Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

Lindenskov, Paal H.H.; Castellheim, Albert; Saugstad, Ola Didrik; Mollnes, Tom Eirik

doi:10.1159/000369373

Cited by 80 publications

(42 citation statements)

References 38 publications

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“…Meconium aspiration syndrome (MAS) is a lung condition that affects newborn infants that inhale meconium prior to or during birth [1]. The pathophysiology is complex, involving a mechanical blockade of the airways, epithelial injury, pulmonary hypertension, surfactant inactivation, and inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

et al. 2018

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Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.

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Section: Introductionmentioning

confidence: 99%

“…We hypothesized that this regimen would dampen the local and systemic inflammatory response evoked by meconium [1]. …”

Section: Introductionmentioning

confidence: 99%

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

et al. 2018

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“…4, 65–69 The pathophysiology has been attributed to: 1) the mechanical effect of meconium, which can obstruct the airways, and 2) the inflammatory effect of meconium. 68, 70 We propose that intra-amniotic inflammation due to intra-amniotic infection or sterile intra-amniotic inflammation accompanied by a fetal inflammatory response predisposes fetuses exposed to MSAF to develop MAS. This concept is based on previous observations that MSAF is more likely to contain bacteria, 71–73 endotoxin, 73,74 and higher concentrations of inflammatory mediators, such as interleukin (IL)-1, tumor necrosis factor (TNF)-α, 73,75,76 IL-8, 67,76 and phospholipase-A2.…”

Section: Introductionmentioning

confidence: 99%

Meconium aspiration syndrome: a role for fetal systemic inflammation

Lee

Romero

Lee

et al. 2016

American Journal of Obstetrics and Gynecology

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Background Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately one of every seven pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intra-amniotic infection/inflammation than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF. Objective To investigate whether intra-amniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS. Study Design A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n=1,281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intra-amniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 (MMP-8) was >23 ng/ml. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord. Results The prevalence of MSAF was 9.2% (118/1,281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each p > 0.1). Mothers whose newborns developed MAS had a higher median AF MMP-8 (456.8 ng/ml vs.157.2 ng/ml; p < 0.05). Newborns exposed to intra-amniotic inflammation had a higher rate of MAS than those who were not exposed to intra-amniotic inflammation [13.0% (10/77) vs. 0% (0/32), p = 0.03], as did those exposed to funisitis [31.3% (5/16) vs. 7.3% (6/82), relative risk, 4.3; 95% confidence interval, 1.5–12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intra-amniotic inflammation and funisitis than in those without intra-amniotic inflammation and funisitis [28.6% (4/14) vs. 0% (0/28), p = 0.009], while the rate of MAS did not show a significant difference between patients with intra-amniotic inflammation alone (without funisitis) and those without intra-amniotic inflammation and funisitis [10.9% (5/46) vs. 0% (0/28)]. Conclusion The combination of intra-amniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models and therapeutic interventions for this disorder.

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“…20 Meconium aspiration syndrome was diagnosed based on respiratory distress in the presence of meconium-stained amniotic fluid. 21 Therapeutic hypothermia is employed in accordance with routine institutional guidelines. 22 For the composite, only one morbidity was counted per neonate.…”

Section: Methodsmentioning

confidence: 99%

New labor management guidelines and changes in cesarean delivery patterns

Rosenbloom

Stout

Tuuli

et al. 2017

American Journal of Obstetrics and Gynecology

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Background In 2010 the Consortium on Safe Labor published labor curves. It was proposed that the rate of cesarean delivery (CD) could be lowered by avoiding the diagnosis of arrest of dilation before 6 cm. However, there is little information on the uptake of the guidelines and on changes in CD rates that may have occurred. Objective To test the hypotheses that: 1) among patients laboring at term, rates of arrest of dilation disorders have decreased leading to a decrease in the rate of CD; 2) in the second stage, pushing duration prior to diagnosis of arrest of descent has increased also leading to reduction in the rate of CD for this indication. As a secondary aim, we investigated changes in maternal and neonatal morbidity. Study Design This was a secondary analysis of a prospective cohort study of all patients presenting at ≥ 37 weeks’ gestation from 2010–2014 with a non-anomalous vertex singleton and no prior history of CD. Rates of CD, arrest of dilation, and changes in rates of maternal and neonatal morbidity were calculated in crude and adjusted models. Cervical dilation at diagnosis of arrest of dilation, time spent at the maximal dilation prior to diagnosis of arrest of dilation, and time in the second stage prior to diagnosis of arrest of descent were compared over the study period. Results There were 7845 eligible patients. The CD rate in 2010 was 15.8% and in 2014 17.7% (p-trend 0.51). In patients undergoing CD for arrest of dilation, the median cervical dilation at the time of CD was at 5.5 cm in 2010 and 6.0 cm in 2014 (p-trend 0.94). In these patients, there was an increase in the time spent at last dilation: 3.8h in 2010 to 5.2h in 2014 (p-trend 0.02). There was no change in the frequency of patients diagnosed with arrest of dilation at <6 cm: 51.4% in 2010 and 48.6% in 2014 (p-trend 0.56). However, in these patients, the median time spent at the last cervical dilation was 4.0h in 2010 and 6.7h in 2014 (p-trend 0.046). There were 206 CDs for arrest of descent. The median pushing time in these patients increased in multiparous patients from 1.1h in 2010 to 3.4h in 2014 (p-trend 0.009); in nulliparous patients these times were 2.7h in 2010 and 3.8h in 2014 (p-trend 0.09). There was a significant trend towards increasing adverse neonatal and maternal outcomes (p<0.001 for each). The aOR for adverse maternal outcome for 2014 compared to 2010 was 1.66 (95%CI 1.27, 2.17); however considering only transfusion, hemorrhage, or infection, there was no difference (p-trend 0.96). The aOR of adverse neonatal outcome in 2014 compared to 2010 was 1.80 (95%CI 1.36, 2.36). Conclusion Despite significant changes in labor management that have occurred over the initial years since publication of the new labor curves and associated guidelines, the primary CD rate was not reduced and there has been an increase in maternal and neonatal morbidity in our institution. A randomized controlled trial is needed.

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Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

Cited by 80 publications

References 38 publications

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Meconium aspiration syndrome: a role for fetal systemic inflammation

New labor management guidelines and changes in cesarean delivery patterns

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