Finn Ebbesen

SURFACTANT THERAPY AND NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE FOR NEWBORNS WITH RESPIRATORY DISTRESS SYNDROME. DANISH-SWEDISH MULTICENTER STUDY GROUP

BACKGROUND In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation. METHODS We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both. RESULTS Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies. CONCLUSIONS In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.

Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels

Background:Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.Methods:Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.Results:Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23–26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800–477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000–131,000), with a 24% risk for death (114,100; uncertainty range: 59,700–172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.Conclusion:Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

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

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 μmol 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 ≥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 ≥32 wk, could be avoided.

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.

Determination of reserve albumin-equivalent for ligand binding, probing two distinct binding functions of the protein

Abstract A method is reported for determination of albumin binding capacity for various ligands in 50-μl sample volumes. A small amount of a radioactively labeled test ligand is added to the undiluted sample and the rate of dialysis of the free ligand into an identical sample without added ligand is measured. The reserve albumin-equivalent concentration is defined as the concentration of a standard albumin preparation which in buffered solution gives the same rate of dialysis and hence the same ratio of free/bound concentrations of the added ligand. It is shown that the reserve albumin-equivalent concentration, thus defined, is identical with the sum of concentrations of carrier species, each multiplied by the first stoichiometric binding constant of the test ligand to the carrier and divided by its first stoichiometric binding constant to the standard albumin. Determinations of this parameter are suitable for studies of the chemical potential and transfer affinities of individual ligands and for determination of interaction among several binding substances. Two test ligands have been used, monoacetyldiaminodiphenyl sulfone and diazepam. The former is bound competitively with bilirubin while diazepam engages another, independent binding function. The method can thus be used for separate determinations of the degree of saturation of two distinct binding functions of albumin. Complex mixtures of several carrier proteins with interacting ligands can be studied.

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) μmol/l (median (range)). The median value of the exchange transfusion limits was 450 μmol/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.

Risk of Infantile Hypertrophic Pyloric Stenosis after Maternal Postnatal Use of Macrolides

A case report has suggested that exposure to erythromycin through breast milk might cause infantile hypertrophic pyloric stenosis. This study therefore examined whether macrolides, transmitted via breast milk, increase the risk of infantile hypertrophic pyloric stenosis in neonates. A population-based cohort study was conducted, based on data from a prescription registry, the Danish Birth Registry and North Jutland Countys hospital discharge registry, Denmark, and comprising 1166 pregnant women who had been prescribed macrolides from birth to 90 d postnatally, and 34,690–41,778 pregnant women as controls. The odds ratios for infantile hypertrophic pyloric stenosis varied between 2.3 and 3.0 according to different periods of postnatal exposure, and after stratification for gender they were 10.3 [95% confidence interval (95% CI) 1.2–92.3] for girls and 2.0 (95% CI 0.5–8.4) for boys. The use of macrolides during breast-feeding increases the risk of infantile hypertrophic pyloric stenosis.

Surveillance of extreme hyperbilirubinaemia in Denmark. A method to identify the newborn infants.

Aim: To describe the incidence of infants born at term or near‐term with extreme hyperbilirubinaemia.

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.

Reversibility of acute intermediate phase bilirubin encephalopathy

Aim:  To show the potential for reversing acute intermediate to advanced phase bilirubin encephalopathy.