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:</claim-text> measuring the level of at least one screening marker from a first trimester of pregnancy ssaying a sample obtained from the pregnant woman at said first trimester of pregnancy for at least one first biochemical screening marker; and/or (ii) measuring at least one first ultrasound screening marker from an ultrasound scan taken at said first trimester of pregnancy; measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one first screening marker from the first trimester of pregnancy, by: (i) assaying a sample obtained from the pregnant woman at said second trimester of pregnancy for at least one second biochemical screening marker; and/or (ii) measuring at least one second ultrasound screening marker from an ultrasound scan taken at said second trimester of pregnancy; and determining the risk of Down's syndrome by comparing the measured levels of both the at least one first screening marker from the first trimester of pregnancy and the at least one second screening marker from the second trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies. view more

A method according to claim 1, wherein the step of determining the risk of Down's syndrome comprises deriving the likelihood ratio of Down's syndrome using a multivariate analysis of the measured levels of the screening markers from both the first ond trimesters of pregnancy based on distribution parameters derived from a set of reference data. view more

A method according to claim 2, wherein said multivariate analysis is a multivariate Gaussian analysis.

A method according to claim 2, wherein the step of determining the risk of Down's syndrome further comprises multiplying the likelihood ratio by an age-specific risk.

A method according to claim 1, further comprising the step of re-expressing each measured level of a screening marker as a multiple of the median level of the respective screening marker in unaffected pregnancies of the same gestational age as the fetus of the pregnant woman. view more

A method according to claim 1, further comprising comparing the determined risk with a predetermined cut-off level to classify the pregnant women as screen-positive or screen negative based on the comparison.

A method according to claim 1, wherein said step of measuring the level of at least one first screening marker from a first trimester of pregnancy includes assaying a serum sample obtained from the pregnant woman during said first trimester of pregnancy for one selected from the group of PAPP-A, free β-hCG and both. view more

A method according to claim 7, wherein said step of measuring the level of at least one second screening marker from a second trimester of pregnancy includes assaying a serum sample obtained from the pregnant woman during said second trimester of pregnancy for one selected from the group of AFP, uE3, inhibin-A, free β-hCG, free α-hCG, total hCG and combinations thereof. view more

A method according to claim 1, further comprising adjusting any or all of the measured levels of the screening markers to allow for one or more factors selected from the group of maternal race, maternal weight, multiple birth and diabetic status.

A method according to claim 1, further comprising the steps of:</claim-text> obtaining said sample from the pregnant woman during said first trimester of pregnancy and/or taking said ultrasound scan during said first trimester of pregnancy; and ning said sample from the pregnant woman during said second trimester of pregnancy and/or taking said ultrasound scan during said second trimester of pregnancy. view more

A method according to claim 1, further comprising:</claim-text> determining a first risk estimate of Down's syndrome using the measured level of the at least one first screening marker from the first trimester of pregnancy; comparing the first risk with a predetermined cut-off level to initially classify the pregnant woman as screen-positive or screen-negative based on the comparison; and performing said steps of measuring the level of at least one second screening marker from a second trimester of pregnancy and determining the risk of Down's syndrome using the measured levels of the screening markers from both the first and second trimesters of pregnancy if the pregnant woman is initially classified as screen-negative. view more

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:</claim-text> measuring the level of at least one first screening marker from a first trimester of by: (i) assaying a sample obtained from the pregnant woman at said first trimester of pregnancy for at least one first biochemical screening marker; and/or (ii) measuring at least one first ultrasound screening marker from an ultrasound scan taken at said first trimester of pregnancy; determining a first risk estimate of Down's syndrome by comparing the measured level of the at least one first screening marker level from the first trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies; comparing the first risk estimate with a predetermined cut-off level to initially classify the pregnant woman as screen-positive or screen-negative based on the comparison; and if the pregnant woman is initially classified as screen-negative: measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one first screening marker from the first trimester of pregnancy, by: (i) assaying a sample obtained from the pregnant woman during said second trimester of pregnancy for at least one second biochemical screening marker; and/or (ii) measuring at least one second ultrasound screening marker from an ultrasound scan taken during said second trimester of pregnancy; and determining the risk of Down's syndrome by comparing the measured level of both the at least one first screening marker from the first trimester of pregnancy and the at least one second screening marker from second trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies. view more

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