Effect of phosphate supplementation to breast fed very low birthweight infants on urinary calcium excretion, serum immunoreactive parathyroid hormone and plasma 1,25-dihydroxy-vitamin D concentration

The effect of two doses of Phosphorus (P) supplementation to pooled breast milk (BM): 0.48 and 0.800 mmol/kg/24 h given during the second month of life was evaluated in 22 very low birthweight infants. The concentration of calcium and phosphorus in serum and urine, the serum concentration of immunoreactive parathyroid hormone (iPTH) and the plasma 1,25-dihydroxy-vitamin D concentration (1,25-OH-D) were compared to the values in 19 control infants. The mean +/- SD concentrations in control infants and adults are 63 +/- 18 microliters Eq/ml for serum iPTH and 85 +/- pmol/l for plasma 1,25-OH-D. With 0.48 P supplementation, urinary Ca (UCa) excretion (median and range) 0.238 mmol/kg/24 h (0.105-0.520) was lower than in the control group 0.288 (0.205-0.679) (p less than 0.05); the reduction of UCa was larger with 0.8 P supplementation: 0.047 (0.023-0.163) (p less than 0.01). P supplementation induced no change in serum Ca concentration but a slight and significant increase in serum iPTH was observed only with the 0.8 P supplementation: 55 microliters Eq/ml (less than 25-80) (p less than 0.05). With 0.8 P supplementation there was no significant change of plasma 1,25-OH-D concentration: 173 pmol/l (106-271) vs. 255 (132-293) in the control group. These data show that with 0.8 P supplementation, the hypercalciuria in BM-fed infant disappears without secondary hyperparathyroidism, but without any change in plasma 1,25-OH-D concentration.     

LATE EVOLUTION OF SERUM IMMUNOREACTIVE PARATHYROID HORMONE, CALCITONIN AND PLASMA 25-HYDROXY CHOLECALCIFEROL CONCENTRATIONS IN VERY LOW BIRTHWEIGHT INFANTS

ABSTRACT. Sunn, L., Rigal, D., Krederich, A. and Lahet, C. (Department of Neonatology, Hopital Debrousse and Laboratory of polypeptide hormones, Hopital E. Herriot, Lyon, France). Late evolution of serum immunoreactive parathyroid hormone, calcitonin and plasma-hydroxycholecalciferol concentrations in very low birthweight infants. Acta Paediatr Scand, 70:479,.–The plasma concentrations of 25-hydroxycholecalciferol (25-OH-CC), immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) were measured at the age of 30 and 66 days in thirteen preterm neonates (birthweight: 970 to 1300 g). At the age of 30 days when all infants were fed only with breast milk (BM) serum iCT and iPTH levels were normal. During the second month 7 infants were fed with BM only (control group) and 6 infants were supplemented with formula (supplemented group). At the age of 66 days, mean ± S.D. serum iPTH concentration was higher in the supplemented group than in the control group: 169±79 vs. 60±33 μlEq/ml (p≤0.01). Serum iCT levels remained undetectable (<150 pg/ml) in both groups. Plasma 25-OH-CC concentrations were normal and similar in both groups. Serum iPTH concentrations were positively correlated with phosphorus intake and negatively correlated with calcium intake from BM only. The results suggest that secondary hyperparathyroidism can be detected in very low birthweight infants supplemented with a formula, probably because of a phosphorus load or decreased intestinal absorption of calcium.     

CONGENITAL HYPERPARATHYROIDISM AND VITAMIN D DEFICIENCY SECONDARY TO MATERNAL HYPOPARATHYROIDISM

Abstract. A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 μlEq/ml (Normal: <50 μlEq/ml). A very low plasma 25-OH-D concentration (<4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remainded high 3 weeks before (210 μlEq/ml) were found to be normal one week after this vitamin D load (37 μlEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.     

EFFECT OF INTRAVENOUS HYDROCORTISONE ADMINISTRATION ON GLUCOSE HOMEOSTASIS IN SMALL FOR GESTATIONAL AGE INFANTS

Abstract. The effects of I.V. hydrocortisone (H) (10 mg/kg) on glucose homeostasis were evaluated at 25 to 85 hours of age in 14 infants who were small for gestational age (SGA) in comparison to 17 control SGA infants. Three hours after H administration, higher levels of plasma glucose than in controls were detected (mean ±S.E.M.): 4.78±0.2 vs. 2.88±0.2 mmol/1 ( p <0.01), while lower levels were found for blood pyruvate (38±7 vs. 89±12 μmol/l— p <0.01), plasma insulin (6.4±0.5 vs. 12±0.8 μIU/ml— p <0.05) and plasma glucagon (62.25±6.6 vs. 81.6±6.6 pmol/l— p <0.05). Three hours after H administration, I.V. injection of l -alanine (150 mg/kg) produced a significant rise over baseline of plasma glucose concentration from 4.78±0.2 to 5.94±0.2 mmol/l at 50 min ( p <0.05), whereas no significant change was observed in controls. There was no significant change in plasma glucagon and insulin concentrations after l -alanine injection in either group. These results show that in SGA infants primed with H, the rise of plasma glucose concentration after l -alanine administration is observed with low plasma insulin levels and without stimulation of glucagon secretion. They suggest that H induced a reduced peripheral utilization of glucose by lowering the plasma levels of insulin and a production of glucose from alanine through gluconeogenesis.     

Effect of Calcium Supplementation on Calcium and Phosphorus Balance and Renal Net Acid Excretion in Preterm Infants Fed a Standard Formula

ABSTRACT. In 19 preterm infants fed a standard formula for prematures (calcium (Ca) 13.5 mmol/l; phosphorus (P) 12.9 mmol/l), biochemical parameters of blood, serum and urine were determined before and during supplementation with Ca-L-lactate (final Ca concentration 20 mmol/l). In 8 preterm boys Ca and P balance were evaluated in addition. During Ca supplementation, the serum Ca levels, urine pH (without supplement 6.31, with supplement 6.73), and calciuria (46 μmol/kg/d vs. 98 μmol/kg/d) were increased, and urinary P (1.05 mmol/kg/d vs. 0.65 mmol/kg/d) and net acid excretion (1.70 mEq/kg/d vs. 0.89 mEq/kg/d) were decreased. Balance studies showed increased net intestinal Ca absorption during supplementation (37 % vs. 56 %) as well as improved Ca (0.8 mmol/kg/d vs. 1.85 mmol/kg/d) and P retention (0.97 mmol/kg/d vs. 1.45 mmol/kg/d). These data show that increased Ca intake given to optimize the Ca:P ratio improves mineral retention in preterm infants fed a standard formula. Ca and P intake should be thoroughly balanced to avoid side-effects like hypercalciuria or high renal net acid excretion.     

CONGENITAL RICKETS Study of the Evolution of Secondary Hyperparathyroidism

Abstract. A case of congenital rickets of nutritional origin is described in a light-for-date premature infant (gestational age 34 weeks, birthweight 1100 g). X-rays of the long bones showed spread, frayed and cupped metaphyses at birth and at the age of 16 days. Serum calcium was 8.2 mg/100 ml, phosphorus 3.4 mg/100 ml and alkaline phosphatase (A.P.): 323 IU/ml (N≤200) at the age of 3 days. Very high level of serum immunoreactive parathyroid hormone (iPTH) was found at the age of 16 days=295 μlEq/ml (N≤50). Evidence of maternal vitamin D deficiency was demonstrated by low plasma 25-hydroxycholecalciferol (25-OH-CC): 1.0 ng/ml (N: 13.2±4.2) soon after delivery; it was found to be normal (10.2 ng/ml) six months later. Ca infusion (15 mg/kg/3 h) resulted in a marked fall of serum iPTH (280 to 84 μlEq/ml). Administration of vitamin D₂ (2400 IU/day for 10 days) induced some healing of the metaphyses; A. P. remained elevated (400 IU/ml); plasma 25-OH-CC was normal 10.2 ng/ml and serum iPTH was 115 μlEq/ml. When 25-OH-CC was given orally for ten days (15 μg/day), plasma 25-OH-CC rose to 64.5 ng/ml with a minor change of serum iPTH (94 μlEq/ml); X-rays of the bones showed osteoporosis. These results suggest a reduced conversion of 25-OH-CC into 1–25-(OH)₂-CC.     

THE PLASMA LEVELS OF 25-HYDROXYVITAMIN D IN PATIENTS WITH VARIOUS LIVER DISEASES AND THE RESPONSE OF 25-HYDROXYVITAMIN D TO VITAMIN D TREATMENT

ABSTRACT. The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D₂ for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5±3.7 (S.E.) ng/ml to 34.0±6.8 (S.E.) ng/ml after administration of vitamin D₂ in controls ( p <0.05). The mean plasma level of 25-OH-D also increased from 8.0±2.1 (S.E.) ng/ml to 22.1±2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group ( p <0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect the plasma levels of 25-OH-D.     

High Total and Free 1,25-Dihydroxyvitamin D Concentrations in Serum of Premature Infants

ABSTRACT. We investigated the relationship between serum total and free 1,25-dihydroxyvitamin D (1,25-OH₂D) and the biochemical regulation of 1,25-OH₂D production in premature infants. We measured 1,25-OH₂D, vitamin D binding protein and related biochemical parameters and calculated the free 1,25-OH₂D index in serum of 17 premature infants (birthweight 810–1700 g; gestational age 31–36 weeks) on two different occasions defined by body weight (Study A: 1750–1850 g, Study B: 2100–2200 g). Dietary calcium (Ca) intake was 1,5 or 2,6 mmol/kg/d, phosphorus (P) intake 1,7 mmol/kg/d and vitamin D intake 1000 IU/d. Biochemical results were similar in infants with different Ca intakes and all were within reference ranges. Concentrations of vitamin D binding protein (Study A 0.15±0.03 g/1, Study B 0.14±0.03 g/1; ± SD) were lower, concentrations of 1,25(OH)₂D (Study A 180±67 pmol/1, Study B 216±53 pmol/1) were higher, and consequently the free 1,25-OH₂D index (Study A 6.6±2.7, Study B 8.8±2.6) was 4 to 6 times higher than in previously studied term infants. 1,25-OH₂D and the free 1,25-OH₂D index increased significantly with age and were not correlated with serum P or parathyroid hormone. The data indicate that in premature infants with normal biochemical parameters of Ca and P metabolism elevated concentrations of 1,25-OH₂D signify an increased fraction of free 1,25-OH₂D and that increased production of 1,25-OH₂D is not due to hypophosphatemia or hyperparathyroidism.     

COPPER DEFICIENCY AND HYPOCALCEMIC RICKETS IN A SMALL-FOR-DATE INFANT

ABSTRACT. A case of copper deficiency associated with hypocalcemia, radiological features of rickets and hyperparathyroidism is described in a small-for-date infant (gestational age 39 weeks, B.W. 1240 g). Neonatal serum copper (Cu) levels were found between 223 and 138 μmol/l. She was given daily 2 400 U of vitamin D₂ and a load dose of 80 000 IU at the age of 55 days. At the age of 79 days, X-rays of the legs and wrist showed spread, cupped and frayed metaphyses. Serum Ca was 1.35 mmol/1, P=0.99 mmol/1 with high alkaline phosphatases (A.P.) 590 II/ml. But plasma level of 25 hydroxycholecalciferol (25-OH-CC) was normal = 10.8 ng/ml. Serum Cu was low=3.14 μmol/l and serum immunoreactive parathormone (iPTH) level was elevated: 520 μlEq/ml (N±100). Administration of vitamin D₂ (15 mg) induced an immediate normalization of serum Ca, normal serum iPTH (68 μlEq/ml) in one month, normal X-rays in two months and normal A.P. in four months. Serum Cu and ceruloplasmin levels increased slowly without any supplementation to subnormal levels at the age of eight months (14.9 and 1.65 μmol/1. Serum Cu concentrations were found to be normal (16.0–33.7 μmol/1) in five children with hypocalcemic rickets. These results suggest a role of Cu deficiency in the occurrence of this transient vitamin D-resistant rickets.     

Estimation of Digoxin Dosage in VLBW Infants Using Serum Creatinine Concentrations

ABSTRACT. Digoxin steady state plasma concentrations (C_ss) and the corresponding serum creatinine concentrations were studied in 17 VLBW infants. Birth weight was in the range of 760-1500 g (mean 1068 g), gestational age ranged from 26 to 32 weeks (mean 28.7 weeks). Digoxin steady state plasma concentrations were found in the range of 0.5-6.5 μg/ml (mean 1.88 μg/ ml) during maintenance therapy with 1.6-8.4 μg/kg BW/24 h (mean 4.4 μg/kg BW724 h) given in two divided doses intravenously. No digoxin-like immunoreactive substance could be detected in the plasma of 18 infants (10 patients with a birth weight <1500 g, 8 patients with a birth weight of 2100-4 730 g) that were not treated with digoxin. The calculated digoxin clearance ranged from 0.38-4.03 ml/min/kg BW. Serum creatinine concentrations were found in the range of 35-274 μmol/l (0.4-3.1 mg/100 ml). A hyperbolic correlation may be derived from the digoxin clearance and the corresponding serum creatinine concentration. A linear relationship was observed between the dose normalized digoxin concentrations (y=C_ss/dose in 24 h) and the respective creatinine concentrations x (v=0.52x-0.05; n=17; 5=0.24; r=0.86; p<0.01). According to this equation we suggest a dosing schedule for digoxin in VLBW infants with impaired renal function. Digoxin maintenance dose is derived from the digoxin target and the creatinine serum concentration. This dose recommendation proved reliable on four VLBW infants (birth weight 770-1260 g) with decreased renal function.     

High total and free 1,25-dihydroxyvitamin D concentrations in serum of premature infants

We investigated the relationship between serum total and free 1,25-dihydroxyvitamin D (1,25-OH2D) and the biochemical regulation of 1,25-OH2D production in premature infants. We measured 1,25-OH2D, vitamin D binding protein and related biochemical parameters and calculated the free 1,25-OH2D index in serum of 17 premature infants (birthweight 810-1700 g; gestational age 31-36 weeks) on two different occasions defined by body weight (Study A: 1,750-1,850 g, Study B: 2,100-2,200 g). Dietary calcium (Ca) intake was 1,5 or 2,6 mmol/kg/d, phosphorus (P) intake 1,7 mmol/kg/d and vitamin D intake 1,000 IU/d. Biochemical results were similar in infants with different Ca intakes and all were within reference ranges. Concentrations of vitamin D binding protein (Study A 0.15 +/- 0.03 g/l, Study B 0.14 +/- 0.03 g/l; means +/- SD) were lower, concentrations of 1,25 (OH)2D (Study A 180 +/- 67 pmol/l, Study B 216 +/- 53 pmol/l) were higher, and consequently the free 1,25-OH2D index (Study A 6.6 +/- 2.7, Study B 8.8 +/- 2.6) was 4 to 6 times higher than in previously studied term infants. 1,25-OH2D and the free 1,25-OH2D index increased significantly with age and were not correlated with serum P or parathyroid hormone. The data indicate that in premature infants with normal biochemical parameters of Ca and P metabolism elevated concentrations of 1,25-OH2D signify an increased fraction of free 1,25-OH2D and that increased production of 1,25-OH2D is not due to hypophosphatemia or hyperparathyroidism.     

VITAMIN D NUTRITIONAL STATUS OF PREMATURE INFANTS SUPPLEMENTED WITH 500 IU VITAMIN D2 PER DAY

ABSTRACT. The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D₂ per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D₃ fortified formula. Gestational age was 32.2±2.4 weeks (mean ± 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values ( r =0.81). The infants' mean plasma concentration increased from 30.6±13.7 nmol/l (mean±1 SD) after birth to 46.3±10.5 nmol/l after 9±1 days ( p <0.0025), and to 65.3±16.6 nmol/l after 37±10 days of vitamin D₂ treatment ( p <0.0005). 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined separately, and it appeared that the rise was accounted for by the D₂ fraction while 25-hydroxyvitamin D₃ concentrations were unchanged. The results demonstrate that vitamin D₂ is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.     

THE CONCENTRATIONS OF TOTAL CORTISOL AND CORTICOSTERONE IN MIXED CORD PLASMA

ABSTRACT: Homoki, J., Teller, W. M., Tschürtz, D., and Fazekas, A. T. A. (Department of Paediatrics, Division of Endocrinology and Metabolism, University of Ulm/Donau, BRD). The concentrations of total Cortisol and corticosterone in mixed cord plasma. Acta Paediatr Scand, 64:587, 1975.–Cortisol and corticosterone were determined in mixed umbilical cord plasma of 43 healthy full-term newborns. The method consisted of a combined thin-layer chromatographic-ftuorimetric procedure which proved to be specific and reliable. The mean concentration in cord plasma of Cortisol was 10.6±4.9 μ.g/100 ml, of corticosterone 1.8±0.8 μg/100 ml. The mean ratio cortisol/corticosterone F/B was 6.3±2.5. Neither the duration nor the time of day of delivery appeared to influence the concentration of Cortisol or corticosterone in umbilical cord plasma. Also, there was no significant difference between male and female infants. In 18 instances of a pathological course of gestation and/or delivery the mean Cortisol level was 9.1±4.7 μg/ml, the mean corticosterone level 2.2±9 μg/100 ml. The mean F/B ratio was slightly but not significantly decreased (4.2±1.4 μg/100 ml; p >0.05). It is speculated that the high corticosterone concentration in umbilical cord plasma reflects a defect in Cortisol biosynthesis (17α-hydroxylase deficiency) in the newborn, compared with later life.     

Neonatal hypercalcemia in preterm infants fed with human milk

Hypercalcemia (serum Ca greater than or equal to 2.83 mmol/l) was detected in 10 premature infants (gestational age: 31-37 weeks and birthweight: 1100-1950 g). All were fed with pooled human breast milk. Urinary Ca excretion was high (greater than 0.200 mmol/kg/24 h) in all but one infant while serum phosphorus (P) concentration and urinary P excretion were low. Serum immunoreactive parathyroid hormone and plasma 25-hydroxyvitamin-D concentrations were normal. A significant positive correlation was found between serum Ca concentration and urinary Ca excretion, and a negative correlation between serum Ca concentration and serum P concentration or urinary P excretion. Hypercalcemia disappeared spontaneously in two patients, was corrected by a humanized milk in three patients and by P supplementation in five patients. These data suggest that neonatal hypercalcemia is related to P depletion induced by human breast milk in premature infants.     

Lipid and apolipoprotein levels and enteral nutrition in very low-birth-weight preterm infants

Lipid, lipoprotein cholesterol and apolipoprotein A-I, A-II and B levels were determined in 10 very low-birth-weight (birth weight 1279 ± 144 g; gestational age 29.2 ± 1.2 weeks, mean ± SD) preterm infants on postnatal days 3, 10 and 21. Feeding with pooled human milk began on day 3 ± 1 and by day 10 all infants were exclusively enterally fed. Both triglyceride and total cholesterol levels increased significantly from day 3 to day 10 (0.84 ± 0.28 versus 1.53 ± 0.72 and 2.42 ± 0.47 versus 3.24 ± 0.80, mmol/l, respectively) ( p <0.01); thereafter no further increase was observed. The increase in total cholesterol level was primarily due to a significant enhancement of very low-density lipoprotein and low-density lipoprotein cholesterol (1.52 ± 0.34 versus 2.29 ± 0.73 mmol/l, p< 0.01). Apo A-I, A-II and B levels did not change between day 3 and day 10. From day 10 to day 21, however, a significant increase in apo A-I concentration was noted (0.57 ± 0.20 versus 0.87 ± 0.17 g/l, p< 0.01), whereas apo A-II levels increased significantly from day 3 to 21 (0.15 ± 0.03 versus 0.27 ± 0.08 g/l, p<0.01). No change in apo B level was seen.     

Role of atrial natriuretic peptide in sodium homeostasis in premature infants

To examine the possible involvement of atrial natriuretic peptide (ANP) in sodium homeostasis in premature infants, two groups of low birth weight infants with different dietary sodium regimens were studied. Sodium balance and plasma concentration of ANP were measured at weekly intervals for 5 weeks. At 1 week of age the study was started by dividing infants into two groups, group 1 with low and group 2 with increased sodium intake. Mean plasma concentrations of ANP were 47.7 +/- 7.6 and 51.4 +/- 9.5 fmol/ml, respectively. A steady decrease in plasma ANP concentration to 18.8 +/- 2.9 fmol/ml was observed in infants with sodium intake 1.5 mmol/kg/d (group 1), which was related to the decrease in serum sodium concentration in this group. In contrast, supplementation with NaCl 4.6 mmol/kg/d (group 2) was associated with a 30% increase in plasma ANP concentration, significantly different (P less than 0.025) from that in infants not given supplement, and was also higher than the values in full-term neonates. Our data suggest that altered sodium homeostasis induces regulatory changes in plasma ANP levels. ANP may provide a sensitive and important hormonal system for the control of sodium balance, even in premature neonates.     

Effect of calcium supplementation on calcium and phosphorus balance and renal net acid excretion in preterm infants fed a standard formula

In 19 preterm infants fed a standard formula for prematures (calcium (Ca) 13.5 mmol/l; phosphorus (P) 12.9 mmol/l), biochemical parameters of blood, serum and urine were determined before and during supplementation with Ca-L-lactate (final Ca concentration 20 mmol/l). In 8 preterm boys Ca and P balance were evaluated in addition. During Ca supplementation, the serum Ca levels, urine pH (without supplement 6.31, with supplement 6.73), and calciuria (46 mumol/kg/d vs. 98 mumol/kg/d) were increased, and urinary P (1.05 mmol/kg/d vs. 0.65 mmol/kg/d) and net acid excretion (1.70 mEq/kg/d vs. 0.89 mEq/kg/d) were decreased. Balance studies showed increased net intestinal Ca absorption during supplementation (37% vs. 56%) as well as improved Ca (0.8 mmol/kg/d vs. 1.85 mmol/kg/d) and P retention (0.97 mmol/kg/d vs. 1.45 mmol/kg/d). These data show that increased Ca intake given to optimize the Ca:P ratio improves mineral retention in preterm infants fed a standard formula. Ca and P intake should be thoroughly balanced to avoid side-effects like hypercalciuria or high renal net acid excretion.     

EFFECT OF INTRAVENOUS L-ALANINE ADMINISTRATION ON PLASMA GLUCOSE, INSULIN AND GLUCAGON, BLOOD PYRUVATE, LACTATE AND BETA-HYDROXYBUTYRATE CONCENTRATIONS IN NEWBORN INFANTS Study in Term and Preterm Newborn Infants

ABSTRACT. Ten term and eleven preterm newborn infants with appropriate weights for their gestational age were infused for one minute with L-alanine (150 mg/kg) at the age of 29 to 76 hours (mean 48 hours) and circulating levels of glucose, lactate, pyruvate, d -betahydroxybutyrate ( d -BOHB), insulin and glucagon were monitored. Plasma glucose concentrations increased from 2.7±0.16 (mean±S.E.M.) to 3.7±0.2 mmol/1 after 50 min (p±0.01) in term infants. In preterm infants, after an initial decrease of the glucose level from 3.1±0.16 to 2.6±0.16 mmol/1 (p±0.05), it returned to the baseline level at 50 min: 3.0±0.2 mmol/1. The blood concentration of d -BOHB decreased in term infants from 192±37 to 112±6 μM/1 (p±0.01) after 40 min. In preterms, its decrease was not significant (p±0.05). Plasma glucagon levels rose from 53±5 to 70±8 pmol/1 after ten minutes (p±0.01) in term infants and from 61±6 to 75±9 after 20 min (p±0.01) in preterm infants. There were no significant changes in plasma insulin concentrations in either group. Forty minutes after l -alanine infusion, I/G ratios were lower in preterm infants (1.26±0.14) than in term infants (1.71±0.25) (p±0.01). There was no relationship between the glycemic responses to l -alanine and the basal levels of d -BOHB.
The data suggest that the glycemic effect of l -alanine infusion and circulating glucagon depends upon a specific stage in maturation. The antiketogenic effect of l -alanine infusion is observed in term infants as in adults.     

Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 ± 14 days) who were randomly assigned to receive either rHuEPO 900 U kg^-1 week^-1 with 6 mg kg^-1 day^-1 of iron for 4 weeks ( n= 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10⁹μgl^-1), serum ferritin (μg1^-1) and iron (μmol 1^-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 ± 5.6 versus 6.2 ± 3.2 mU ml^-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 ± 0.03 versus 0.28 ± 0.05 ( p = O.001). rHuEPO therapy increased the reticulocyte count from 130 ± 70 to 430 ± 200 ( p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and it-on levels from 321 ± 191 to 76 ± 58 $uMgl^-1 ( p = 0.04) and from 18 ± 5 to 13 ± 4 μmoll^-1 ( p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.     

Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism.

A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.