This study investigated umbilical cord blood concentrations of the protein survivin in pregnancies complicated by intrauterine growth restriction (IUGR) or large-for-gestational age (LGA) babies due to gestational diabetes, and compared them to appropriate-for-gestational age (AGA) controls. The study found no statistically significant differences in survivin concentrations between the three groups. Additionally, survivin levels were independent of factors like birthweight, gestational age, gender, mode of delivery, and parity. The study concludes that cord blood survivin levels do not reflect disturbances in fetal-placental apoptosis seen in IUGR and LGA pregnancies.

1. Fetal survivin
concentrations in normal
and complicated
pregnancies at term
Ariadne Malamitsi-Puchner 1 , Maria Boutsikou 1 , Sophia
Liosi 1 , Dimitrios Gourgiotis 2 , Venetia-Maria Vraila 2 ,
Dimitrios Hassiakos 1 , Stavroula Baka 1 , Despina D.
Briana 1
1. Neonatal Division, 2nd Department of Obstetrics and
Gynecology, Athens University Medical School, Athens, Greece
2.Research Laboratories, 2nd Department of Pediatrics, Athens
University Medical School, Athens, Greece

2. Apoptosis
•
•
•
Programmed cell death
regulates cell proliferation
contributes to tissue and organ
homeostasis
• important for the development of normal
human placenta

3. Disturbances in feto-placental
apoptosis seem to be associated
with abnormal pregnancy outcome
• fetal macrosomia, due to maternal
diabetes mellitus (DM)
• intrauterine growth restriction (IUGR)

4. IUGR/ Fetal macrosomia
• IUGR
is correlated with
-increased incidence of apoptosis in IUGR-affected fetal
membranes
-abnormal expression of proteins involved in apoptosis
and cell turnover
• Fetal macrosomia
is correlated with
-decreased apoptosis in placental cells

5. Survivin
• 16.5 kD protein
• member of the inhibitors of apoptosis (IAP)
family
• prominently expressed in fetal tissues and overexpressed in cancer cells
•
•
important for normal fetal development
plays critical roles in placental cell survival and
cytotrophoblast cell differentiation

6. HYPOTHESIS OF THE STUDY
• Umbilical cord blood concentrations of survivin in
IUGR and large-for-gestational-age (LGA-due to
gestational DM) cases may differ from
respective concentrations in appropriate-forgestational-age (AGA) controls, since the former
are associated with excessive and reduced
feto-placental apoptosis, respectively.

7. AIM OF THE STUDY
•
Investigate cord blood survivin concentrations
in IUGR, LGA and AGA pregnancies at birth
•
Correlate determined concentrations with
gestational age, gender and mode of delivery .

8. SUBJECTS OF THE STUDY
• 160 healthy, singleton full-term
pregnancies
- 101 AGA (placental weight: 480-621 g)
- 48 asymmetric IUGR ( placental weight 230-420 g)
- 11 LGA (placental weight: 650-810 g)
• Apgar scores:>8 in 1st and 5th minute

9. Gestation Related Optimal
Weight (GROW) computergenerated programme
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10. CAUSES OF INTRAUTERINE
GROWTH RESTRICTION
• Preeclampsia ( n=19 )
• Hypertensive disease of pregnancy
(n=16 )
• Various diseases : severe type I DM
•
( n=2) ,iron deficiency anemia (n=4),
hypothyroidism (n=4)
Maternal smoking ( n=10 )

11. DEMOGRAPHIC DATA OF THE
STUDY POPULATION
•
•
•
•
•
•
IUGR
Gestational age (weeks)
38 .4 ±1 .4 *
BW (g)
256 6 ±34 3 *
BW centile
5. 33±3 .8 *
Gender (male/female)
23/25
Mode of delivery (VD/ECS)** 24/24
Parity (1st /other)
31 / 17
* values are mean ± SD
**VD: vaginal delivery/ ECS: elective cesarian section
LGA
38 . 4±0 .9*
3781±173 *
94 . 1 ±3 .1 *
9/2
6/5
7/4
AGA
39 .0 ± 1.0 *
319 7 ±29 6*
39 . 3±23 .4*
60/41
77/24
70/31

12. Methods
•
•
•
Blood collected from:
Doubly-clamped umbilical cords (m ixed
arteriovenous blood ) – reflecting fetal
state
Determination of plasma survivin
concentrations by enzyme immunoassay
( Human Total Survivin EIA , Assay
Designs, 5777 Hines Drive, Ann Arbor,
MI 48108, U.S.A )
Statistical analysis (non-parametric
tests)

13. Fig. 1. Cord blood survivin concentrations
in AGA, IUGR and LGA pregnancies .
400
Survivin concentrations (pg/ml)
300
200
100
0
AGA
IUGR
LGA

14. Results
• No statistically significant differences in
cord blood survivin concentrations
between IUGR, LGA and AGA groups.

15. Results
• In the three groups
• The effect of group (IUGR, LGA, AGA) (Fig.1),
birthweight, customized centile, gestational age, gender,
mode of delivery and parity on circulating survivin
concentrations was not significant
• Reference survivin values (median, range): 138.49
pg/mL and 71.54 - 349.89 pg/mL, respectively

16. Conclusions 1
• Cord blood survivin concentrations in full-term
pregnancies are independent of intrauterine
growth
• Cord blood survivin concentrations probably do
not reflect the disturbances of feto-placental
apoptosis expected in IUGR and fetal
macrosomia, due to gestational DM

17. Conclusions 2
• Parity, gender and mode of delivery
(vaginal or elective cesarean section) do
not seem to have any impact on umbilical
cord blood survivin concentrations

18. Conclusions 3
• Reference values (median) for
cord blood survivin concentrations
at term were 138.49 pg/mL