title: Circulating angiogenic proteins in trisomy 13.
abstract: OBJECTIVE
  Women who are carrying a trisomy 13 fetus are more prone to develop preeclampsia. Excess circulating soluble fms-like tyrosine kinase-1 has been implicated recently in the pathogenesis of preeclampsia. Since the fms-like tyrosine kinase-1/soluble fms-like tyrosine kinase-1 gene is located on chromosome 13q12, we hypothesized that the extra copy of this gene in trisomy 13 may lead to excess circulating soluble fms-like tyrosine kinase-1, reduced free placental growth factor level, and increased soluble fms-like tyrosine kinase-1/placental growth factor ratio. This may then contribute to the increased risk of preeclampsia that has been observed in these patients. Our objective was to characterize the maternal circulating angiogenic proteins in trisomy 13 pregnancies.
  
  
  METHODS
  Maternal serum samples of trisomy 13, 18, 21 and normal karyotype pregnancies were obtained from first and second trimester screening programs. We chose 17 cases of trisomy 13 that were matched for maternal age, freezer storage time, and parity with 85 normal karyotype control samples. Additionally, 20 cases of trisomy 18 and 17 cases of trisomy 21 were included. Cases and control samples were assayed for levels of soluble fms-like tyrosine kinase-1 and placental growth factor by enzyme-linked immunosorbent assay in a blinded fashion. Because of the skewed distributions of soluble fms-like tyrosine kinase-1 and placental growth factor, nonparametric analytic techniques were used, and the results are reported as median and ranges.
  
  
  RESULTS
  In early pregnancy trisomy 13 cases and control samples, the median circulating soluble fms-like tyrosine kinase-1/placental growth factor ratios were 17.0 (range, 1.2-61.3) and 6.7 (range, 0.8-62.9), respectively (P = .003). The median soluble fms-like tyrosine kinase-1/placental growth factor ratios in trisomy 18 and 21 were 4.8 (range, 0.9-53.9) and 5.1 (range, 1.0-18.1), which were not significantly different than the control samples. Furthermore, the differences between trisomy 13 and control samples were more pronounced in the second trimester specimens than in the specimens from the first trimester.
  
  
  CONCLUSIONS
  These data suggest that alterations in circulating angiogenic factors may be involved intimately in the pathogenesis of preeclampsia in trisomy 13. A larger clinical study that measures these factors longitudinally and correlates them with pregnancy outcomes is needed to further establish the link between trisomy 13, altered angiogenic factors, and preeclampsia.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Bdolah
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.forename: Tali
authors.initials: T
authors.lastname: Bdolah-Abram
authors.forename: Marlene
authors.initials: M
authors.lastname: Goldman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levine
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Sachs
authors.forename: James E
authors.initials: JE
authors.lastname: Haddow
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
mesh_terms: D042501:Angiogenic Proteins / Q000097:blood*; D016022:Case-Control Studies; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004314:Down Syndrome; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011247:Pregnancy / Q000097:blood*; D011257:Pregnancy Proteins / Q000097:blood; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D016037:Single-Blind Method; D014314:Trisomy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D042501:Angiogenic Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1