Prenatal screening tests facilitate risk assessment - Cover Story

Medical Laboratory Observer, Feb, 2002 by Sharon M. Miller, Jeanne M. Isabel

Knowledge often provides the power to positively influence outcomes. One of our nation's health goals for the new millennium as articulated in the document Healthy People 2010 is improved maternal, infant and child well-being.(1) There are many ways to accomplish this goal; one means is by increasing maternal understanding of testing available during pregnancy. Informed mothers can hope to have healthier babies. The development and application of new assays and technologies for prenatal screening provide more accurate assessment of risk for birth defects. Integration of screening results from first and second trimester testing offers a higher detection rate, with much lower false positive rate, for Down syndrome (DS).(2) A clearer understanding of the extent to which certain birth defects are preventable may result in more women of childbearing age modifying dietary practices or taking a folic acid supplement to reduce the risk for an affected pregnancy.

The laboratory as part of a prenatal screening can measure a variety of maternal biochemical markers. Although the routine specimen for assay is maternal serum, in some instances maternal urine is also acceptable. Interpretation of data provided by various configurations of screening tests has significantly reduced the need for follow-up with the more costly, risky diagnostic procedures of amniocentesis, and chorionic villus sampling (CVS). Procedure-related risks of amniocentesis include miscarriage, fetal puncture, bleeding, and possible infection.(3) If the rate of miscarriage might be expected to be 2 percent to 3 percent, the procedure of amniocentesis carries with it an additional increase in risk of 0.5 percent to 0.8 percent.(4) For CVS, in which a small amount of tissue is taken from the placenta for karyotyping, the fetal loss rate is increased by 1 percent to 2 percent for an overall miscarriage risk of 3 percent to 5 percent.(5)

A positive test result can have profound consequences for expectant parents. The potentially adverse psychological impact of prenatal screening test results requires that any facility undertaking such testing have an experienced counseling staff available to work with families. Currently the most common benefit of prenatal diagnosis is better counseling for prospective parents and family members.

There are already tangible benefits from prenatal screening, and even more are likely in the future. Neural tube defects (NTDs) are classified as open if neural tissue is exposed because of openings in the skull and spine.(6) Fetal surgery to repair open NTDs is relatively new and is risky for both mother and child. It has been successful, though it is available only on a very limited basis.(7) Such early surgical repair protects the fetus' previously exposed neural tissue from additional damage by contact with the amniotic fluid (AF) and intrauterine movement, and from trauma during passage through the birth canal. There is even evidence that certain fetal brain malformations may "correct" themselves following surgery. There is a 30 percent to 50 percent reduction in the need for surgical shunting to reduce hydrocephalus, a common condition in newborns with spina bifida. Corrective surgery on newborns is far less problematic and more widely available. In the future, in utero or neonatal corrective gene ther apy may be feasible.

Primary prevention is preferable to remediation. Healthy People 2010 includes specific objectives to reduce the occurrence of developmental disabilities and neural tube defects. One objective is to increase the proportion of pregnancies begun with optimal levels of the B vitamin folic acid.(1) Recent federal initiatives in food fortification with synthetic folic acid are already showing positive results.

Since Jan. 1, 1998, when the U.S. Food and Drug Administration required all enriched cereal grains to be fortified with 140 [micro]g of synthetic folic acid per 100 g of grain, the birth prevalence of NTDs has declined by 19 percent.(8) Continued health education efforts to raise public awareness regarding the beneficial effects of folic acid supplementation by women capable of childbearing remain critical.(9)

Second trimester screening

About 30 years ago, elevated alpha fetoprotein (AFP) levels in maternal serum and in amniotic fluid were first linked to the occurrence of fetal NTDs.(10) In 1977, findings of a large collaborative study in the United Kingdom confirmed the value of measuring maternal serum AFP (MSAFP) in screening for NTDs.(11) Prior to that, unless a woman or a close female relative had had a previous NTD-affected pregnancy, there was essentially no way to predict how likely she was to be carrying an NTD-affected fetus.

In the early 1980s the Food and Drug Administration (FDA) first licensed an AFP kit, and maternal serum AFP measurements became best practice in this country for detecting NTDs. By the mid-1980s, the merit of MSAFP use in screening for Down syndrome among women younger than 35 had been recognized. By the end of that decade, two additional biochemical markers, human chorionic gonadotropin (hCG) and unconjugated estriol (uE3), had been identified as providing valuable information on the developing fetus.