OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.
OBJECTIVE:Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amnioticIL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.
Authors: Roberto Romero; Digna R Velez Edwards; Juan Pedro Kusanovic; Sonia S Hassan; Shali Mazaki-Tovi; Edi Vaisbuch; Chong Jai Kim; Tinnakorn Chaiworapongsa; Brad D Pearce; Lara A Friel; Jacquelaine Bartlett; Madan Kumar Anant; Benjamin A Salisbury; Gerald F Vovis; Min Seob Lee; Ricardo Gomez; Ernesto Behnke; Enrique Oyarzun; Gerard Tromp; Scott M Williams; Ramkumar Menon Journal: Am J Obstet Gynecol Date: 2010-05 Impact factor: 8.661
Authors: Roberto Romero; Lara A Friel; Digna R Velez Edwards; Juan Pedro Kusanovic; Sonia S Hassan; Shali Mazaki-Tovi; Edi Vaisbuch; Chong Jai Kim; Offer Erez; Tinnakorn Chaiworapongsa; Brad D Pearce; Jacquelaine Bartlett; Benjamin A Salisbury; Madan Kumar Anant; Gerald F Vovis; Min Seob Lee; Ricardo Gomez; Ernesto Behnke; Enrique Oyarzun; Gerard Tromp; Scott M Williams; Ramkumar Menon Journal: Am J Obstet Gynecol Date: 2010-07-31 Impact factor: 8.661
Authors: Pallavi P Patwari; Peggy O'Cain; Denise M Goodman; Melita Smith; Julia Krushkal; Caiquin Liu; Grant Somes; Michael W Quasney; Mary K Dahmer Journal: Pediatr Crit Care Med Date: 2008-11 Impact factor: 3.624
Authors: Jerome F Strauss; Roberto Romero; Nardhy Gomez-Lopez; Hannah Haymond-Thornburg; Bhavi P Modi; Maria E Teves; Laurel N Pearson; Timothy P York; Harvey A Schenkein Journal: Am J Obstet Gynecol Date: 2017-12-14 Impact factor: 8.661