Double versus single intensive phototherapy with LEDs in treatment of neonatal hyperbilirubinemia.

OBJECTIVE: We investigate whether double phototherapy reduces total serum bilirubin concentration faster than single light during intensive phototherapy with high levels of irradiance using light-emitting diodes. STUDY DESIGN: Eighty-three infants with gestational age ⩾33 weeks and uncomplicated hyperbilirubinemia were randomized to either double (n=41) or single phototherapy (n=42) for 24 h. The mean irradiance was 64.8 µW cm-2 nm-1 from above and 39 µW cm-2 nm-1 from below. RESULTS: The percentage decreases of total serum bilirubin after 12 h of double vs single phototherapy were (mean (95% confidence interval (CI))) 39% (37 to 42) vs 30% (27 to 32), respectively (P<0.001). After 24 h, the decreases were 58% (56 to 61) vs 47% (44 to 50), respectively (P<0.001). The results were still significant after adjustment for confounding. The only side effect was loose stools. CONCLUSION: Even with intensive phototherapy increasing spectral power by increasing the irradiated body surface area, the efficacy of phototherapy is improved.

Hypothermia at neonatal intensive care unit admission was not associated with respiratory disease or death in very preterm infants.

AIM: This study investigated the association between hypothermia and respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) or death in very preterm infants admitted to a Danish neonatal intensive care unit (NICU). METHODS: We studied 675 infants born at Aalborg University Hospital before 32 weeks and admitted to the NICU from April 1997 to December 2011. Hypothermia was defined as a core temperature of <36.5°C on admission. The primary outcome was severe RDS or death within the first three days of life, and the secondary outcome was BPD or death before 36 postmenstrual weeks. The multivariable logistic regression was adjusted for early-onset infection, gestational age, Apgar score, sex, treatment year and birth weight. RESULTS: Infants with hypothermia had a twofold increase (OR) in the odds for RDS or death (2.03), but the adjusted OR was not statistically significant (1.36). They also demonstrated a twofold increase (OR) in the odds for BPD or death (2.28), but again the adjusted OR was not statistically significant (1.03). CONCLUSION: After adjusting for confounders, we found that the association between hypothermia on admission to the NICU and RDS or death, or BPD or death was statistically insignificant.

De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning.

Clinical hepatocyte transplantation is hampered by low engraftment rates and gradual loss of function resulting in incomplete correction of the underlying disease. Preconditioning with partial hepatectomy improves engraftment in animal studies. Our aim was to study safety and efficacy of partial hepatectomy preconditioning in clinical hepatocyte transplantation. Two patients with Crigler-Najjar syndrome type I underwent liver resection followed by hepatocyte transplantation. A transient increase of hepatocyte growth factor was seen, suggesting that this procedure provides a regenerative stimulus. Serum bilirubin was decreased by 50%, and presence of bilirubin glucuronides in bile confirmed graft function in both cases; however, graft function was lost due to discontinuation of immunosuppressive therapy in one patient. In the other patient, serum bilirubin gradually increased to pretransplant concentrations after ≈600 days. In both cases, loss of graft function was temporally associated with emergence of human leukocyte antigen donor-specific antibodies (DSAs). In conclusion, partial hepatectomy in combination with hepatocyte transplantation was safe and induced a robust release of hepatocyte growth factor, but its efficacy on hepatocyte engraftment needs to be evaluated with additional studies. To our knowledge, this study provides the first description of de novo DSAs after hepatocyte transplantation associated with graft loss.

Lamellar body counts on gastric aspirates for prediction of respiratory distress syndrome.

AIM: To develop a rapid method for diagnosing lung maturity at birth with the purpose of administering surfactant early to infants with immature lungs and to spare infants with mature lungs from this treatment. METHODS: Lamellar body counts (LBC) on gastric aspirates from 191 newborns were counted in the platelet window in automatic blood cell counters. A preliminary study was performed on 108 aspirates from 2000 in infants with <32 weeks' gestation. Furthermore, 83 aspirates from 2004 to 2005 in infants with <30 weeks' gestation were analysed. RESULTS: Lamellar bodies in gastric aspirate were identified by electron microscopy. Seventy of the aspirates from 2004 to 2005 were analysed with a Sysmex XE-2100 (Sysmex, Holbaek, Naestved, Odense and Rigshospitalet, Denmark) counter. Twenty-four of these infants developed moderate to severe respiratory distress syndrome (RDS). The best cut-off value was 8000/µL with a sensitivity of 75% and a specificity of 72%. Forty-four of the 70 aspirates from 2004 to 2005 were analysed by Sysmex, Advia 120 and Cell-Dyn 4000. Thirteen other aspirates from 2004 to 05 were analysed by Sysmex and Coulter Counter LH755. Using Advia and Coulter the results were similar to Sysmex, but LBC obtained with Cell-Dyn were not correlated with the development of RDS. CONCLUSION: Lamellar body counts on gastric aspirate is a promising tool for prediction of development of RDS in infants of <30 weeks` gestation.

Effect of infants' position on serum bilirubin level during conventional phototherapy.

AIM: To compare the decrease in total serum bilirubin (TSB) concentration during conventional phototherapy in infants treated in supine position exclusively versus infants alternated between exposure in supine and prone position every third hour. Moreover, to survey current practice patterns in two Scandinavian countries as far as alternating exposure. METHODS: A total of 112 infants with non-haemolytic hyperbilirubinaemia, but otherwise healthy, and a gestational age > or =33 weeks were randomized to one of the treatment groups. All infants received phototherapy for 24 h. TSB was measured at start of phototherapy and after 12 and 24 h of treatment. Questionnaires about routines for position changes in infants during phototherapy were sent to all 41 neonatal departments in Denmark and Norway. RESULTS: No statistically significant differences in the decrease in TSB were observed between the two treatment groups: at 12 h of therapy, TSB decreased 32% in both groups and at 24 h 49% and 50%, respectively. In two-thirds of Danish and Norwegian departments, the infants were routinely turned during phototherapy, most often every third hours. CONCLUSION: The decrease in TSB was not significantly associated with positioning of the infant during conventional phototherapy. Alternating exposure is widely practiced in Scandinavia but is unnecessary.

Early and late markers for the detection of early-onset neonatal sepsis.

INTRODUCTION: In this study we tested how a combination of early and late paraclinic markers could predict early onset neonatal sepsis (EONS). METHODOLOGY: The first 24 hours after the suspicion of EONS, we measured interleukine (IL)-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha (TNF-alpha), interferon gamma (INF-gamma), procalcitonin (PCT) and C-reactive protein (CRP) at 8-hour intervals on 123 neonates clinically suspected for EONS. The neonates were divided into two groups. The sepsis group: 1A with blood culture verified bacteraemia and 1B strongly suspected sepsis (29 patients). The no sepsis group: 2A treated with antibiotics (37 patients) and 2B not treated with antibiotics (57 patients). RESULTS: Combined evaluation of each of the early markers with PCT > 25 ng/ml for prediction of EONS at time 0, gave the following sensitivities and specificities: IL-6 > 250 pg/ml: 71% and 88%; IL-8 > 900 pg/ml: 50% and 88%; IL-10 > 40 pg/ml: 43% and 87%; and immature/total (I/T) ratio > 0.35: 59% and 88%. The results of IL-18, TNF-alpha and IFN-gamma did not predict EONS. CONCLUSION: IL-6 combined with PCT values is a fair way to evaluate EONS at the time of suspicion of infection. The "old" early marker, I/T ratio, is almost as efficient as IL-6. By combining an early and a late marker it may be possible to reduce the diagnostic "non-conclusive" period of paraclinic values.

Extreme hyperbilirubinaemia in term and near-term infants in Denmark.

AIM: To determine the incidence amongst infants born at term or near-term of extreme hyperbilirubinaemia, i.e., with a serum concentration of unconjugated bilirubin exceeding the limit above which an exchange transfusion was indicated according to the authorized guidelines. METHOD: The investigation period covered 2 y, 1 January 2000 to 31 December 2001, and included all infants born alive at term or near-term in Denmark. All infants with extreme hyperbilirubinaemia admitted to paediatric departments were recorded. RESULTS: Thirty-two infants developed extreme hyperbilirubinaemia, i.e., an incidence of 25 per 100 000. The maximum total serum bilirubin concentration (TSB) was 492 (385-689) micromol/I (median (range)). The median value of the exchange transfusion limits was 450 micromol/l. Twelve infants had signs and symptoms of central nervous system involvement; 11 had acute bilirubin encephalopathy phase-1 symptoms; and one had phase-2 symptoms. Nineteen infants developed extreme hyperbilirubinaemia during primary admission to the maternity ward or neonatal department; the others after having been discharged. There was no difference in maximum TSB between those infants not discharged from hospital and those infants admitted to hospital from home. Maximum TSB appeared latest amongst those infants admitted from home (p < 0.01), and these more often had signs and symptoms of central nervous system involvement (p < 0.05). Ten infants were of non-Caucasian extraction. Less than half of all Danish mothers receive both verbal and written information after birth on jaundice in the infant. CONCLUSION: Twenty-five per 100 000 infants born at term or near-term developed extreme hyperbilirubinaemia, the majority of them whilst in hospital. Infants admitted from home more often had signs and symptoms of central system involvement.

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

Phototherapy with turquoise versus blue light.

Preterm jaundiced infants were treated by phototherapy with a new turquoise fluorescent lamp. This was more effective in reducing plasma total bilirubin in relation to light irradiance than the ubiquitously used blue fluorescent lamp.

Weekly oral vitamin K prophylaxis in Denmark.

AIM: To evaluate oral vitamin K prophylaxis at birth by giving 2 mg phytomenadione, followed by weekly oral vitamin K prophylaxis; 1 mg was administered by the parents until 3 mo of age. METHODS: A total of 507850 live babies were born in Denmark during the study period, November 1992 to June 2000. Of these infants, 78% and 22% received oral and intra-muscular prophylaxis, respectively; i.e. about 396000 neonates received oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants as long as they were mainly breastfed. A survey of possible cases of vitamin K deficiency bleeding (VKDB) was carried out by repeated questionnaires to all Danish paediatric departments and by checking the National Patient Register. RESULTS: No cases of VKDB were revealed, i.e. the incidence was 0-0.9:100000 (95% CI). The questionnaires were used to evaluate compliance with the regimen. Parents of 274 infants participated. A dose of vitamin K was regarded as having been given if the infant received a drop of vitamin K or was mostly formula-fed that week, and the prophylaxis was regarded as completed if the infant had received at least 9 doses. Compliance was good, with 94% of the infants completing the course of prophylaxis. CONCLUSION: Weekly oral vitamin K supplementation during the first 3 mo of life was an efficient prophylaxis against VKBD. Parental compliance with the regimen was good.

Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks' gestation.

AIM: There is a need for a rapid method to identify infants who will develop respiratory distress syndrome (RDS) soon after birth, to allow early treatment of affected infants with surfactant. The microbubble stability test (MST) may be one such method, but clinical experience is sparse. METHODS: The MST was performed on gastric aspirates from 188 infants with a mean gestational age of 29 (range 23-31) wk. RESULTS: 87 infants developed moderate to severe RDS, corresponding to a prevalence of 46%. The sensitivity, specificity and predictive values for identification of infants with moderate to severe RDS were determined for the average diameter of bubbles, the proportion of microbubbles with different diameters and the total number of microbubbles. The proportion of microbubbles with diameters <20 or 25 microm gave the best prediction, with a sensitivity of 78-79%, a specificity of 57-58%, a positive predictive value of 62% and a negative predictive value of 76%. Early treatment with nasal continuous positive airway pressure probably mitigated the development of RDS in some infants with a low-degree surfactant deficiency and this may explain the relatively low specificity. CONCLUSION: In infants of <32 wk gestation RDS can be predicted by computerized image analysis of the size distribution of microbubbles generated in gastric aspirates.

Difference in plasma bilirubin concentration between monozygotic and dizygotic newborn twins.

AIM: To investigate whether inherited factors, other than those already known, influence the bilirubin concentration in neonates of northern European descent, by comparison of monozygotic and dizygotic twins with respect to differences in the plasma bilirubin concentrations between the twins. METHODS: 77 healthy pairs of twins of the same gender with a gestational age > or = 250 d and of northern European descent were included. Fourth postnatal day blood sampling was done. A multiple linear regression analysis was carried out with the difference in serum bilirubin concentration between the twins as the independent factor, and zygosity, gender, gestational age, postnatal age, maternal smoking, ABO blood-type incompatibility, and the differences between the twins in blood haemoglobin concentration, formula feeding and weight loss as dependent factors. RESULTS: 27 pairs of twins were monozygotic and 50 pairs dizygotic. The analysis showed that the difference in serum bilirubin concentration between the twins was dependent on whether the twins were monozygotic or dizygotic, i.e. the estimated difference in serum bilirubin concentration between the monozygotic twins was 17.8 micromol l(-1) [SE 6.6 micromol l(-1), p = 0.02, 95% confidence interval (95% CI) 3.4, 32.3 micromol l(-1)] less than the difference between the dizygotic twins, adjusted for the above-mentioned potential confounders. The difference in serum bilirubin concentration between the twins was positively correlated to the difference in weight loss (%) between the twins (adjusted estimate 5.2 micromol l(-1), SE 2.1 micromol l(-1) , p = 0.01, 95% CI 1.2, 9.3 micromol l(-1)). CONCLUSION: In a population of northern European descent, other genetic factors than gender and ABO blood type were significant for the plasma bilirubin concentration in healthy infants.

A new transcutaneous bilirubinometer, BiliCheck, used in the neonatal intensive care unit and the maternity ward.

UNLABELLED: Transcutaneous bilirubin (TcB) was measured with a new bilirubinometer, BiliCheck, in 261 jaundiced infants in the neonatal intensive care unit (NICU) [gestational age (GA) 25-43 wk] (group 1) and in 227 healthy jaundiced term and near-term infants (GA 35-43 wk) (group 2). Imprecision of a single determination of TcB measured on the forehead [TcB(h)], expressed as 1 standard deviation, was 15-18 micromol l(-1). No statistically significant difference between intraoperator and interoperator imprecision was found. There was a good correlation between TcB(h) and total serum bilirubin (TSB) in both groups of infants, although TcB(h) was on average lower than TSB. In the NICU infants, TcB(h), other things being equal, was lower in males than in females, and decreased with increasing postnatal age, for the same TSB level. In the infants in both groups who had a GA > or = 35 wk, sick infants had a higher TcB(h) than healthy infants for the same TSB level. The differences were statistically significant, but small and of minor clinical significance. Blood haemoglobin concentration, GA and ethnic origin were not found to influence TcB(h), i.e. BiliCheck corrects sufficiently for these factors. In all 488 infants, TcB was measured at four different body sites. Measurements on the forehead and sternum [TcB(s)] correlated well with TSB, while measurements on the knee and foot correlated less well. In the NICU infants TcB(h) predicted TSB statistically significantly better than TcB(s), while in the healthy term and near-term infants TcB(h) and TcB(s) predicted TSB equally well. Therefore, the preferable body site for measurement of TcB under routine conditions is the forehead. By retrospective analysis of the data, a screening model is presented whereby TcB(h) can be used to screen infants who require phototherapy. We found that using screening limits for TcB(h), which are 70% of the currently used phototherapy limits for TSB, 80% of blood samples in healthy term and near-term infants, and 42% of NICU infants with GA > or = 32 wk, could be avoided. CONCLUSION: BiliCheck is suitable for screening both NICU and healthy newborn infants with jaundice, with regard to the need for phototherapy. The authors recommend using a TcB(h) limit which is 70% of the currently recommended TSB limits for phototherapy, to decide whether TSB needs to be measured.

Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to pivmecillinam: a population-based cohort study with 414 exposed pregnancies.

Concerns have been raised as to the safety of using pivaloyl-conjugated beta-lactam antibiotics during pregnancy as they cause carnitine depletion. Restrictions have been recommended in some Scandinavian countries as drug-induced carnitine depletion could constitute a risk to the developing foetus. One of these drugs, pivmecillinam, is widely used against urinary tract infections but few data exist concerning its safety in pregnancy. In a cohort study, we compared the prevalences of congenital abnormalities, pre-term delivery, low birth weight, low Apgar score and neonatal hypoglycaemia in the offspring of 414 women who had at least 1 prescription for pivmecillinam redeemed during pregnancy with those of the offspring of 7472 pregnant women for whom no drugs were prescribed during pregnancy. The prevalence of congenital abnormalities was 1.7% among 119 infants exposed in the first trimester and 3.7% among the reference group [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.11-1.86]. We found no significantly increased risks in either pre-term delivery (OR 0.91, 95% CI 0.11-1.86), low birth weight (OR 0.57, 95%, CI 0.23-1.41), low Apgar score (OR 2.32, 95% CI 0.30-18.16) or hypoglycaemia (OR 0.73, 95% CI 0.18-3.00) that were induced by carnitine depletion. No significantly increased risk in adverse birth outcome was therefore found in women treated with pivmecillinam.

Recurrence of kernicterus in term and near-term infants in Denmark.

UNLABELLED: Classical acute bilirubin encephalopathy (kernicterus) in term and near-term infants had not been seen in Denmark for at least 20 y until 1994. From 1994 to 1998. however, six cases were diagnosed. Aetiology of the hyperbilirubinaemia was known in two infants; spherocytosis and galactosaemia, most likely known in two infants; possible A-O blood type immunization, and unknown in two infants. However, one of these last-mentioned infants had a gestational age of only 36 wk. The maximum plasma total bilirubin concentrations were 531-745 micromol/L. The increase in the number of cases of kernicterus was considered to have been caused by: (i) a decreased awareness of the pathological signs, (ii) a change in the assessment of the risk of bilirubin encephalopathy, (iii) early discharge of the infants from the maternity ward, (iv) so-called breastfeeding-associated jaundice, (v) demonstration of bilirubin being an antioxidant, and (vi) difficulty in estimating the degree of jaundice in certain groups of immigrants. Accordingly, for prevention: (a) Attempt to change the healthcare workers' understanding of the risk of bilirubin encephalopathy, (b) give further instructions, both orally and in writing, to mothers before discharge from the maternity ward, (c) be more liberal in giving infant formula supplements, (d) conduct home visits by the community nurse at an earlier stage, (e) follow authorized guidelines for phototherapy and exchange transfusion, (f) lower plasma bilirubin concentration limits as an indication for phototherapy and exchange transfusion, (g) screen all term and near-term infants, and (h) measure the skin's yellow colour with a device that corrects for the skin's melanin content. CONCLUSIONS: Audit of the six cases presented indicates that measures are necessary in both the primary and secondary healthcare sectors if the risk of kemicterus is to be avoided. Screening may be considered, but in order to identify the problems it would first be reasonable to perform a larger prospective study in which audit is performed on all newborn infants, born at term and near-term, who develop a plasma bilirubin concentration above the exchange transfusion limit.

Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate.

AIMS: To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms. METHODS: Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8). RESULTS: Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02). CONCLUSIONS: Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed.

Blood glucose levels in a population of healthy, breast fed, term infants of appropriate size for gestational age.

AIM: To determine blood glucose levels in a population of healthy, breast fed, term infants of appropriate size for gestational age. METHODS: In a cross sectional study, the blood glucose concentration of 223 healthy, breast fed, term infants of appropriate size for gestational age was determined at different times (between one and 96 hours) after delivery. One sample of blood glucose was taken from each infant independent of the feeding time. The glucose concentration was correlated with sex, method of delivery, delivery with or without analgesia, smoking status of the mother, gestational age, umbilical cord pH, and Apgar score. Infants suspected of suffering from intrapartum hypoxia were excluded. RESULTS: Blood glucose concentration one hour after delivery was not significantly lower than at any other time. Only two infants had low blood glucose concentrations one hour after delivery (1.4 and 1.9 mmol/l). There were no significant differences in blood glucose concentration between sexes, methods of delivery, infants delivered with or without analgesia, and infants born to smokers or non-smokers, and there was no further correlation between blood glucose concentration and gestational age, umbilical cord pH, or Apgar score. DISCUSSION: Very few healthy, breast fed, term infants of appropriate size for gestational age have low blood glucose levels, and there is no indication for blood glucose monitoring in these infants.

Impact of blood sampling in very preterm infants.

In a prospective investigation, 99 very preterm infants (gestational age (GA) 24 32 weeks, birthweight 560-2,255 g) were studied during the first 4 weeks of life. The infants were divided into two groups: infants born extremely early (GA <28 weeks, n = 20) and infants of GA 28 - 32 weeks; the groups were then subdivided into critically ill or not. Diagnostic blood sampling and blood transfusion events were recorded. In total, 1905 blood samples (5,253 analysis) were performed, corresponding to 0.7 samples (1.9 analysis) per day per infant. The highest frequencies were found during the first week, in infants with extremely low GA and in critically ill infants. The mean blood loss and transfusion volume values were 13.6 ml/kg and 6.3 ml/kg, respectively. In total, 19 infants (19%) received 34 transfusions corresponding to 0.3 transfusions per infant. Thirteen out of 20 infants of extremely low GA received 28 blood transfusions, corresponding to 27.0 ml/kg of blood on average during the study period. Four developed late anaemia; thus, in total, 14 (70%) of the infants born extremely early received 35 transfusions during the first 3 months of life, corresponding to a total mean of 34.8 ml/kg. For the extremely preterm infants a significant correlation between sampled and transfused blood volume was found (mean 37.1 and 33.3 ml/kg, respectively, r = + 0.71, p = 0.0003). The most frequently requested analyses were glucose, sodium and potassium. Few blood gas analyses were requested (1.9/ infant). No blood losses attributable to excessive generous sampling were detected. The results show an acceptable low frequency of sampling and transfusion events for infants of GA 28-32 weeks. The study emphasizes the necessity of thorough reflection and monitoring of blood losses when ordering blood sampling in extremely preterm, critically ill infants.

Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks' gestation.

OBJECTIVE: To determine whether early versus late treatment with porcine surfactant (Curosurf) reduces the requirement of mechanical ventilation in very preterm infants primarily supported by nasal continuous positive airway pressure (nasal CPAP). DESIGN: Multicenter randomized, controlled trial. PATIENTS: The study population comprised 60 infants <30 weeks' gestation with respiratory distress syndrome (RDS) who had an arterial to alveolar oxygen tension ratio (a/APO2) of 0.35 to 0.22. The cohort from which the study population was generated comprised 397 infants. RESULTS: The need for mechanical ventilation or death within 7 days of age was reduced from 63% in the late-treated infants to 21% in early-treated infants. Increasing numbers of antenatal steroid doses also improved the outcome, especially in the early-treated infants. Six hours after randomization mean a/APO2 rose to 0.48 in the early-treated infants compared with 0.36 in the late-treated. The need of mechanical ventilation before discharge was reduced from 68% in the late-treated to 25% in the early-treated infants. CONCLUSIONS: Nasal CPAP in combination with early treatment with Curosurf significantly improves oxygenation and reduces the subsequent need for mechanical ventilation in infants <30 weeks' gestational age with RDS.

[High-frequency oscillatory ventilation of newborn infants]. / Højfrekvens oscillatorisk ventilation af nyfødte børn.

Ventilator-induced lung injuries remain an important factor regarding morbidity and mortality in newborns requiring assisted ventilation. Numerous different modes of ventilation have been tried without achieving recognition. High-frequency oscillatory ventilation (HFO) is a new mode of ventilation which employs active inspiration and expiration at frequencies up to 20 Hz with a tidal volume below dead space. Progression of severe respiratory distress syndrome may be reduced by applying early HFO beside modern treatment modes. It has been demonstrated that immediate initial treatment of premature babies with high tidal volumes can cause lung damage. Clinical studies of HFO indicate, that it is possible to improve oxygenation, reduce short-term mortality, surfactant redosing, ventilator-time, use of extra corporeal membrane oxygenation (ECMO) and costs of hospitalization. Morbidity related to lung injury and cerebral damage is apparently unchanged compared to conventional mechanical ventilation. The use of HFO in milder cases awaits further clinical studies.