Low AFP is usually associated with chromosomal defects. There are several screening methods, which utilize the combination of AFP and other maternal serum proteins (serum markers) in order to identify fetuses at higher risk for Down syndrome. The accuracy of the test may vary from 50-80% depending on the methodology used. Abnormally low AFP does not mean that the baby necessarily has Down syndrome. Instead, it simply means that the mother has a higher risk than the average pregnant woman of giving birth to a baby with Down syndrome. Ultrasound targeted anatomical assessment combined with fetal cardiac echo may reduce this risk to normal. For patients who wish to have the highest level of diagnostic accuracy and to reliably exclude the presence of Down syndrome, amniocentesis for fetal chromosomal analysis may be the best solution. However, amniocentesis is an invasive procedure and therefore caries a normal pregnancy loss risk of 1 in 300.