I.F. Csaba

Postnatal development of renin-angiotensin-aldosterone system, RAAS, in relation to electrolyte balance in premature infants.

Summary: In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160–1850 g, and mean gestational age of 31 weeks, range: 30–32 weeks, were selected for the study.Due to the increased urinary Na loss, negative Na balance developed in the first 2 weeks followed by positive balance thereafter. PRA, PA, and UAE increased tremendously from the initially high values of 18.2 ± 4.1 ng/ml/hr, 1.7 ± 0.5 ng/ml, and 2.6 ± 0.4 μg/day, mean and SEM, to their maximum of 78.6 ± 18.1 ng/ml/hr, P < 0.01,6.8 ± 3.7 ng/ml, P < 0.05, and 26.4 ± 2.9 μg/day, P < 0.01, in the 3rd week, respectively. Later on, gradual declines occurred, however, PRA, PA, and UAE remained highly elevated even at the 6th week with values of 45.5 ± 15 ng/ml/hr, 1.6 ± 0.5 ng/ml, and 14.5 ± 1.4 μg/day, respectively.It is suggested that late hyponatremia of premature infants is due to tubular unresponsiveness to aldosterone and not to inadequate response of RAAS to stimulation.Speculation: The initially high urinary sodium excretion in premature infants is coupled with low urinary potassium excretion indicating limited renal sodium reabsorption in exchange for potassium. Later on, progressive increase in renal sodium-potassium exchange occurs and the plasma sodium and potassium concentrations gradually approach the normal values.On the basis of these observations, one can assume the physiologic role of both the increasing activity of RAAS and also the increase in renal tubular responsiveness to aldosterone with advancing postnatal age.

Relationship between Maturity, Electrolyte Balance and the Function of the Renin-Angiotensin-Aldosterone System in Newborn Infants

Simultaneous measurement of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) was made using the RIA method along with determination of Na and K balance in 1-week-old neonates with gestational age of 30-41 weeks (mean 35.9 weeks) and birth weight of 1,160-4,670 g (mean 2,680 g). It was demonstrated that PRA decreased from the value of 36.3 +/- 6.3 ng/ml/h (mean +/- SE) to a level of 10.2 +/- 2.1 ng/ml/h (p less than 0.001), PA did not change and UAE increased from 3.3 +/- 0.8 to 7.8 +/- 1.4 microgram/day (p less than 0.01) as the gestational age advanced from 30-32 to 39-41 weeks. There was no correlation between either PRA and PA and UAE. PRA showed a significant positive correlation with urinary Na excretion (p less than 0.001) and plasma K concentration (p less than 0.05), but it was negatively related to Na balance (p less than 0.001). Significant negative correlations were found between UAE and urinary Na excretion (p less than 0.05), urinary Na/K ratio (p less than 0.01 (and plasma K concentration (p less than 0.05); however, UAE positively correlated with Na balance (p less than 0.01). It is concluded that, in response to renal salt wasting and to the subsequent negative salt balance, premature infants can augment their PRA above values found for full-term infants. Their adrenals, however, failed to respond adequately to this stimulation.

On the Mechanism of Renal Sodium Handling in Newborn Infants

In an attempt to delineate the specific tubular defect in sodium reabsorption in low-birth-weight neonates, fractional sodium excretion (CNa/CCr), distal tubular sodium delivery (CNa+CH2O), and tubular sodium reabsorption [(CH2O/CH2O+CNa) X 100] were determined in 8 healthy premature and 10 full-term newborn infants. The mean birth weight was 1,701 g (range: 1,240--2,120 g) and the mean gestational age was 32.6 weeks (range: 28--35 weeks) for premature; and 3,199 g (range: 2,670--3,670 g) and 38.9 weeks (range: 38--41 weeks) for full-term neonates. It was demonstrated that the significantly higher fractional sodium excretion in premature infants (1.44 +/- 0.33 SE versus 0.36 +/- 0.09%), p less than 0.01) resulted from significantly decreased proximal (CNa+CH2O : 0.674 +/- 0.105 versus 0.360 +/- 0.069 ml/min/1.73m2, p less than 0.05) and distal [(CH2O/CH2O+CNa) X 100:69.9 +/- 3.3 versus 85.8 +/- 3.4%, p less than 0.01] tubular sodium reabsorption.

Postnatal Changes in Urinary Prostaglandin E Excretion in Premature Infants

Urinary PGE excretion was measured by radioimmunoassay in a group of 11 healthy premature infants with a mean birth weight of 1,502 g (range 1,050--1,950 g) and a mean gestational age of 31.6 weeks (range 29--33 weeks), respectively. Measurements were made on the 7th day of life and at weekly intervals thereafter until the 5th week of life. It was demonstrated that urinary PGE excretion significantly increased from the very low level of 6.23 +/- 0.70 ng/24 h (mean +/- SE) on the 7th day to a value of 17.99 +/- 3.53 ng/24 h by the end of the 3rd week (p less than 0.005). Later on it remained practically unchanged. It is suggested that its rapid increase during the first 3 weeks of life may be the result of the highly elevated activity of the renin-angiotensin-aldosterone system and it may play a role in controlling renal blood flow.

Postnatal Development of Plasma Prolactin Level in Premature Infants with and without NaCl Supplementation

The role of prolactin in the adaptation of premature infants to the alterations of sodium balance was investigated by measuring plasma prolactin levels serially in 7 low birth weight, premature infants with (group I) and without (group II) NaCl supplementation. The study was performed on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3-5 mEq/kg/day and 1.5-2.5 mEq/kg/day for 8-21 days and 22-35 days, respectively. It was demonstrated that before NaCl supplementation plasma prolactin concentration was similarly elevated in the two groups (6,490 +/- 1,291 mU/l in group I versus 7,661 +/- 1,094 mU/l in group II), and without supplementation it remained at about the same level throughout the study. When supplemental sodium was given, the plasma prolactin level declined with age at a steady rate to the mean value of 3,516 +/- 502 mU/l by the end of 5th week. In the 3rd-5th weeks it proved to be significantly higher in group II than in group I. It is concluded that physiological sodium depletion may account for the prolonged hyperprolactinemia and prolactin might have some importance in the control of sodium homeostasis in low birth weight, premature infants.

The effect of metoclopramide administration on electrolyte status and activity of renin-angiotensin-aldosterone system in premature infants

ABSTRACT: The present study has been carried out to define whether endogenous dopamine contributes to the regulation of renal sodium handling and the function of the renin-angiotensin-aldosterone system in low birth weight premature infants. Twelve premature infants with mean birth weight of 1420 g and mean gestational age of 29.2 wk were given metoclopramide (MTC) in a dose of 0.1 mg/ kg/day to treat delayed gastric emptying, regurgitation, and abdominal distension at the age of 17-23 days. Infants were kept on either a low (2-3 mEq/kg/day) or high (4-7 mEq/kg/day) sodium diet to modulate activity of RAAS. Prior to and after a 3-day period of MTC administration, blood samples were taken, and in six male infants 24-h urine collections were made to determine plasma and urine electrolytes, plasma renin activity, plasma aldosterone concentration, and urinary aldosterone excretion. We demonstrated that plasma sodium and potassium concentrations and plasma renin activity were not altered by MTC. On the other hand, in response to MTC, there was a significant increase in urinary sodium excretion (1.8 ±0.3 versus 2.3 ±0.3 mEq/kg/day) and a decrease in potassium excretion (1.2 ±0.2 versus 0.8 ±0.1 mEq/kg/day); plasma aldosterone concentration and urinary aldosterone excretion decreased significantly from initial values of 2101 ±274 pg/ml and 2.91 ±0.52 μg/day to 1500 ±207 pg/ml (p < 0.01) and 2.21 ±0.43 μg/day (p < 0.01), respectively, after MTC. These alterations were independent of the pretreatment hormone levels. We conclude that in low birth weight premature infants endogenous dopamine has no influence on plasma renin activity and enhances rather than inhibits aldosterone production and renal tubular sodium reabsorption.

Plasma Prolactin Levels in Full-Term Newborn Infants with Idiopathic Edema: Response to Furosemide

In an attempt to explore the possible role of prolactin (PRL) in the control of neonatal electrolyte homeostasis, this study has been carried out to compare plasma electrolyte concentrations, urine volume and urinary electrolyte excretion as well as plasma PRL levels in healthy full-term neonates with idiopathic edema prior to and after furosemide treatment. No differences in plasma sodium and potassium were demonstrated, edematous neonates, however, had less urine volume and sodium excretion than neonates without edema. Plasma PRL proved to be significantly higher in the edematous group (11.0 +/- 1.9 vs. 4.2 +/- 3.1 U/l, p less than 0.01) but it remained unaltered by furosemide challenge (8.5 +/- 1.5 U/l) in spite of the marked elevation of urine flow and sodium excretion. It is concluded that PRL may be involved in the control of the volume and composition of the body fluids in the neonate but further studies are needed to define the effect of changes in body composition on the neonatal PRL secretion.

Induction of ovulation with phenobarbital in anovulatory states: a preliminary report

Phenobarbital was used as an enzyme-inducing drug in 12 women with anovulatory cycles and menstrual irregularities. 5 women had Stein-Leventhal syndrome and 7 had secondary amenorrhea. 200 mg of phenobarbital was given for 6 weeks and 50 mg for the remaining 4 1/2 months. Ovulatory cycles occurred in 11 women during treatment. Plasma cortisol levels decreased significantly after treatment (p<.005) and pregnanediol excretion increased markedly in all the women after treatment. 1 patient became pregnant 6 months after treatment; others developed rapidly growing bilateral ovarian cysts or regression of hirsutism. The mechanism of phenobarbital action was not discovered.

Changes in the Alkaline Phosphatase Activity of Granulocytes from the First to the Sixth Day of Life in Newborns

GAP activity was studied in 40 newborns, from the first to the sixth day of life after normal pregnancy and labor. Evaluation of GAP activity was performed in stained blood smears by the method of Kaplow. The results of this study indicate, that GAP activity on the first day of life was higher (121.0 +/- 16.7 GAP score) than on the sixth day (68.6 +/- 12.0 GAP score). The authors, discussing the possible cause of the increased alkaline phosphatase activity in granulocytes during the first day of life, cannot exclude the possibility that the GAP activity is influenced by estrogens of maternal origin.

49 MATERNAL METOCLOPRAMIDE TREATMENT AND PROLACTIN CONCENTRATION IN HUMAN MILK

The breast milk prolactin (PRL) has been claimed to play a role in the control of electrolyte composition of the milk. Since metoclopramide has been shown to increase milk production in humans, we have made an attempt to investigate the production, the PRL and sodium concentrations in milk with and without maternal metoclopramide treatment (5 days, 30 mg/day). Both groups consisted of 11 mothers and their full-term newborn infants. The daily milk production was significantly higher in the treated group (276.4 ± 36.6 vs 150.9 ± 25.3 ml/day, p<0.01). The PRL measured by RIA was similar in the milk samples of the metoclopramide treated and control groups (80.5 ± 17.7 vs 90.7 ± 27.3 ng/ml). The sodium concentration in the milk of mothers taking metcclopramide was 22.1 ± 1.6 mmol/l and 24.3 ± 3.2 mmol/l in the control group (p=0.59). On the 5th postnatal day the plasma PRL of the newborns of mothers treated with metoclopramide does not differ from the value of the control babies (29.8 ± 2.6 vs 30.7 ± 2.4 ng/ml) indicating that the amount of metoclopramide transferred into the milk has no apparent influence on the hypothalamo-hypophyseal axis of the neonate.In conclusion: the maternal metoclopramide treatment augments the milk production without having any effect on the PRL and sodium concentration of human “mature” milk.