Does early erythropoietin therapy decrease transfusions in anemia of prematurity ?

Objective. To investigate the effect of early erythropoietin treatment on induction of erythropoiesis and the need for transfusion in Very Low Birth Weight (VLBW) infants with acute neonatal problems.Methods. The study group consisted of 14 VLBW prematures with gestational ages less than 32 weeks who were given subcutaneous erythropoietin (600 U/kg per week) and oral iron (3 mg/kg per day) during the first 7–8 weeks of their life, while 13 other VLBW prematures that were given placebo constituted the control group. Weekly hemotocrit, (Hct) reticulocyte (Ret) values and the volume of blood drawn and transfused were recorded in the both groups.Results. The groups were comparable regarding with birth weights and gestational ages. The volume of the blood drawn (76.8 ± 42.5 and 37.0 ± 15.2) was higher and the volume of the transfusions (51.84 ± 49.30 and 68.84 ± 41.2) was lower in the study group but the differences between the groups were not significant (p>0.05). The hemotocrit, the reticulocyte and the ferritin values were similar in both the groups at the end of the therapy.Conclusion. Under the neonatal intensive care circumstances of developing countries where blood volumes needed for laboratory analysis are still very high, phlebotomy losses can not be avoided. Thus early erythropoietin and iron therapy at these doses are not effective in decreasing the need for transfusion and induction of endogenous erythropoiesis.     

Bone mineral density of the lumbar spine in very-low-birth-weight infants: a longitudinal study

To examine osteopenia in very low birth weight (VLBW) infants we used repeated dual-energy X-ray absorptiometry in a prospective study of lumbar spinal bone mineral density (BMD) in Japanese VLBW infants (birthweight 426–1498 g; n = 61, group 1) aged 40 weeks postconception to 3 years of age. Control subjects were Japanese infants with birthweight 1500–1999 g (group 2), 2000–2499 g (group 3), or more than 2500 g (group 4). BMD in group 1 during the early period after birth was very low, increased rapidly for 1 year, and then gradually increased until 3 years of age (r =  0.931, P < 0.0001). BMD at the age of 40 weeks postconception was 0.085 ± 0.026, 0.132 ± 0.039, 0.178 ± 0.042, and 0.196 ± 0.046 g/cm² in groups 1, 2, 3, and 4, respectively (P < 0.0001). However, at 1 and 2 years of age no differences were observed among the groups in BMD. Conclusion This study shows that lumbar spinal BMD in VLBW infants can normalize by the age of 2 years. Received: 12 May 1999 / Accepted: 11 October 1999     

Prevention of necrotizing enterocolitis in extremely low birth weight infants by IgG feeding?

Oral immunoglobulin has been described as preventing necrotizing enterocolitis(NEC) in preterm infants. To prevent NEC in extremely low birth weight infants (ELBW), we have carried out oral IgG prophylaxis since April 1991. The efficacy of this prophylaxis was examined in a study comparing historical cohorts. ELBW infants delivered in the Department of Obstetrics and Gynaecology of the University of Ulm and treated until day 28 in the level III intensive care nursery, Division of Neonatology, University of Ulm were included. Cohort 1, born between 1.1.1988 and 31.3.1991, received no oral IgG and served as a control [n=84, gestational age: median 26 weeks, range 24–34; birth weight: 811 g, 490–990], cohort 2, born between 1.4.1991 and 31.12.1995 [n=137, gestational age: 26 weeks, 22–32; birth weight: 760 g, 362–995], received 6 × 100 mg/kg human IgG (Beriglobin) orally on days 1–28. NEC, stage 2a and higher according to the modified classification of Bell, was observed in 9 of 84 (10.7%) infants of cohort 1 and in 11 of 137 (8%) infants of cohort 2 until day 28. The difference did not reach statistical significance (P=0.63 Fisher's exact test). Conclusion In this historical cohort study, ELBW infants were not protected against NEC by oral IgG. The present published evidence does not allow recommendation of oral human IgG administration in preterm infants as a prophylactic measure against NEC. Received: 8 June 1997 / Accepted in revised form: 1 January 1998     

Fractional anisotropy in white matter tracts of very-low-birth-weight infants

Background Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods We retrospectively analysed DTI images of 28 VLBW infants (26–32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1–3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm²) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age.     

Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake

There is no consensus regarding protein intake and the doses of recombinant human erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity (AOP). This open, randomized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In addition, two different protein supplements have been compared; lyophilized human milk protein and a commercial cow’s milk product. Total protein intake was 3 g/kg per day. Daily iron dose was 18–36 mg. “Healthy” preterm infants (n = 32, birth weight: 800–1400 g, gestational age ≤ 31 weeks) were studied from age 3 to 8 weeks. The two protein regimens yielded no differences in body growth, reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment; higher levels were, however, found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency, soluble transferrin receptor increased in both groups, more rapidly and to higher levels in the 100 IU/kg group. In addition, the number of infants having more than 8% hypochromic red cells increased in both groups. Conclusions Commercial cow’s milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis. Received: 20 January 1996 / Accepted: 2 February 1996     

Comparison of the effects of theophylline and caffeine on serum erythropoietin concentration in premature infants

Theophylline administration has been shown to attenuate erythropoietin (EP) production in adults; the effect of caffeine is not known. Our aim was to determine whether caffeine and theophylline had similar effects on EP production in the premature newborn. If caffeine was found to have a greater effect, this would influence prescribing habits. Fifty preterm infants (mean gestational age 28 weeks) who had clinically significant apnoea were randomized to receive theophylline (4 mg/kg then 2 mg/kg twice daily) or caffeine (10 mg/kg then 2.5 mg/kg once daily). The methylxanthines were continued at least until discharge from the NICU and the dosage altered to keep the levels within the therapeutic range. As an assessment of EP production, serum EP concentrations were measured. Blood for EP, haemoglobin, reticulocyte count, theophylline and caffeine levels was obtained prior to treatment and at least during weeks 3 and 7. There was no significant difference in the mean EP level in the two groups taken prior to treatment at a median age of 2 days of life. There were similar falls in haematocrit and haemoglobin in the two groups during the study period compared to pre-treatment values. At that time, however, the median reticulocyte count was higher in the caffeine compared to the theophylline treated infants (P < 0.05). This was associated with a rise compared to baseline (median 10.0–0.2 mU/ml) in the mean EP levels in the caffeine group and a decrease from a median of 10.1 to 8.3 mU/ml in the theophylline group, but the EP levels in the two groups at week 7 did not differ significantly. Conclusion These results suggest that caffeine does not have a greater impact than theophylline on EP production. Received: 14 April 1997 / Accepted in revised form: 10 September 1997     

Calcium metabolism and growth during early treatment of children with X-linked hypophosphataemic rickets

To evaluate the effect of early treatment on calcium metabolism and growth of infants with X-linked hypophosphataemic rickets (XLH), we enrolled eight infants (one boy) with XLH in a prospective study before and during combined treatment with 40–60 mg/kg per day phosphate and 20–40 ng/kg per day 1,25(OH)₂D₃ (calcitriol). The duration of treatment ranged from 12 to 68 months (median 27 months). We measured the height and several indices of calcium and bone metabolism before and at intervals of 6 weeks to 3 months thereafter during treatment. The diagnosis XLH was established between the age of 3 to 12 weeks by the detection of elevated alkaline phosphatase activities (n=8) and urinary hydroxyproline (n=7), whereas only five patients had also hypophosphataemia. Six of seven untreated patients had decreased 1,25(OH)₂ vitamin D levels in serum. During treatment alkaline phosphatase and hydroxyproline decreased to normal or slightly elevated levels, whereas serum phosphate remained below the normal range. Several patients treated with more than 40–50 mg/kg per day phosphate developed secondary hyperparathyroidism. One patient receiving a low dose of 20 ng/kg per day calcitriol had prolonged radiological and biochemical signs of rickets and growth delay. The other patients presented with no or only slightly transient signs of rickets. Three patients developed moderate nephrocalcinosis. The statural growth rate decreased slightly below 2 SDs without a further decrease in two patients and remained within the normal range in the other patients. Only four patients developed moderate leg deformities. Conclusions Early treatment with calcitriol at a daily dose of at least 30–40 ng/kg and phosphate at a daily dose of maximal 40–50 mg/kg improves mineral metabolism and seems to obviate severe growth delay and leg deformities. Received: 11 February 1998 / Accepted in revised form: 31 May 1998     

Oral iron supplementation in preterm infants treated with erythropoietin

BACKGROUND: It is not known whether a moderate dose of oral iron supplementation would further enhance erythropoiesis in recombinant human erythropoietin (EPO)-treated very low-birthweight (VLBW) infants. METHODS: In total, 24 preterm infants with birthweights 750-1499 g were enrolled at the age of 14-28 days to receive 400 IU/kg per week EPO subcutaneously for 8 weeks. The infants were randomly allocated either to receive oral iron supplementation 4 mg/kg per day or to serve as controls. RESULTS: Hemoglobin and the absolute reticulocyte count in the iron supplementation and the control groups remained identical throughout the study period, whereas serum ferritin was significantly lower in the control group at study exit and follow up. Rates of treatment success (no need for transfusion and hemoglobin never below 8 g/dL) also did not differ between the groups. CONCLUSIONS: In this study we did not find a clear advantage in a moderate dose of oral iron supplementation on erythropoiesis in EPO-treated VLBW infants. Whether a higher dose would lead to enhanced erythropoiesis remains to be answered.     

Early versus late dexamethasone treatment in preterm infants at risk for chronic lung disease: a randomized pilot study

The purpose of this controlled, prospective pilot study was to compare the short-and long-term efficacy of early versus late treatment with dexamethasone (Dex) in preterm infants at risk for chronic lung disease (CLD). Thirty ventilated premature infants with a birth weight ≤ 1250 g were randomized to receive Dex either from day 7 or from day 14. Dex was administered over 16 days tapering from 0.5 mg/kg per day to 0.1 mg/kg per day. The infants of the early treatment group could be weaned significantly earlier from the ventilator – after 14 days (median; range 9–24) versus 24 days (median; range 8–44) in the late treatment group. The need for supplemental oxygen was shorter if Dex was started early – 24 days (median; range 10–57) versus 40 days (median; range 10–74). Oxygen dependency at 28 days of age was similar between the groups – 6 out of 14 infants (42.9%) versus 10 out of 16 patients (62.5%). The long-term efficacy of the two Dex regimens on lung function was evaluated by body plethysmographic measurements made at the age of 3 months. Thoracic gas volume and airway resistance were measured and specific airway conductance calculated. No statistically significant differences between the groups were demonstrated. Conclusion Early dexamethasone treatment led to earlier extubation in our study population, but was not associated with significant advantages regarding oxygen dependency at 28 days of life and pulmonary function test at 3 months of age. Received: raised 31 July 1997 / Accepted in revised form: 15 March 1998     

Persistent coagulase-negative staphylococci bacteremia in very-low-birth-weight infants

This study sought to expand current knowledge on the clinical and epidemiological characteristics of persistent coagulase-negative Staphylococcus (CoNS) bacteremia in very-low-birth-weight (VLBW) infants. Background and disease-related data were collected prospectively on 143 VLBW infants diagnosed with CoNS bacteremia at a pediatric tertiary medical center in 1995–2003. Findings were compared between those with persistent (positive blood cultures for >72 h under appropriate treatment ) and nonpersistent disease. Fifty-eight infants (40.6%) were found to have persistent bacteremia. There were no between-group differences in maternal characteristics, mode of delivery, newborn characteristics, dwell time of central venous and umbilical catheters, complications of prematurity, or mean hospital stay. The persistent bacteremia group had significantly higher rates of hypothermia at presentation (37.9% vs. 17.6%, p < 0.04), creatinine >1.2 mg% on treatment day 7 (13.7% vs. 2.4%, p < 0.02; transient phenomenon), and endocarditis (p < 0.03); one infant had an aortic thrombus. Predominantly breast-fed infants had a higher rate of negative cultures within 72 h of appropriate treatment than predominantly formula-fed infants (60% vs. 19%, p < 0.02). In conclusion, persistence of CoNS bacteremia is common in VLBW infants. Endocarditis should be excluded in all infants with persistent disease. Breast-feeding is associated with a shorter disease duration.     

Total serum bilirubin levels during the first 2 days of life and subsequent neonatal morbidity in very low birth weight infants: a retrospective review

To determine the relationship between total serum bilirubin (TSB) during the first 2 days of life and subsequent neonatal morbidity in very low birth weight (VLBW, less than 1500 g) infants. We performed a prospective study of 582 VLBW infants born between July 1, 2005 and December 31, 2009. TSB was measured in umbilical cord blood (UCB), at 24 and 48 h after birth. Demographic and clinical characteristics of infants in hospital were recorded. The interaction between TSB variables during the first 48 h of life and subsequent neonatal morbidity were assessed in logistic regression analyses adjusted for multiple risk factors. It was found that TSB in UCB was in a negative correlation with occurrence of respiratory distress syndrome (RDS) [OR 0.626, 95% confidence interval (95% CI): 0.446–0.879, p = 0.007], and there was also a negative correlation between TSB in UCB and occurrence of intraventricular hemorrhage (IVH) [OR 0.695, 95% CI 0.826–0.981, p = 0.020]. However, TSB in UCB positively correlated with hyperbilirubinemia [OR 2.471, 95% CI 1.326–3.551, p = 0.012], and TSB at 24 h after birth was also in a positive correlation with early onset sepsis (EOS) [OR 1.299, 95% CI 1.067–1.582, p = 0.011]. VLBW infants with low TSB levels in UCB were more likely to develop RDS and IVH, and those with low TSB levels in UCB were less likely to develop hyperbilirubinemia. Infants with high TSB levels at 24 h after birth were more likely to develop EOS. The protective effect of raised TSB in UCB with respect to RDS and IVH warrants further investigation.     

Effect of recombinant human erythropoietin on transfusion needs in preterm infants

OBJECTIVE: To study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very low birthweight (VLBW) infants. METHODS: We conducted a non-blind randomized controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day 10. Transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g. RESULTS: VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. Of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant. Blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of VLBW infants. CONCLUSION: r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth.     

Nephrocalcinosis in full-term infants receiving furosemide treatment for congestive heart failure: a study of the incidence and 2-year follow up

In order to study the incidence and course of nephrocalcinosis in full-term infants with congestive heart failure receiving long-term furosemide treatment, 36 such infants (median age 2.9 months, range 1.2–8.0) and 36 full-term control infants not receiving any diuretics (median age 3.4 months, range 1.1–8.4) were studied by renal ultrasonography and random urine calcium variables. The infants with nephrocalcinosis were followed at 3–6 month intervals up to 2 years of age, or until ultrasonic resolution. Nephrocalcinosis was found in 5 out of the 36 (14%) treated infants, but in none of the controls (P = 0.03). The dose of furosemide was higher in the infants with nephrocalcinosis than in those without (1.9 ± 0.6 vs. 1.3 ± 0.4 mg/kg per day; P = 0.01). The urinary calcium concentration was higher in the infants receiving furosemide than in& controls and a similar trend was observed in the urinary calcium/creatinine ratio, but& these variables did not differ between the study infants with and without nephrocalcinosis. Ultrasonic resolution of nephrocalcinosis was observed in 3 of the 5& infants at 12 months, but in the other 2 the condition still persisted at 24 months. Conclusions Long-term furosemide treatment in full-term infants with congestive heart failure entails a considerable risk of developing nephrocalcinosis. Renal ultrasonography is warranted in these patients within a few months after initiation of the treatment and in the case of nephrocalcinosis alteration of the diuretic regimen is to be considered. Received: 8 September 1998 / Accepted in revised form: 12 January 1999     

Pharmacokinetics of oral fluconazole in premature infants

Systemic infections with Candida albicans in neonates are a frequent and well recognized problem. The therapeutic gold standard in this situation is the combined intravenous antimycotic treatment with amphotericin B and flucytosine. Potential adverse effects of this regimen have encouraged the search for desirable alternatives. We report on the use of oral fluconazole in neonates with Candida albicans septicaemia. Three premature infants were treated with four courses of therapy. Pharmacokinetic studies were performed during each course. At oral doses of 4.5–6 mg/kg once a day, serum levels of fluconazole were within the therapeutic range during the entire dosage interval. Follow up showed microbiological and clinical cure in all patients with no side-effects. In one patient a dosage of 4 mg/kg per day lead to a microbiological relapse with sub-therapeutic serum levels. Conclusions Oral fluconazole seems to be a safe and effective treatment for Candida albicans septicaemia even in premature infants. Received: 6 March 1997 / Accepted in revised form: 12 November 1997     

Bedside detection of low systemic flow in the very low birth weight infant on day 1 of life

We aimed to assess the relationship between the clinical and biochemical parameters of perfusion and superior vena cava (SVC) flow in a prospective observational cohort study of very low birth weight (VLBW) infants. Newborns with congenital heart disease were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Capillary refill time (forehead, sternum and toe), mean blood pressure, urine output and serum lactate concentration were also measured simultaneously. Thirty-eight VLBW infants were examined. Eight patients (21%) had SVC flow less than 40 ml/kg/min. There was a poor correlation between the capillary refill time (in all sites), mean blood pressure, urine output and SVC flow. The correlation coefficient for the serum lactate concentration was r = −0.28, p = 0.15. The median serum lactate concentration was 3.5 (range 2.8–8.5) vs. 2.7 (range 1.2–6.9) mmol/l (p = 0.01) in low flow versus normal flow states. A serum lactate concentration of >2.8 was 100% sensitive and 60% specific for detecting a low flow state. Combining a capillary refill time of >4 s with a serum lactate concentration of >4 mmol/l had a specificity of 97% for detecting a low SVC flow state. Serum lactate concentrations are higher in low SVC flow states. A capillary refill time of >4 s combined with serum lactate concentrations >4 mmol/l increased the specificity and positive and negative predictive values of detecting a low SVC flow state.     

Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants

Nasal continuous positive airway pressure (CPAP) applied shortly after birth is said to be an effective treatment of respiratory distress in very low birth weight infants (VLBW). We tested the hypothesis that the use of early nasal CPAP (applied as soon as signs of respiratory distress occurred, usually within 15 min after birth) reduces the need for intubation, the duration of intermittent mandatory ventilation and the incidence of bronchopulmonary dysplasia. All liveborn VLBW infants (birth weight < 1500 g) admitted to our tertiary neonatal intensive care unit in 1990 (historical controls) and in 1993 (early nasal CPAP group) entered the study. The intubation rate was significantly lower after introduction of nasal CPAP (30% vs 53%, P = 0.016). Median duration of intubation was 4.5 days (interquartile range 3–7 days) before versus 6.0 days (2.8–9 days) after nasal CPAP was introduced (P = 0.73). The incidence of bronchopulmonary dysplasia was not reduced significantly (32% vs 30%, P = 0.94). Survival until discharge was 89.5% before versus 92.9% after introduction of nasal CPAP (P = 0.54). Conclusion Early nasal CPAP is an effective treatment of respiratory distress in VLBW infants, significantly reducing the need for intubation and intermittent mandatory ventilation, without worsening other stan dard measures of neonatal outcome. We found no significant decrease in the incidence of bronchopulmo nary dysplasia. Received: 5 February 1996 and in revised form: 12 September 1996 / Accepted: 23 October 1996     

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.     

Carbamazepine in phenobarbital-nonresponders: experience with ten preterm infants

 Carbamazepine is a standard anticonvulsant in children and adults. Until now there is only little information available on its use in neonates. We investigated the oral administration of carbamazepine in refractory neonatal seizures treated with phenobarbital. Ten preterm infants (gestational age 23 + 6 – 34 + 6 weeks, birth weight 640 g–3080 g) with neonatal seizures were refractory to a primary therapy with phenobarbital. All patients subsequently received carbamazepine exclusively as a second choice anticonvulsant. A daily dose of 7–23 mg/kg carbamazepine was administered orally in two to three aliquots. All patients reached therapeutic plasma drug levels (3–12 mg/l; 13–50 μmol/l). In nine out of ten patients (complete group of small preterms with gestational age under 30 weeks and weight less than 1000 g), therapeutic success was excellent. Carbamazepine was continued for 1–5 months. After termination of therapy no further seizures occurred, also on EEG recordings. Finally, no carbamazepine-induced adverse effects were observed. Conclusion This is the first report on the use of carbamazepine in small preterm infants. Carbamazepine may provide a useful and effective oral maintenance therapy in the management of neonatal seizures in these patients. Received: 15 November 2000 / Accepted: 20 February 2001     

Prediction of extubation failure in preterm neonates

The aim of this study was to compare the results of lung function measurements made before and after extubation and ventilator settings recorded immediately prior to extubation with regard to their ability to predict extubation success in mechanically ventilated, prematurely born infants. Immediately after extubation all infants were nursed in an appropriate amount of humidified oxygen bled into a headbox. Functional residual capacity, spontaneous tidal volume and compliance of the respiratory system were measured both within 4 h before and within 24 h after extubation. The peak inspiratory pressure and inspired oxygen concentration immediately prior to extubation were recorded. The results were related to extubation failure: requirement for continuous positive airways pressure or re-ventilation within 48 h of extubation. A total of 30 infants, median gestational age 29 weeks (range 25–33 weeks) were studied at a median postnatal age of 3 days (range 1–6 days). Extubation failed in ten infants, who differed significantly from the rest of the cohort with regard to their post extubation functional residual capacity (FRC) (median 23, range 15.6–28.7 ml/kg versus 28.6, range 18.1–39.2 ml/kg, P < 0.01) and their requirement for a higher inspired oxygen concentration post extubation (median 0.30, range 0.21–0.40 versus 0.22, range 0.21–0.36, P < 0.05). An FRC of less than 26 ml/kg post extubation had the highest positive predictive value in predicting extubation failure. Conclusion A low lung volume performed best in predicting extubation failure when compared to the results of other lung function measurements and commonly used `clinical' indices, i.e. ventilator settings. A low gestational age, however, was a better predictor of extubation failure than a low lung volume. Received: 1 November 1998 / Accepted: 16 April 1999     

Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months

As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of >400 μmol/l (23.4 mg/dl) were enrolled and screened with a neonatal neurological examination (NNE). The cause of jaundice was low birth weight in 22 (44%), ABO incomptability in 8 (16%), sepsis in 8 (16%) and congenital syphilis (6%) in 3 infants. In 9 infants a cause could not be determined. At 4 months, 2 infants had died and 3 were lost to follow up, leaving 45 infants for the infant motor screen (IMS) at 4 months of age. Mean TSB in the neonatal period was 485 μmol/l (28.2 mg/dl), and 7 infants received an exchange transfusion. Mean TSB of the infants with an exchange transfusion was 637 μmol/l (37.2 mg/dl) (range 429–865 μmol/l (25–50.3 mg/dl)) and of the infants without transfusion 459 μmol/l (26.8 mg/dl) (range 400–740 μmol/l (23.4–43 mg/dl)) (P < 0.0001). The TSB was not associated with birth weight, gestational age, gender or head circumference of the baby. On the IMS, 6 of 45 (13.3%) infants scored abnormal, 6 (13.3%) suspect and 33 (73%) scored normal. Three of the six (50%) remaining infants who received an exchange transfusion scored abnormal on the IMS while only 3 of the 39 (8%) infants without exchange transfusion were abnormal. Conclusion More than 25% of infants with a TSB of >400 μmol/l (23.4 mg/dl) scored abnormal or suspect at 4 months of age and half of these infants already showed irreversible neurological symptoms. All infants who scored abnormal or suspect on the IMS with bilirubin levels between 400 and 500 μmol/l (23.4 and 29.2 mg/dl) had haemolytic disease or were premature. Received: 4 October 1996 / Accepted: 5 February 1997