Joseph E. O'Brien

Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values.

OBJECTIVE: Folic acid fortification of breads and grains was implemented in the United States in 1998 in an attempt to reduce the incidence of neural tube defects. Outcome data from birth registries have shown a 20% drop—less than originally predicted. In this study, we ascertain if the impact of folic acid fortification is better seen at the time of midtrimester prenatal diagnosis by looking at incidence of high maternal serum alpha-fetoprotein (MSAFP) values. METHODS: Data regarding MSAFP levels in 61,119 patients undergoing maternal serum screening at a large commercial laboratory were categorized by multiples of the median (MoM). The data were compared between 2 groups: before mandatory supplementation in the United States in 1997 and after mandatory supplementation in 2000. High MSAFP values were further categorized as high (2.75–4.00 MoM) or very high (more than 4.00 MoM). Data were analyzed by χ2 analysis. RESULTS: Comparative data showed a 32% decrease of patients with MoM greater than 2.75 + (2.5% −1.7%). Further categorizations revealed similar decreases. CONCLUSION: The introduction of folic acid fortification has produced a profound decrease in the number of high MSAFP values, reflective of a decreased incidence of neural tube defects. Our results help to validate the decision to fortify food with folic acid, which represents a highly successful public health policy for primary prevention of birth defects. LEVEL OF EVIDENCE: II-2

Similarity of insulin-dependent diabetics' and non-insulin-dependent diabetics' levels of beta-hCG and unconjugated estriol with controls: no need to adjust as with alpha-fetoprotein.

Objective: To determine if the same systematic alteration of serum values seen for alpha-fetoprotein (AFP) in diabetic patients is also seen for β-hCG and unconjugated estriol (uE3). Methods: Serum AFP, β-hCG, and uE3 results were obtained in 18,639 patients for whom complete follow-up information was obtained. Patients were divided into euglycemic (n = 18,088), insulin-requiring diabetics (n = 104), and non-insulin-requiring diabetics (n = 437), as well as by race. Results: The 20% adjustment used for AFP appropriately corrects serum values. No such systematic variation is seen for either β-hCG or uE3 by glycemic status or race. Conclusion: No adjustment for β-hCG or uE3 is necessary for diabetes for biochemical screening programs.

Screening for aneuploidy

Over the past 15 years, biochemical screening for chromosomal abnormalities, particularly Downs syndrome, has advanced from being extremely naive, to now somewhat more sophisticated. Sensitivities have gone from 20% to 60-70%. Considerable work is still required to not only increase the sensitivity, but also the specificity to keep health care costs down.