Different indices of fetal growth predict bone size and volumetric density at 4 years of age

We have demonstrated previously that higher birth weight is associated with greater peak and later‐life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z‐scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks' gestation from ultrasound measurements in participants in the Southampton Women's Survey. A total of 380 of the offspring underwent dual‐energy X‐ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19‐ to 34‐week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19‐ to 34‐week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks' gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density. © 2010 American Society for Bone and Mineral Research

[1]  L. Chitty,et al.  Fetal Size and Dating: Charts Recommended for Clinical Obstetric Practice , 2009 .

[2]  K. Godfrey,et al.  Commentary: Maternal constraint is a pre-eminent regulator of fetal growth. , 2008, International journal of epidemiology.

[3]  M. Hamrick,et al.  Leptin and the sympathetic connection of fat to bone , 2008, Osteoporosis International.

[4]  S. Norris,et al.  Infant programming of bone size and bone mass in 10-year-old black and white South African children. , 2007, Paediatric and perinatal epidemiology.

[5]  C. Cooper,et al.  Cohort profile: The Southampton Women's Survey. , 2006, International journal of epidemiology.

[6]  C. Cooper,et al.  Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study , 2006, The Lancet.

[7]  R. Rizzoli,et al.  Childhood Fractures Are Associated With Decreased Bone Mass Gain During Puberty: An Early Marker of Persistent Bone Fragility? , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  C. Cooper,et al.  Umbilical Cord Leptin Predicts Neonatal Bone Mass , 2005, Calcified Tissue International.

[9]  C. Cooper,et al.  Birth Weight and Weight at 1 Year Are Independent Determinants of Bone Mass in the Seventh Decade: The Hertfordshire Cohort Study , 2005, Pediatric Research.

[10]  F. Minuto,et al.  The IGF system and bone. , 2005, Journal of endocrinological investigation.

[11]  T. Hangartner,et al.  Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. , 2005, The American journal of clinical nutrition.

[12]  C. Cooper,et al.  Umbilical Venous IGF‐1 Concentration, Neonatal Bone Mass, and Body Composition , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  J. Auwerx,et al.  Leptin: cutting the fat off the bone , 2003, The Lancet.

[14]  G. S. Beaupré,et al.  A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis , 2003, Osteoporosis International.

[15]  D. Altman,et al.  Charts of fetal size: limb bones , 2002, BJOG : an international journal of obstetrics and gynaecology.

[16]  S Kertschanska,et al.  Liver blood perfusion as a possible instrument for fetal growth regulation. , 2002, Placenta.

[17]  K. Godfrey,et al.  Neonatal Bone Mass: Influence of Parental Birthweight, Maternal Smoking, Body Composition, and Activity During Pregnancy , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  S. Hauguel-de Mouzon,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Prenatal Leptin Production: Evidence That Fetal Adipose Tissue Produces Leptin , 2000 .

[19]  P. Marie,et al.  Reciprocal control of osteoblast/chondroblast and osteoblast/adipocyte differentiation of multipotential clonal human marrow stromal F/STRO‐1+ cells , 2001, Journal of cellular biochemistry.

[20]  B. Hartmann,et al.  Umbilical Venous Leptin Concentration and Gender in Newborns , 2001, The Journal of the Society for Gynecologic Investigation: JSGI.

[21]  R. Eastell,et al.  Intrauterine programming of adult body composition. , 2001, The Journal of clinical endocrinology and metabolism.

[22]  G. Karsenty,et al.  Leptin controls bone formation through a hypothalamic relay. , 2001, Recent progress in hormone research.

[23]  J. Tuomilehto,et al.  Maternal Height, Childhood Growth and Risk of Hip Fracture in Later Life: A Longitudinal Study , 2001, Osteoporosis International.

[24]  D. Dunger,et al.  Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. , 2000, The Journal of clinical endocrinology and metabolism.

[25]  S. Y. Kim,et al.  The Relationship of the Levels of Leptin, Insulin-like Growth Factor-I and Insulin in Cord Blood with Birth Size, Ponderal Index, and Gender Difference , 2000, Journal of pediatric endocrinology & metabolism : JPEM.

[26]  M. Jensen,et al.  Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. , 1999, Endocrinology.

[27]  C. Mantzoros,et al.  Cord blood leptin concentrations in relation to intrauterine growth , 1999, Clinical endocrinology.

[28]  A. Carrascosa,et al.  Leptin Values in Placental Cord Blood of Human Newborns with Normal Intrauterine Growth after 30–42 Weeks of Gestation , 1999, Hormone Research in Paediatrics.

[29]  G Pearce,et al.  Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study. , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[30]  G A Naughton,et al.  Prospective Ten‐Month Exercise Intervention in Premenarcheal Girls: Positive Effects on Bone and Lean Mass , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  K. Nakao,et al.  Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans , 1997, Nature Medicine.

[32]  I. Yokota,et al.  Serum leptin concentration in cord blood: relationship to birth weight and gender. , 1997, The Journal of clinical endocrinology and metabolism.

[33]  S. Atkinson,et al.  Improvement in the Accuracy of Dual Energy X-ray Absorptiometry for Whole Body and Regional Analysis of Body Composition: Validation Using Piglets and Methodologic Considerations in Infants , 1997, Pediatric Research.

[34]  R. Rizzoli,et al.  Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. , 1997, The Journal of clinical investigation.

[35]  R. Braylan,et al.  Assessment of the contribution of the spleen to granulocytopoiesis and erythropoiesis of the mid-gestation human fetus. , 1996, Early human development.

[36]  O Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. , 1996, BMJ.

[37]  P Royston,et al.  Calculation of unconditional and conditional reference intervals for foetal size and growth from longitudinal measurements. , 1995, Statistics in medicine.

[38]  P. Egger,et al.  Childhood growth, physical activity, and peak bone mass in women , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[39]  G. Naus,et al.  Estimation of hepatic hematopoiesis in second and third trimester singleton gestations using flow cytometric light scatter analysis of archival autopsy tissue. , 1992, Early human development.

[40]  D R Carter,et al.  New approaches for interpreting projected bone densitometry data , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[41]  M. Binoux,et al.  Heterogeneity of insulin-like growth factor binding proteins and relationships between structure and affinity. 1. Circulating forms in man. , 1987, European journal of biochemistry.

[42]  R. Little Mother's and father's birthweight as predictors of infant birthweight. , 1987, Paediatric and perinatal epidemiology.