The effect of childhood stunting and wasting on adolescent cardiovascular diseases risk and educational achievement in rural Uganda : a retrospective cohort study

Background: Little is known about the long-term effects of early childhood undernutrition on adolescent cardiovascular disease risk and educational performance in low-income countries. We examined this in a rural Ugandan population. Objective: To investigate if stunting or wasting among children aged 2-5 years is associated with cardiovascular disease risk or educational achievement during adolescence. Methods: We conducted analyses using data from a cohort of children followed from early childhood to adolescence. Weight and height were measured in 1999-2000 when the children were 2-5 years of age and repeated in 2004/2005 and 2011. We compared cardiovascular disease risk parameters (mean blood pressure, lipids, HbA1c) and schooling years achieved in 2011 among 1054 adolescents categorised into four groups: those who experienced stunting or wasting throughout follow-up; those who recovered from stunting or wasting; those who were normal but later became stunted or wasted; and those who never experienced stunting or wasting from childhood up to adolescence. We controlled for possible confounding using multiple generalised linear regression models along with Generalised Estimating Equations to account for clustering of children within households. Results: Wasting was negatively associated with systolic blood pressure (-7.90 95%CI [-14.52,-1.28], p = 0.02) and diastolic blood pressure (-3.92, 95%CI [-7.42, -0.38], p = 0.03). Stunting had borderline negative association with systolic blood pressure (-2.90, 95%CI [-6.41, 0.61] p = 0.10). Recovery from wasting was positively associated with diastolic blood pressure (1.93, 95%CI [0.11, 3.74] p = 0.04). Stunting or wasting was associated with fewer schooling years. Conclusion: Recovery from wasting rather than just an episode in early childhood is associated with a rise in blood pressure while educational achievement is compromised regardless of whether recovery from undernutrition happens. These findings are relevant to children exposed to undernutrition in low-income settings

Functional development of the meso- and metanephros

This review highlights the important roles the mesonephros may play in development. In the ovine fetus it is an excretory and endocrine organ and may contribute to the formation of normal gonads and adrenals. The metanephros of the ovine fetus has the important function of providing large quantities of dilute urine for the maintenance of amniotic and allantoic fluid volumes, essential for normal placentation and development

THE EFFECT OF GRADED HEMORRHAGE ON ERYTHROPOIETIN PRODUCTION IN THE IMMATURE OVINE FETUS

1. Basal and haemorrhage-stimulated erythropoietin (Epo) and ACTH levels were measured in the chronically cannulated immature ovine foetus (< 125 days) by radio immunoassay (RIA)

Renal, hormonal, and cardiovascular responses to chronic angiotensin I infusion in the ovine fetus

Long-term infusion of angiotensin I (ANG I) into the ovine fetus has been shown to cause excess accumulation of fetal fluid in the allantoic compartment. It was hypothesized that this resulted from sustained increases in fetal urine production. and the hormonal basis was examined. ANG I (6.7 mu g/h, n = 6) or isotonic saline (n = 6) was infused for 3 days into chronically cannulated ovine fetuses (112-122 days of gestation). ANG I caused an immediate and progressive increase in mean arterial blood pressure (from 42 +/- 2 to 57 +/- 4 mmHg), increased urine flow rate (from 15 +/- 3 to 48 +/- 8 ml/h), and increased glomerular filtration rate (from 97 +/- 15 to 146 +/- 24 ml/h), without significant changes in fetal plasma concentrations of aldosterone, atrial natriuretic factor (ANF), adrenocorticotropin, or cortisol. There were substantial increases in sodium and chloride excretion, due to both increased fetal urine concentrations and fetal urine flow, without significant changes in urine osmolality (from 134 +/- 9 to 147 +/- 12 mosmol/kg water). There were no significant changes in any parameter in the saline-infused fetuses. Neither amniotic or allantoic fluid volume was significantly changed by ANG I infusion, but allantoic fluid Cl- concentration increased significantly. The conclusions are that ANG I caused a diuresis and natriuresis in the fetal sheep independent of changes in cortisol or ANF

Kidney development and the fetal programming of adult disease

Recent evidence, from both epidemiological and animal experimental studies, suggest that the very first environment, the intrauterine, is extremely important in determining the future health of the individual. Genetic and 'lifestyle' factors impinge on, and can exacerbate, a 'programming' effect of an adverse fetal environment. In this review, we present compelling evidence to suggest that one of the major organs affected by an unfavourable prenatal environment is the kidney. Many of the factors that can affect fetal renal development (i.e. exposure to excess glucocorticoids, insufficient vitamin A, protein/calorie malnutrition (in rats) and alterations in the intrarenal renin angiotensinogen system), also produce hypertension in the adult animal. When nephron number is compromised during kidney development, maladaptive functional changes occur and can lead, eventually, to hypertension and/or renal disease. Surprisingly, it is during the very earliest stages of kidney development that the vulnerability to these effects occurs

Glucocorticoid programming of adult disease

Fetal exposure to elevated levels of glucocorticoids can occur naturally when maternal glucocorticoids are elevated in times of stress or when exogenous glucocorticoids are administered. Epidemiological studies and animal models have shown that, whereas short-term benefits may be associated with fetal glucocorticoid exposure, long-term deleterious effects may arise. This review compares the effects of exposure to natural versus synthetic glucocorticoids and considers the ways in which the timing of the exposure and the sex of the fetus may influence outcomes. Some of the long-term effects of glucocorticoid exposure may be explained by epigenetic mechanisms

The Effect of Hemorrhage On Erythropoietin Concentration in the Mature Ovine Fetus

This study examines the response in plasma erythropoietin values to haemorrhage of 20% of the estimated blood volume in chronically cannulated ovine fetuses, of gestational ages 128-144 days. Blood samples were collected at 0, 2, 4, 6 and 24h with respect to the haemorrhage. In 5 control experiments there was no significant change in plasma erythropoietin concentration, across this time period, values being 6.1 +/- 2.3 and 6.4 +/- 2.4 mU/ml at 0 and 24h respectively. Values are mean +/- SEM. Haemorrhage reduced the haematocrit and haemoglobin values, significantly, to 83 +/- 6% and 85 +/- 4% (n = 5) of the initial value, respectively, but did not cause a statistically significant increase in plasma erythropoietin concentrations (7.2 +/- 2.4 and 20.7 +/- 8.2 mU/ml; P = 0.131). A larger degree of haemorrhage, in four fetuses reduced the haematocrit to 64 +/- 2.8 % of initial, over 24-54h and increased erythropoietin values very significantly (from 11.9 +/- 3.6 to 91 +/- 8.3 mU/ml; P = 0.001)

Angiotensin-(1-7) in the ovine fetus

In the adult animal, ANG-(1-7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1-7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers (n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1-7), and ANG II were 86 +/- 21, 13 +/- 2, and 14 +/- 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 +/- 4 fmol/ml, P< 0.05) as were concentrations of ANG-(1-7) (2.9 +/- 0.6 fmol/ml), whereas ANG II concentrations were not different (10 +/- 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 +/- 1.1 pmol ANG I.ml(-1).h(-1)) than in the ewe (0.9 +/- 0.2 pmol.ml(-1).h(-1), P< 0.05). Infusion of ANG-(1-7) (similar to9 mug/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1-7) reaching a maximum of 448 +/- 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days (n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1-7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT(1) receptor, and AT(2) receptor were elevated in kidneys of fetuses that received infusions of ANG-(1-7). Infusion of an ANG-(1-7) antagonist {[D-Ala(7)]ANG-(1-7), 20 mug/h} for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1-7) may play a role in the fetal kidney