Systems and methods to identify and treat subjects at risk for obstetrical complications

1. A method of treating an angiogenic and anti-angiogenic imbalance in a female human subject comprising:

identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance by a method comprising:

obtaining a sample derived from the subject;

assaying the sample for the concentration of PIGF and sVEGFR-1;

analyzing the concentrations by assessing a ratio of PIGF/sVEGFR-1 in the sample;

determining a Multiples of the Median (MoM) maternal plasma concentration ratio of PIGF/sVEGFR-1;

comparing the determined MoM maternal plasma concentration ratio to a threshold; and

identifying the subject as having or at risk of an angiogenic and anti-angiogenic imbalance based on the comparison of the MoM maternal plasma concentration ratio to the threshold, wherein a MoM concentration of <0.12 for PIGF/sVEGFR-1 is indicative of an angiogenic and anti-angiogenic imbalance; and

administering an effective amount of a water-soluble statin to the subject, thereby treating the angiogenic and anti-angiogenic imbalance.

2. The method of claim 1 , wherein the treating of the angiogenic and anti-angiogenic imbalance treats an obstetrical complication.

3. The method of claim 2 , wherein the obstetrical complication is fetal death (FD).

4. The method of claim 3 , wherein the FD is associated with maternal floor infarction or placental lesions consistent with maternal vascular underperfusion.

5. The method of claim 1 , wherein the water-soluble statin is pravastatin.

6. The method of claim 5 , wherein the effective amount of pravastatin is 20 mg/day.

7. The method of claim 5 , further comprising administering heparin and aspirin to the subject.

8. The method of claim 1 , wherein the identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance further comprises:

assaying the sample for the concentration of sEng;

analyzing the concentrations by assessing a ratio of PIGF/sEng in the sample;

determining a Multiples of the Median (MoM) maternal plasma concentration ratio of PIGF/sEng;

comparing the determined MoM maternal plasma concentration ratio to a threshold; and

identifying the subject as having or at risk of an angiogenic and anti-angiogenic imbalance based on the comparison of the MoM maternal plasma concentration ratio to the threshold, wherein and a MoM concentration of <0.3 for PIGF/sEng is indicative of an angiogenic and anti-angiogenic imbalance.

9. The method of claim 1 , wherein the sample is blood or serum.

10. The method of claim 1 , comprising determining a ratio of PIGF/sVEGFR-1 and a ratio of PIGF/sEng.

11. The method of claim 1 , wherein the sample is obtained during a third trimester of a pregnancy.

12. The method of claim 1 , wherein the sample is obtained between a 24th week of pregnancy and a 28th week of pregnancy.

13. The method of claim 1 , wherein the sample is obtained between a 30th week and a 34th week of pregnancy.

14. The method of claim 1 , wherein the identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance further comprises:

assaying a maternal plasma sample derived from the subject sample for the concentration of sEng;

analyzing the concentrations from the assaying by assessing a ratio of ratio of PIGF/sEng in the sample;

determining, using the analyzing, a MoM maternal plasma concentration ratio of PIGF/sEng;

identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance based on the comparison of the MoM maternal plasma concentration ratio to a threshold, wherein:

a MoM concentration of <0.12 for PIGF/sVEGFR-1 is indicative of an angiogenic and anti-angiogenic imbalance; and

a MoM concentration of <0.3 for PIGF/sEng is indicative of an angiogenic and anti-angiogenic imbalance.

15. The method of claim 1 , wherein the identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance comprises:

immunoassaying a maternal plasma sample derived from the subject sample for the concentration of PIGF, sVEGFR-1 and sEng, wherein the maternal plasma sample is obtained from the female human subject either:

between a 30th week and a 34th week of pregnancy; or

between a 24th week and a 28th week of pregnancy;

analyzing the concentrations from the immunoassaying by assessing a ratio of PIGF/sVEGFR-1 and a ratio of PIGF/sEng in the sample;

determining, using the analyzing, a MoM maternal plasma concentration ratio of PIGF/sVEGFR-1 and a MoM maternal plasma concentration ratio of PIGF/sEng;

identifying the subject as having or at risk of the angiogenic and anti-angiogenic imbalance based on the comparison of the MoM maternal plasma concentration ratio to a threshold, wherein:

a MoM concentration of <0.12 for PIGF/sVEGFR-1 is indicative of an angiogenic and anti-angiogenic imbalance; and

a MoM concentration of <0.3 for PIGF/sEng is indicative of an angiogenic and anti-angiogenic imbalance; and

identifying the female human subject as being at risk for pregnancy complications based on that indication of an angiogenic and anti-angiogenic imbalance.

16. The method of claim 1 , wherein:

the sample is obtained between the 30th week and the 34th week of pregnancy, and the MoM maternal plasma concentration ratio of PIGF/sVEGFR-1 of <0.12 is indicative of a risk for: severe late preeclampsia (PE) and/or fetal death (FD); or delivery of a small for gestational age (SGA) neonate; or

the sample is obtained between the 24th week of pregnancy and the 28th week of pregnancy, and an anti-angiogenic PIGF/sVEGFR-1 ratio of <10 percentile of uncomplicated pregnancies is indicative of a risk for stillbirth, PE, delivery of an SGA neonate, or pre-term labor.