Meconium aspiration syndrome: a role for fetal systemic inflammation.
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.


METHODS
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)].


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
JoonHo
J
Lee
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI. Electronic address: romeror@mail.nih.gov.
Roberto
R
Romero
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kyung A
KA
Lee
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Eun Na
EN
Kim
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
Steven J
SJ
Korzeniewski
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
Piya
P
Chaemsaithong
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: yoonbh@snu.ac.kr.
Bo Hyun
BH
Yoon
D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002821:Chorioamnionitis / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008471:Meconium Aspiration Syndrome / Q000209:etiology*; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers
amniocentesis; fetal inflammatory response syndrome; funisitis; intraamniotic inflammation; matrix metalloproteinase-8; meconium-stained amniotic fluid; pregnancy