The long-term goal is to elucidate the processes leading to trisomy. Trisomy is the most frequent chromosomal aberration among births and clinically recognized spontaneous abortions and gives rise (as trisomy 21) to the most prevalent form of severe or moderate mental retardation. Advancing chronologic maternal age is the primary risk factor for trisomy. The proposed project tests whether trisomy arises as a function of the size of the oocyte pool and, in particular, the hypothesis that risk at given chronologic ages is increased in women with accelerated rates of oocyte atresia and hence smaller oocyte pools. Since atresia rate is a determinant of age at menopause, this hypothesis leads to the prediction that menopause occurs earlier among women with trisomic pregnancies than women with chromosomally normal pregnancies at the same chronologic age. The study draws on private patients who enrolled in a previous study over the period 1974-1986. The sample includes women with spontaneous abortions of known karyotype and a control group of women with deliveries at 28 weeks or later. Women who are 45 years or older who had trisomic spontaneous abortions (n=149), chromosomally normal spontaneous abortions (n=210), or chromosomally normal live births (n=261) will be located and interviewed about menstrual function and other factors. The roughly two- thirds (n=397) who will not yet have reached menopause will be followed at six-month intervals over 48 months.
The specific aims are: 1. To test whether age at menopause is earlier among women with prior trisomic spontaneous abortions than among women with chromosomally normal spontaneous abortions or with chromosomally normal live births, controlling both by design and analysis for chronologic age at study pregnancy and follow-up. 2. To take advantage of menstrual data collected during follow-up to explore whether onset of menstrual cycle irregularity, an indicator related both to size of the oocyte pool and to hormonal changes, is earlier among women with prior trisomic spontaneous abortions than among women with chromosomally normal spontaneous abortions or live births.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010251-05
Application #
2001401
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Bellino, Francis
Project Start
1993-01-01
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1998-12-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Kinney, Ann; Kline, Jennie; Levin, Bruce (2006) Alcohol, caffeine and smoking in relation to age at menopause. Maturitas 54:27-38
Taylor, Sylvia M; Kinney, Ann M; Kline, Jennie K (2004) Menopausal transition: predicting time to menopause for women 44 years or older from simple questions on menstrual variability. Menopause 11:40-8
Kline, J; Kinney, A; Levin, B et al. (2000) Trisomic pregnancy and earlier age at menopause. Am J Hum Genet 67:395-404
Kline, J; Kinney, A; Levin, B et al. (2000) Alzheimer's disease in the parents of women with trisomic spontaneous abortions. Neuroreport 11:795-9