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 1 of every 7 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 intraamniotic inflammation/infection 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: We sought to investigate whether intraamniotic 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 = 1281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intraamniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-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% (118/1281), 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 > .1). Mothers whose newborns developed MAS had a higher median of AF matrix metalloproteinase-8 (456.8 vs 157.2 ng/mL, P < .05). Newborns exposed to intraamniotic inflammation had a higher rate of MAS than those who were not exposed to intraamniotic inflammation [13.0% (10/77) vs 0% (0/32), P = .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 intraamniotic inflammation and funisitis than in those without intraamniotic inflammation and funisitis [28.6% (4/14) vs 0% (0/28), P = .009], while the rate of MAS did not show a significant difference between patients with intraamniotic inflammation alone (without funisitis) and those without intraamniotic inflammation and funisitis [10.9% (5/46) vs 0% (0/28)].

Conclusion: The combination of intraamniotic 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.

Keywords: amniocentesis; fetal inflammatory response syndrome; funisitis; intraamniotic inflammation; matrix metalloproteinase-8; meconium-stained amniotic fluid; pregnancy.

Figure 1

Amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) in the context of neonatal development of meconium aspiration syndrome (MAS). The median AF MMP-8 was higher in newborns with MAS than in those without MAS (median 456.8 ng/mL; range, 36.6 to 11,754.7 ng/mL vs. median 157.2 ng/mL; range, 0.3 to 7163.4 ng/mL; p < 0.05).

Figure 2

The frequency of neonatal development of meconium aspiration syndrome (MAS) in the context of intra-amniotic inflammation and funisitis. Neonates exposed to both intra-amniotic inflammation and funisitis were at significantly greater risk of MAS than newborns exposed to neither of these two conditions [28.6% (4/14) vs. 0% (0/28); p = 0.009]. In contrast, newborns exposed to only intra-amniotic inflammation, without funisitis, were not at greater risk of MAS than newborns exposed to neither of these two conditions [10.9% (5/46) vs. 0% (0/28)]. MAS did not occur in the absence of the intra-amniotic inflammation.