Antenatal Detection of Down’s Syndrome
ABSTRACT & COMMENTARY
Synopsis: Although Down’s syndrome can be diagnosed antenatally by maternal serum screening for decreased levels of alphafetoprotein and by the detection of atrioventricular cardiac anomaly, almost half of affected pregnancies would result in live-born babies.
Source: Wyllie JP, et al. Strategies for antenatal detection of Down’s syndrome. Arch Dis Child 1997;76:F26-F30.
In order to predict the theoretic effect of maternal triple serum analyte (alphafetoproteinAFP; human choreionotic gonadotrophinHCG; and unconjugated estrogenUG) screening and fetal echocardiography on the birth prevalence of Down’s syndrome, the outcome of all Down’s syndrome pregnancies in the northern health region of the United Kingdom between 1985 and 1991 were ascertained. Down’s syndrome was identified in 412 pregnancies, and 76% of those resulted in live births. If no antenatal screening was available, 31 stillbirths and 381 affected infants could be expected. In this same theoretic population, screening would detect 169 affected infants. If these pregnancies were terminated, 229 affected infants would still be born. Even if prenatal screening were totally effective in detecting affected infants and even if all of these pregnancies were terminated, about half of all affected pregnancies will result in live-born infants.
COMMENT BY MARGRETTA SEASHORE, MD, FAAP
The reader may question the potential utility of the information presented in this paper and the validity of the model as it pertains to the United States. The goal of any screening program for genetic disorders is to identify people at risk in order to offer intervention to lessen the effect of the condition. The paper measures prenatal screening to identify fetuses with Down’s syndrome against this goal. The model they present suggests that such screening programs fall short of this goal if the desired intervention is reduction in the number of liveborn babies with Down’s syndrome. The authors’ model of hypothetical population, a program of triple analyte serum screening and age-based amniocentesis resulted in an approximate 50% reduction in the number of liveborn babies with Down’s syndrome. Little was added by surveillance for congenital heart disease by fetal ultrasound examination.
This outcome is not entirely explained by lack of sensitivity of the tests. Fewer than 50% of women accept the tests when offered, and only about one-fourth of the women whose fetuses are identified with Down’s syndrome select pregnancy termination. Wyllie et al argue that this result means that such prenatal screening programs will not eliminate the need for services for individuals with Down’s syndrome. This is a valid point but not a very useful one. In the first place, even if there were no live-born babies with Down’s syndrome, there are many other conditions, both congenital and acquired, that result in special needs. No program in the near future will eliminate the need for this kind of health care. The authors do not consider the utility of information about pregnancy outcome in preparing the mother for the birth of a child with special needs. For many families, such information provided by prenatal screening serves a very useful function.
The model compares the outcome in the population studied to that in a predicted theoretical population in which screening is not undertaken. It is not entirely clear why this is superior to comparison to historical control populations or incidence figures in the recent past prior to the development of prenatal screening programs.
The data studied in the United Kingdom and reported in the actual population resemble those seen in prenatal screening programs in the United States. About one-third of women use triple analyte serum screening, and no more than half of eligible women accept age-related amniocentesis. The Wyllie study leaves unanswered the question of why acceptance of this kind of testing is so low. For amniocentesis, women must weigh the value of the information gained against the risk of the procedure to the unborn baby, factors that surely inhibit acceptance of the testing. But, why is acceptance of serum screening so low? Perhaps the relatively high rate of false-positive test results is a factor; if that is the case, improvement in specificity of testing will make the test more attractive to women. Wyllie et al mention the analysis of fetal cells from maternal serum as a possibility, but this is not yet on the clinical horizon. Some investigators have claimed to detect as many as 80% of fetuses with Down’s syndrome by adding the measurement of inhibin A to triple analyte screening. This may be an over estimate, and the false-positive rate is comparable to triple analyte screening.
With the current use of prenatal screening for Down’s syndrome, about half of all pregnancies with Down’s syndrome will result in live-born affected babies. Lack of specificity and sensitivity of the testing methods accounts for part of this outcome, but there is also a lack of acceptance of testing on the part of pregnant women. Further studies of prenatal screening need to address both the methods used for testing and the factors that influence decisions that women at risk make. (Dr. Seashore is Professor of Pediatrics and Genetics at Yale University School of Medicine.)
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