Stillbirth

stillbirth norman meyer uthsc memphis pregnancy ob gyn

1. Stillbirth
N.L. Meyer
University of Tennessee

2. Definitions
•Fetal death
•Death prior to the complete expulsion or extraction
from its mother of a product of human conception,
irrespective of the duration of pregnancy and which is
not an induced termination of pregnancy
1

•Delivery of a fetus showing no signs of life
•Absence of breathing, heart beat, umbilical cord
pulsations, definitive voluntary movements
•Excludes
•Transient cardiac contractions
•Fleeting respiratory efforts (gasps)
1
National Center for Health Statistics

3. Definitions
•Not all fetal deaths are stillbirths
•World Health Organization
•Fetal death late in pregnancy
•Allows each country to define gestational age at which
fetal death is considered stillbirth
•16 to 28 weeks
•National Center for Health Statistics
•Most states use 20 weeks or a fetal weight of ≥ 350 g
or ≥ 500 g
•28 weeks (late stillbirth)
•Tennessee Code Annotated
•Fetal death ≥ 500 g or in the absence of weight, ≥ 22
completed weeks gestation

4. Incidence
•> 3 million stillbirths each year worldwide
•2005 rate of 6.2/1000 total births in US
•Rate of early stillbirth has remained stable
•Rate of late fetal loss has decreased by 29%
since 1990
•African Americans have 2x stillbirth rate as
Caucasians
•DM, HTN, abruption, PPROM

5. Urban Child Institute
•July 2009 report
•Variation in 2006 Infant Mortality in Tennessee
•No universal method for calculating IMR
•Discrepancies in reports may be artificial
•Wide variation in reporting practices among
counties
•Suggest Tennessee Office of Vital Records implement
criteria to differentiate fetal death vs live birth vs
infant death
•American Academy of Pediatrics
•Threshold for live birth 400 gm or 23 weeks

6. Etiology
•Unknown in 25 – 60% of cases
•Identifiable causes can be attributed to
•Maternal conditions
•Fetal conditions
•Placental conditions

7. Maternal Conditions
•Prolonged pregnancy
•Diabetes (poorly controlled)
•SLE
•APAS
•Infection
•HTN
•Preeclampsia
•Eclampsia
•Hemoglobinopathy
•AMA
•Rh disease
•Uterine rupture
•Maternal trauma or death
•Inherited thrombophilia

8. Fetal conditions
•Multiple gestation
•IUGR
•Congenital anomaly
•Genetic abnormality
•Infection
•Hydrops

9. Placental Conditions
•Cord accident
•Abruption
•PROM
•Vasa previa
•Fetomaternal hemorrhage
•Placental insufficiency

10. Maternal Risk Factors
Sickle cell diseaseMultiple gestation
MalariaSmoking
Poor nutritional status
Infection – Parvovirus B19, syphilis,
streptococcal infection, listeria
Congenital anomaliesHypertensive disease, preeclampsia
Hypertensive disease – complications of
preeclampsia and eclampsia
Medical disease – diabetes, SLE, renal
disease, thyroid, cholestasis
Infection – syphilis and gram-negative
infection
Growth restriction/placental anomalies
Obstructed prolonged labor and
associated asphyxia, infection, injury
Congenital and karyotypic anomalies
Developing CountriesDeveloped Countries

11. Risk Factors in Developed Countries
•Non-Hispanic black race
•Nulliparity
•Advanced maternal age
•Obesity
ACOG Practice Bulletin #102 March 2009

12. Abruptio placenta
(12%)
Abruptio placenta
(18%)
Anomalies (14%)
Fetal malnutrition
(14%)
Fetal malnutrition
(19%)
Abruptio placenta
(14%)
Unexplained (40%)Unexplained (26%)Infection (19%)
37+ weeks28 - 37 weeks24 - 27 weeks
Most Frequent Types of Stillbirth According to GA
Fretts et al. Ob Gyn 1992;79:35-9
Fretts and Usher. Contem Rev Ob Gyn 1997;9:173-9

13. Infection
•Most common cause of stillbirth 24 – 27 weeks
•Contribution to stillbirth rate is difficult to define
•Some pathogens are clearly causally related
•Parvo B-19
•CMV
•Toxoplasmosis
•Some are associated with stillbirth but absent evidence of
causal relationship
•Ureaplasma urealyticum
•Mycoplasma hominis
•GBS
•Colonization common among healthy women

14. Infection
•Most stillbirths occur in premature fetuses
•19% of stillbirths < 28 weeks
•2% of stillbirths at term
•No change despite widespread use of antibiotics
•Viral pathogens are the most common source of
hematogenous infection of the placenta
•Fetal death resulting from maternal infection is rare
•Diagnostic criteria are not well defined
•High frequency of asymptomatic maternal
colonization

15. Multiple Gestations
•19.6 / 1,000 stillbirth rate (4x singletons)
•Complications specific to multiple gestations
•TTTS
•Increased risk of common complications
•AMA
•Fetal anomalies
•Growth restriction

16. Advanced Maternal Age
•Lethal congenital and chromosomal anomalies
•Medical complications associated with age
•Multiple gestations
•HTN
•DM
•AMA is an independent risk factor
•Unexplained fetal demise is the only type that
is statistically more common (late pregnancy)

17. Advanced Maternal Age
Antepartum vs Intrapartum
4.4
3.6
0.8
3.6
3.2
0.6
4.4
3.7
0.6
6.3
5.3
1
10.5
9.3
1.2
0
2
4
6
8
10
12
20 - 24 25 - 29 30 - 34 35 - 39 > 40
Stillbirth
Antepartum
Intrapartum
Maternal age (yrs)
Rate per 1000
Saliu et al. J Obstet Gynaecol 2008;34:843

18. Obesity (BMI ≥ 30)
•Increased risk
•Behavioral, socioeconomic and obstetric factors
•Smoking, diabetes, preclampsia
•Risk remains even after controlling for above
•Theories
•Perception of fetal movements
•Hyperlipidemia
•Apnea – hypoxia events

19. Obesity
11 / 1000≥ 40
8 / 100030 – 39.9
5.5 / 1000< 30
Stillbirth Rate per 1000BMI

20. Chromosomal Abnormalities
•Abnormal karyotype found in 8 – 13% stillbirths
•> 20% with anatomic abnormalities or growth
restriction
•4.6% with normally formed fetuses
•Most common abnormalities
•Monosomy X (23%)
•Trisomy 21 (23%)
•Trisomy 18 (21%)
•Trisomy 13 (8%)
•Karyotypic analysis underestimates risk

21. Chromosomal Abnormalities
28%Fetal tissue sampling
85%Amniocentesis / CVS
Success RateMethod
Korteweg et al 2008 Ob Gyn 111;865

22. Fetal Tissue
•Umbilical cord – 32.1%
•Fascia lata – 29.9%
•Cartilage – 24.2%
•Fetal blood – 22.2%
•Pericardium – 0%
•Other tissue – 19.2%
•Placenta, skin, unknown

23. Chromosomal Abnormalities
Korteweg et al 2008 Ob Gyn 111;865

24. Cord Accidents
•30% of normal pregnancies
•Account for only 2.5% of stillbirths in autopsy
case series
•Attribution requires
•Cord occlusion and hypoxic tissue on autopsy
•Exclusion of other causes
•Actual proportion remains uncertain

25. Thrombophilia
•Relationship with late fetal death is more
consistent than with early losses
•Have been associated with late loss but lack of
evidence of causal relationship
•Inconsistent studies
•OR range from 1.8 to 12
•Thrombophilias are not uncommon
•15 – 25% of Caucasian populations

26. Thrombophilia
•Some but not all studies show a relationship
with adverse outcomes
•Most are retrospective or case-controlled
•Prospective longitudinal studies are needed
•Inappropriate or no controls
•No evaluation for other causes
•At least one type of thrombophilia is seen in
30% of normal controls

27. Thrombophilia
Gonen R et al. Absence of association of inherited thrombophilia
with unexplained third-trimester intrauterine fetal death. AJOG
2005;192:742-6

28. Evaluation
•Fetal autopsy
•Single most useful test
•Examination of placenta, cord and membranes
•Karyotype evaluation
•8 – 13% of stillbirths
•Comparative genomic hybridization
•Useful when fetal cells cannot be cultured

29. Infection
•Autopsy and histologic evaluation of placenta,
membranes, and cord provide best evidence of
infectious etiology
•Value of routine cultures and serology is
controversial
•Parvovirus serology
•Screening for syphilis
•TORCH titers questionable utility
•Placental culture problematic
•Incidence in live birth is unknown
•DNA test associated with false positives

30. Hematologic Etiology
•Fetal – maternal hemorrhage
•Kleihauer-Betke test
•Typically underestimates fetal cell count with
large FMH
•Red cell alloimmunization
•Indirect Coombs’ test
•Autopsy and placenta assessment useful

31. Thrombophilia
•Routine testing is controversial
•Evidence to support limited testing
•Evidence of placental insufficiency
•IUGR
•Placental infraction
•Recurrent fetal loss
•Personal or family history of thrombosis

32. Medical Complications
•Exclude clinically overt diabetes and thyroid
dysfunction
•GDM has stillbirth rate similar to normal
•Subclinical thyroid disease has not been
proven as cause of still birth
•Screening for subclinical disease is of unproven
benefit

33. Silver et al. Work-up of stillbirth: a review of the evidence. AJOG 2007;196:433-444.

34. Antepartum Surveillance
•Little evidence-based data to guide testing with
previous unexplained stillbirth
•32 – 34 weeks
•2 – 4 weeks before gestational age of
previous still birth
•Most subsequent pregnancies have a favorable
outcome
•Increased risk of iatrogenic prematurity

35. Antepartum Surveillance
•300 women with previous stillbirth
•49% unexplained
•1 recurrent stillbirth despite reassuring testing
•Perinatal mortality 3.3/1000
•Earliest delivery associated with a positive test
result was 32 weeks
Weeks et al. Antepartum surveillance for a history of stillbirth:
When to begin. AJOG 1995;172:486-92.

36. Antepartum Testing Protocol
Weeks et al.

37. •Protocol may not be appropriate for all previous
stillbirths
•Nonrecurring conditions
•Perinatal infection
•Fetal anomalies
•Maternal trauma
•Stillbirths following OB complications that can
recur but cannot be predicted
•Abruption
•Prolapse
•Uterine rupture
Antepartum Testing Protocol

38. ACOG Practice Bulletin #102
•Little evidence-based data to guide antepartum
surveillance with prior unexplained stillbirth
•Antepartum testing may be initiated at 32 – 34 weeks
•Associated with potential morbidity and costs
•16.3% delivery at or before 39 weeks
•1% delivery before 36 weeks
Management of Stillbirth March 2009

39. ACOG Practice Bulletin #102
•Antenatal testing before 37 weeks gestation
•1.5% rate of iatrogenic prematurity for
intervention based on false-positive test
•Excess risk of infant mortality due to late
preterm birth
•8.8 / 1000 at 32 – 33 weeks gestation
•3 / 1000 at 34 – 36 weeks gestation