Chronic Maternal Undernutrition in the Rat Leads to Delayed Postnatal Growth and Elevated Blood Pressure of Offspring

To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p < 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

[1]  A. Jackson,et al.  Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. , 1994, Clinical science.

[2]  P. Gluckman,et al.  A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth. , 1996, The Journal of endocrinology.

[3]  C Osmond,et al.  Fetal and infant growth and impaired glucose tolerance at age 64. , 1991, BMJ.

[4]  T. Unterman,et al.  Maternal Hypoxia as a Model for Intrauterine Growth Retardation: Effects on Insulin-Like Growth Factors and Their Binding Proteins , 1993, Pediatric Research.

[5]  D. Barker.  The fetal origins of adult hypertension. , 1992, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[6]  E. van Marthens,et al.  In-utero fetal and placental development following maternal protein repletion in rats. , 1978, The Journal of nutrition.

[7]  R. Martorell,et al.  Influence of maternal nutrition on birth weight. , 1975, The American journal of clinical nutrition.

[8]  J. Houtkooper,et al.  Energy supplementation during pregnancy and postnatal growth , 1992, The Lancet.

[9]  C Osmond,et al.  The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. , 1993, BMJ.

[10]  K. Godfrey,et al.  The effect of maternal anaemia and iron deficiency on the ratio of fetal weight to placental weight , 1991, British journal of obstetrics and gynaecology.

[11]  C. Fall,et al.  Fetal and infant origins of cardiovascular disease. , 1993, Archives of disease in childhood.

[12]  K. Godfrey,et al.  Maternal nutritional status in pregnancy and blood pressure in childhood , 1994, British journal of obstetrics and gynaecology.

[13]  R. Benediktsson,et al.  Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. , 1996, Placenta.

[14]  D. Cook,et al.  Early influences on blood pressure: a study of children aged 5-7 years. , 1989, BMJ.

[15]  R. Benediktsson,et al.  Glucocorticoid exposure in utero: new model for adult hypertension , 1993, The Lancet.

[16]  T. Unterman,et al.  Circulating levels of insulin, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins in the small for gestational age fetal rat. , 1993, Endocrinology.

[17]  C Osmond,et al.  Early growth and death from cardiovascular disease in women. , 1993, BMJ.

[18]  C Osmond,et al.  Initiation of hypertension in utero and its amplification throughout life. , 1993, BMJ.

[19]  H. Munro,et al.  Rat placental protein synthesis and peptide hormone secretion in relation to malnutrition from protein deficiency or alcohol administration. , 1979, The Journal of nutrition.

[20]  Clive Osmond,et al.  Fetal and placental size and risk of hypertension in adult life. , 1990, BMJ.

[21]  D. Barker,et al.  WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE , 1989, The Lancet.

[22]  B. Johnston.  Fetal growth retardation and increased placental weight in the spontaneously hypertensive rat. , 1995, Reproduction, fertility, and development.

[23]  M. Rechler,et al.  Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting. , 1991, Endocrinology.

[24]  P. Gluckman,et al.  Fetal nutrition and cardiovascular disease in adult life , 1993, The Lancet.

[25]  D J Barker,et al.  The maternal and fetal origins of cardiovascular disease. , 1992, Journal of epidemiology and community health.

[26]  G. Anderson,et al.  Effect of maternal dietary restriction during pregnancy on maternal weight gain and fetal birth weight in the rat. , 1980, The Journal of nutrition.

[27]  T. Jansson,et al.  Low birth weight is associated with elevated adult blood pressure in the chronically catheterized guinea-pig. , 1992, Acta physiologica Scandinavica.

[28]  B. Folkow.  The fourth Volhard lecture: cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. , 1978, Clinical science and molecular medicine. Supplement.

[29]  P. Gluckman,et al.  Fetal Growth in Late Gestation — A Constrained Pattern of Growth , 1990, Acta paediatrica Scandinavica. Supplement.

[30]  A Lucas,et al.  Programming by early nutrition in man. , 2007, Ciba Foundation symposium.

[31]  M. Pinsky,et al.  Conversion of maternal cortisol to cortisone during placental transfer to the human fetus. , 1974, American journal of obstetrics and gynecology.

[32]  S. Lederman,et al.  Effects of food restriction on fetal and placental growth and maternal body composition. , 1980, Growth.

[33]  P. Rymark,et al.  Low birth weight and risk of high blood pressure in adulthood , 1988, British medical journal.

[34]  R. Buñag.  Validation in awake rats of a tail-cuff method for measuring systolic pressure. , 1973, Journal of applied physiology.

[35]  M. Susser,et al.  Early origin of coronary heart disease (the “Barker hypothesis”) , 1995, BMJ.

[36]  J. Whelan,et al.  The Childhood environment and adult disease , 1991 .

[37]  J Golding,et al.  Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. , 1989, BMJ.