title: Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klotho.
abstract: OBJECTIVE
  The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM).
  
  
  METHODS
  A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA.
  
  
  RESULTS
  i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P<0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; P=0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; P=0.045). iv) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P=0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (P=0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P<0.001); however, this difference was not observed in patients with MIAC.
  
  
  CONCLUSIONS
  Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers.
authors.affiliation: Perinatology Research Branch, Wayne State University/Hutzel Women ’ s Hospital, MI 48201, USA. jla@med.wayne.edu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lam-Rachlin
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.forename: Alyse G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Edgar
authors.initials: E
authors.lastname: Hernandez-Andrade
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000097:blood; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D000090265:Klotho Proteins; D008297:Male; D007752:Obstetric Labor, Premature / Q000097:blood; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000209:etiology; D012907:Smoking / Q000009:adverse effects* / Q000097:blood*; D014807:Vitamin D / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014807:Vitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins