Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic L-amino acid decarboxylase deficiency.

Aromatic L-amino acid decarboxylase (AADC) is a vitamin B 6 requiring enzyme involved in the biosynthesis of the neurotransmitters dopamine (DA) and serotonin. Lack of AADC leads to a combined deficiency of the catecholamines DA, norepinephrine (NE), epinephrine (E) as well as of serotonin. Here we describe premature twins who presented with severe seizures, myoclonus, rotatory eye movements and sudden clonic contractions. The patients showed an improvement of the clonic contractions under vitamin B 6 supplementation but died in the third week of life. In CSF and urine a biochemical pattern indicative of AADC deficiency was revealed. Concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were decreased, in association with increased concentrations of 3-ortho-methyldopa (3-OMD) in CSF and significantly increased vanillactic acid in urine. The AADC enzyme substrates L-dopa and 5-hydroxytryptophan (5-HTP) were elevated in CSF. Elevated concentrations of threonine as well as of an unidentified compound in CSF rounded off the biochemical pattern. AADC activity was found to be increased in plasma and deficient in the liver. Molecular studies effectively ruled out a genetic defect in the AADC gene. The basis for the epileptic encephalopathy in the twins may be located in the metabolism of vitamin B 6 and remains to be defined.

Neonatal outcome in small for gestational age infants: do they really better?

BACKGROUND: There still is a controversy as to the neonatal outcome of small for gestational age (SGA) infants compared to a appropriate for gestational age (AGA) preterm infants. As a part of a randomized multicenter trial on timing of bovine surfactant therapy, we aimed at investigating short-term outcome variables in SGA-infants compared with AGA-infants. METHODS: SGA-infants were classified weighing below the 10th percentile at birth and were compared to AGA-infants in terms of prenatal and neonatal characteristics and neonatal outcome. RESULTS: A total of 317 infants were enrolled, 59 SGA- and 258 AGA-infants. Both groups did not differ in gestational age, however, SGA-infants had a lower birth weight. Preterm premature rupture of fetal membranes was observed more frequently in AGA-, preeclampsia in SGA-infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary airleaks and days on the ventilator did not differ between both groups. However prolonged nasal CPAP, supplemental oxygen therapy and chronic lung disease at 28 days and 36 weeks was diagnosed more often in SGA-infants. Furthermore mortality was significantly higher in SGA-infants as well as total NICU and total hospital days. CONCLUSION: As SGA-infants have an increased mortality rate and an increased risk for developing chronic lung disease, further studies should focus on prevention of intrauterine growth restriction and its complications.

Early versus late surfactant treatment in preterm infants of 27 to 32 weeks' gestational age: a multicenter controlled clinical trial.

OBJECTIVE: To investigate whether early (<1 hour after birth) surfactant administration would be superior to late treatment (2-6 hours after birth) in preterm infants. STUDY DESIGN: Randomized controlled multicenter clinical trial. PATIENTS AND METHODS: Prenatal randomization of all infants of 27 to 32 weeks' gestational age stratified by center after parental informed consent. Early treatment: 100 mg/kg body weight bovine surfactant (SF-RI1, Alveofact; Dr K. Thomae, Biberach, Germany) to infants requiring intubation after birth. Late treatment: identical dosage to infants requiring intubation up to 6 hours of age with the fraction of inspired oxygen >0.4 at 2 to 6 hours after birth. Primary endpoint: the time on mechanical ventilation. Main secondary endpoints: mortality, bronchopulmonary dysplasia, intraventricular hemorrhage >/=grade III, and periventricular leukomalacia. Sample size calculation: at least 280 infants to prove superiority of either approach (alpha = 0.05; beta = 0.90). RESULTS: Enrollment of 317 infants, 154 randomized to early surfactant treatment, 163 to late surfactant treatment. Study infants (all following data intent-to-treat groups: early versus late surfactant) were similar with respect to: gestational age, 29.5 +/- 1.6 weeks versus 29.7 +/- 1.6 weeks; birth weight, 1227 +/- 367 g versus 1269 +/- 334 g; and the rate of prenatal corticosteroids, 79.9% versus 72.8%. Duration of mechanical ventilation: 3 days (0-8) versus 2 days (0-6) (median, interquartile); further outcome variables: death or bronchopulmonary dysplasia (day 28) 25.9% versus 23.9%, mortality 3.2% versus 1.8%, intraventricular hemorrhage >/=grade III 6.5% versus 3.7%, and periventricular leukomalacia 5.2% versus 5.5% not differing statistically. CONCLUSION: In preterm infants with a high rate of prenatal glucocorticoids, early surfactant administration was not found to be superior to late treatment in terms of relevant outcome variables.

Modified cow's milk formula with reduced renal acid load preventing incipient late metabolic acidosis in premature infants.

BACKGROUND: Premature infants receiving alimentation with cow's milk formulas are at a considerably high risk of developing incipient late metabolic acidosis, an early stage in the development of manifest late metabolic acidosis. Is it possible to reduce this risk by modification of the composition of a standard formula? METHODS: The mineral composition of a cow's milk preterm formula A was modified (formula B) with the aim of reducing the alimentary load to that of human milk. 160 premature infants were fed either mother's milk (n = 50) or the modified formula B (enriched with sodium and potassium) (n = 110), and their urine pH was tested twice a week. Randomly collected subgroups of infants were studied in detail for nutrient balances. The results were compared with earlier observations of 282 premature infants fed either mother's milk (n = 28) or the standard formula A (n = 254). RESULTS: Incipient late metabolic acidosis was observed in nine of 78 premature infants receiving mother's milk, 53 of 254 premature infants receiving the standard formula A, and only one of 110 premature infants fed the modified formula B. Net acid excretion was 0.58 mmol/kg/day in 11 premature infants receiving alimentation with the modified formula B compared with 1.73 mmol/kg/day in 23 premature infants fed formula A. This reduction was mainly due to an increased alkali excess (sodium + potassium-chloride) in intake and urine. CONCLUSIONS: Reduction of renal acid load with the modified formula B had a preventive effect on the rate of development of incipient late metabolic acidosis in premature infants.

Alkali therapy versus sodium chloride supplement in low birthweight infants with incipient late metabolic acidosis.

Two hundred and eighty-two patients with birthweights below 2.0 kg were routinely screened for spontaneous development of maximum renal acid stimulation (urine-pH < 5.4). Sixty episodes in 53 patients of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to oral therapy with 2 mmol/kg/day of either NaHCO3 or NaCl for 7 days. All 27 patients on NaHCO3 therapy, but only 15 from 26 patients on NaCl therapy, showed an increase in urine pH values, combined with a relatively high gain in body weight and a tendency to increased N-assimilation. Eleven patients on NaCl therapy showed persistent maximal renal acid stimulation on all 7 days with possibly lower weight gain and no clear change in N-assimilation. Thus, in patients with incipient late metabolic acidosis, NaCl therapy is not as beneficial as NaHCO3 therapy.

[Supplementation of premature infant nutrition with calcium and phosphor for improving mineral supply of premature and small-for-gestational age newborn infants]. / Anreicherung einer Frühgeborenenmilchnahrung mit Kalzium und Phosphor zur Verbesserung der Mineralstoffversorgung Früh- und Mangelgeborener.

A standard preterm formula was supplemented with calcium (Ca) and phosphorus (P) (F-CaP: Ca 87 mg/dl, P 43 mg/dl) and compared to the non-supplemented form (F: Ca 62 mg/dl, P 36 mg/dl). VLBW and small-for-gestational-age infants (n = 79) were included in the study which was performed to look for adverse effects and to decide about a reasonable start and duration of supplementation. In preterm infants with a birth weight lower than 1500 g and a body weight of more than 2000 g, the additional supplementation with Ca and P lead to a significant higher Ca- and P-retention without further load for the kidney. In addition, preterm infants with a body weight lower than 1500 g also had a better retention of Ca and P. Both, F-CaP and F lead to a high urinary excretion of phosphorus, a high renal net acid excretion and a relatively high activity of serum alkaline phosphatase. Anthropometric measurements did not reveal any evidence for an impaired caloric absorption due to an increased fecal fat excretion. Hypercalcemia or hyperphosphatermia was not seen. Hypercalciuria occurred in less than 5% of the samples studied. The results of this study indicate that a continuation of the supplementation with Ca and P is justified in VLBW infants with a body weight of more than 2000 g. There was no evidence for adverse effects of Ca and P supplementation in VLBW infants with a body weight lower than 1500 g, who might therefore also benefit from supplementation. Further studies are necessary to investigate unsatisfactory metabolic conditions of these children e.g. the high renal load.

Urinary excretion of aldosterone, arginine vasopressin and cortisol in premature infants with maximum renal acid stimulation.

Of 452 low-birth-weight infants who were routinely screened for maximum renal acid stimulation (MRAS) (urine pH < 5.4), 149 episodes of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to either a control group or treatment with NaHCO3 or NaCl (2 mmol/kg/day each) for 7 days. Urinary excretion of aldosterone-18-glucuronide (Aldo), arginine vasopressin (AVP) and cortisol was determined in timed urine samples. On day 1, patients with MRAS showed a tendency towards increased urinary excretion of Aldo compared with infants without MRAS. In patients who received alkali therapy, urinary excretion of Aldo, AVP and cortisol decreased or showed a trend to lower values from day 1 to day 7, whereas in patients with MRAS but no specific therapy, Aldo and AVP showed a tendency to increase. We concluded that persistent MRAS is not only characterized by a reduced rate of weight gain and a tendency to decreased nitrogen assimilation, but also increased secretion of Aldo and AVP.

Increased renal net acid excretion in prematures below 1,600 g body weight compared with prematures and small-for-date newborns above 2,100 g on alimentation with a commercial preterm formula.

In 76 low birth weight infants with an actual body weight ranging from 1,210 to 2,540 g and fed a commercial preterm formula, urine samples were collected and blood acid base status was measured on day 38 (+/- 17, mean +/- SD) of life. Infants with an actual body weight below 1,600 g demonstrated a higher daily weight gain (22 +/- 3 vs. 14 +/- 5 g/kg/day), lower blood pCO2 (35.4 +/- 5.0 vs. 38.9 +/- 3.8 mm Hg), lower urine pH (5.8 +/- 0.5 vs. 6.5 +/- 0.3), higher renal net acid (1.86 +/- 0.38 vs. 1.28 +/- 0.55 mmol/kg/day) and higher phosphorus excretion (0.67 vs. 0.52 mmol/kg/day) than infants with an actual body weight above 2,100 g. Urinary ionogram data of these 2 groups of infants show that the increased renal net acid excretion of the smaller prematures is the result of a lower urinary excretion of sodium, potassium and chloride, due to a higher daily weight gain, probably a higher retention of these minerals, and a higher urinary phosphorus excretion probably due to an age-specific lower intestinal calcium absorption, and therefore a lower rate of calcium and phosphorus retention. Considering the low renal capacity for hydrogen ion excretion, very low birth weight infants still run a considerable risk for disturbances of acid base metabolism due to the high mean level of net acid excretion in nutrition with preterm formulas and an additional age-specific augmentation of renal acid load.

Decreased growth rate of low-birth-weight infants with prolonged maximum renal acid stimulation.

In a prospective randomized study, the urine pH of 170 premature and small-for-gestational-age (SGA) newborns was routinely screened to detect patients with spontaneously developing maximum renal acid stimulation, an obligatory early stage in the development of late metabolic acidosis. Nitrogen assimilation was evaluated from the ratio of urinary nitrogen excretion and intake. Forty-two premature infants and 10 SGA prematures and newborns after intensive care therapy with body weights greater than 1.5 kg and 25 prematures (including 7 SGA infants) with body weights less than 1.5 kg, spontaneously showed urine pH values below 5.4 on two consecutive days, suggesting maximum renal acid stimulation. These patients were randomly given either oral alkali therapy with sodium bicarbonate 2 mmol/kg/day or no therapy for a period of seven days. In both groups, urine pH was controlled daily. Patients in the control group without alkali therapy and with urine pH values less than 5.4 for seven days showed a significant decrease in weight gain and a tendency to decreased nitrogen assimilation. We assume that a regular check of urine pH in low-birth-weight infants is a useful non-invasive method of detecting patients in the early stages of development of late metabolic acidosis, i.e. in the stage of "incipient late metabolic acidosis". This would provide the possibility of starting early effective therapy and thereby reduce the mean duration of admission to neonatal wards.(ABSTRACT TRUNCATED AT 250 WORDS)

Low renal net acid excretion, high calciuria and biochemical signs of sodium deficiency in low-birth-weight infants fed a new low-phosphorus formula.

In 11 infants (birth weight greater than 1800 g) fed a new type of humanized formula with a low phosphorus (P) content (calcium (Ca) 11 mmol/l, P 7.2 mmol/l, sodium (Na) 8.3 mmol/l) biochemical parameters of blood, serum and urine were determined. In nine boys Ca and P balances were evaluated also. Renal net acid excretion was low (0.85 mmol/kg/day). Mean concentrations of P and Ca in urine were 0.34 mmol/kg/day (10.5 mg/kg/day) and 0.1 mmol/kg/day (4 mg/kg/day), respectively. In four infants, Ca concentration in urine was, however, greater than 0.15 mmol/kg/day) (6 mg/kg/day). In infants with birth weights greater than 1800 g fed the new, low-P formula, the low renal net acid excretion, the normal P and the high Ca concentrations in urine were comparable to term infants fed human milk. The high calciuria in several infants may be normal physiologic values. However, it remains to be established that the urinary solubility product of infants fed the new, low-P formula is in the same range as those for infants fed human milk. Unexpectedly, low urinary Na excretion (0.26 mmol/kg/day) and increased urinary excretion of aldosterone-18-glucuronide indicated biochemical evidence of Na deficiency secondary to low Na intake and a high weight gain. If the new, low-P formula is to be fed to infants with a birth weight as low as 1800 g. Na content should be higher than in mature human milk because of the often relatively higher weight gain.

Effect on renal net acid excretion of various mineral contents in three lots of a common pre-term formula.

Three common lots (A, B, C) of a common formula for pre-term infants, which contained unintended, high differences in mineral contents were fed consecutively in a neonatal unit. In each feeding period parameters of calcium-phosphorus and acid-base metabolism were determined prospectively. Infants fed lot C showed unexpectedly high renal net acid excretion. In order to discover the origin of this different renal net acid excretion, the urinary concentration of further electrolytes, sulfate, urea and organic acids were determined retrospectively in three randomly selected groups with 10 pre-term infants each. Infants fed lot C showed a higher renal net acid excretion (2.97 mmol/kg per day) than infants fed lot A (1.75 mmol/kg per day) or lot B (1.72 mmol/kg per day). Based on the data of mineral and nitrogen intake and the urinary values of all main ions and urea it is assumed that the increased renal acid load in infants fed lot C is due to the additive effect of different mineral concentrations resulting in a low "alkali excess" (Na + K - Cl) of lot C and a decreased protein assimilation. The production of infant formulas for prematures should be more closely monitored to avoid marked deviation of the mineral contents in individual lots from the concentrations shown on the label.

Renal handling of hydrogen ion excretion in relation to maturity indices in premature infants fed human milk.

In 40 premature infants fed human milk with an actual gestational age of 261 +/- 16 days and an actual body weight of 1.06-2.75 kg, 44 urine samples were collected, and blood acid-base status was measured on day 32 (+/- 16) of life. In the urine, the following results (mean +/- SD) were obtained: urine pH 6.05 +/- 0.65, titratable acidity 0.24 +/- 0.14 mmol/kg/day, ammonium 0.78 +/- 0.25 mmol/kg/day, net acid excretion 0.83 +/- 0.47 mmol/kg/day. There was no significant correlation between renal net acid or ammonium excretion and actual body weight. However, urine pH was positively correlated with body weight. Obviously, premature infants with an actual body weight below 1.5 kg need a higher stimulation of renal hydrogen ion secretion to excrete the same amount of ammonium than those with an actual body weight of about 2.5 kg. The limited renal acidification capacity of very low birth weight infants is a risk factor for the development of late metabolic acidosis.

Suboptimal mineral composition of cow's milk formulas: a risk factor for the development of late metabolic acidosis.

Late metabolic acidosis was observed in a term baby boy with renal tubular acidosis type 4 who received two cow's milk formulas in succession. Suboptimal mineral composition of the formulas turned out to be an important risk factor for the development of late metabolic acidosis.

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.

[Total laryngo-tracheo-esophageal cleft with situs inversus totalis, aplasia of the right diaphragm and hypoplasia of the lung on the right side]. / Totale laryngo-tracheo-oesophageale Spalte in Kombination mit Situs inversus totalis, Zwerchfellaplasie rechts und Hypoplasie der rechtsseitigen Lunge.

A report is presented on a newborn with congenital malformations of the respiratory and gastrointestinal tract associated with total laryngo-tracheo-oesophageal cleft (type III). The history, the clinical course with respiratory distress after birth, the intra vitam diagnostic procedures with x-ray and laryngoscopy and the autopsy are reported. Additionally a situs inversus totalis, an aplasia of the right diaphragm and a hypoplasia of the lung on the right side were found. To the best of our knowledge this type of association has not been previously reported.

[Renal osteodystrophy in children. Therapy with 1,25-dihydroxy-cholechalciferol (author's transl)]. / Renale Osteodystrophie bei Kindern Therapieversuch mit 1,25-dihydroxy-cholecalciferol.

Growth arrest and renal osteodystrophy are major problems in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy in 14 dialyzed children using 1,25-DHCC for 12 months. Values in plasma of Ca, P, Mg, alkaline phosphatase, iPTH, 25-OH-D, and 1,25-DHCC were determined regulary. Skeletal X-rays and analysis of iliac crest biopsies were obtained in each child. In treatment with 1,25-DHCC episodes of severe but reversible hypercalcemia occurred. Alkaline phosphatase and iPTH normalized completely. Radiographic examinations revealed marked improvement. Histological signs of fibro-osteoclasia and resorptive defects disappeared but there was no recovery of osteomalacia. A reduction of osteoblast population and of bone transformation was obvious. 1,25-DHCC failed to normalize growth in uremic children. In short, neither vitamin D nor 1,25-DHCC can guarantee complete recovery of renal osteodystrophy and growth arrest in uremic children.

[Influence of vitamin D therapy on renal osteodystrophy in children (author's transl)]. / Einfluss der Vitamin-D3-Therapie auf die renale Osteodystrophie im Kindesalter.

Growth arrest and renal osteodystrophy is a major problem in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy by using vitamin D3 for 24 months. Values in plasma of Ca, Mg, alkaline phosphatase, iPTH, 25-OH-D were determined regularly. Skeletal X-rays and analysis of iliac crest bone biopsies were obtained in each child. In treatment with vitamin D3 no hypercalcemia was seen despite high serum levels of 25-OH-D. Plasma-Ca, alkaline phosphatase, and iPTH normalized nearly. Radiographic abnormalities improved. Bone biopsies showed improvement in signs of secondary hyperparathyroidism and ostitis fibrosa, whereas osteomalacia remained unchanged. Osteoblast population showed a small reduction. No real increment in body growth was seen.

[Glucose in the newborn. A kinetic study (author's transl)]. / Glukose beim Neugeborenen. Eine kinetische Studie.

At birth, serum glucose concentration in the newborn is correlated to the maternal glucose level. In the following hours glucose concentration declines to a low level and remains there for some days. Intravenous glucose loading five hours after delivery leads to a decrease of the glucose level in the same pattern as is found immediately after birth. Compared to older children the turnover rate of glucose in the newborn is reduced. Therefore the decrease of serum glucose concentration immediately after birth cannot be explained by an increased glucose consumption. At birth there is a stop of the glucose supply via the umbilical cord. The results show that the decreasing glucose concentration after birth can be explained as an adaptation of the steady state from the higher maternal level to a lower newborn level.