Circulatory biomarkers for placental or fetal health
AssigneeThe University of Melbourne
InventorsStephen TONG, Tu'uhevaha Joy LINO, Teresa Mary MACDONALD, Susan Philippa WALKER
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Abstract
Disclosed are assays, protocols and reagents to facilitate clinical management of pregnancy with improved pre- and post-natal health outcomes for fetuses developing in an environment of placental insufficiency.
Claims41
An assay to determine the state of placental health in a female mammalian subject, said method comprising determining the circulating levels of SPINT1 and/or SYNDECAN-1 wherein a reduction in the concentration of SPINT1 and/or SYNDECAN-1 relative to a control or over time or a change in ratio relative to a control or over time is indicative of placental insufficiency and an elevation in SPINT-1 and/or SYNDECAN-1 is a measure of placental sufficiency or an improvement in placental sufficiency.
An assay to detect abnormal fetal weight such as in macrosomia in a female mammalian subject, said method comprising determining the maternal circulating levels of SPINT1 and/or SYNDECAN-1 wherein an elevation in the concentration of SPINT1 and/or SYNDECAN-1 relative to a control or over time or a change in ratio relative to a control or over time is indicative of potential macrosomia.
An assay to detect abnormal fetal weight in a female mammalian subject, said method comprising determining the maternal circulating levels of SPINT1 and/or SYNDECAN-1 wherein an elevation in the concentration of SPINT1 and/or SYNDECAN-1 relative to a control or over time or a change in ratio relative to a control or over time is indicative of potential high fetal weight and a reduction in the concentration of SPINT1 and/or SYNDECAN-1 relative to a control or over time or a change in ratio relative to a control or over time is indicative of potential low fetal weight or small-for-gestational age or fetal growth restriction.
A clinical management protocol for a pregnant mammalian subject, said protocol comprising determining the levels of circulating SPINT1 and/or SYNDECAN-1 wherein a reduction over time in SPINT1 and/or SYNDECAN-1 compared to a control or a statistically validated level or a change in ratio reflecting a lowering of levels of SPINT1 and/or SYNDECAN-1 is indicative of placental insufficiency and wherein the fetus is monitored or subject to early delivery.
A clinical management protocol for macrosomia in a pregnant human subject, said protocol comprising determining the levels of circulating SPINT1 and/or SYNDECAN-1 wherein an elevation over time in SPINT1 and/or SYDNECAN-1 compared to a control or a statistically validated level or a change in ratio reflecting elevation of levels of SPINT1 and/or SYNDECAN-1 is indicative of macrosomia wherein the fetus is monitored and potentially subject to earlier delivery.
An assay for determining the state of placental sufficiency in a subject, the assay comprising determining the concentration of biomarkers in a circulating biological sample from the subject selected from SPINT1 and SYNDECAN-1;
- subjecting the levels to an algorithm or analytics function or process or other data processing means generated from a first knowledge base of data comprising the levels of the same biomarkers from a subject or cohort of subjects of known status with respect to placental sufficiency wherein the algorithm or analytics or data processing provides an index of probability of the subject having or not having placental insufficiency or placental sufficiency.
Use of a knowledge base of training data comprising levels of biomarkers selected from SPINT1, SYNDECAN-1, both SPINT1 and SYNDECAN-1;
- or one of SPINT1 or SYNDECAN-1 and at least one other biomarker from a subject with known placental sufficiency status to generate an algorithm or analytics function or process or other data processing means which, upon input of a second knowledge base of data comprising levels of the same biomarkers from a patient with an unknown placental sufficiency status, provides an index of probability that predicts the nature of the placenta.
A panel of biomarkers for the detection of placental insufficiency or state of placental health or dysfunction in a subject, the panel comprising agents which bind specifically to biomarkers, the biomarkers selected from SPINT1, SYNDECAN-1, both SPINT1 and SYNDECAN-1;
- or one of SPINT1 or SYNDECAN-1 and at least one other biomarker to determine levels of the biomarkers and then optionally subjecting the levels to an algorithm or analytics function or process or other data processing means generated from a first knowledge base of data comprising the levels of the same biomarkers from a subject of known status with respect to the conditions wherein the algorithm or analytics or data processing provides an index of probability of the subject having or not having placental insufficiency.
A method for monitoring the progression of a pregnancy in a patient, comprising:
- (a) providing a circulatory fluid sample from a patient;
- (b) determining the level of SPINT1, SYNDECAN-1, both SPINT1 and SYNDECAN-1;
- or one of SPINT1 or SYNDECAN-1 and at least one other biomarker and subjecting the levels to an algorithm or analytics function or process or other data processing means to provide an index of probability of the patient having a placental sufficiency or insufficiency;
- and
- (c) repeating steps (a) and (b) at a later point in time and comparing the result of step (b) with the result of step (c) wherein a difference in the index of probability is indicative of the progression of the placental health.
The method, use or panel of claim 32, further comprising inputting one or more risk factors associated with increased risk of abnormal fetal weight.
A method of detecting the state of placental health in a subject comprising:
- (a) providing a circulatory fluid sample from the patient;
- (b) extracting a nucleic acid molecule comprising mRNA encoding a biomarker or portion thereof from the sample or cells within a sample;
- (c) amplifying the extracted mRNA using the polymerase chain reaction;
- (d) determining the level of mRNA encoding the biomarker;
- and
- (e) subjecting the levels of the biomarker to an algorithm or analytics function or process or other data processing means which provides an index of probability of the patient having placental sufficiency or insufficiency.
A method of allowing a user to determine the status of a subject with respect to a level of placental sufficiency or insufficiency, the method including:
- (a) receiving data in the form of levels or concentrations of SPINT1, SYNDECAN-1, both SPINT1 and SYNDECAN-1;
- or one of SPINT1 or SYNDECAN-1 and at least one other biomarker from the user via a communications network;
- (b) processing the subject data via an algorithm or analytics function or process or other data processing means which provides a disease index value;
- (c) determining the status of the subject in accordance with the results of he disease index value in comparison with predetermined values;
- and
- (d) transferring an indication of the status of the subject to the user via the communications network.
An assay for determining the state of fetal macrosomia in a subject, the assay comprising determining the concentration of biomarkers in a circulating biological sample from the subject selected from SPINT1 and SYNDECAN-1;
- subjecting the levels to an algorithm or analytics function or process or other data processing means generated from a first knowledge base of data comprising the levels of the same biomarkers from a subject or cohort of subjects of known status with respect to fetal macrosomia wherein the algorithm or analytics or data processing provides an index of probability of the subject having or not having a baby with fetal macrosomia.
A composition comprising a sample obtained from a pregnant mammalian subject and an antibody that binds specifically to SPINT1 or SYNDECAN-1.
Dependencies are inferred from the claim text.