1. The USC Stillbirth Experience
Marc H. Incerpi, M.D.
Division of Maternal-Fetal Medicine
Keck School of Medicine
University of Southern California

2. Goal
To develop a comprehensive and efficient stillbirth protocol in order to identify potential etiologies

3. Benefits of Stillbirth Evaluation
Parental grieving and parental right to know
Why did this happen?
Will it happen again?
Influence parental reproductive decision making
Prenatal assessment in future pregnancies
Perinatal management in future pregnancies
Increase scientific understanding of causes
Decrease in appropriate litigation

4. Causes of Fetal Death - 1987 Cause of Death Percent of Deaths
Hypertensive Disease
5-25
Medical Complications
5-10
Rh disease
3-15
Cord & placental complications
10-20
Congenital malformations
Intrauterine infection
5-15
Unexplained
~50
Pitkin RM Am J Obstet Gynecol 1987;157:583-9

5. Causes of Fetal Death Total (n = 745)
Prenatally diagnosed anomalies (n = 57)
Elective termination
(n = 44)
Unexplained (n = 466)
Explained by H & P
(n = 178)
Further tests*
Unexplained (n = 268)
Explained ( n = 198)
*lab tests, placenta, autopsy
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

6. Elective Termination (n= 44)
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

7. Prenatally Diagnosed Anomalies (n = 57)
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

8. Explained after Maternal History & Gross Examination (n=178)
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

9. Explained after Further Testing (n = 198) (Laboratory tests, Placenta pathology, Autopsy)
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

10. Value of Additional Testing in Unexplained Stillbirths
# Performed
# Abnormal
# Causal
Attributed to cause
Autopsy
308 91
30%
Placenta
352
104 89
25%
Kleihauer-Betke
219 18 7 3%
RPR
466 15 8 2%
TORCH*
360 1
0.3%
ANA
419 55 0%
Toxoplasmosis, Other viruses, Rubella, Cytomegalovirus, Herpes

11. Eliminating Unnecessary Tests?

12. “TORCHure”
520/745 patients tested for the presence of toxoplasmosis, cytomegalovirus, & herpes simplex virus
28/520 (5%) had positive IgM Ab
In only one case did placenta & autopsy findings support diagnosis of viral infection
One patient had placenta & autopsy findings c/w viral infection, however IgM Ab were negative

13. Kleihauer-Betke Test
1982 – Laube reported that 4/29 patients with unexplained fetal death had positive K-B test1
Our experience demonstrated positive K-B test in 18/219 patients tested2
½ of patients with positive K-B had fetuses with major congenital anomalies
1Laube DW Obstet Gynecol 1982;60:649-51
2Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

14. Antinuclear Antibodies (ANA)
Unexplained Fetal Deaths
Controls
ANA assayed
286
299
Positive titer
33 (11.5%)
43 (14%)
Incerpi MH J Matern-Fet Med 1998;7:61-4

15. Placental Pathology/Autopsy
Of 529 placentas examined, significant pathology was detected in 160 (30%)
Abruption
Severe amnionitis
Occlusive vasculopathy
Villitis
In otherwise unexplained causes of stillbirth, autopsy determined a cause 30% of the time
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

16. Fetal Weight Related Autopsy Rate
Fetal Wt (g) n
Yes No
Rate
Anomaly
<1000
284
133
151
47%
61 (40%)
113 82 31
73%
32 (39%) 80 53 27
66%
20 (38%) 58 24
71%
19 (33%)
>2500
186
136 50
32 (24%)
Total
745
462
283
62%
164 (35%)
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

17. Causes of Fetal Death (1990-1994)
Number
Percent
Fetal
216
29%
Placental
165
22%
Maternal 96
13%
Unexplained
268
36%
Total
745
100%
Incerpi MH Am J Obstet Gynecol 1998;178:1121-5

18. Stillbirth Evaluation
INITIAL EVALUATION
INITIAL EVALUATION
Physical exam of stillborn
-Physical exam of stillborn
-Complete stillbirth evaluation form
Placental pathology
Autopsy consent
Fasting blood glucose, Kleihauer-Betke
HbA1C* & urine toxicology as indicated
ABNORMAL PHYSICAL EXAM
NORMAL PHYSICAL EXAM
-Tissue for karyotype
- Thrombophilia workup
PATHOLOGY DEPARTMENT
-Medical photography
-Xrays as indicated
*if fasting glucose > 120 or any value > 200

19. Thrombophilia Work-Up
Heritable
Acquired
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden
Prothrombin mutation
Hyperhomocysteinemia
Antiphospholipid syndrome

20. Causes of Fetal Death (1990-2003)
Number
Percent
Fetal
332
31%
Placental
255
24%
Maternal
185
17%
Unexplained
298
28%
Total
1070
100%

21. Conclusions The etiologies of stillbirth are many and varied
Up to 30% of stillbirths may be due to intrinsic fetal abnormalities
The stillbirth evaluation should be systematic and comprehensive, including placental pathology and autopsy
In cases of unexplained fetal loss, thrombophilia evaluation may prove to be beneficial