermore, we reported only 18 children with birth weight less than 2,500 g and 23 children

Discussion

Our population-based prospective cohort study shows for the first time that kidney size tracks from the third trimester of pregnancy to early childhood. Maternal anthropometrics before pregnancy and fetal growth characteristics in the third trimester of pregnancy are associated positively with kidney volume at the age of 2 years. Preferential fetal blood flow to the brain also is associated with smaller kidneys.

The major strength of our study is its prospective design from early fetal life and

Acknowledgements

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 Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond, Rotterdam. We gratefully acknowledge the contribution of general practitioners, hospitals, midwives, and pharmacies in Rotterdam.

Support: The first phase of

References (43)

  • A.A. Baschat et al.

    Fetal growth restriction due to placental disease

    Semin Perinatol

    (2004)
  • I.M. Schmidt et al.

    Impaired kidney growth in low-birth-weight children: Distinct effects of maturity and weight for gestational age

    Kidney Int

    (2005)
  • M.F. Schreuder et al.

    Prenatal programming of nephron number and blood pressure

    Kidney Int

    (2007)
  • G.C. Curhan et al.

    Birth weight and adult hypertension, diabetes mellitus, and obesity in US men

    Circulation

    (1996)
  • R.G. Nelson et al.

    Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus

    Am J Epidemiol

    (1998)
  • D.T. Lackland et al.

    Low birth weights contribute to high rates of early-onset chronic renal failure in the southeastern United States

    Arch Intern Med

    (2000)
  • N. Zidar et al.

    Effect of intrauterine growth retardation on the clinical course and prognosis of IgA glomerulonephritis in children

    Nephron

    (1998)
  • S.A. Hinchliffe et al.

    Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle

    Lab Invest

    (1991)
  • J.R. Nyengaard et al.

    Glomerular number and size in relation to age, kidney weight, and body surface in normal man

    Anat Rec

    (1992)
  • H. Bassan et al.

    Experimental intrauterine growth retardation alters renal development

    Pediatr Nephrol

    (2000)
  • G. Celsi et al.

    Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring

    Pediatr Res

    (1998)

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    Originally published online as doi:10.1053/j.ajkd.2008.07.030 on October 13, 2008.

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    Copyright © 2009 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.