Surgical closure of patent ductus arteriosus in very-low-birth-weight infants.

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.

Short- and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn.

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.

Role of HLA in congenital heart block: susceptibility alleles in children.

Congenital heart block (CHB) is a syndrome of uncertain pathogenesis leading to cardiac conduction disturbances in the foetus and newborns. It has been proposed that maternal antibodies transmit immunological injury in the developing foetal heart, thus causing irreversible damage of the atrioventricular node, leading to third-degree atrioventricular block. However, some genetic or environmental factors may also be involved. We have searched for genetic markers that play a role in immune response and that would be pathognomonic for the disease, either in mothers by regulating their immune response or in children by affecting antigen presentation and target for the maternal immune response. We have compared HLA class I and II alleles of the children with their mother and with healthy individuals and searched for HLA markers that would be emphasized in children. We have shown that particular DQ alleles in the child predispose to CHB, perhaps serving as antigen-presenting molecules on site. In addition, the HLA-Cw3 allele is involved, although its function remains to be clarified. In our results, children with CHB were often identical to their mothers in alleles of DRB, DQA and DQB loci, thus affecting foetomaternal recognition and suggesting that cell-mediated mechanisms could be involved in the pathogenesis.

Hemodynamic control of atrial natriuretic peptide plasma levels in neonatal respiratory distress syndrome.

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)

Hypoglycemia is common in preterm infants in intensive care.

The blood glucose concentration was measured once daily during the first five days of life in forty appropriate-for-gestational age preterm infants in intensive care. They received human milk and 10% glucose perorally and intravenously. Moderate hypoglycemia (B-Gluc < 2.5 mmol/l) was common in these infants (42%) during the first three days of life. Four infants had severe hypoglycemia (B-Gluc < 0.6 mmol/l) during the first day of life. These data suggest that screening for hypoglycemia will be needed for optimal treatment in preterm infants in intensive care.

Plasma endothelin-1 in the neonatal respiratory distress syndrome.

In order to study the contribution of the vasoconstrictory peptide endothelin-1 (ET-1) to the elevation of the pulmonary vascular resistance in the neonatal respiratory distress syndrome (RDS) seven preterm infants were studied at 2, 24 and 48 hours of age for plasma ET-1 concentrations and systolic pulmonary artery pressure (PAP), measured by Doppler sonography. Plasma ET-1 levels were high during the first day after birth, but declined soon to normal levels thereafter. During the study period, the systolic PAP also decreased, whereas the systemic pressure remained unchanged. There were no correlations between plasma ET-1 and vascular pressures, but there was a significant association between ET-1 and the requirement of supplemental oxygen and the arterial-alveolar oxygen tension ratio. Our results thus suggest that high plasma ET-1 levels in the acute phase of RDS reflect the severity of the pulmonary disease, but may not significantly contribute to the elevation of the pulmonary vascular resistance in the RDS.

Incidence of bronchopulmonary dysplasia during an 11-year period in infants weighing less than 1500 g at birth.

We studied the occurrence of bronchopulmonary dysplasia (BPD) during an 11-year period in infants weighing less than 1500 g at birth and looked for differences between the periods 1980-1985 (216 infants) and 1986-1990 (217 infants). During the neonatal period, 91 infants died, which gives a neonatal survival rate of 79%. Forty-nine infants developed BPD, which is 11% of all infants and 14% of the infants surviving the neonatal period. The incidence of BPD did not change during the two study periods (11.6% and 11.1%). On the other hand, the study populations changed in many respects. The number of infants with a birth weight of less than 1000 g increased, the incidence of severe RDS increased, and infant mortality decreased. Hence, there was a small decrease in the incidence of BPD in infants surviving the neonatal period from 14.9% to 13.8%. Severe RDS and a birth weight of less than 1000 g were clearly related to the development of BPD. In these two risk-groups the decrease in the incidence of BPD in neonatal survivors was pronounced.

Short-term primary cultures in studies of post-natal maturation of the rat proximal tubule-proton and bicarbonate transport.

This is a review of recent work based on an in vitro model which has allowed us to investigate the postnatal maturation of renal epithelial cells. Renal proximal tubule cells from 8- to 40-day-old Sprague-Dawley rats were studied after 48 h of primary culture. The regulation of intracellular pH (pHi) was measured by quantitative fluorescence microscopy using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Recordings were made under basal conditions and after imposing a cytoplasmic alkalosis or acidosis using 15 mM ammonium salt. The ability of the cells to recover from both acidosis and alkalosis improved during post-natal maturation. The improvement in recovery from intracellular acidosis could be entirely accounted for by an increase in the rate of Na+/H+ exchange. The capacity for Na+/H+ exchange was independent of the cellular growth rate, but depended on cellular differentiation. A developmental increase in the activity of Cl-/HCO3- exchange between 12 and 14 days of age was also demonstrated. No developmental change was seen in either steady-state pHi (7.27-7.35) or in cytoplasmic buffer capacity (37.6-44.4 mM/pHi). The characteristics of transporter maturation revealed by these experiments are very similar to those observed in isolated perfused proximal tubules of developing rabbits.

Atrial natriuretic peptide in the preterm infant. Lack of correlation with natriuresis and diuresis.

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.

Intracellular pH regulation in cultured renal proximal tubule cells in different stages of maturation.

This study examines the ontogeny of cellular pH regulation in renal proximal tubule cells (RPTC). RPTC from 8- to 40-day-old Sprague-Dawley rats (RPTC-8 to RPTC-40) were studied after 48 h of primary culture. Intracellular pH (pHi) was measured by quantitative fluorescence microscopy using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Recordings were made under basal conditions and after imposing a cytoplasmic alkalosis and acidosis using 15 mM NH4+ salt. The net recovery rate (dpHi/dt) from intracellular acidosis increases significantly between 10 and 12 days of age from 0.39 +/- 0.04 to 0.54 +/- 0.06 pH units/min (P < 0.05, n = 10 vs. 6). This increase can be completely accounted for by an increase in the rate of amiloride (100 microM)-inhibitable Na(+)-H+ exchange (0.29 +/- 0.04 vs. 0.42 +/- 0.05 pH units/min, P < 0.05, n = 6 vs. 6). The rate of Na(+)-H+ exchange increases similarly in RPTC-10 and RPTC-40 when the transmembrane Na+ gradient is increased by Na+ depleting the cells (48 and 49%, respectively). The amiloride-insensitive recovery is Na+ independent and insensitive to 4-acetamido-4'-isothiocyanostilbene-2-2'-disulfonic acid (SITS, 500 microM) (range 0.08-0.14 pH units/min). The net recovery rate from intracellular alkalosis is significantly lower in RPTC-10 than in RPTC-40 (0.16 +/- 0.02 vs. 0.28 +/- 0.02 pH units/min, P < 0.01, n = 4 vs. 5). SITS (500 microM) inhibits the recovery by 27 +/- 8 and 26 +/- 9%, respectively, whereas amiloride has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathoadrenal activity in preterm infants during the first five days of life.

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.

Mode of delivery, plasma catecholamines and Doppler-derived cardiac output in healthy term newborn infants.

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 significant 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.

Renal function in preterm infants during the first five days of life: influence of maturation and early colloid treatment.

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 less than 30 weeks (G less than 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 less than 30 and no FFP (8 infants), G less than 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 less than 30 or G 30-34. CCr was significantly lower (p less than 0.001) and fractional urinary sodium excretion significantly higher (p less than 0.002) in infants of G less than 30 than in infants of G 30-34. Infants of G less than 30 had significantly higher plasma potassium concentrations (p less than 0.01) than infants of G 30-34. Despite the low CCr and the high urinary sodium excretion rate, infants of G less than 30 had stable fluid and electrolyte balance.

Extracellular volume in preterm infants: influence of gestational age and colloids.

We assessed the effect of fresh frozen plasma (FFP) on extracellular volume (ECV) during the first few days of life in two groups of preterm infants, group 1 (gestational age less than 30 weeks) and group 2 (gestational age 30-34 weeks). The infants were randomly assigned to one of two treatment groups, one receiving FFP, the other not; group 1 infants receiving no treatment (n = 8) and group 1 infants receiving FFP (n = 11), and group 2 infants receiving no treatment (n = 9) and group 2 receiving FFP (n = 10). FFP was given at a dose of 10 ml/kg daily during a two-hour period for the first three days of life. ECV was measured on day 1 before FFP was given and on day 4 by the distribution of bromide. There was a significant correlation between birth weight and initial ECV (r = 0.85, P less than 0.001). In group 1 ECV was significantly higher than in group 2 (P less than 0.02). In group 1 receiving no treatment mean weight loss and mean decrease in ECV were equal (84 g/kg and 78 ml/kg, respectively), but no correlation between the two parameters could be found (r = 0.68, P = 0.06). In the other study groups, mean weight loss was higher than mean decrease in ECV, with no correlation between weight loss and change in ECV.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of extracellular fluid volume by bromide dilution in infants less than 1000 grams birth weight.

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.

Grading of left-to-right shunting ductus arteriosus in neonates with bedside pulsed Doppler ultrasound.

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.

Stable glucose balance in premature infants with fluid restriction and early enteral feeding.

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.