The goal of this project is to explore the relationship between sub-clinical intrauterine infection, preterm labor and the complications of prematurity. This year the Branch focused on establishing whether the human fetus can be affected by a systemic inflammatory response syndrome and the relationship between this condition and the onset of premature labor and perinatal morbidity. The following observations were made: 1) Definition of the """"""""fetal inflammatory response syndrome"""""""": a fetal plasma IL-6 concentration of 11 pg/ml or more was used to defined the presence of a systemic inflammatory response in the human fetus. This condition was observed in approximately 20% of fetuses presenting with preterm labor and intact membranes and 45% of those presenting with preterm PROM. Importantly, 77.8% of fetuses affected with this syndrome develop severe morbidity after birth. Fetal plasma IL-6 concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1-18.5) after adjustment for gestational age at delivery, amniotic fluid culture and other relevant variables. 2) The role of the human fetus in preterm parturition: To determine if the fetus plays a role in the onset of parturition, the relationship between the presence of a """"""""fetal inflammatory response syndrome"""""""" and the subsequent onset of labor was studied in patients admitted with preterm PROM and who were not in labor. Fetuses affected by the syndrome had a higher rate of spontaneous preterm delivery within 24, 48, and 72 hours of the procedure than those without this syndrome (56% vs. 24%; 81% vs. 36% and 88% vs. 40%, respectively, p < 0.05 for each). Fetal plasma IL-6 was the only covariate significantly associated with the duration of pregnancy after adjusting for gestational age, amniotic fluid IL-6 and the microbiologic state of the amniotic cavity. These observations indicate that a systemic fetal cytokine response is associated with the impending onset of spontaneous preterm labor in patients with preterm PROM and therefore provide evidence for a role of the human fetus in determining the timing of preterm labor and delivery. 3) Expression of mRNA for anti-microbial peptides by the lower genital tract and gestational tissues: A crucial question is why some women develop an ascending intrauterine infection and others do not. Previous observations suggests that the cervical mucus which forms, the mucus plug during pregnancy, inhibits bacterial growth. The Branch provided evidence that chorionic tissue, endocervical tissue, endometrial tissue and an endometrial cell line, expressed mRNA for defensin 5, an epithelial anti-microbial peptide. The human placenta was also found to express defensin-1 (a hematopoietic defensin). These observations suggests that the expression of anti-microbial peptides may be a mechanism of host defense against ascending and transplacentally acquired infections.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Intramural Research (Z01)
Project #
1Z01HD002400-06
Application #
6162520
Study Section
Physical Biochemistry Study Section (PB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Vaisbuch Md, Edi; Romero M D, Roberto; Erez, Offer et al. (2010) The clinical significance of early (<20 weeks ) versus late (20-24 weeks) detection of a sonographic short cervix in asymptomatic women in the mid-trimester. Ultrasound Obstet Gynecol :
Hirsch, Emmet; Filipovich, Yana; Romero, Roberto (2009) Failure of E. coli bacteria to induce preterm delivery in the rat. J Negat Results Biomed 8:1
Tarca, Adi Laurentiu; Draghici, Sorin; Romero, Roberto (2009) Developing classifiers for the detection of cancer using multi-analytes. Methods Mol Biol 520:259-72
Imudia, Anthony N; Suzuki, Yoko; Kilburn, Brian A et al. (2009) Retrieval of trophoblast cells from the cervical canal for prediction of abnormal pregnancy: a pilot study. Hum Reprod 24:2086-92
Soto, Eleazar; Romero, Roberto; Richani, Karina et al. (2009) Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection. J Matern Fetal Neonatal Med :1-10
Kusanovic, Juan Pedro; Romero, Roberto; Jodicke, Cristiano et al. (2009) Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med :1-16
Chaiworapongsa, Tinnakorn; Romero, Roberto; Tarca, Adi et al. (2009) A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study. J Matern Fetal Neonatal Med :1-18
Erez, Offer; Romero, Roberto; Vaisbuch, Edi et al. (2009) Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation. J Matern Fetal Neonatal Med :1-12
Erez, Offer; Romero, Roberto; Vaisbuch, Edi et al. (2009) Maternal anti-protein Z antibodies in pregnancies complicated by pre-eclampsia, SGA and fetal death. J Matern Fetal Neonatal Med :1-10
Fejzo, Marlena S; Poursharif, Borzouyeh; Korst, Lisa M et al. (2009) Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum. J Womens Health (Larchmt) 18:1981-7

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