Systems and methods to identify and treat subjects at risk for obstetrical complications
Inventors
Chaiworapongsa, Tinnakorn • Romero, Roberto • Hassan, Sonia S.
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-12298315-B2
Publication Date
2025-05-13
Expiration Date
2035-03-27
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Abstract
Provided are systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an angiogenic and anti-angiogenic imbalance. Also provided are methods of treating an angiogenic and anti-angiogenic imbalance with water-soluble statins, such as pravastatin.
Core Innovation
The invention provides systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an imbalance between angiogenic and anti-angiogenic factors. It involves the use of biomarkers such as placental growth factor (PIGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and soluble endoglin (sEng). By measuring the ratios of these factors, specifically PIGF/sVEGFR-1 and PIGF/sEng, in maternal blood or serum samples, the method determines whether an angiogenic and anti-angiogenic imbalance exists, which is linked to various pregnancy-related disorders.
The invention addresses the need for reliable identification and treatment of subjects at risk for obstetrical complications such as preeclampsia (PE), small for gestational age (SGA) neonates, stillbirth, and massive perivillous fibrin deposition (MPFD). The background highlights the lack of effective ways to identify women at increased risk of fetal death and other complications, especially those associated with placental dysfunction and maternal vascular underperfusion.
The core innovation further includes treating detected angiogenic and anti-angiogenic imbalances, and associated obstetrical complications, by administering water-soluble statins like pravastatin. This therapeutic intervention can be utilized after risk assessment using the biomarker ratios. The system encompasses both diagnostic (identification of risk) and therapeutic (treatment to reverse the identified imbalance) components, described in detail, including relevant thresholds, sample timings, and supporting kit configurations.
Claims Coverage
The patent comprises multiple inventive features as outlined in the independent claims.
Method of treating an imbalance of angiogenic and anti-angiogenic factors in a pregnant human subject
This feature consists of: - Identifying a pregnant human subject as having or at risk of an imbalance of angiogenic and anti-angiogenic factors, where the angiogenic factor includes PIGF, and the anti-angiogenic factors include sVEGFR-1 and/or sEng. - Administering to the subject an effective amount of a water-soluble statin to treat the imbalance of angiogenic and anti-angiogenic factors.
Method of identifying subjects at risk using biomarker ratios
This feature includes: - Obtaining a blood or serum sample from a subject. - Assaying the sample for concentrations of PIGF, sVEGFR-1, and/or sEng. - Determining the ratio of PIGF/sVEGFR-1 and/or PIGF/sEng as a multiple of the median (MoM). - Comparing the MoM ratio to a threshold, where a MoM less than 0.12 for PIGF/sVEGFR-1 or less than 0.3 for PIGF/sEng is indicative of an imbalance. - Identifying the subject as having or at risk of the imbalance based on these thresholds.
Method for treating obstetrical complications associated with angiogenic and anti-angiogenic imbalance
This feature describes: - Treating an identified imbalance of angiogenic and anti-angiogenic factors, which in turn treats obstetrical complications such as preeclampsia, small for gestational age neonates, fetal death, preterm labor, early-onset fetal growth restriction, placental perivillous fibrin deposition, maternal floor infarction, maternal vascular underperfusion, placental lesions, placental abruption, mirror syndrome, molar pregnancy, or twin-to-twin transfusion syndrome, by administering a water-soluble statin.
Method of treating an imbalance with specific statins and adjunctive agents
This inventive feature includes: - Administering pravastatin as the water-soluble statin, optionally at an effective amount of 20 mg/day. - Optionally further administering heparin and aspirin to the subject.
In summary, the inventive features include methods for risk assessment using specific biomarker ratios, therapeutic intervention using water-soluble statins (including pravastatin), and adjunctive therapies, all to address imbalances of angiogenic and anti-angiogenic factors associated with obstetrical complications.
Stated Advantages
The methods allow risk assessment for obstetrical complications with high specificity and sensitivity using biomarker ratios measured at key gestational intervals.
The use of multiple of the median (MoM) for biomarker ratios provides results that are easier to interpret and more generalizable to independent populations.
Administration of water-soluble statins, such as pravastatin, has the potential to reverse angiogenic and anti-angiogenic imbalances and prevent or treat associated pregnancy complications.
The approach supports early identification and intervention in subjects who did not receive earlier prenatal care or testing.
The disclosed diagnostic approach outperforms traditional clinical risk factors and Doppler assessments, especially in the third trimester, for late obstetrical complications.
Documented Applications
Assessment of the risk or presence of obstetrical complications, including preeclampsia, severe preeclampsia, small for gestational age neonates, stillbirth, fetal growth restriction, maternal vascular underperfusion, placental abruption, and mirror syndrome.
Treatment of angiogenic and anti-angiogenic imbalances and associated obstetrical complications by administering water-soluble statins, such as pravastatin, to pregnant subjects.
Use in clinical trials and as a risk stratification tool for prevention of stillbirth and severe late preeclampsia.
Providing kits for assaying PIGF, sVEGFR-1, and sEng biomarkers, including reagents and instructions for calculating the relevant ratios and thresholds.
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