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Background: Preterm infants with very low birth weight < 1500 g (VLBW) have a higher risk of developmental disorders. In addition to the common estimation of the mean intelligence values, we studied the distribution of intelligence at preschool age in VLBW infants and the risk factors influencing this distribution., Patients and Methods: A prospective cohort study of 277 VLBW infants < 32 weeks born in 1991-1995 and treated according to a standardized regimen in one Perinatal Center was carried out, including measurement of intelligence (Kaufman-Assessment Battery for Children) at age 5. Statistical methods employed were: explorative data analysis, correlation, chi (2)- and t-tests; the tested variables were: small for gestational age (< third percentile), perinatal acidemia (umbilical arterial pH < 7.10), perinatal hypoxia (BE < - 10), hypothermia (< 36 degrees C), hypoglycemia after the first day of life (< 30 mg / dL), bronchopulmonary dysplasia (FiO (2) > 0.21 > or = 36 weeks), intraventricular hemorrhage, ventricular dilation, periventricular leukomalacia, seizures, abnormal acoustic evoked potentials, and hyperexcitability at discharge., Results: The distribution of intelligence in 137 VLBW infants < 32 weeks (60 % follow-up rate) was similar to a symmetrical Gaussian bell curve. The intelligence increased very slightly with birth weight (Pearson correlation: 0.172; p = 0.045) and was significantly lower in children with hypoglycemia after the first day of life (- 13.35; 95 % confidence interval: - 20.08 to - 6.63; p = 0.002), hyperexcitability at discharge (- 16.28; 95 % confidence interval: - 25.26 to - 7.31; p = 0.005), and bronchopulmonary dysplasia (- 7.00; 95 % confidence interval - 11.71 to - 2.29; p = 0.039)., Conclusions: At preschool age, the intelligence of VLBW infants is normally distributed and correlates only slightly with the very low birth weight. Hypoglycemia after the first day of life and bronchopulmonary dysplasia are risk factors for lower intelligence. Hyperexcitability at discharge seemed to represent a promising prognostic factor for a later intelligence reduction.

We report our experience of pacemaker treatment in a premature infant of 832 grams with congenital complete atrioventricular block due to maternal Sjögren's Syndrome. She was delivered by cesarean section at an estimated gestational age of 26 weeks because of fetal bradycardia, decreasing fetal movements and hydrops. Immediate postnatal transesophageal ventricular pacing was not successful, whereas transthoracic pacing with self-adhesive patch electrodes adapted to body size resulted in an effective increase of the infant's heart rate until operative application of temporary epimyocardial pacing wires ensured the external stimulation of the heart.

Background: Although nonoliguric hyperkalemia of the premature infant is a common problem, in many hospitals it is not observed. It is characterized by an excessive increase in serum potassium concentration (serum-[K (+)]) at 24 hours after birth. Recently, salbutamol has been recommended to treat hyperkalemia. There are no controlled trials in premature infants. During the first minutes of salbutamol infusions paradoxical increases in serum-[K (+)] may occur. We asked for possible reasons for the variable incidence of the disorder. We wanted to know if salbutamol is currently applied and if initial increases in serum-[K (+)] during salbutamol infusions have been observed., Materials and Methods: National survey in Germany., Results: Questionnaires of 132 hospitals caring for premature infants < 30 gestational weeks. The incidence of hyperkalemia was 0 - 40 %. At least 25 % of all hospitals measured serum-[K (+)] not before the second day after birth. 52 hospitals had applied salbutamol. Nine hospitals reported increases in serum-[K (+)] associated with salbutamol therapy. However, it was common practice to measure serum-[K (+)] 1 hour (median, range 0.25 - 12 hours) after the start of the infusion. Two cases of cardiac arrhythmias during salbutamol infusion were reported., Discussion and Conclusions: The variable incidence of hyperkalemia may result from the fact that many hospitals do not measure serum-[K (+)] on the first day after birth. Common practice made it potentially impossible to determine the frequency of initial increases in serum-[K (+)] during salbutamol infusion. However, these data should be available, before controlled trials on salbutamol treatment in premature infants can be initiated.

Objectives: We review the efficacy of oral sugar solutions for treating procedural pain in neonates and address the following questions: Do newborns need analgesic therapy for procedural pain during blood sampling? How do sugars influence pain-reactions of neonates? What is the efficacy of sugar solutions in clinical practice?, Methods: We searched for relevant articles in the PubMed database from 1990 to September 2000., Results: Treatment of procedural pain in newborns is desirable because they are more sensitive to pain than adults, they show marked pain reactions during blood sampling and repeated acute pain in the newborn period results in longterm behavioural changes. Oral sugar solutions have been studied for treatment of procedural pain in neonates. Their initial effect is the result of orotactile stimulation by the intraoral fluid. The orogustatory stimulation by the sweet taste prolongs the effect for up to 10 minutes through endorphin release. In randomized-controlled trials oral sugar solutions (2 ml of 25% sucrose or 30% glucose) reduced pain reactions and crying and attenuated the heart rate increase after capillary and venous blood sampling in term and preterm neonates. They are more effective than traditional calming strategies, like cuddling by parents, use of a pacifier, or breast feeding. Yet, sugar solutions provide no adequate analgesia for more severe pain, e.g. during circumcision., Conclusions: Sugar solutions effectively relieve procedural pain during blood sampling in neonates. Additional studies are needed to determine the minimal effective dose and the efficacy and side effects of repeated sugar doses in the same patient.

We report our experience of pacemaker treatment in a premature infant of 830 g with congenital complete atrioventricular block due to maternal Sjögren's Syndrome. The infant was delivered by cesarean section at an estimated gestational age of 26 weeks because of fetal bradycardia, decreasing fetal movements, and hydrops. Immediate postnatal transesophageal ventricular pacing was not successful, whereas transthoracic pacing with self-adhesive patch electrodes adapted to body size resulted in an effective increase of the infant's heart rate until operative application of temporary epimyocardial pacing wires allowed external stimulation of the heart.

Objective: This prospective study reports on the prevalence of hearing impairment in an at-risk neonatal intensive care unit (NICU) population., Design: From 1990 to 1998, 1062 neonates were screened with the use of transitory evoked otoacoustic emissions (TEOAE) and brainstem evoked response audiometry (BERA)., Results: 934 infants passed the primary screen for both ears, 75 for one ear, adding up to 95%. 17 infants (1.6%) were lost to follow-up. In fourteen infants (1.3%), bilateral hearing impairment above 30 dB was confirmed. While all children with hearing impairment belonged to the group of 862 children receiving aminoglycosides, only one of them presented no other risk factors. In twelve of the hearing impaired children other anamnestic factors, i.e. dysmorphism, prenatal rubella or cytomegaly, family history of hearing loss or severe peri- and postnatal complications seem to be more probable causes of the identified hearing loss. In one of these children, delayed onset or progression of hearing loss is suspected., Conclusions: From our data, aminoglycosides are not an important risk factor for hearing impairment, when serum levels are continuously monitored, as in our cohort. After adjustment for other risk factors, birth weight between 1000 gr and 1500 gr and a gestational age between 29 and 31 weeks were no predictive markers for hearing impairment. It might be speculated that the improved medical treatment in a NICU reduces the probability of hearing impairment for those two groups. Conductive hearing loss as a possible additional cause for hearing impairment was not studied in detail, but the high percentage of malformations detected (four out of fourteen hearing impaired infants) demands further monitoring, close follow-up, adequate treatment and counselling.

In a retrospective study we investigated the mortality and the most important complications of all very low birth-weight infants (VLBW; < or = 1500 g and/or < or = 32 weeks) born with vital signs between 1984 and 1992 at the Klinikum Grosshadern, Munich University Hospital. During this period 859 premature infants fulfilled the entrance criteria. The perinatal mortality rate was 174/859 infants (20%). During the study period the mortality rate dropped significantly from 25% (1984-1986) to 15% (1990-1992). Premature infants born after 26 gestational weeks showed the most significant decrease in mortality. Excluding non viable infants with extreme immaturity ( < 24 weeks of gestation) or lethal malformations; the mean corrected mortality rate was 11%, decreasing over the years from 16% (1984-1986) to 5% (1990-1992). Caesarean section was performed in 70% of all children (602/859), vaginal delivery in 28% (239/859), delivery by forceps in 1% (7/859), and the mode of delivery was not clearly registrated in 1% (11/859). The incidence of Caesarean section increased significantly from 55% (1984-86) to 79% (1990-92). Evaluating the mode of delivery in relation to mortality, a significant difference was found between the infants delivered vaginally (40%, 95/239) and those delivered by Caesarean section (11%, 67/602). This improved survival after Caesarean section was statistically significant for the group with a birth weight of less than 1500 g. The rate of pneumothorax also declined significantly from 19% to 9%. The rate of intracranial haemorrhage (ICH) remained almost constant during these years, but the incidence of ICH grade 3 and 4 decreased from 15% (1984-1986) to 6% (1990-1992). Probably because of improved antenatal care and the progress in neonatal intensive care, the chance of survival for VLBW infants has substantially improved over the last decade. Estimations of the prognosis of VLBW infants based on data from the 1980s are out of date.

In acute hypoxemic respiratory failure of term and near-term neonates, extra- and intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation-perfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near-term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2 from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose-response measurements performed during the first 8 hr of NO inhalation were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions., Methods: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward., Results: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02)., Conclusions: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

In 9 ventilated preterm infants (birth weight 810-1310 g, gestational age 26-30 weeks) we measured total body water (D2O dilution), extracellular volume (sucrose dilution) and renal function parameters at birth and when postnatal weight loss exceeded 5% of birth weight together with day to day changes of weight, fluid balance, and serum electrolytes. A significant postnatal weight loss (-89 +/- 47 g) occurred together with a reduction of total body water (-102 +/- 95 ml) and extracellular volume (-98 +/- 59 ml) in the first three days of life. The intracellular volume did not change. At the same time fluid balance was negative due to a high extrarenal water loss on day 1 and an increasing diuresis on the following days. The serum sodium concentration remained unchanged during postnatal water loss, because the negative fluid balance was accompanied by a negative sodium balance.

Red cell mass (RCM) was estimated using 125I-labelled human serum albumin in 128 premature infants born after 26 to 36 weeks gestation. Infants of three different gestational periods (26--29, 30--32, and 33--36 weeks) with respiratory distress (RD) averaged lower one-minute Apgar scores and lower RCM than infants without RD (P less than 0.05). The incidence of RD was significantly (P less than 0.05) higher in infants with Apgar scores below 6 and in infants with RCM of less than 35 ml/kg than in the infants with greater values. The highest incidence of RD and the highest mortality rate were found in the infants with low Apgar scores and low RCM values. Prematures with similar Apgar scores showed a higher incidence of RD when RCM was low, and infants with similar RCM showed a higher incidence of RD when Apgar scores were low. Our results suggest that both birth asphyxia and deficiency of red cell mass interfere with postnatal cardio-respiratory adaptation. In high-risk premature infants, erythrocytes should be transfused when the venous haematocrit is below 0.459

Trends in relative susceptibility of clinical isolates, mostly from newborns with nosocomial infections, to the aminoglycosides in use in a hospital for children are described and related to practical therapeutic aspects. Currently, amikacin is the most effective of the available antibiotics against many gram-negative bacterial species, and its administration appears to be as complicated as that of other aminoglycosides. With 5 mug/ml taken as the cut-off point for susceptibility in vitro, 90% of 211 clinical isolates (Pseudomonas aeruginosa, Escherichia coli, Klebsiella, Serratia, and other species) could be considered sensitive to amikacin; the respective figures for sensitivity to sisomicin, gentamicin, and tobramycin were 80.5%, 66%, and 70%. Cross-resistance of microorganisms to amikacin and gentamicin, sisomicin, or tobramycin has not been demonstrated. Treatment with amikacin was successful in 13 of 15 children (premature and normal newborns with primarily septicemia); death of two patients was attributable to the underlying disease. For neonatal infections we recommend 12 mg of amikacin/kg per day; determination of the minimal inhibitory concentration for the causative pathogen and monitoring of serum concentrations are desirable.