Pre eclampsia

1. RECENT ADVANCE: USE OF MOLECULAR BIOLOGY IN
PRE-ECLAMPSIA/ECLAMPSIA PREDICTION

2. INTRODUCTION
 Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The
early identification of patients with an increased risk for preeclampsia is therefore one of the most
important goals in obstetrics.
 The availability of highly sensitive and specific physiologic and biochemical markers would allow
not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis,
timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies
looking at therapeutic medications and additional prospective markers. Today, several markers may
offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools

4. WHAT IS SFLT1?
 sFlt1 is an antiangiogenic molecule that antagonizes VEGF and PlGF.
 VEGF is important in both angiogenesis (the growth of new blood vessels) and in the maintenance of endothelial cell health
in the basal state.
 Although the function of PlGF is still ill defined, it appears to act synergistically with VEGF and may be necessary for wound
healing and angiogenesis in ischemic tissues.
 VEGF has a family of receptors, the most important of which are Flt1 (VEGFR1) and Flk1 (VEGFR2).
 sFlt1 is a truncated form of the Flt1 receptor (Fig. 1). It includes the extracellular ligand-binding domain, but not the
transmembrane and intracellular domains; it is secreted (hence “soluble”) and antagonizes VEGF and PlGF in the circulation
by binding and preventing their interaction with their endothelial receptors.
 The regulation of Flt1 splicing to produce the full Flt1 receptor versus the truncated sFlt1 remains unexplored. It was recently
shown that hypoxic trophoblasts grown in vitro produces excess quantities of sFlt-1, however, whether this phenomenon
occurs in vivo remains unknown. Although sFlt1 is made in small amounts by other tissues (endothelial cells and monocytes),
the placenta seems to be the major source of circulating sFlt1 during pregnancy, as evidenced by the dramatic fall in
circulating concentrations of sFlt1 after the deliv- ery of the placenta.

6. SFIT:PIGF

7.  BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor
(PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive
value in women with suspected preeclampsia is unclear.
 METHODS:Prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to
PlGF that would be predictive of the absence or presence of preeclampsia in the short term in
women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks
weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below
a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether
high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks.

11.  RESULTS: In the development cohort (500 women), the study identified an sFlt-1:PlGF ratio cutoff of 38
as having important predictive value. In a subsequent validation study among an additional 550 women,
an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent
subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI,
51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF

12. LATE PE
 Chrinic HPT
 How to diagnose PE
 Time of delivery
 IUD

13. DIAGANOSIS PE
 US maker
 Uterine artery doppler
 Clinical
 Proteinuria
 Serum maker
 sFlt-1:PIGF

14.  Grill, S., Rusterholz, C., Zanetti-Dällenbach, R. et al. Potential markers of preeclampsia – a
review. Reprod Biol Endocrinol 7, 70 (2009).
 Maynard, S., Venkatesha, S., Thadhani, R. et al. Soluble Fms-like Tyrosine Kinase 1 and Endothelial
Dysfunction in the Pathogenesis of Preeclampsia. Pediatr Res 57, 1–7 (2005).
 Wikström AK, Larsson A, Eriksson UJ, Nash P, Nordén-Lindeberg S, Olovsson M (June 2007).
"Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset
preeclampsia". Obstetrics and Gynecology. 109 (6): 1368–74.
 Hod T, Cerdeira AS, Karumanchi SA. Molecular Mechanisms of Preeclampsia. Cold Spring Harb
Perspect Med. 2015;5(10):a023473. Published 2015 Aug 20. doi:10.1101/cshperspect.a023473
 Zeisler H, Elisa L, Frederic C, Manu V, Anne C, Maria S, et al. Predictive Value of the sFlt-1: PlGF Ratio
in Women with Suspected Preeclampsia. N Engl J Med. 2016;374 (1):13-22.