Meconium is a potent activator of complement in human serum and in piglets

Department of Pediatric Research, Rikshospitalet University Hospital, Oslo 0027, Norway.
Pediatric Research (Impact Factor: 2.84). 03/2004; 55(2):310-8. DOI: 10.1203/01.PDR.0000100902.76021.8E
Source: PubMed

ABSTRACT Meconium aspiration syndrome (MAS) is a clinical condition in the newborn infant with a significant morbidity and mortality. The complex pathophysiology of MAS, leading to both pulmonary and systemic complications, is characterized by an incompletely understood inflammatory reaction. Treatment is symptomatic, mainly limited to airway cleaning and ventilatory support. In this study, we show for the first time that meconium is a potent activator of complement, a key mediator of inflammation. In vitro, meconium activated the alternative complement pathway in human umbilical cord serum as judged by a substantial increase in the alternative pathway convertase C3bBbP. The activation proceeded through C3 (C3bc) and the terminal C5-9 pathway (terminal SC5b-9 complement complex), whereas the classical and lectin pathways were not activated (C1rs-C1-inhibitor complexes and C4bc). The lipid fraction, containing, e.g. free fatty acids, and the water fraction, containing, e.g. bile acids, contributed equally to the complement activation. A blocking antibody to factor D (alternative pathway) completely inhibited the meconium-induced complement activation, whereas blocking antibodies to mannose-binding lectin (lectin pathway) and C2 (classical and lectin pathway) had no effect. In vivo, meconium induced systemic complement activation in a piglet model of MAS, paralleling the increase in lung dysfunction. In conclusion, meconium is a potent activator of the complement system both in vitro and in vivo. Complement may be important in the pathogenesis of MAS, and specific complement inhibition might be a possible treatment approach in MAS.

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    ABSTRACT: Backround Meconium aspiration syndrome is a disease of the newborn mature or post mature. The acute pulmonary consequences can be extremely severe. In the few studies of the long-term pulmonary sequelae, it seems that certain children surviving meconium aspiration syndrome keep an obstructive syndrome. The aim of our study was to assess long term respiratory residual damage from meconium aspiration syndrome. Methods During a seven-year period going from 1994 to 2000, we reviewed the files of children hospitalized in neonatology departement of Sfax for meconium aspiration syndrome. The children who were convoked (group M: n = 27), underwent spirometry, followed by an exercise stress. An age matched control group (group C: n = 23) of healthy children was investigated in the same way. Results The group M comprised 15 boys and 12 girls aged four to 11, an average of 7 ± 1.9 years. With the study of the respiratory function, we did not find an obstructive syndrome. Spirometry revealed a total pulmonary capacity in an average of 133 ± 55.65% of theoretical (group M) versus 105.5 ± 27.96% of theoretical (group C) (P < 0,01), testifying to alveolar hyperinflation. Spirometry fulfilled 5, 10 and 15 min after exercise showed a FEV1 reduction of respectively 8.5 versus 2 (P < 0.05); 9.5 versus 3 (P < 0.01) and 10.5 versus 4 (P < 0.05). Conclusion Children surviving meconium aspiration syndrome tend to develop alveolar hyperinflation and airway hyperreactivity to exercise.
    Archives de Pédiatrie 02/2008; 15(2):105-110. DOI:10.1016/j.arcped.2007.10.026 · 0.41 Impact Factor
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    ABSTRACT: Abstract Background: Meconium-stained amniotic fluid (MSAF) represents passage of fetal colonic content into the amniotic cavity. Meconium aspiration syndrome (MAS) is complication that occurs in a subset of infants with MSAF. Secreted phospholipase A2 (sPLA2) is detected in meconium and is implicated in the development of MAS. We measured sPLA2 in MSAF and clear fluid among women in spontaneous labor at term. Materials and Methods: This was a cross-sectional study of patients in spontaneous term labor who underwent amniocentesis (n=101). The patients were divided into 2 study groups: 1) MSAF group (n= 61), and 2) clear fluid (n=40). The presence of bacteria and endotoxin as well as interleukin-6 (IL-6) and sPLA2 concentrations in the amniotic fluid were determined. Statistical analyses were performed to test for normality and bivariate analysis. Spearman correlation coefficient was used to study the relationship between sPLA2 and IL-6 concentrations in the amniotic fluid. Results: Patients with MSAF have a higher median sPLA2 concentration (ng/mL) in amniotic fluid than those with clear fluid [1.7 (0.98-2.89) vs. 0.3 (0-0.6), p<0.001]. Among patients with MSAF, those with either microbial invasion of the amniotic cavity (MIAC, defined as presence of bacteria in the amniotic cavity), or bacterial endotoxin have a significantly higher median sPLA2 concentration (ng/mL) in amniotic fluid than those without MIAC or endotoxin [2.4 (1.7-6.0) vs. 1.7 (1.3-2.5), p<0.05]. There was a positive correlation between sPLA2 and IL-6 concentrations in the amniotic fluid (Spearman Rho=0.3, p<0.05). Conclusion: MSAF that contains bacteria or endotoxin has a higher concentration of sPLA2, and this may contribute to induce lung inflammation when meconium is aspirated before birth.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 09/2013; 27(10). DOI:10.3109/14767058.2013.847918 · 1.21 Impact Factor
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    ABSTRACT: Background: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. Objective: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. Methods: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. Results: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. Conclusion: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome. © 2013 S. Karger AG, Basel.
    Neonatology 12/2013; 105(2):128-135. DOI:10.1159/000356065 · 2.37 Impact Factor

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