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In many very-low-birth-weight (VLBW) infants the ductus arteriosus fails to close spontaneously, and they subsequently develop signs and symptoms of poor tissue perfusion and heart failure. This study evalutes the results of early surgical closure of patent ductus arteriosus (PDA). We retrospectively reviewed the records of all 101 VLBW infants who weighed 1,500 g or less when their PDA was surgically ligated in Turku University Hospital between 1988 and 1998. The mean gestational age at birth was 27.2 weeks and mean birth weight 963+/-239 g. The operation was performed at 12+/-8 days of age; the infants' weight at operation was 969+/-231 g and they were tracheally extubated 11+/-14 days after the operation. The surgery-related mortality was 3% (3/101) and overall mortality 10% (10/101). We conclude that surgical closure of PDA is safe and effective in VLBW infants.

Objectives. Few data are available in the literature regarding the long-term outcome of newborns with congenital complete heart block (CHB). The aims of this retrospective study were to assess neonatal morbidity and mortality, incidences of dilated cardiomyopathy (DCM), and associated heart defects, and to establish prenatal and postnatal factors that might predict adverse outcome in children with CHB. Design and Setting. The cohort includes 91 infants with CHB diagnosed in 5 tertiary centers in Finland between 1950 and 1998. Patients. Maternal connective tissue disease was evident in 89% of the patients. At birth, the median gestational age was 37.1 weeks, and the median weight was 2969 g. Of the 91 infants, 60 (66%) were girls and 7 (8%) were twins. Results. Incidences of perinatal morbidity and mortality were 58% and 7%, respectively. The total mortality of CHB was 16%; 11 of 15 (73%) died during the first 12 months. Cumulative probability of survival at 10 years old was 82%. Pacing as a newborn was indicated in 48 of 90 cases (53%), and 36 received pacemakers at older ages. Cardiac defects not causally related to CHB were found in 38 of 90 patients (42%), of whom 22 were operated on. DCM was found in 21 (23%), of whom 13 died. During the follow-up, among 75 survivors with a median age of 9 years, 54 (72%) are free from symptoms. Poor outcome defined as clinically or pathologically evident congestive DCM was associated with intrauterine hydrops, low fetal and neonatal heart rate, low birth weight, male sex, and neonatal problems attributable to prematurity or neonatal lupus. Conclusions. Despite early pacing, CHB carries high mortality during the first 12 months of life. High incidences of DCM and associated heart defects indicate close echocardiographic monitoring of all children with CHB.

A 10-month-old girl was referred to our institution for evaluation of recurrent loss of consciousness that occurred for 30 seconds 1 to 3 times a day. The seizures occurred after crying, pain, or frustration. Because of tonic-like seizures before the loss of consciousness, the girl was initially remitted to pediatric neurology, where a movie-assisted electroencephalography was registered (Movie I of the online-only Data Supplement). When the girl was crying, she held breath, stiffened, and the recording showed a significant bradycardia and a 30s asystole followed by flattening of assisted electroencephalography activity and loss of consciousness consistent with anoxia. Consciousness returned rapidly after …

Background: The aim of the study was to evaluate the safety and reliability of automatic ventricular pacing threshold measurement, the Medtronic Capture Management™ (CM), in children with epicardial pacing leads. CM has not been recommended for use with epicardial leads due to lack of pertinent data. Methods: During a 2-year study period, 34 children (mean age 6.1 years, range 0 days to 17.7 years) with epicardial leads were prospectively enrolled. The CM measurements were compared with in-office ventricular pacing threshold measurements. Thirty bipolar and five unipolar epicardial leads were assessed. Results: CM measurements were successful and reliable in 30 out of 35 leads (86%). The mean threshold with CM was 1.16 V (95% CI 1.07–1.26 V), and with standard measurement was 1.18 V (95% CI 1.09–1.28 V), at a pulse width of 0.40 ms. The reasons for failure were evoked response undersensing in two cases (5.7%), and high intrinsic rate in one case. High pacing thresholds prevented accurate CM measurements in two cases. Conclusions: CM automatic threshold measurements are consistent with standard ventricular pacing threshold measurements in children with epicardial leads. We recommend a period of monitoring CM performance before programming it to adjust output according to automatic threshold measurements, in order to find the patients in whom it does not work. The CM feature provides increased pacing safety when it measures well (86% of leads). A larger study is needed to prove the tendency for extending battery life in children with epicardial leads.

To evaluate the contribution of the pulmonary and ductal hemodynamics on the cardiac atrial natriuretic peptide (ANP) synthesis and release in neonatal respiratory distress syndrome, serial blood samples for plasma C-terminal end, and the more stable N-terminal end (NT-proANP) of the propeptide were obtained. Simultaneous evaluation of the systolic pulmonary artery pressure (PAP) and magnitude of ductal shunting by the Doppler method were made of 37 distressed infants during the first 4 days of life. Both plasma ANP and NT-proANP rose after birth, peaked at 48 hours of age, and correlated significantly (r = 0.66; p < 0.001; n = 78) with each other. The initially high systolic PAP and, since the systemic arterial pressure (SAP) did not change, the PAP/SAP ratio declined slowly during the study period, as did the magnitude of ductal left-to-right shunting after an initial increase during the first hours after birth. Plasma NT-proANP had a positive correlation to the magnitude of ductal left-to-right shunting both during the first 2 and 4 days of life, but did not correlate with PAP, SAP, or PAP/SAP ratio during the same time periods. Eight infants with delayed closure of the ductus maintained elevated plasma NT-proANP values after the second day of life.(ABSTRACT TRUNCATED AT 250 WORDS)

We assessed the relation of atrial natriuretic peptide (ANP) to renal function on postnatal day 2 and day 5 in preterm infants. Plasma ANP concentration was measured by radioimmunoassay in two groups of preterm infants: group 1, gestational age less than 30 weeks, n = 10; and group 2, gestational age 30-34 weeks, n = 11. The identity of the immunoreactivity as ANP-28 was confirmed by HPLC. Plasma ANP was significantly higher in group 1 than in group 2 on day 2 and day 5 (p < 0.01) and ANP concentration decreased by day 5 in both groups (group 1, p < 0.01; group 2, p < 0.02). The results showed no correlation between plasma ANP concentration and urinary sodium excretion or creatinine clearance, which may be due to a blunted renal response to ANP, but other factors may be involved also. We conclude that preterm infants are able to release large amounts of ANP, but a high plasma ANP concentration does not correlate directly with renal regulation of sodium and water balance.

We measured plasma concentrations of epinephrine (E), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) as well as urinary concentrations of metanephrine (M), normetanephrine (NM) and 3-methoxy-4-hydroxymandelic acid (MOMA) on day 2 and day 5 in preterm infants; gestational age less than 30 weeks (G less than 30; n = 16) and gestational age 30-34 weeks (G 30-34; n = 19). Concentrations of E (0.00-2.28 nmol/l) and NE (0.6-9.1 nmol/l) in plasma were much lower than those previously reported during preterm and term delivery. The E:NE ratio decreased from 1:10 on day 2 to 1:30 on day 5, and the M:NM ratio decreased from 1:4 on day 2 to 1:8 on day 5, indicating relatively higher catecholamine secretion from the adrenals than from the sympathetic nerve terminals in preterm infants during postnatal adaptation. Plasma concentrations of DOPAC and DHPG were significantly higher in G less than 30 than in G 30-34 (DOPAC, p = 0.0494; DHPG, p = 0.0092), probably relating to a low urinary excretion rate of catecholamine metabolites in infants in G less than 30. Plasma and urinary concentrations of catecholamines and their metabolites varied considerably, and no significant correlations to postnatal events could be demonstrated.

We measured the influence of maturation and early freshly frozen plasma infusion (FFP) on renal function (day 2 and day 5) in preterm infants in intensive care; they were divided into two groups, those with gestational ages < 30 weeks (G < 30) and those with gestational ages of 30–34 weeks (G 30–34). A total of 35 infants was studied. The infants were randomly assigned to one of two treatment groups, one receiving FFP, the other not, yielding four study groups; G < 30 and no FFP (8 infants), G < 30 and FFP (8 infants), G 30–34 and no FFP (9 infants) and G 30–34 and FFP (10 infants). The infants in the two FFP groups received FFP 10 ml/kg on days 1–3. FFP did not significantly influence creatinine clearance (Ccr) or the urinary sodium excretion rate either in G < 30 or G 30–34. CCr was significantly lower (p < 0.001) and fractional urinary sodium excretion significantly higher (p < 0.002) in infants of G < 30 than in infants of G 30–34. Infants of G < 30 had significantly higher plasma potassium concentrations (p < 0.01) than infants of G 30–34. Despite the low CCr and the high urinary sodium excretion rate, infants of G < 30 had stable fluid and electrolyte balance.

Umbilical cord arterial and venous concentrations of epinephrine, norepinephrine and the catecholamine metabolites 3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid were determined in 41 healthy newborn infants delivered vaginally, vaginally with epidural analgesia, by cesarean section under general anesthesia or by cesarean section under epidural anesthesia. Doppler-derived cardiac output and arterial blood pressure were repeatedly measured during the first 48 h of life. There were fairly small differences in umbilical arterial and venous plasma concentrations of epinephrine and norepinephrine between the groups, with the highest levels of norepinephrine in infants delivered vaginally without analgesia (about 10 times as high as in the cesarean, general anesthetized group). No signficant differences were found in the metabolite concentrations. Doppler-derived cardiac output and heart rate decreased in all groups during the study period and, in spite of increased catecholamine levels in the vaginally delivered infants, the differences between the groups were marginal. Healthy term infants with no signs of asphyxia were well prepared for a normal hemodynamic adaptation irrespective of mode of delivery or mode of obstetric anesthesia/analgesia.

We measured extracellular fluid volume by bromide dilution within 12 h of birth in 32 infants less than 1000 g birth weight. Mean ( ± S.D.) birth weight and gestational age were 763 ± 123 g and 26 ± 1 week, respectively. Mean extracellular fluid volume was 360 ± 86 ml (477 ± 107 ml/kg). These results are similar to extracellular fluid volume estimates from previous carcass analysis data. Wide variability is observed with both methods suggesting that biologic variability may be important.

A nonimaging pulsed Doppler technique was used to grade the magnitude of flow in left-to-right shunting ductus arteriosus. The results were compared with those obtained with a color Doppler flow mapping technique. The correlation between the grading results by these two methods was 0.91 (p less than 0.01). To determine hemodynamic influence of left-to-right shunting ductal flow, simultaneous measurements of Doppler-derived cardiac output were done. Results showed significantly higher cardiac output in infants with grade III shunting than in infants with grade 0 and grade I shunting. The nonimaging pulsed Doppler ultrasound technique used in the present study proved to be a clinically useful and accurate grading system of left-to-right shunting at the ductal level. The simple grading system with nonimaging Doppler is a valuable adjunct to the color Doppler flow mapping technique. It allows a regular evaluation of ductal flow as well as cardiac output.

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Animal studies have suggested a possible role of ET-1 in alveolar hypoxia. ET-1 may be of pathophysiological significance in the fetal as well as in the maternal circulation in pregnancies complicated with hypertension. ET-1 has been shown to induce a dose-related constriction in vitro of strips of ductus arteriosus from mature fetal lambs. It has also been shown to contract human umbilical vessels at extremely low concentrations. Its role in the newborn infant is not known. In the present study we measured plasma ET-1 levels in preterm and term infants soon after birth as well as in healthy infants and children of different ages. ET-1 was determined by a commercial radioimmunoassay kit (RIK 6071, Peninsula Laboratories Europe Ltd). The plasma levels of ET-1 were as follows (mean, range, pg/ml): preterm (

TRANSFORMING GROWTH FACTOR β1 (TGFβ1) INHIBITS PROUFERATION BUT DOES NOT INDUCE DIFFERENTIATION IN INFANT RENAL EPITHEUAL CELLS

In the neonate, the role of ANP in the regulation of fluid balance is not clear. We assessed the relation of ANP in preterm infants to renal function and PDA on days 2 and 5. P-ANP was measured by RIA; Gl (

BPD is an important cause of late morbidity in preterm infants with RDS. We investigated the development of BPD in 216 neonates weighing less than 1500 g during a 6-y period. The criteria for BPD and severity of RDS were defined. The results are shown in the table. In infants with BW ≥1250 g only one infant of 75 developed BPD. Incidence of PDA was higher in infants with BPD than without BPD (p

Colloid osmotic pressure of umbilical cord plasma was measured in 242 healthy infants, in 34 infants with respiratory distress syndrome (RDS), in 18 infants with asphyxia, in 13 infants who were small for gestational age, in 15 infants born to mothers with diabetes mellitus, and in 18 infants born to mothers with pregnancy-induced hypertension. In healthy infants, colloid osmotic pressure correlated highly significantly with umbilical cord blood total protein level, gestational age, and birth weight. In infants with RDS, no correlation between colloid osmotic pressure and gestational age or birth weight was found. Infants with RDS and gestational age between 36 and 38 weeks had significantly lower colloid osmotic pressure than healthy infants, whereas colloid osmotic pressure of infants with RDS and gestational age between 32 and 35 weeks did not differ from that of healthy infants of corresponding gestational age. Healthy term infants delivered by cesarean section had significantly lower colloid osmotic pressure than infants delivered vaginally. Infants with asphyxia had significantly higher colloid osmotic pressure than healthy infants. Colloid osmotic pressure is related to the lung maturity of the near-term and term neonate. Infants with a colloid osmotic pressure greater than 16 mm Hg are unlikely to develop RDS.

Serum chloramphenicol levels were evaluated in 52 children with severe infection treated intravenously with chloramphenicol succinate and orally with chloramphenicol palmitate, chloramphenicol monostearoylglycolate or chloramphenicol in capsules. Effective serum levels were recorded with all chloramphenicol preparations. The variability was largest with chloramphenicol monostearoylglycolate. In a case of neonatal Escherichia coli meningitis good serum levels of chloramphenicol were achieved with chloramphenicol palmitate orally, supporting the view that oral chloramphenicol palmitate can be used to treat serious infections in this age group. Our data and those in the literature show that monitoring of serum chloramphenicol levels in neonates is necessary. After the neonatal period monitoring of serum chloramphenicol levels is useful in avoiding too high concentrations. On the other hand, toxic effects of high concentrations can be recognized from reticulocyte and haemoglobin, neutrophil and platelet counts, which should be performed every three to four days.

Gastric aspirate L/S ratio and cord blood protein concentration were measured in 150 newborn infants, 33 of whom developed respiratory distress syndrome (RDS). 46.6% of the infants with low gastric aspirate L/S value (less than or equal to 3) and 33.3% of the infants with serum protein of less than or equal to 46 g/l developed RDS. The sensitivity of both parameters was 81.8%. Combination of these two methods yielded a higher predictive value (62.2%) but decreased the sensitivity (69.7%). The patterns of phospholipids reflect lung maturity, but also serum protein levels indicating overall maturity and the osmotic powers of microcirculation may be of diagnostic value in featuring developing RDS.

Colloid osmotic pressure (COP) of blood plasma during the first 4 days of life was measured in 63 neonates: 16 healthy preterm infants, 36 infants with respiratory distress syndrome (RDS), and 11 infants born to mothers with premature rupture of membranes. The relation between COP and total protein content of blood was significant in all groups over times from 1-3 h to 96 h. COP rose significantly by the age of 3 h compared to COP of umbilical cord plasma in all groups investigated. Infants with RDS showed a significant increase in COP during the investigation period. In healthy preterm infants the increase was less significant. In infants with RDS there was a negative correlation between changes in COP and body weight not seen in the other groups investigated. COP in neonates seems to reflect the compartmentation between vascular and interstitial spaces. Measurement of COP could be clinically useful in assessing hemodynamic adaptation after birth and also in assessing edema formation and water balance in infants with RDS.

One of the main targets of fluid therapy in premature infants is to avoid variations in osmolality, which mainly means providing a stable sodium, glucose, and acid-base balance. Water, sodium, and acid-base balance were measured in 20 infants appropriate-for-gestational age with a gestational age less than or equal to 34 weeks. The infants were randomly assigned to one of two treatment groups. Fluid intake was restricted and air humidity in the incubator was high in order to minimize insensible water loss. Sodium intake in Group 1 was 2 mmol/kg/day and consisted of sodium chloride. Sodium intake in Group 2 was 4 mmol/kg/day and consisted of both sodium chloride and acetate. Weight loss was appropriate in both groups. In the high sodium intake group there was a tendency towards a more stable plasma sodium concentration than in the low sodium intake group. The use of sodium acetate was efficient and practical as normal acid-base balance was maintained. The protocol with restricted fluid intake (1st day 50 ml/kg, 2nd day 70 ml/kg, 3rd day 90 ml/kg, and 4th day 110 ml/kg), high air humidity, a sodium supply of 3 to 4 mmol/kg/day, and a slow correction of metabolic acidosis with sodium acetate, yields suitable guidelines in planning fluid and electrolyte therapy in premature infants less than or equal to 34 weeks' gestation.

Hyperglycemia readily develops during intravenous glucose administration in premature infants. In this study glucose homeostasis was measured in 24 infants appropriate-for-gestational age with a gestational age between 27 and 34 weeks and a birthweight between 1,150 and 2,610 g. The infants were randomly assigned to one of two treatment groups. Fluid intake consisted of intravenous infusion of 5% glucose in Group 1 and 10% glucose in Group 2, and increasing amounts of human milk from the first day of life. The infants were treated in incubators with high air humidity in order to minimize insensible water loss and total fluid intake was restricted. The fluid restriction and early enteral feeding decreased the total amount of glucose given parenterally and thereby the risk of hyperglycemia. Glucose homeostasis was efficiently maintained in both groups and under the conditions described hydration by intravenous infusion of 5% and 10% glucose appear equally well tolerated.

In Reply .—Kasik and colleagues criticize our use of sodium acetate in the fluid therapy of premature infants. In our study we set up a goal to avoid variations in osmolality by providing a stable water, sodium, and acid-base balance. Naturally, we made all efforts to establish adequate ventilation, cardiac output, peripheral perfusion, and renal output, as well as to control infection and provide appropriate nutrition. But parallel to these managements, we wanted to find guidelines for planning the fluid and electrolyte therapy. The infants were treated according to a restricted fluid regimen in an environment minimizing insensible water loss. It is our view that this approach gives the best opportunity to control water balance and water losses after birth. Furthermore, we believe that in all situations, other than those with an alkalosis, a base anion could routinely be a part of fluid administration. Sodium acetate, without the problems of

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.