Biochemical screening for Down’s syndrome in the first trimester of pregnancy

Macintosh, M. C. M.; Chard, Tim

doi:10.1017/s0965539500000875

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…Intact hCG, placental alkaline phosphatase, and pregnancyspecrfic pl glycoprotein are weak markers for Down's syndrome in the first trimester (Brock er al., 1990;Aitken et al, 1993) and although UE3 levels have been reported to be reduced in Down's syndrome pregnancies in both the first and the second trimesters (Aitken et aZ., 1993), the available assays are not optimized for routine first-trimester screening. Several studies have shown that PAPP-A levels are sigmfkantly reduced in first-trimester Down's syndrome pregnancies (Brambati et aL, 1993;Macintosh and Chard, 1993;Spencer et al, 1994) but that levels are unchanged in the second trimester . The potential of PAPP-A as a marker is therefore complicated by the apparent normalization in levels in abnormal pregnancies between the first and second trimesters.…”

Section: Discussionmentioning

confidence: 99%

Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

Berry¹,

Aitken²,

Crossley³

et al. 1995

Prenatal Diagnosis

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The aim of this study was to determine the maternal population, pregnancy, serum alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotrophin (F beta hCG) parameters in a large series of women attending prenatal clinics before 15 weeks' gestation and to assess the practical problems of population screening for Down's syndrome in the first trimester using these markers. Serum samples were collected from 8600 women attending prenatal clinic booking visits. Maternal serum AFP and F beta hCG medians were calculated for each day of gestation (49-104 days), using both dates and ultrasound estimates of gestation. The effects of maternal weight, twin pregnancies, and threatened abortion on AFP and F beta hCG levels were analysed. The median age of the population was 27.1 years and the median weight 62.1 kg. Twenty-six per cent of samples were collected before 70 days and 50 per cent before 78 days' gestation. Eighty-nine per cent of all samples had gestational estimates by dates, 60 per cent by ultrasound and 52 per cent by both dates and ultrasound. The AFP median was 5 kU/l at 49 days, 5.9 kU/l at 70 days, and 17.9 kU/l at 100 days. The peak median F beta hCG level was 66.4 ng/ml at 64 days, falling to 20.6 ng/ml at 100 days' gestation. Both AFP and F beta hCG levels showed log Gaussian distributions but the standard deviation for AFP was 20 per cent greater than that found in the second trimester. AFP and F beta hCG levels showed an inverse relationship with maternal weight and were increased in twin pregnancies (1.68 and 1.97 multiples of the median, respectively). AFP and F beta hCG can be readily measured in a large screening population in the first trimester. Down's syndrome screening protocols based on these markers could be refined by the use of gestations in individual days but AFP is likely to be a less effective marker and detection rates are likely to be lower than in the second trimester. To realize the potential of first-trimester screening, more women should be encouraged to attend the prenatal clinic in early pregnancy and ultrasound dating should be carried out for all pregnancies at this stage.

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Section: Discussionmentioning

confidence: 99%

Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

Berry¹,

Aitken²,

Crossley³

et al. 1995

Prenatal Diagnosis

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“…AFP, P-hCG, and estriol are commonly used in screening for Down's syndrome [4], However, efforts to enable earlier diagnosis have expanded the search for other possible markers, including PAPP-A, Inhibin, and urinary (3-core hCG [5,6], Estradiol, PAI-2, and many other protein markers have also been theorized to predict pregnancy outcomes. Serum progesterone has been used to discrimi nate between normal and abnormal pregnancies.…”

Section: Introductionmentioning

confidence: 99%

Urinary β-Core Fragment as a Predictor of Abnormal Pregnancy at 4–6 Weeks’ Gestation

et al. 1997

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Currently, transvaginal ultrasound and serial serum β-hCG measurements are used to differentiate normal versus abnormal gestations in the first trimester of pregnancy. These techniques have been found to be ineffective when the gestations are earlier than 6 weeks. This study was conducted to determine if urinary β-core fragment, the urine degradation product of β-hCG, could be used to distinguish normal from abnormal gestations between 4 and 6 weeks. Urine samples were obtained from 27 patients on initial presentation to the emergency room or outpatient settings with gestations at 4–6 weeks by sure last menstrual period. The urine was then frozen at ––40 °C and sent for β-core assay analysis. Eighteen women with normal intrauterine pregnancies and nine abnormal pregnancies, including ectopics and spontaneous abortions, were studied. Pearson correlations were performed with a p < 0.05 considered significant. In the normal gestations, there was a positive correlation between β-core fragment and gestational age at 4–6 weeks (r = 0.461, p < 0.05). This correlation was not evident in abnormal gestations (r = 0.360, p = 0.34). In early pregnancy, β-core fragment correlates positively with gestational age which is not apparent in abnormal counterparts. This finding suggests that urinary β-core fragment may be a promising marker to differentiate normal early pregnancies from abnormal gestations.

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“…However, it would be desirable if sensitive and specific screening could be applied in the first trimester, affording earlier termination of pregnancy if indicated. To this end, a number of fetal and placental proteins have undergone initial evaluation of their usefulness as first-trimester maternal serum markers for Down's syndrome (Macintosh and Chard, 1993). Also, it has been recently reported that immunoreactive inhibin, a glycoprotein of placental origin in pregnancy (Abe et al, 1990;Tovanabutra et al, 1993), did not appear useful in first-trimester screening for Down's syndrome (van Lith et al, 1994;Wallace et al, 1994), although some potential value in the second trimester has been suggested (van Lith et al, 1992;Spencer et al, 1993;Cuckle et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of maternal serum dimeric inhibin a as a first‐trimester marker of down's syndrome

et al. 1995

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While second-trimester prenatal screening programmes for Down's syndrome have become established in prenatal care, it would be advantageous to be able to offer screening in earlier pregnancy. To this end, we have evaluated a new potential maternal serum marker, dimeric inhibin A, as a possible first-trimester marker. Dimeric inhibin A was measured in prospectively collected maternal serum from 23 cases of Down's syndrome and matched chromosomally normal controls, at 11-13 weeks' gestation. Levels of this protein were significantly elevated in the Down's pregnancies compared with the control pregnancies. The median multiple of the normal median (MOM) for the Down's samples was 2.46 (95 per cent confidence interval: 2.11-3.26, P < 0.0001 vs. controls). These results suggest that dimeric inhibin A is a useful discriminator of Down's-affected pregnancies from normal pregnancies in the first trimester and that sensitive screening in combination with maternal age and other possible markers may be practicable in the first trimester.

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Biochemical screening for Down’s syndrome in the first trimester of pregnancy

Abstract: Link to this article: http://journals.cambridge.org/abstract_S0965539500000875How to cite this article: MCM Macintosh and T Chard (1993). Biochemical screening for Down's syndrome in the rst trimester of pregnancy.

Cited by 10 publications

References 58 publications

Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

Urinary β-Core Fragment as a Predictor of Abnormal Pregnancy at 4–6 Weeks’ Gestation

Evaluation of maternal serum dimeric inhibin a as a first‐trimester marker of down's syndrome

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