Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury.
Fetal development and growth occur in a sterile amniotic cavity while first exposure to microorganisms happens at birth. However, at least 25% of all preterm births, the leading cause of perinatal morbidity and mortality worldwide, occur in mothers with microbial invasion of the amniotic cavity. Microbial attack of the fetus takes place in approximately 10% of pregnancies with intra-amniotic infection, and the human fetus is capable of deploying an inflammatory response (cellular and humoral) in the mid-trimester of pregnancy. The onset of premature labor in the context of infection is mediated by pro-inflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha), as these cytokines are produced by intrauterine tissues in response to microbial products, can stimulate prostaglandin production, and induce labor in animals. Moreover, knockout experiments suggest that infection is less likely to lead to premature labor when the IL-1 and TNF signaling pathways are disrupted. A fetal inflammatory systemic response occurs in a fraction of fetuses exposed to microorganisms in utero, and is associated with the impending onset of labor as well as multisystem organ involvement. Neonates born with funisitis, the histologic marker of such inflammation, are at increased risk for neurologic handicap and cerebral palsy. Evidence has begun to accumulate that gene-environment interactions determine the likelihood of preterm labor and delivery and, probably, the risk of fetal injury. Fetal inflammation has emerged as a major mechanism of disease responsible for complications in the perinatal period (in utero and in the first 28 days of life), as well as in infancy. Moreover, reprogramming of the fetal immune response may predispose to diseases in adulthood.
Romero
Roberto
R
Perinatology Research Branch, NICHD/ NIH/DHHS, Hutzel Women's Hospital Detroit, MI 48201, USA. nichdprbchiefstaff@mail.nih.gov
Gotsch
Francesca
F
Pineles
Beth
B
Kusanovic
Juan Pedro
JP
D002821:Chorioamnionitis / Q000276:immunology / Q000382:microbiology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D007744:Obstetric Labor Complications; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D049188:Prenatal Injuries; D012098:Reproduction / Q000502:physiology*