Methods and apparatus for screening for chromosomal abmormalities

Abstract

This invention generally relates to methods, apparatus, and computer program code for antenatal screening for chromosomal abnormalities, in particular Down's Syndrome. A method of determining a likelihood of a fetus carried by a pregnant mother having a chromosomal abnormality, a first biological, parameter being suitable for screening said fetus for said chromosomal abnormality, the method comprising: receiving first data from a first stage of pregnancy of said mother, said first data comprising data representing a first value of said first biological parameter, receiving second data from a second, later stage of said pregnancy, said second data comprising data representing a second value of said first biological parameter, and determining likelihood data from said first and second data, said likelihood data representing the likelihood of said fetus having a chromosomal abnormality.

1 . A method of determining a likelihood of a fetus carried by a pregnant mother having a chromosomal abnormality, a first biological, parameter being suitable for screening said fetus for said chromosomal abnormality, the method comprising: 
 receiving first data from a first stage of pregnancy of said mother, said first data comprising data representing a first value of said first biological parameter;    receiving second data from a second, later stage of said pregnancy, said second data comprising data representing a second value of said first biological parameter; and    determining likelihood data from said first and second data, said likelihood data representing the likelihood of said fetus having a chromosomal abnormality.    
     
     
         2 . A method as claimed in  claim 1  wherein said first biological parameter is a marker for said chromosomal abnormality at one of said first and second stages of pregnancy and has substantially no value as a marker during the other of said first and second stages of pregnancy.  
     
     
         3 . A method as claimed in  claim 1  wherein said first biological parameter has a logarithm multiple of median (log MoM) value closer than one standard deviation to zero.  
     
     
         4 . A method as claimed in  claim 1  wherein in a cohort of pregnancies having said abnormality said first biological parameter is selected such that a correlation coefficient of said first and second values of said parameter is greater than 0.3, preferably greater than 0.5, more preferably greater than 0.6, most preferably greater than 0.8.  
     
     
         5 . A method as claimed in  claim 1  wherein said first biological marker comprises one of total hCG, PAPP-A, Inhibin-A, AFP, uE 3 .  
     
     
         6 . A method as claimed in  claim 1  wherein said first biological marker is not free β-LCG.  
     
     
         7 . A method as claimed in  claim 1  wherein said first data further comprises data representing a first value of a second biological parameter, wherein said second data further comprises data representing a second value of said second biological parameter, wherein said second biological parameter is suitable for screening said fetus for said chromosomal abnormality.  
     
     
         8 . A method as claimed in  claim 7  wherein said second biological parameter is a marker for said chromosomal abnormality at one of said first and second stages of pregnancy and has substantially no value as a marker during the other of said first and second stages of pregnancy.  
     
     
         9 . A method as claimed in  claim 7  wherein in a cohort of pregnancies having said abnormality biological parameter is selected such that a correlation coefficient of said first and second values of said parameter is greater than 0.3, preferably greater than 0.5, more preferably greater than 0.6, most preferably greater than 0.8.  
     
     
         10 . A method as claimed in  claim 7  wherein said second biological marker comprises on of total hCG, PAPP-A, Inhibin-A, AFP, uE 3 .  
     
     
         11 . A method as claimed in  claim 7  wherein said second biological marker is not free β-LCG.  
     
     
         12 . A method as claimed in  claim 1  wherein said first data further comprises data obtained from an ultrasound scan performed on said mother.  
     
     
         13 . A method as claimed in  claim 1  wherein said determining of said likelihood data comprises determining likelihood ratio data, said likelihood ratio data comprising a ratio of a probability of obtaining said first and second data in a pregnancy without said abnormality to a probability of said first and second data being obtained in a pregnancy in which said fetus has said abnormality.  
     
     
         14 . A method as claimed in  claim 13  further comprising adjusting said first and second data responsible to one or more covariates prior to determining said likelihood ratio.  
     
     
         15 . A method as claimed in  claim 13  further comprising adjusting said likelihood ratio by a prior probability factor dependent upon an age of said mother.  
     
     
         16 . A method as claimed in  claim 1  wherein said first stage of pregnancy comprises a first trimester of said pregnancy and said second stage of said pregnancy comprises a second trimester of said pregnancy.  
     
     
         17 . A method as claimed in  claim 1  wherein said first stage of pregnancy comprises a stage of said pregnancy from 8 to 13 weeks, and wherein said second stage of said pregnancy comprises a stage of said pregnancy from 14 to 22 weeks.  
     
     
         18 . A method as claimed in  claim 1  wherein said fetus is a human fetus.  
     
     
         19 . A method as claimed in  claim 1  wherein said chromosomal abnormality comprises Down's Syndrome.  
     
     
         20 . A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down's Syndrome, the method comprising the steps of: 
 measuring at least one screening marker level from one of a first and second stage of pregnancy by assaying a sample obtained from the pregnant woman at said first or second stage of pregnancy for at least one biochemical screening marker;    measuring a level of the same said at least one screening marker at the other of said first and second stage of pregnancy by assaying a sample obtained from the pregnant woman at said other stage of pregnancy for said at least one biochemical screening marker; and    determining a quantitative estimate of the risk of Down's Syndrome using the measured screening marker levels from both the first and second stages of pregnancy.    
     
     
         21 . A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down's Syndrome, the method comprising the steps of: 
 measuring at least one screening marker level from one of a first and second stage of pregnancy by assaying a sample obtained from the pregnant woman at said first or second stage of pregnancy for at least one biochemical screening marker;    determining a first quantitative estimate of the risk of Down's syndrome using said measured screening marker level from the first stage of pregnancy;    measuring a level of the same said at least one screening marker at a second stage of pregnancy by assaying a sample obtained from the pregnant woman at said second stage of pregnancy for said at least one biochemical screening marker; and    determining a quantitative estimate of the risk of Down's Syndrome using the measured screening marker levels from both the first and second stages of pregnancy.    
     
     
         22 . A method as claimed in  claim 20  wherein said at least one biochemical screening marker is a marker at one of said first and second stages of pregnancy but not at the other.  
     
     
         23 . A method as claimed in  claim 20  wherein said measured screening marker levels from said first and second stages of pregnancy are highly correlated with one another.  
     
     
         24 . A method as claimed in  claim 20  further comprising: 
 measuring a second screening marker level from one of said first and second stage of pregnancy by:    assaying a sample obtained from the pregnant woman at said first or second stage of pregnancy for said a second biochemical screening marker;    measuring a level of said second screening marker at the other of said first and second stage of pregnancy by:    assaying a sample obtained from the pregnant woman at said other stage of pregnancy for said second biochemical screening marker; and    wherein said determining determines said Down's risk estimate further using the measured second screening marker levels from both said first and second stages of pregnancy.    
     
     
         25 . A method as claimed in  claim 24  wherein said second biochemical screening marker is a marker at one of said first and second stages of pregnancy but not at the other.  
     
     
         26 . A method as claimed in  claim 24  wherein said measured second screening marker levels from said first and second stages of pregnancy are highly correlated with one another.  
     
     
         27 . A method as claimed in  claim 20  further comprising: 
 measuring at least one ultrasound screening marker from an ultrasound scan taken at one of said first and second stages of pregnancy; and    wherein determining determines said Down's risk estimate further using said ultrasound screening marker.    
     
     
         28 . A carrier carrying processor control code to, when running, implement the method of  claim 1 .  
     
     
         29 . A carrier carrying the processor control code to, when running, implement the method of  claim 20 .  
     
     
         30 . A computer program to, when running, determine a pregnant woman's risk of having a fetus with Down's syndrome, the computer comprising code to: 
 input measurement data from a measurement of at least one screening marker level from one of a first and second stage of pregnancy obtained by assaying a sample obtained from the pregnant woman at said first or second stage of pregnancy for at least one biochemical screening marker;    input measurement data from a measurement of a level of the same said at least one screening marker at the other of said first and second stage of pregnancy obtained by assaying a sample obtained from the pregnant woman at said other stage of pregnancy for said at least one biochemical screening marker; and    determine a quantitive estimate of the risk of Down's syndrome using the measured screening marker levels from both the first and second stages of pregnancy.    
     
     
         31 . (canceled)  
     
     
         32 . A computer system for providing risk data representing a likelihood of a fetus carried by a pregnant mother having a chromosomal abnormality, a first biological parameter being suitable for screening said fetus for said chromosomal abnormality, the computer system comprising: 
 a data store operable to store data to be processed;    an instruction store storing processor implementable instructions; and    a processor coupled to said data store and to said instruction store and configured to load and implement said stored instructions, said instructions comprising instructions for controlling the processor to:    input first data from a first stage of pregnancy of said mother, said first data comprising data representing a first value of said first biological parameter;    input second data from a second, later stage of said pregnancy, said second data comprising data representing a second value of said first biological parameter;    determine said risk data from said first and second data; and    output said determined risk data.    
     
     
         33 . A method as claimed in  claim 21  wherein said at least one biochemical screening marker is a marker at one of said first and second stages of pregnancy but not at the other.  
     
     
         34 . A method as claimed in  claim 21  wherein said measured screening marker levels from said first and second stages of pregnancy are highly correlated with one another.  
     
     
         35 . A method as claimed in  claim 21  further comprising: 
 measuring a second screening marker level from one of said first and second stage of pregnancy by:    assaying a sample obtained from the pregnant woman at said first or second stage of pregnancy for said a second biochemical screening marker;    measuring a level of said second screening marker at the other of said first and second stage of pregnancy by:    assaying a sample obtained from the pregnant woman at said other stage of pregnancy for said second biochemical screening marker; and    wherein said determining determines said Down's risk estimate further using the measured second screening marker levels from both said first and second stages of pregnancy.    
     
     
         36 . A method as claimed in  claim 35  wherein said second biochemical screening marker is a marker at one of said first and second stages of pregnancy but not at the other.  
     
     
         37 . A method as claimed in  claim 35  wherein said measured second screening marker levels from said first and second stages of pregnancy are highly correlated with one another.  
     
     
         38 . A method as claimed in  claim 21  further comprising: 
 measuring at least one ultrasound screening marker from an ultrasound scan taken at one of said first and second stages of pregnancy; and    wherein determining determines said Down's risk estimate further using said ultrasound screening marker.    
     
     
         39 . A carrier carrying processor control code to, when running, implement the method of  claim 21.