Inventors: Canick; Jacob A. (Newton, MA); Wald; Nicholas J. (London, GB); Haddow; James E. (Sebago Lake, ME); Cuckle; Howard S. (London, GB) Assignee: 3i Research Exploitation Limited (London, GB2) Appl. No.: 908875 Filed: July 7, 1992

Primary Examiner: Parr; Margaret Assistant Examiner: Grun; James L. Attorney, Agent or Firm: Nixon & Vanderhye United States Patent 5,506,150 April 9, 1996

Parent Case Text
This is a continuation of application Ser. No. 07/457,687, filed Jan. 9, 1990, now abandoned.

Claims
We claim:

1. A screening method to determine if a pregnant woman is carrying a fetus having an increased risk of Down's syndrome comprising the steps of:

(a) obtaining a sample of serum from the pregnant woman at a stage before the beginning of the third trimester of pregnancy,

(b) immunologically assaying said sample to determine a level of at least one primary serum constituent selected from the group consisting of unconjugated oestriol, progesterone, and dehydroepiandrosterone sulfate,

(c) comparing the level of the at least one primary constituent determined for the sample with control levels of the at least one primary constituent determined for serum samples obtained at said stage of pregnancy from women carrying fetuses known to be affected or unaffected by Down's syndrome, and thereby determining an increased risk of Down's syndrome fix the fetus carried by the woman.

2. The method as claimed in claim 1 which comprises the additional step of:

(d) determining the maternal age of the pregnant woman, wherein advanced maternal age is indicative of an increased risk of Down's syndrome for the fetus carried by the woman.

3. The method as claimed in claim 1 which comprises the additional steps of:

(d) immunologically assaying said sample or another sample of serum from the pregnant woman obtained at a stage before the beginning of the third trimester of pregnancy to determine a level of another maternal serum constituent which is alpha-fetoprotein,

(e) comparing the level of alpha-fetoprotein determined for the sample or the another sample to control levels of alpha-fetoprotein determined for serum samples obtained at said stage of pregnancy from women carrying fetuses known to be unaffected by Down's syndrome, wherein a decreased level of alpha-fetoprotein in the sample or the another sample from the woman is indicative of an increased risk of Down's syndrome for the fetus carried by the woman.

4. The method as claimed in claim 3 which comprises the additional step of:

(f) determining the maternal age of the pregnant woman, wherein advanced maternal age is indicative of an increased risk of Down's syndrome for the fetus carried by the woman.

5. The method as claimed in any one of claims 1 to 4 which comprises the additional steps of:

(g) immunologically assaying said sample or said another sample to determine a level of another maternal serum constituent which is human chorionic gonadotrophin,

(h) comparing the level of human chorionic gonadotrophin determined for the sample or the another sample to control levels of human chorionic gonadotrophin determined for serum samples obtained at said stage of pregnancy from women carrying fetuses known to be unaffected by Down's syndrome, wherein an increased level of human chorionic gonadotrophin in the sample or the another sample from the woman is indicative of an increased risk of Down's syndrome for the fetus carried by the woman.

6. The method according to claim 5 wherein the at least one primary constituent is unconjugated oestriol, and levels of both alpha-fetoprotein and human chorionic gonadotrophin are determined.

7. The method according to claim 5 wherein the at least one primary constituent is both dehydroepiandrosterone sulfate and unconjugated oestriol, and levels of both alphafetoprotein and human chorionic gonadotrophin are determined.

Description
BACKGROUND OF THE INVENTION

This invention relates to antenatal screening for risk of Down's Syndrome in a foetus.

Risk of Down's syndrome in a foetus is known to increase with the age of the mother and it is this fact which forms the basis for selection of mothers for further investigation. Further testing involves sampling of the amniotic fluid by amniocentesis, a procedure which is not completely free from risk to the mother or foetus induction of miscarriage being a recognised hazard.

The amniotic fluid test for Down's syndrome (the recognition of an extra chromosome 21 in foetal cells) is diagnostic.

There is a need for a screening method which will identify pregnancies most at risk so as to justify amniocentesis with its attendant risks.

An object of the present invention is to provide an improved screening procedure.

[...]

In many existing screening programmes about 5% of women are selected for amniocentesis on the basis of advanced age alone. The method of this invention using assays for AFP, hCG, and unconjugated oestriol, in combination with maternal age detects over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing screening programmes. As an illustration, this method has the potential to reduce the number of Down Syndrome births in the United Kingdom from about 900 per year, in the absence of screening, to about 350 per year.

The rate of detection may be further enhanced by ultrasound screening, using, for example, fetal femur length measurement as a complementary technique.