First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was −0.21 which was statistically significant (p=0.02, 95% confidence interval −0.38 to −0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal screening for Down syndrome and neural tube defects in twin pregnancies

Prenatal screening and diagnosis in a twin pregnancy is not straightforward. Once a twin pregnancy has been identified, women and their partners need time to consider the implications and decide whether they wish the pregnancy to be screened for Down syndrome or neural tube defects. We discuss here how multiple marker screening for Down syndrome and alpha-fetoprotein screening for neural tube defects can be carried out, given that this is the parents' chosen option and that the health professionals involved are capable of performing a diagnosis and selective feticide, should this arise. Copyright © 2005 John Wiley & Sons, Ltd.     

Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies

A method is described to combine the ultrasound marker nuchal translucency (NT) with serum markers so that they can be used together in prenatal screening for Down syndrome in twin pregnancies. For monochorionic twin pregnancies (taken as monozygous), the two fetus-specific NT measurements are averaged before risk is calculated and before the contribution of the serum markers is incorporated. For dichorionic twin pregnancies (taken as dizygous), the risk for each fetus based on the individual NT measurements is calculated, the two fetus-specific risks are added together, and then the contribution of the serum markers is incorporated. In this way, all the screening markers can be used in combination to produce a pregnancy-specific ‘pseudo-risk’, rather than a fetus-specific pseudo-risk. We refer to pseudo-risk because in the absence of sufficient data on the screening markers in affected twin pregnancies, a true risk estimate cannot be calculated. Tentative estimates are given of screening performance in twins using NT, the combined test (NT with first-trimester serum markers), and the integrated test (NT with first- and second-trimester serum markers), all interpreted with maternal age. Copyright © 2003 John Wiley & Sons, Ltd.     

Vaginal bleeding in pregnancies associated with fetal Down syndrome

It has been suggested that vaginal bleeding in pregnancy is associated with an increased risk of fetal Down syndrome. To investigate this, information on vaginal bleeding, collected at the first antenatal visit, was abstracted from the medical notes of 70 pregnancies associated with Down syndrome and 140 unaffected controls matched for maternal age. Fourteen cases (20 per cent) and 23 controls (16 per cent) had some evidence of bleeding (relative risk estimated as the odds ratio= 1.3; P=0.26, one-sided; 95 per cent confidence interval 0.6–2.8). When these results were pooled with those from the two other controlled studies already published the combined relative risk estimate was 1.8 (P=0.02, two-sided; 95 per cent confidence interval 1.1–3.0). On the basis of present evidence, there is some reason to regard vaginal bleeding prior to the first antenatal visit as a risk factor for Down syndrome but the association and its biological significance remains uncertain.     

Abnormal amniotic fluid levels of CA 125 in second-trimester Down syndrome pregnancies

The aim of this study was to evaluate the concentration of CA 125 in second trimester amniotic fluid from Down syndrome pregnancies. CA 125 was measured in stored amniotic fluid samples from pregnancies of 14–19 weeks' gestation with and without Down syndrome fetuses. CA 125 levels were expressed in multiples of the median (MOM) for normal pregnancies of the same gestational age. Twenty-one pregnancies with Down syndrome fetuses and 63 unaffected controls matched for maternal age, gestational age, and duration of storage were studied. The median MOM values of the affected pregnancies were significantly higher than those of the controls (1·41 MOM versus 0·99 MOM). These findings show that there is an increased concentration of CA 125 in second-trimester amniotic fluid from Down syndrome pregnancies.     

Maternal serum levels of total activin-A in first-trimester trisomy 21 pregnancies

Maternal serum total activin-A concentration was measured in 45 pregnancies affected by trisomy 21 and 493 control unaffected pregnancies at 10–14 weeks of gestation. In the trisomy 21 pregnancies total activin-A concentration was significantly higher (1.36 MoM of the unaffected pregnancies) and in 16% of cases the level was above the 95th centile of normal. The log₁₀ SD for the control group and the trisomy 21 group were 0.17 and 0.22, respectively. The median pregnancy associated plasma protein-A (PAPP-A) in this trisomy 21 series was 0.49 and for free β-hCG was 2.05. In the trisomy group there were significant positive associations between total activin-A and PAPP-A (0.6071) and free β-hCG (0.4255). The low median difference and the high overlap in values between trisomic and unaffected pregnancies make total activin-A of little practical use in first-trimester screening for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.