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.

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.

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.

[Neonatal mortality and morbidity in gestational age shorter than 30 weeks for babies treated primarily in a central hospital. Follow-up studies of an unselected, consecutive patient group]. / Neonatal mortalitet og morbiditet ved svangerskabslaengde mindre end 30 fulde uger for børn behandlet primaert på et centralsygehus. Efterundersøgelse af en uselekteret, konsekutiv patientgruppe.

AIM: The aim of the study was to investigate the mortality and morbidity of very premature babies treated at a Danish county hospital in the mid-1990s. MATERIALS AND METHOD: The 62 survivors of 70 consecutive babies born in 1993-1997 were given a neuropaediatric follow-up examination at a corrected mean age of 49 (22-69) months. The mean gestational age was 27 (24-29) weeks and the mean birth weight was 1012 (550-1374) g. RESULTS: Eight babies (11%) died within 28 days of birth. Four (6%) had an intracerebral haemorrhage, grade 3-4; four (6%) had retinopathy of prematurity; and three (4%) had bronchopulmonary dysplasia at 36 weeks of gestation. Four of the survivors developed cerebral palsy. Two of these babies and a neurologically normal baby had visual impairments. None developed epilepsy. DISCUSSION: Thus, our babies had a low mortality and only a few complications at long-term follow-up. Early nasal continuous positive airway pressure and early supplementation with a surfactant seem to be essential for these positive results in our most premature babies.

Soluble intercellular adhesion molecule and C-reactive protein as early markers of infection in newborns.

In order to find a reliable early marker of infection in newborns a study with simultaneous determination of soluble Intercellular Adhesion Molecule-1 (sICAM-1) and C-Reactive Protein (CRP) was planned. Prospectively 90 babies < 5 days of age suspect of infection were included. Retrospectively this population was classified into an "infected" group (n = 45) and a "non-infected" group (n = 45). For each of these two groups we calculated the sensitivity, specificity and predictive values of sICAM-1 and CRP as early markers of infection. We determined the best cut-off level for sICAM-1 to be 300 micrograms/l and for CRP 5 mg/l. As a biochemical test for infection in the newborns the sensitivity and negative predictive value for CRP were 0.69 and 0.73 respectively. When sICAM-1 was added and CRP and s-ICAM-1 were used in combination the sensitivity improved significantly to 0.93, p < 0.01 and the negative predictive value improved to 0.92, p < 0.05. In normal 5-8 days old babies' sICAM-1 was significantly higher than at birth (cord blood), p < 0.0001. In conclusion, sICAM-1 and CRP in combination are better than CRP as a primary test for identification of infection in babies < 5 days of age.

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.

[Neonatal mortality, morbidity and late sequelae in infants with birth weight under 1.501 gr or gestational age under 31 weeks, primarily admitted to a central hospital]. / Den neonatale mortalitet, morbiditet og senfølger hos børn med fødselsvaegt mindre end 1.501 g eller svangerskabslaengde mindre end fulde 31 uger, primaert indlagt på et centralsygehus.

The purpose of the study was during a three year period from 1990 to 1992 to describe the neonatal mortality, morbidity and the late complications of 75 very low birth weight infants primarily treated in the neonatal department of a County Hospital. The study was performed retrospectively. The mean birth weight was 1292 g in (range 755-2046 g) and the mean gestational age 29.9 weeks (range 25-37 weeks). The primary choice of treatment was nasal continuous positive airway pressure (nasal-CPAP) and "minimal handling" regime. When needed surfactant administration and/or mechanical ventilation was used. Twenty neonates (27%) received mechanical ventilation, and 14 (19%) were treated with surfactant (Curosurf). The mortality (8%) (95% confidence limits 2.9%-16.6%) and morbidity is low. Late complications such as cerebral palsy or mental retardation were seen in eight infants (12.1%) (95% confidence limits 5.4-22.5%). The results of our treatment seem acceptable, and confirm an increasing survival among very low birth weight infants.

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.

[Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. / Surfaktantbehandling af nyfødte med respiratorisk distress-syndrom primaert behandlet med nasalt kontinuerligt positivt luftvejstryk. En pilotundersøgelse.

In this pilot study, Curosurf (200 mg/kg) was administrated to 34 patients with the respiratory distress syndrome in nasal-CPAP therapy with FiO2 requirements greater than 0.60 and/or TcPCO2 greater than 8 kPa. The surfactant was instilled during a short period of intubation or in a few cases via an intratracheal catheter (Ch. 6). The age of the patients on surfactant treatment ranged from two to 72 hours. Eighteen patients could be maintained on nasal-CPAP after treatment with Curosurf and only a few complications were seen in these infants. The other 16 patients subsequently required artificial ventilation and had a higher incidence of pulmonary and extrapulmonary complications. On the basis of these observations, we plan a randomized trial to investigate whether, administration of surfactant reduces the need for ventilator treatment and improves the odds for uneventful recovery in this category of patients.

[Treatment of severe respiratory distress syndrome with surfactant]. / Surfaktantbehandling af svaert respiratorisk distress-syndrom.

The first Danish experience of treatment of the respiratory distress syndrome (RDS) in preterm infants with exogenous surfactant is described. Fifteen infants with birthweights of 645-1,865 g and gestational ages of 25-32 weeks, all receiving artificial ventilation with at least 60% oxygen for severe RDS, were treated with purified porcine surfactant (Curosurf) within the first 28 hours of life. Pulmonary function improved immediately in all of the infants. Four infants (27%) died, four (27%) developed bronchopulmonary dysplasia (pulmonary fibrosis) and two (13%) had late neurological sequelae. These preliminary results are considered to be promising and they are in complete agreement with the results of randomised, controlled investigations from abroad. Systematic registration is, however, still necessary.

[Surfactant to premature neonates]. / Surfaktant til praemature nyfødte.

Surfactant is a lipoprotein complex which reduces alveolar surface tension, thus reducing the work of respiration. Defective secretion of surfactant in the premature newborn infant gives rise to the respiratory distress syndrome (RDS). Several surfactant preparations, natural (purified) and synthetic, have been evolved. They have been used for prophylaxis and also therapy. Several controlled studies have shown decreased mortality, while the effect on neonatal complications and late results are still uncertain.

Anal tonometry in the neonatal period for the diagnosis of Hirschsprung's disease.

A double balloon technique was used for anal tonometry in 22 infants. The weight was less than 2,500 g in 10 of the infants. Ileus or delayed passage of meconium was seen in 9 infants. Thirteen infants had not revealed any symptoms of intestinal obstruction during the first week of life. In all cases, except one, it was possible to demonstrate reflexes from the internal anal sphincter. In 18 infants normal curves were registered from the internal anal sphincter. None of these developed Hirschsprung's disease. In 3 infants a pathological pattern of contractions of the internal anal sphincter was demonstrated. Two of them proved to have Hirschsprung's disease. In the third case normal reflexes were registered after one year. Possibly the innervation of rectum and the internal anal sphincter was disrupted during the neonatal period in connection with enterocolitis and ileus, thus representing a reversible case of achalasia.

Captopril treatment in Bartter's syndrome.

A 13-year-old girl presented with lassitude, polyuria and hypokalemia. Plasma renin concentration and urinary prostaglandin excretion were elevated, whereas plasma aldosterone concentration, urinary aldosterone excretion and blood pressure were normal. A diagnosis of Bartter's syndrome was made. The result of treatment with oral potassium was unsatisfactory. Treatment with acetylsalicylic acid had some effect, but an allergic reaction rendered withdrawal necessary. Treatment with the angiotensin converting enzyme inhibitor captopril and oral potassium led to clinical and biochemical improvement.

Late-onset rubella syndrome: coexistence of immune complex disease and defective cytotoxic effector cell function.

We studied a classical case of late-onset rubella syndrome characterized by multi-organ disease and persistence of live rubella virus in spite of high titres of specific antirubella antibodies and presence of large amounts of circulating immune complexes. When first studied at the age of 5 months there was a low proportion of T8+ lymphocytes. Functional studies revealed decreased activity of K and NK cells as well as alloreactive direct cytotoxic cells (CTL). Removal of cell-bound immunoglobulin and immune complexes tended to improve K and NK cell function in vitro. Plasma exchange transfusions carried out at 9 months of age resulted in clinical improvement. Normalization of cytotoxic effector cell functions and cessation of viremia accompanied recovery from active disease. The results indicate that defective cytotoxic effector cell function is the primary cause for the defective virus elimination in this syndrome.