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.     

Frequency and clinical consequences of extremely high maternal serum PAPP-A levels

A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan's syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan's syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified. Copyright © 2003 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.