Lower risk for Down syndrome associated with longer oral contraceptive use: a case-control study of women of advanced maternal age presenting for prenatal diagnosis.

BACKGROUND: Maternal trisomy 21 ovarian mosaicism might provide the major causative factor for fetal Down syndrome. The small proportion of trisomy 21 oocytes thought to be retarded in their maturation in comparison to normal disomic ones, and the maternal age effect can be based on an accumulation of trisomy 21 oocytes in the ovarian reserve. By lowering the number of unnecessary ovulations, a greater portion of disomic oocytes might be saved. STUDY
DESIGN: Between September 2009 and September 2011, we performed genetic amniocentesis for fetal chromosomal analysis in 5222 pregnancies. We detected 119 structural or numerical chromosomal abnormalities. We collected data from 37 cases who were in advanced maternal age and where fetal trisomy 21, 18 or 13 was confirmed. We had 92 control patients. Detailed information was taken from those factors that influence the number of ovulations in reproductive life.
RESULTS: From the factors checked, patients with a trisomic fetus had a shorter overall mean length of oral contraceptive pill use before the trisomic pregnancy (3.4 vs. 6.0 years, p<.0014), and the estimated number of mean ovulations was higher (274.6 vs. 224, p<.0003).
CONCLUSION: We found that a history of longer oral contraceptive pill use and fewer ovulatory cycles were associated with fewer common trisomies of the fetus. Additional research is needed to rule out potential confounding factors, but our results are consistent with the maternal ovarian mosaicism causal model.