Describe the maternal age effect associated with Down syndrome.

For unknown reasons, the nondisjunctional event that produces Down syndrome occurs more frequently during oogenesis in women older than age 35.

The median maternal serum alphafetoprotein (AFP) level at 14-20 weeks' gestation in 61 pregnancies associated with Down syndrome was 0·72 multiples of the median (MoM) value for a series of 36 652 singleton pregnancies unaffected by Down syndrome or neural-tube defect—a statistically significant reduction. The difference is great enought to form the basis of a screening test. By selecting for amniocentesis women with serum AFP levels ≤0·5 MoM at 14-20. weeks' gestation (excluding any of these that ultrasound cephalometry shows to have been due to the overestimation of gestational age) 21% of pregnancies with Down syndrome would be identified as well as 5% of unaffected pregnancies. If amniocentesis were offered to all women aged 38 years or more and, in addition, to younger women with serum AFP below specified maternal age-dependent cut-off levels (≤1·0 MoM at 37 years, ≤0·9 at 36, ≤0·8 at 35,≤0·7 at 34,≤0·6 at 32-33, ≤0·5 at 25-31) 40% of pregnancies with Down syndrome and 6·8% unaffected pregnancies would be selected.