Cellfree DNA levels during deliveries at term and preterm

1
Cell-free DNA levels during deliveries at term
and preterm

• Sandra Majer, Eva Magnet, Margit Bauer, Wolfgang
  Schöll, Andrea Strele, Uwe Lang and Barbara Pertl
• Department of Obstetrics and Gynecology
• Medical University of Graz
• Austria

2
Preterm birth (Delivery before 37th week of
gestation)

• Risk factors
• Strongest risk factor maternal or fetal
  predisposition women born preterm
• Previous preterm deliveries
• Genotype of immunoregulatory genes
• Malformation of the uterus
• Infections during pregnancies
• Twin pregnancies
• Maternal age

3
Cell-free fetal DNA and preterm deliveries

• Leung et al. (1998) cell-free fetal DNA
  (cff-DNA) levels were increased in women who
  delivered preterm compared to women with preterm
  labor and final delivery at term

4
Cff-DNA as risk factor for spontaneous preterm
deliveries

• Farina et al (2005)
• High concentrations of cff-DNA in maternal serum
  were associated with an increased risk of
  spontaneous preterm deliveries
• The cumulative rate of early preterm delivery
  (lt30 week of gestation) was significantly higher
  for women with cff-DNA concentrations of 1.82
  multiples of the median than those with
  concentrations below this cut-off (P0.008)

5
Cff-DNA during labor at term

• Ingargiola et al., (2003) determined the cff-DNA
  levels during vaginal deliveries at term
• Serially every hour and one hour after delivery
  venous blood samples, induction of labor
• Could not demonstrate any changes during labor
• No effect on fetal DNA release at term

6
Aim of the study

• cff-DNA levels a marker for preterm birth?
• Aim of our study
• to evaluate cff- and total DNA levels during
  deliveries (vaginal and cesarean section) at term
  and preterm
• to compare the cff- and total DNA levels between
  deliveries at term and preterm

7
Study design I

• Venous blood samples were serially collected
  every two hours during delivery and a final ones
  two hours postpartum from 27 women pregnant with
  male fetuses.
• 18 women delivered at term (37th to 41st week of
  gestation)
• 9 delivered preterm (24th to 36th week of
  gestation).
• Controls
• 15 women pregnant with female fetuses (33rd to
  42nd week of gestation)
• 148 pregnant women without labor

8
Study design II

• The amount of cff-DNA was determined by
  quantitative real-time PCR using the SRY-assay
  and the total DNA was determined using the
  ß-Globin-assay
• Statistical analysis Mann Whitney-Test

9
Results I

• Cff-DNA levels are significantly increased during
  spontaneous deliveries at term compared to
  spontaneous preterm deliveries with uterine
  contraction (plt0.01)

• Cff-DNA levels are significantly increased during
  deliveries at term compared to cesarean sections
  without any uterine contraction (plt0.05)

10
Results II

• In contrast to the published data by Ingargiola
  et al. (2003), the cff-DNA levels were
  significantly increased in pregnant women during
  labor when compared to pregnant women without
  labor at term (37th to 42nd week of gestation)
  (p0.014)
• No significant difference was found in the
  cff-DNA levels at different times of blood
  collection during labor
• No significant difference was determined in the
  total DNA levels during deliveries at term and
  preterm
• No SRY-specific DNA was found in the 15 plasma
  samples obtained from women pregnant with female
  fetuses

11
Future plans

• To increase the sample size
• To collect and analyze blood samples from
  pregnant women in second trimester of gestation
  as controls
• To analyse samples of pregnant women with PROM,
  chorioamnionitis, etc

12
Thanks to

• SAFE-Network
• Medical University of Graz
• Center for Medical Research
• for financial support