Baldvin Jonsson

Early increase of TNFα and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants

AIM To investigate if early changes in concentrations of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF) from preterm infants could be used to detect infants at risk of chronic lung disease (CLD) and help in the selection of patients for early steroid treatment. METHODS Twenty eight preterm infants less than 34 weeks of gestation (median 26 weeks) were intubated and daily measurements of TAF concentrations of tumour necrosis factor α (TNFα) and the interleukins IL-1β, IL-6, and IL-8 were made, using enzyme immunoassay techniques. RESULTS Seventeen of the infants developed CLD. The infants who developed CLD had significantly increased concentrations of TNFα, IL-1ß, IL-6 on days 2 and 3. TNFα, IL-6, and IL-8 concentrations were significantly related to gestational age and duration of supplemental oxygen; TNFα, IL-6, and IL-8 concentrations also correlated with length of time on the ventilator. CONCLUSION These data indicate that tracheobronchial aspirate fluid cytokine concentrations may be used as a predictor of subsequent CLD and may help select a group of preterm infants at high risk of developing CLD for early treatment.

Amphetamine addiction during pregnancy: 14‐year follow‐up of growth and school performance

Sixty‐five children born to women who all abused amphetamine during pregnancy have been followed prospectively since their birth in 1976‐77. At the age of 14‐15 years, information about growth and school achievement was collected from school records. For comparison of school achievements the means of schoolmates were used, and for growth a group of Stockholm children born in the same year. By the age of 14 years only 14 children (22%) had stayed with their biological mothers for the whole period since birth. In the eighth grade, 10 (15%) were one grade lower than indicated by their biological age. The norm for Sweden is less than 5%. The means of the points in mathematics, Swedish language and sports were statistically below those of their classmates. At the age of 10 years the girls were significantly shorter and lighter than their peers born in 1976. At the age of 14 years the boys were statistically taller and heavier than their peers. It can be concluded that maternal amphetamine abuse during pregnancy will influence children at least up to the age of 14–15 years even though many of them have been living in foster homes since a young age.

Implementation of surfactant treatment during continuous positive airway pressure

Objective:To study the effects of implementing a method for surfactant administration by transient intubation, INSURE (i.e. INtubation SURfactant Extubation) during nasal continuous positive airway pressure (nCPAP) for moderately preterm infants with respiratory distress syndrome (RDS).Study design:A descriptive, retrospective, bi-center study in Stockholm, Sweden, comparing mechanical ventilation (MV) rates, surfactant use, treatment response and outcome of all inborn infants with gestational age 27 to 34 weeks and RDS, (n=420), during the 5-year periods before and after the introduction of the INSURE-strategy at one of the centers (Karolinska Huddinge) in 1998. The other center (Karolinska Solna) continued conventional surfactant therapy in conjunction with MV throughout the study.Results:Implementation of INSURE at Karolinska Huddinge reduced the number of infants requiring MV by 50% (P<0.01), resulted in earlier surfactant administration and increased overall surfactant use. INSURE-treatment improved oxygenation and the treatment response was sustained over time with only 17% of the infants requiring >1 dose of surfactant. At Karolinska Solna, the MV rates were unaltered between the first and second 5-year period.Conclusion:Implementing a strategy of surfactant administration by transient intubation during nCPAP reduces the need for MV without adverse effects on outcome and may be an option to more effectively treat RDS, particularly in a care setting where transfer is necessary to provide MV.

Genetic susceptibility to retinopathy of prematurity.

OBJECTIVES. The goals were to isolate and to estimate the genetic susceptibility to retinopathy of prematurity. METHODS. A retrospective study (1994–2004) from 3 centers was performed with zygosity data for premature twins who were born at a gestational age of ≤32 weeks and survived beyond a postmenstrual age of 36 weeks. Retinopathy of prematurity was diagnosed and staged by pediatric ophthalmologists at each center. Data analyses were performed with mixed-effects logistic regression analysis and latent variable probit modeling. RESULTS. A total of 63 monozygotic and 137 dizygotic twin pairs were identified and analyzed. Data on gestational age, birth weight, gender, respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, duration of ventilation and supplemental oxygen use, and length of stay were comparable between monozygotic and dizygotic twins. In the mixed-effects logistic regression analysis for retinopathy of prematurity, gestational age and duration of supplemental oxygen use were significant covariates. After controlling for known and unknown nongenetic factors, genetic factors accounted for 70.1% of the variance in liability for retinopathy of prematurity. CONCLUSION. In addition to prematurity and environmental factors, there is a strong genetic predisposition to retinopathy of prematurity.

Continuous Positive Airway Pressure and Surfactant

Nasal continuous positive airway pressure (nCPAP) is an effective treatment of respiratory distress syndrome. Due to long-standing experience of early nCPAP as the primary respiratory support option in preterm infants, this approach is sometimes labeled ‘the Scandinavian Model’. Mechanical ventilation is potentially harmful to the immature lungs and cohort studies have demonstrated that centers using more CPAP and less mechanical ventilation have reduced rates of bronchopulmonary dysplasia. However, there is a lack of evidence in the form of larger, randomized controlled trials to prove the superiority of either method. Surfactant is essential in the treatment of respiratory distress syndrome and has generally been reserved for infants on mechanical ventilation. With the development of INSURE (INtubation SURfactant Extubation), in which surfactant is administered during a brief intubation followed by immediate extubation, surfactant therapy can be given during nCPAP treatment further reducing need for mechanical ventilation. In this review the history, current knowledge and techniques of CPAP and surfactant are discussed.

Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates.

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [n= 155; median GA 26 (23–29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu‐colonized infants had lower mean gestational ages than the culture‐negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks’postconceptual age (p< 0:05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants (n= 14) and those not treated (n= 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.

Resuscitation and ventilation strategies for extremely preterm infants: a comparison study between two neonatal centers in Boston and Stockholm

Aim: To evaluate if different resuscitation and ventilatory styles exist between two neonatal units, and if the less aggressive approach has a beneficiary effect on BPD outcome.

Ureaplasma urealyticum -Induced Production of Proinflammatory Cytokines by Macrophages

Ureaplasma urealyticum is relatively common in the respiratory tract of very low birth weight infants and has been hypothesized to be involved in the development of chronic lung disease. The purpose of this study was to investigate whether U. urealyticum could stimulate macrophages to produce proinflammatory cytokines in vitro, which are early pathologic changes in the lung during the development of chronic lung disease. A human monocytic cell line (THP-1) differentiated to macrophages, a rat alveolar macrophage cell line (Nr8383), and human lung macrophages from tracheobronchial aspirate fluid in preterm infants were exposed to U. urealyticum antigen for 24 h. The protein levels of human IL-6, tumor necrosis factor-α (TNF-α), and rat TNF-α were measured with ELISA. Rat IL-6 was analyzed with a specific bioassay. The mRNA levels of these cytokines were detected by reverse transcriptase-PCR. The production of TNF-α and IL-6 increased after stimulation with U. urealyticum in both the human and rat macrophage cell lines. In tracheobronchial aspirate fluid macrophages, U. urealyticum increased the production of TNF-α from 14 to 84% and IL-6 from 46 to 268% above control levels. U. urealyticum also induced gene expression of TNF-α and IL-6. In conclusion, U. urealyticum could be an important factor in the development of chronic lung disease because of its ability to induce alveolar macrophage proinflammatory cytokine production.

Nasal CPAP and surfactant for treatment of respiratory distress syndrome and prevention of bronchopulmonary dysplasia

The Scandinavian approach is an effective combined treatment for respiratory distress syndrome (RDS) and prevention of bronchopulmonary dysplasia (BPD). It is composed of many individual parts. Of significant importance is the early treatment with nasal continuous positive airway pressure (nCPAP) and surfactant treatment. The approach may be supplemented with caffeine citrate and non‐invasive positive pressure ventilation for apnoea. The low incidence of BPD seen as a consequence of the treatment strategy is mainly due to a reduced need for mechanical ventilation (MV).

Downregulatory cytokines in tracheobronchial aspirate fluid from infants with chronic lung disease of prematurity.

Chronic lung disease of prematurity (CLD) is associated with an inflammatory response in the preterm lung and increased levels of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF). We investigated TAF levels of transforming growth factor‐ß1(TGF‐ß1), interleukin‐10 (IL‐10), interleukin‐4 (IL‐4) and interleukin‐12 (IL‐12) cytokines possibly important in downregulating the proinflammatory response and/or inducing lung fibrosis in infants with developing and established CLD. Infants with CLD (n = 24) were compared with preterm infants with RDS that resolved (n = 22) and postoperative infants without lung disease (n= 23). TAF levels of TGF‐ß1, IL‐10, IL‐4 and IL‐12 were studied by quantitative enzyme immunoassay. Levels of TGF‐ß1 were significantly higher during the first week of life in infants who developed CLD, remained high at 2 wk and past 4 wk of age. TAF levels of TGF‐ß1 did not decrease significantly in six infants with CLD after treatment with steroids. TAF IL‐10 was detected in 12/46 (26%) preterm infants. Infants with CLD or RDS were more likely to have measurable TAF levels of IL‐10, compared with the postoperative infants without lung disease (p < 0.02 and 0.04, respectively). TAF levels of IL‐4 or IL‐12 were below the detection limits in all samples.