Meconium aspiration syndrome: a role for fetal systemic inflammation

Abstract

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.

Prediction of adverse perinatal outcome by fetal biometry: comparison of customized and population‐based standards

“…Neonatal hypothermia was defined as a neonatal axillary temperature < 36.5°C. Meconium aspiration syndrome was diagnosed in infants who had dyspnea, tachycardia, need for supplemental oxygen within the first hours after delivery and diffuse irregular patchy infiltrates on chest radiographs. Of note, infants with meconium below the vocal cords but with no clinical or radiographic evidence of disease were not diagnosed with aspiration syndrome.…”

Comparison of different dosing strategies of intratracheally instilled budesonide on meconium injured piglet lungs

“…Decreasing the level of lung inflammation has been shown to have a positive correlation with an improvement in pulmonary function among MAS patients . Recently investigators have found that there is a relationship between MAS and a combination of intra‐amniotic inflammation and fetal systemic inflammation . In a 25 years retrospective survey, a close link between the severity of MAS and several inflammatory criteria among patients without a co‐existent bacteria infection has been identified .…”

“…relationship between MAS and a combination of intra-amniotic inflammation and fetal systemic inflammation. 8 In a 25 years retrospective survey, a close link between the severity of MAS and several inflammatory criteria among patients without a co-existent bacteria infection has been identified. 9 These studies have reemphasized the role of inflammation in MAS pathophysiology and the importance of anti-inflammatory therapy when carrying out MAS management.…”

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation

“…Clinical chorioamnionitis at term is associated with adverse maternal events [2,7,8] and increased maternal admission to the intensive care unit [2,9]. Importantly, neonates born to mothers with clinical signs of chorioamnionitis have a high risk of neonatal mortality [4] in addition to short-and long-term complications such as neonatal sepsis [10][11][12][13][14], meconium aspiration syndrome [15][16][17][18], stillbirth [19,20], and neurodevelopmental disorders including cerebral palsy [21][22][23][24][25][26][27][28][29][30][31].…”