Steroidogenesis patterns in common trisomies

Abstract

Objective: By determining the early patterns of steroidogenesis in the most common aneuploidies, we have shown that there are differences between aneuploid and euploid pregnancy steroidogenesis patterns. We hypothesize that there are differences in steroidogenesis between specific trisomies, as well.

Methods: The records of all patients with a cytogenetic diagnosis of aneuploidy were studied. Serial data on progesterone(P), estradiol(E2) and beta-HCG(bHCG) was collected in the first trimester of aneuploid pregnancies. A matched group of normals at the same gestational ages was used as a control group. The specific trisomies of the above group were catalogued.

Results: 31 aneuploid pregnancies were reviewed for progesterone, estradiol and beta-HCG in the first trimester. Data was available for three or more patients with trisomy 16, 18, 21 and 22. Serial measurements between 5 and 10 weeks of pregnancy were obtained for P, E2, and bHCG. Gestational age was determined by LMP and serial sonograms. The progesterone, estradiol and beta-HCG levels were evaluated by calculating the rates of change between 5 and 10 weeks, rather than threshold values. The natural log of the values was used to plot serial data and reduce scatter due to the large natural variation in values between patients. The rates of change of P, E2 and b-HCG in the trisomic pregnancy groups were compared to matched normal pregnancies. The slopes of the curves for the trisomies and euploid pregnancies were calculated and compared. We determined that the rate of change of HCG for each of the trisomies was no different from euploid pregnancies, which is consistent with earlier data. In examining estradiol, trisomy 22 did not have a statistically different pattern of steroidogenesis, where trisomies 16, 18 and 21 were different than euploid (p < 0.05). With progesterone, trisomies 16, 18 and 22 had statistically different rates of change (p < 0.05), however trisomy 21 did not.

Conclusions: As we have shown, in pregnancies with aneuploidy, there is a different pattern of steroidogenesis from euploid pregnancies. The difference is detectable in the first trimester by serial measurements of P and E2. In determining steroidogenesis in trisomies 16, 18, 21, and 22, we demonstrate that there is a difference in progesterone and estradiol levels over 5 to 10 weeks among the trisomies that can assist in the diagnosing of abnormal pregnancies in the first trimester. Furthermore, by looking at the rates of change of the individual steroids, the specific aneuploidy may be suspected. A large prospective study may reveal the clinical utility of these observations for early prenatal diagnosis of aneuploidy or probable spontaneous abortion.