sFlt-1:PlGF Ratio in Diagnosing Superimposed Preeclampsia

Preeclampsia: associated with poor placentation, incomplete uteroplacental spiral arteries remodeling. Result: ischemia, re-perfusion injury, oxidative stress.

A low-grade systemic inflammatory response is more pronounced in preeclampsia. This results in an imbalance between maternal circulating pro-angiogenic (PlGF \& VEGF) \& anti-angiogenic factors (sFlt-1).

PlGF \& VEGF function as vasodilators \& preserve structure \& function of glomerular endothelium. sFlt-1 blocks these actions, resulting in hypertension, endothelial dysfunction \& nephropathy.

Various stressors, including hypoxia, villous crowding, angiotensin II, \& oxidative stress are associated with preeclampsia \& mediate secretion of soluble vascular growth factor 1 (sVEGFR-1 or sFlt-1) by GADD45 (Growth Arrest and DNA Damage-45). GADD45 is one of a family of stress-induced genes sFlt-1 releases into maternal circulation. Excess sFlt-1 leads to endothelial dysfunction, hypertension \& proteinuria.

Exogenously administered sFlt-1 results in syndrome of nephrotic range proteinuria, hypertension, and glomerular endotheliosis in animal models.

Women with preeclampsia tend to have higher sFlt-1 \& lower PlGF, resulting in an increased ratio (sFlt-1:PlGF). The difference is greater in women who develop early-onset preeclampsia (before 34 wks gestation).

Verlohren, et al., showed an increased sFlt-1/PlGF ratio in patients with preeclampsia as compared to controls \& patients with chronic/gestational hypertension.

Other work has examined the longitudinal changes in the individual values of sFlt-1 \& PlGF over the course of the pregnancy, as well as the ratio.

Given the low prevalence of preeclampsia in the population, the positive predictive value remained low, however the negative predictive value approached 97% late in gestation. This suggests that the utility of the sFlt-1/PlGF may be in its ability to rule out preeclampsia.

More recently the PROGNOSIS study was designed to investigate the value of the sFlt-1/PlGF ratio for the prediction of the presence or absence of preeclampsia in the short term \& found that a cutoff point of 38 for the sFlt-1/PlGF ratio is useful for predicting the short-term absence of preeclampsia in women with suspected disease (Negative predictive value 99.3% for ruling out preeclampsia within 1 week).

Hypothesis: In women with chronic hypertension, the sFlt-1/PlGF ratio will better predict the development of superimposed preeclampsia than clinical criteria alone.

Subjects with a diagnosis of chronic hypertension made prenatally or in the first 20 weeks of pregnancy (+/- medical therapy). The clinical diagnosis of preeclampsia will follow the current criteria outlined by ACOG (American College of Obstetricians \& Gynecologists) 10.

Study/Project Procedures:

* Blood draw at the time of initial presentation at the time of a clinically indicated blood draw (10cc maternal blood via venipuncture)
* Blood draw at 2-7 days after initial presentation if undelivered at the time of a clinically indicated blood draw(10 cc maternal blood via venipuncture)
* Laboratory analysis will be performed in batches after all clinical history, clinically indicated laboratory information, delivery information, and clinical outcomes recorded for sFlt-1 level, PlGF level, and the sFlt-1/PlGF ratio (not part of routine care and will be performed for research purposes only at the cost of the investigators).
* Urine protein creatinine ratio performed as clinically indicated (will not be altered for research purposes)
* Maternal CBC (Complete Blood Count), CMP (Complete Metabolic Profile), LDH (Lactate dehydrogenase), Uric acid as indicated clinically (will not be altered for research purposes)
* Ultrasound performed by the investigators for research purposes only evaluating the uterine artery Doppler, middle cerebral artery Doppler, umbilical artery Doppler, estimated fetal weight, and amniotic fluid volume on a weekly basis from the time of enrollment until delivery.
* Medical record abstraction of medical history, laboratory and clinical findings for both the mother and fetus.

Eligibility Criteria:
Inclusion Criteria:

* Gestational age at enrollment: 20 0/7 weeks to 38 6/7 weeks gestation Pregnant women aged 14 to 45 years
* Presenting for admission for suspected superimposed preeclampsia
* Diagnosis of chronic hypertension made prenatally or in the first 20 weeks of pregnancy (+/- medical therapy)
* The clinical diagnosis of preeclampsia will follow the current criteria outlined by ACOG 10.

Exclusion Criteria:

* Age 45 years;
* Gestational age 19 6/7 weeks or less or 39 weeks or more ;
* Multiple gestations.