Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience

Abstract

Objective To evaluate the performance of screening for fetal trisomy 21 in the first trimester of twin pregnancies by a combination of maternal serum biochemistry and ultrasonography. Design Three year retrospective review of screening performance.Setting District General Hospital maternity unit.Population All women booked to receive routine antenatal care at Harold Wood Hospital between 1 June 1998 and 30th September 2001. The population included 13,940 women of all ages presenting with pregnancies between 10 weeks 3 days and 13 weeks 6 days gestation. Of these, 230 had a twin pregnancy. Methods Women booked into the clinic were offered screening using a combination of maternal serum free h-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness.Women at increased risk of carrying a fetus with trisomy 21 or trisomy 13/18 ( 1 in 300 at sampling) were offered counselling and an invasive diagnostic procedure. Follow up of the outcome of all pregnancies was carried out. For women who on examination were at 14 weeks of gestation or greater, or for women presenting as late bookers beyond 14 weeks, screening was performed in the same time frame using only maternal serum free h-hCG and a-fetoprotein. Main outcome measures The first trimester detection rate for trisomy 21 and all aneuploides, false positive rate, uptake of screening, uptake of invasive testing in women identified at increased risk and fetal loss rates after invasive testing. Results Overall, 97.4% of the women with twins (224/230) accepted first trimester screening. The rate of detection of trisomy 21 was 75% (3/4). Fetal death at presentation was found in 3.4% of fetuses (16/460). Of women who accepted screening, 4.3% (10/230) presented too late for fetal nuchal translucency measurement and 10.0% of women (23/230) presented too early. A risk for trisomy 21 was calculated for each fetus based on the individual fetal nuchal translucency thickness and the maternal biochemistry. The false positive rate among those eligible for first trimester screening was 9.0% (19/206) of pregnancies and 6.9% of fetuses (28/412). Uptake of invasive testing was 59% (10/17) with chorionic villus sampling in eight cases and amniocentesis in two. No fetal loss occurred within 28 days of chorionic villus sampling and no loss occurred after amniocentesis. One case of trisomy 21 was identified for every three invasive procedures. Conclusion First trimester screening for trisomy 21 in twin pregnancies is both theoretically possible and practically achievable using a combination of nuchal translucency thickness and maternal serum biochemistry. However, dilemmas for the mother and health professionals when both nuchal translucency thickness measurements are normal might suggest that greater reliance be placed on the nuchal translucency thickness risk alone when counselling women about invasive testing.

Current concepts of Down syndrome screening tests in assisted reproduction twin pregnancies: another double trouble

“…In a later study, Spencer and Nicolaides (2003) reported their experience for DS screening in the first trimester of 230 twin pregnancies (21% conceived by ART) by the combination of maternal serum biochemistry and NT: 9.2% of these pregnancies were found to be screen positive similar to our current NT screening results. Therefore, adding first-trimester maternal serum biochemistry to NT may improve the detection rate by about 5-6% (Spencer and Nicolaides, 2003). However, when invasive testing is indicated, NT alone is the screening modality women should be counseled to chose, since ultrasound is the best means of specifically locating the affected co-twin (Spencer and Nicolaides, 2003).…”

“…However, in contrast to second-trimester screening, chorionicity had no impact on the first-trimester serum biochemical marker levels in twin pregnancies (Spencer, 2001). In a later study, Spencer and Nicolaides (2003) reported their experience for DS screening in the first trimester of 230 twin pregnancies (21% conceived by ART) by the combination of maternal serum biochemistry and NT: 9.2% of these pregnancies were found to be screen positive similar to our current NT screening results. Therefore, adding first-trimester maternal serum biochemistry to NT may improve the detection rate by about 5-6% (Spencer and Nicolaides, 2003).…”

“…Serum screening was introduced before the other methods so that there is more experience with it worldwide. It is now accepted, however, that DS serum screening is of limited value in twin pregnancies (Cuckle, 1998a;Wald et al, 1991) because the unaffected co-twin masks the abnormal maternal serum distribution seen in singleton analyses (Cuckle, 1998a,b whilst a pregnancy at high risk may be identified, serum biochemistry results will not be able to pinpoint which twin is affected (Spencer and Nicolaides, 2003; see also Wald and Rish, this issue). Despite these limitations, centers still offer mid-gestation serum screening for twin pregnancies, either because of a limited capacity for firsttrimester screening or due to women booking late for prenatal care.…”

“…The methods currently widely used for Down syndrome (DS) screening in twins include maternal age, midgestation maternal serum screening and first-trimester nuchal translucency (NT) measurements (with or without serum markers). Screening of twin pregnancies is considered to be extremely difficult because of the clinical, technical and ethical challenges posed for diagnosis and clinical management of such pregnancies (Cuckle, 1998a;Spencer and Nicolaides, 2003) (see Wald and Rish, this issue) with some centers not offering DS screening in twin pregnancies (Spencer and Nicolaides, 2003;Wald et al, 2003). Twin pregnancies are becoming more frequent in most developed countries due to the increased use of assisted reproductive technologies (ART) and advanced maternal age.…”

“…The combined effect results in older women having a greater chance of conceiving twins (Spencer, 2000). This incidence had increased from 0.97% in 1979 to 1.43% by 1999 in the United Kingdom (Spencer and Nicolaides, 2003) and comprised 2-3% of live births in the United States in 1997 (Guyer et al, 1998). These pregnancies present numerous diagnostic and management challenges from conception to delivery.…”