Circulating Immunoreactive Parathyroid Hormone Levels in Premature Infants and the Response to Calcium Therapy

ABSTRACT. Serum immunoreactive parathyroid hormone (iPTH), calcium, magnesium, and phosphorus levels were measured in 13 premature infants during the first 96 hours of life. Hypocalcemia at 12–24 hours of age was associated with a markedly elevated mean serum iPTH level. Six of the hypocaicemic infants received a continuous infusion of calcium while seven were not treated. In the untreated infants, the mean serum calcium remained in the hypocaicemic range while the serum iPTH progressively increased. By contrast, the mean serum calcium in the treated infants increased to 2.35 mmol/l at 96 hours of age and was accompanied by a decline in serum iPTH. At 72 and 96 hours, the mean serum iPTH was twofold greater in the untreated than in the treated infants. The results indicate that the parathyroid glands of premature infants respond to calcium signals and that a factor(s), other than parathyroid insufficiency, plays an etiologic role in the hypocalcemia of prematurity.     

Partial hypoparathyroidism. A variant of transient congenital hypoparathyroidism.

We encountered three children who had neonatal hypocalcemia followed by a period of normocalcemia and recurrence of hypocalcemia later in childhood. They were full-term infants with normal birth weights who developed hypocalcemia within the first 48 hours after birth. The hypocalcemia resolved in 1 week, 3 months, and 14 months in the three patients. The recurrences of hypocalcemia occurred at 4, 7, and 12 years of age. Their plasma parathyroid hormone concentrations were consistently low but detectable. We suggest that partial hypoparathyroidism is the underlying abnormality in these patients and that neonatal hypocalcemia in otherwise healthy infants indicates the need for calcium measurements during childhood and adolescence.     

Effects of exogenous surfactant therapy on dynamic compliance during mechanical breathing in preterm infants with hyaline membrane disease

In a prospective, randomized, controlled clinical trial, the immediate and the longitudinal effects of exogenous surfactant therapy on pulmonary mechanics were evaluated in extremely premature infants during mechanical respiration. Ninety-four infants weighing between 600 and 1250 gm received either exogenous surfactant or sham (air) therapy in the delivery room and up to three additional doses in the first 48 hours of life if they were ventilator-dependent, had fractional inspiratory oxygen requirements greater than or equal to 0.30, and radiographic findings consistent with hyaline membrane disease. Each infant underwent pulmonary mechanics assessment (dynamic compliance, total pulmonary resistance, tidal volume) immediately before and 1 hour after each dose, and at 24, 48, and 72 hours and 7 days of age. There were no significant differences in dynamic compliance, total pulmonary resistance, and tidal volume in the surfactant (n = 47) and control (n = 47) groups before and 1 hour after each dose. However, dynamic compliance was 50% greater in the surfactant group at 24 hours of age (p less than or equal to 0.009); this difference steadily increased to 94% at 7 days of age (p less than or equal to 0.009). Oxygenation, assessed by the ratio of alveolar to arterial oxygen pressure, was significantly greater in the surfactant group during the first 72 hours of life; the greatest difference was noted at 24 hours (p less than or equal to 0.001). Mean airway pressure requirements in the surfactant group were significantly less than in the control group at all times during the first week. We conclude that exogenous surfactant therapy, administered at birth and during the first 48 hours of life in extremely premature infants with hyaline membrane disease, improves dynamic compliance and gas exchange during mechanical breathing.     

Early determinants of cardiovascular risk factors in adults. A. Plasma lipids

The aim of the study was to examine the effect of birth weight, infant nutrition, body mass and social status from early childhood and adulthood on plasma lipid levels in 192 adult subjects examined in the first three years of life (mean age 1.4 years in males and 1.3 years in females) and again as adults (mean age 19.9 years in males and 19.6 in females). According to the results obtained, total cholesterol was significantly higher in adult male subjects breast fed for the shortest period of time ( p<0.05 ). Those males who were leanest in the first three years of life and fattest as adults had the highest levels of total cholesterol (p = 0.03) and LDL cholesterol ( p = 0.02). Birth weight had no significant influence on plasma lipid levels in adult subjects. When data on nutrition, anthropometry and social status from both age periods were included in multivariate regression analyses, the most significant predictors of higher levels of total cholesterol and LDL cholesterol in males were lower adult height and poor social status in early childhood, while in females they were a shorter duration of breast feeding and earlier introduction of solids.     

Early determinants of cardiovascular risk factors in adults. A. Plasma lipids

The aim of the study was to examine the effect of birth weight, infant nutrition, body mass and social status from early childhood and adulthood on plasma lipid levels in 192 adult subjects examined in the first three years of life (mean age 1.4 years in males and 1.3 years in females) and again as adults (mean age 19.9 years in males and 19.6 in females). According to the results obtained, total cholesterol was significantly higher in adult male subjects breast fed for the shortest period of time ( p<0.05 ). Those males who were leanest in the first three years of life and fattest as adults had the highest levels of total cholesterol (p = 0.03) and LDL cholesterol ( p = 0.02). Birth weight had no significant influence on plasma lipid levels in adult subjects. When data on nutrition, anthropometry and social status from both age periods were included in multivariate regression analyses, the most significant predictors of higher levels of total cholesterol and LDL cholesterol in males were lower adult height and poor social status in early childhood, while in females they were a shorter duration of breast feeding and earlier introduction of solids.     

PHOSPHORUS DEPLETION IN CHILDREN ON LONG-TERM TOTAL PARENTERAL NUTRITION1

ABSTRACT: Ricour, C, Millot, M. and Balsan, S. (Laboratoire des tissus calcifies and Unité de Recherche sur les Maladies du Métabolisme chez l'Enfant, Hopital des Enfants Malades, Paris, France). Phosphorus depletion in children on long-term total parenteral nutrition. Acta Paediatr Scand, 64:385, 1975.–The retention of nitrogen, calcium and phosphorus was studied in nine infants on total parenteral nutrition. The amounts of calcium, nitrogen and phosphorus were varied singly or simultaneously. The results demonstrate close interrelationships in the retention of these three elements. Not only the absolute amount of phosphorus perfused daily but also the amounts of nitrogen and/or calcium perfused simultaneously account for the phosphorus depletion that may lead to severe hypophosphatemia. The decrease in serum phosphorus concentration with a simultaneous fall of urinary phosphorus excretion to undetectable levels and a rise in urinary calcium output to 10 mg/kg/24 hours or more are warning symptoms of phosphorus depletion. Such a complication was observed in our first seven children on total parenteral nutrition. Phosphorus depletion can be prevented by using the following amounts of these elements in the perfusate: per 100 Kcal/kg/24 hours, 400 mg/kg/24 hours of nitrogen, 35 mg/kg/24 hours of calcium and 40 mg/kg/24 hours of phosphorus. With such a technique no phosphorus depletion was observed in any of the 63 subsequent patients whom we treated with total parenteral nutrition for periods varying from 20 days to 9 months.     

The serum level of ionized calcium, total calcium, and magnesium in neonates (author's transl)]

In the first three days of life ionized and total calcium and magnesium were determined in the serum and compared with perinatal parameters in a heterogenous groups of newborn infants (n equals 33). The findings allow the following conclusions: 1. There is a relative good correlation between ionized and total calcium. 2. There is no statisticly proven correlation between magnesium and ionized or total calcium. 3. There is a close relation between APGAR-score and the levels of calcium in the first hours of life. But apparently there is no relation between the gestational age or the weight of birth and magnesium, between the gestational age or the weight of birth and ionized or total calcium there is no close correlation.     

FREE AND BOUND TRYPTOPHAN IN HUMAN PLASMA DURING THE PERINATAL PERIOD

Abstract. The concentration of tryptophan and the degree of binding of the amino acid to protein were examined in human plasma during the perinatal period. Both total and unbound (free) tryptophan were higher in cord vein plasma than in the maternal circulation, the concentration gradient being approximately 1: 2. The proportion of the total plasma tryptophan concentration that was not bound to protein was less in cord vein plasma than in the maternal circulation. After birth the proportion in infant plasma fell significantly. Both total and free tryptophan fell during the first 24 hours of postnatal life. Total tryptophan returned to the cord vein plasma level 6–8 days after birth whilst free tryptophan failed to increase during the period of the observations. In premature infants total and free tryptophan also declined in concentration 12–24 hours after birth, suggesting the phenomenon to be related to birth rather than to gestational age. Phenylalanine remained unchanged whilst tyrosine increased in concentration during the first 80 hours of postnatal life. Thus, the availability of tryptophan to the tissues appears to decline during the immediate postnatal period and the results suggest that the requirement for tryptophan during this time may exceed the supply from standard artifical milk preparations.     

Slow sodium acetate infusion in the correction of metabolic acidosis in premature infants

The treatment of metabolic acidosis is one of many problems encountered in the premature infant during the first days of life. In this study, 11 infants with gestational ages of no more than 34 weeks were given sodium acetate as a continuous infusion from the first day of life. The daily sodium supply was set at 3 mEq/kg. The arterial serum pH was less than 7.30 in infants at the following ages: 1 to 3 hours, four; 24 hours, two; 48 hours, one; and 72 hours, one. The base deficit was calculated to be less than 5 in four infants at the age of 1 to 3 hours, in one infant at 24 hours, in one infant at 48 hours, and in no infants at 72 hours. The serum sodium concentrations were normal. The continuous infusion of sodium acetate seems to be suitable for the slow correction of metabolic acidosis, and the daily sodium supply of 3 mEq/kg gives a stable serum sodium concentration in the premature infant with a gestational age of no more than 34 weeks.     

Frequency of vitamin D insufficiency in healthy children between 1 and 16 years of age in Turkey

Background: The aim of this study was to establish the frequencies of vitamin D deficiency and insufficiency among healthy children aged 1–16 years and also to determine the factors affecting the levels of vitamin D in Turkey. Methods: A total of 849 healthy individuals whose ages ranged from 1 to 16 years were included in the study. Serum 25(OH)D, calcium, phosphorous and alkaline phosphatase l levels were measured at the end of the winter period. The approximate daily calcium intake was calculated by using a 1‐week diet history. Results: We determined that the prevalence of vitamin D deficiency (<20 ng/mL) was 8% and that of vitamin D insufficiency (20–29 ng/mL) was 25.5% in the population investigated. The average daily intake of calcium was especially low in the >8‐year‐old age group (<1300 mg/day). Conclusion: Vitamin D insufficiency was found to be very common in the population investigated. The daily calcium intake was below the adequate levels especially in school children. Vitamin D supplementation after the first year of life could be beneficial especially for school children and adolescents. The government must develop public policies for the fortification of milk, milk products, and fruit juices with vitamin D.     

Free and bound tryptophan in human plasma during the perinatal period.

The concentration of tryptophan and the degree of binding of the amino acid to protein were examined in human plasma during the perinatal period. Both total and unbound (free) tryptophan were higher in cord vein plasma than in the maternal circulation, the concentration gradient being approximately 1 : 2. The proportion of the total plasma tryptophan concentration that was not bound to protein was less in cord vein plasma than in the maternal circulation. After birth the proportion in infant plasma fell significantly. Both total and free tryptophan fell during the first 24 hours of postnatal life. Total tryptophan returned to the cord vein plasma level 6--8 days after birth whilst free tryptophan failed to increase during the period of the observations. In premature infants total and free tryptophan also declined in concentration 12--24 hours after birth, suggesting the phenomenon to be related to birth rather than to gestational age. Phenylalanine remained unchanged whilst tyrosine increased in concentration during the first 80 hours of postnatal life. Thus, the availability of tryptophan to the tissues appears to decline during the immediate postnatal period and the results suggest that the requirement for tryptophan during this time may exceed the supply from standard artifical milk preparations.     

INTRAVENOUS GLUCOSE TOLERANCE, PLASMA INSULIN, FREE FATTY ACIDS AND β-HYDROXYBUTYRATE IN UNDERWEIGHT NEWBORN INFANTS

Blood glucose, plasma insulin, FFA and β-hydroxybutyrate values during intravenous glucose tolerance were reported in 20 small for gestational age (SGA) and 15 appropriate for gestational age (AGA) low birthweight infants. The babies were divided into three groups according to their age when tested; <24 hours, 24–48 hours and >48 hours. Both the SGA and AGA infants cleared glucose more rapidly with increasing age. The change was more marked in the SGA babies. The clearance rates were similar to those reported in normal full-sized infants. The insulin values before the glucose load were similar in all groups and comparable to those reported in normal newborn infants. The insulin response to glucose was variable. There were no significant differences with increasing age or between the two groups of infants. The insulin curve of the individual infant followed one of three patterns. Most commonly seen was a double-peak curve. The infants who showed a single-peak insulin response had a better but not significantly different glucose tolerance than that of the other babies. Infants with no appreciable insulin response still removed glucose from plasma at a rate similar to those with a double-peak insulin curve. It is concluded that insulin as measured in peripheral plasma could not explain the rate of removal of glucose from the plasma of the newborn low birthweight infant. Infants of low birthweight had higher plasma FFA values as compared to that reported in normal full term infants. The FFA values in SGA infants were higher than those in AGA babies. In both groups of infants, the jS-hydroxybutyrate values were comparable to those reported in normal full-term babies. Thus there was an unexpected discrepancy between the high FFA and relatively low β-hydroxybutyrate levels in plasma. The fall in plasma FFA and β-hydroxybutyrate after glucose was minimal but similar in both groups of infants. The findings are compatible with a decreased sensitivity to insulin in the infants studied.     

Comparison of carboplatin pharmacokinetics between an anephric child and two children with normal renal function

Carboplatin, a promising second generation platinum compound, is an effective antitumor drug and appears to be less nephrotoxic than cisplatin. We report comparative pharmacokinetics of carboplatin in an anephric child and two children with normal renal function. All three children were infused with carboplatin over 4 hours, the anephric child receiving 100 mg/m² (25% of the dose received by the other two children). This dose was well tolerated and 18 days later the anephric patient received a second course of carboplatin at 50% of the regular dose received by the control patients. Following this dose the girl experienced severe pancytopenia and recovered with the use of GM-CSF, blood, and platelet transfusion. Blood samples were obtained at timed intervals for 24 hours in the control subjects and for 40 hours in the anephric patient. Plasma and plasma ultrafiltrates were analyzed for total and free platinum. The results show that elimination half-life of total platinum was 13 hours in the children with normal renal function and 42 hours in the anephric child following the 100 mg/m² dose. The elimination T_1/2 of free platinum was 8 hours in a child with normal GFR and 32 hours in the anephric child. In the anephric child the clearance of ultrafiltrable platinum was 10% of the normal total body clearance. We suggest that, in children with renal insufficiency, the dose of platinum derivatives should be carefully chosen, proportionally to the degree of renal impairment. © 1993 Wiley-Liss, Inc.     

Predictors of significant jaundice in late preterm infants

Objectives

To study (i) the incidence and course of jaundice, and (ii) the predictors of ??significant jaundice?? in late preterm infants.

Design

Prospective analytical study.

Setting

Urban perinatal center.

Patients

Inborn late preterm infants (post menstrual age of 34 0/7 to 36 6/7 weeks).

Methods

Infants were followed till day 14 of life or till onset of significant jaundice. Relevant maternal, perinatal and neonatal variables were prospectively recorded. Transcutaneous bilirubin (TcB) was measured in each infant twice daily for the first 48 hours of life.

Outcomes

Significant jaundice defined as requirement of phototherapy/exchange transfusion as per hour specific total serum bilirubin (TSB) nomogram of AAP guidelines.

Results

216 infants were enrolled, of which 123 (57%) had significant jaundice. 36% of the jaundiced infants had TSB greater than 15 mg/dL. The mean duration of onset of significant jaundice was 61 ± 32 hours. The mean duration of phototherapy was 49 ± 26 hours. Large for gestation, lower gestational age, birth trauma and previous sibling with jaundice predicted severe jaundice. TcB measured at 24?C48 hrs was a better predictor of ??significant jaundice with onset after 48 hrs?? than clinical risk factors.

Conclusion

There is a high incidence of significant jaundice in late preterm infants. TcB measured at 24?C48 hrs of life better predicts ??significant jaundice after 48 hours of life??, in comparison with clinical risk factors.     

Randomized trial of high-frequency oscillatory ventilation versus conventional ventilation: effect on systemic blood flow in very preterm infants

OBJECTIVE: Low superior vena cava (SVC) flow is common in very preterm infants in the first day and strongly associated with periventricular hemorrhage and disability. We examined the effect of high-frequency oscillatory ventilation (HFOV) compared with conventional ventilation (CV) on SVC flow and right ventricular output. METHODS: Forty-five infants <29 weeks were randomized before 1 hour of age to HFOV or CV. Echocardiography was performed on 43 infants at 3, 10, and 24 hours of age. Infants with low SVC flow (<50 mL/kg/min) or hypotension (mean blood pressure < or =20) were treated with volume and inotrope. RESULTS: Infants allocated to HFOV (n=23) and to CV (n=20) were well matched. There was a nonsignificant trend toward more infants on HFOV having SVC flow <50 mL/kg/min (48% vs 20%) and receiving volume and inotropes (61% vs 40%). There were no significant differences in mean SVC flow or right ventricular output at 3, 10, or 24 hours. Infants on HFOV had a significantly higher calculated upper body vascular resistance at 10 hours and mean blood pressure at 24 hours. CONCLUSIONS: There were no significant adverse effects of HFOV on systemic blood flow in very preterm infants during the first 24 hours of life.     

POSTNATAL CHANGES IN THE ABILITY OF PLASMA ALBUMIN TO BIND BILIRUBIN

ABSTRACT. The plasma concentrations of total albumin, unconjugated bilirubin and reserve albumin for bilirubin binding were determined in 407 healthy infants of various age up to eight days. The albumin reserve was measured using monoacetyldiaminodiphenyl-sulfone (MADDS) as a deputy ligand for bilirubin. The fraction of albumin capable of binding bilirubin was calculated as the sum of the concentrations of bilirubin and reserve albumin, divided by the total albumin concentration. Our data showed that this fraction was low (average 0.36) and did not change during the first 24 hours of life, and in this period it was independent of the maturity of the infant, as expressed by its birth weight or gestational age. From about 24 hours of life, the fraction began to increase. This increase came to an end about 60 hours after birth, and no further changes were seen during the following five days. The level of the bilirubin-binding fraction reached 60 hours after birth was related to the maturity of the infant: It increased with increasing birth weight up to 3000 g and with increasing gestational age up to 275 days, when on an average it was about 0.58. The fraction of binding albumin was independent of the sex.     

Postnatal changes in the ability of plasma albumin to bind bilirubin

The plasma concentrations of total albumin, unconjugated bilirubin and reserve albumin for bilirubin binding were determined in 407 healthy infants of various age up to eight days. The albumin reserve was measured using monoacetyldiaminodiphenyl-sulfone (MADDS) as a deputy ligand for bilirubin. The fraction of albumin capable of binding bilirubin was calculated as the sum of the concentrations of bilirubin and reserve albumin, divided by the total albumin concentration. Our data showed that this fraction was low (average 0.36) and did not change during the first 24 hours of life, and in this period it was independent of the maturity of the infant, as expressed by its birth weight or gestational age. From about 24 hours of life, the fraction began to increase. This increase came to an end about 60 hours after birth, and no further changes were seen during the following five days. The level of the bilirubin-binding fraction reached 60 hours after birth was related to the maturity of the infant: It increased with increasing birth weight up to 3000 g and with increasing gestational age up to 275 days, when on an average it was about 0.58. The fraction of binding albumin was independent of the sex.     

The association of serum 25-hydroxyvitamin D3 and D2 with depressive symptoms in childhood--a prospective cohort study

Background: Depression in adolescence is common and early onset predicts worse outcome in adulthood. Studies in adults have suggested a link between higher total 25‐hydroxyvitamin D [25(OH)D] concentrations and lower risk of depression. Objectives: To investigate (a) the association between serum 25(OH)D₂ and 25(OH)D₃ concentrations and depressive symptoms in children, and (b) whether the associations of 25(OH)D₂ and 25(OH)D₃ are different from, and independent of, each other. Methods: Prospective cohort study with serum 25(OH)D₂ and 25(OH)D₃ concentrations measured at mean age of 9.8 years and depressive symptoms assessed with the Mood and Feelings Questionnaire by a trained interviewer at the mean ages of 10.6 years (n = 2,759) and 13.8 years (n = 2,752). Results: Higher concentrations of 25(OH)D₃ assessed at mean age 9.8 years were associated with lower levels of depressive symptoms at age 13.8 years [adjusted risk ratio (RR; 95% confidence interval (CI)): 0.90 (0.86–0.95)], but not at age 10.6 years [adjusted RR (95% CI): 0.98 (0.93–1.03)] and with increased odds of decreasing symptoms between age 10.6 and 13.8 years [adjusted RR (95% CI): 1.08 (1.01–1.16)]. Serum 25(OH)D₂ concentrations were not associated with depressive symptoms. Conclusions: This is the first study in children to suggest that the association between 25(OH)D₃ concentrations and depression emerges in childhood. The association is independent of a wide range of potential confounding factors, and appears to be stronger with greater time separation between assessment of 25(OH)D₃ and assessment of depressive symptoms. Confirmation of our findings in large prospective studies and trials would be valuable.     

Early single-channel aEEG/EEG predicts outcome in very preterm infants

Aim: To characterize early amplitude‐integrated electroencephalogram (aEEG) and single‐channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long‐term outcome. Patients: Forty‐nine infants with median (range) gestational age of 25 (22–30) weeks. Methods: Amplitude‐integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0–12, 12–24, 24–48 and 48–72 h, for background pattern, sleep–wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single‐channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development‐II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment. Results: Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst‐suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%). Conclusion: Long‐term outcome can be predicted by aEEG/EEG with 75–80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.     

Hypocalcemia in the Newborn

Healthy term babies undergo a physiological nadir in serum calcium levels by 24–48 hours of age. This nadir may be related to the delayed response of parathyroid and calcitonin hormones in a newborn. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. This early onset hypocalcemia which presents within 72 hours, requires treatment with calcium supplementation for at least 72 hours. In contrast late onset hypocalcemia usually presents after 7 days and requires long term therapy. Ionized calcium is crucial for many biochemical processes and total serum calcium is a poor substitute for the diagnosis of hypocalcemia.