Angiotensin converting enzyme activity in infancy is related to birth weight

Abstract

Aims: (a) To measure infant angiotensin converting enzyme (ACE) activity in healthy term infants at birth and during the first three months of life. (b) To determine the relation between serum ACE activity and infant feeding practice during this period. (c) To investigate the relation between serum ACE activity and birth weight and other potential contributing factors including acid-base status at birth, gestation, and maternal ACE genotype. Methods: Prospective study of term infants, with clinical and feeding data collected from parents and medical records, and serum ACE measured in the infant at birth and 1 and 3 months of age, and in the mother at the time of birth and one to three months after birth. Results: At birth and 1 and 3 months of age, infant serum ACE activity was twice that of maternal ACE activity. Infant ACE activity at birth and 1 and 3 months did not significantly differ between breast and formula fed infants. There was a highly significant negative correlation between infant ACE activity at 3 months and birth weight (r = 20.52; p , 0.001). This persisted after the conversion of birth weights to z scores (r = 20.34; p = 0.03). ACE activity at 3 months was also related to placental weight (r = 20.30; p = 0.02) and maternal age (r = 20.30; p = 0.05). The strong correlation between serum ACE activity and birth weight z score persisted after adjustment for maternal age and placental weight (r = 20.34; p = 0.03). Conclusion: As ACE is increasingly identified as a risk factor for cardiovascular disease, serum ACE activity in infancy may contribute to the link between low birth weight and later cardiovascular events.T here are numerous reports of low birth weight being associated with coronary heart disease, hypertension, stroke, and non-insulin dependent diabetes. 1 These associations are thought to be the consequence of a stimulus or an insult occurring at a critical period of early life and resulting in permanent effects on structure and metabolism. 2 There is evidence that this concept of ''programming'' may not be exclusive to intrauterine life, and nutritional interventions during the postnatal period may also influence later health.3 For example, recent data indicate that children who are breast fed in infancy have lower blood pressures during later childhood and adolescence than children who are formula fed. [4][5][6] Although there are several constituents of breast milk that are possible causes, including hormones, nutrients, and trophic substances, 5 the underlying mechanisms remain uncertain.Angiotensin converting enzyme (ACE) not only has a key role in the regulation of peripheral blood pressure, 7 but it is now increasingly being identified as a major risk factor for cardiovascular disease.8 9 There is some evidence that ACE activity may be increased in preterm infants especially those with respiratory distress syndrome in the newborn period. 11Infant lung capillaries are a rich source of ACE, and hypoxic mice are known to have raised serum ACE activity at birth. 11Whether this increase...

Programming of Hypertension

“…16,17 However, in humans, the data are limited to a few studies examining the RAS in preterm infants 22 or in early infant life, reporting increased angiotensin II levels in small-for-gestational-age children in the neonatal period 23 and increased angiotensinconverting enzyme activity at 3 months of age. 24 Whether this is related to subsequent hypertension has not been explored, although a recent small study suggested RAS activation in association with low birthweight and hypertension in boys born small for gestational age. 25 There is also some evidence of associations between low birthweight and polymorphisms in components of the RAS, 26 -28 but these have not yet been linked with current or later blood pressure measurements.…”

Consequences of Intrauterine Growth Restriction for the Kidney

“…Nine-month-old sheep born after maternal food restriction show similar AT1 and AT2 receptor expression, but an increase in renal cortex ACE expression [116] . ACE activity in humans shows no correlation with birth weight at birth and 1 month of age, but there is a negative cor- relation at the age of 3 months [199] . In rats, plasma [124] and pulmonary ACE activity is raised [118,122] , but renal ACE activity is unaltered [118,129] .…”

Circulating renin–angiotensin system and catecholamines in childhood: is there a role for birthweight?

“…So far, it has been proposed that both the sympathoadrenal system and the RAS (renin-angiotensin system) are probably altered in children with a history of low birthweight [7][8][9][10][11][12]. In fact, subjects with lower birthweight have higher sympathetic tone not only in infancy [7], but also in childhood [8] and as adults [9].…”

“…Moreover, increased plasma AngII (angiotensin II) levels have been reported in SGA (smallfor-gestational age) infants during early neonatal life [11]. Forsyth et al [12] demonstrated that the activity of ACE (angiotensin-converting enzyme) is significantly related to birthweight in infants 3 months of age. Whether this increased activation of both the RAS and the sympathoadrenal profile is related to hypertension or other cardiovascular disease in SGA children has not been determined.…”