placental evaluation in cases of fetal demise
TRANSCRIPT
Courtesy of Dr. Pete Peterson, Ob/Gyn, Michigan ‘59
Placental
Pathology
Lithopedion
Placental Evaluation in the Investigation of Fetal Demise
Richard W. Lieberman, MD, FCAP, FACOG University of Michigan Health System
Department of Pathology
Department of Obstetrics & Gynecology
2
Intrauterine Fetal Demise Cases –
Sometimes the Answer is in the Placenta
Listen to the history
perhaps it contributes, but if it doesn’t seem to
fit the histopathology…
keep in mind the gestational age dependent
differential diagnoses
every so often you need to as “should the
Medical Examiner get involved?”
3
Case: Clinical Scenario
23 y/o woman, G1P0, 17 weeks pregnant Extreme abdominal cramping and nausea following a
prepared meal that she described as “tasting funny”
“Water broke” in hospital parking lot
FOB did not want a child
Concerned about “morning-after pill” poisoning FOB had many friends who are doctors, could get
“anything he wanted”
4
Stillbirth or Miscarriage?
Michigan Definition
Miscarriage
death of fetus prior to 20 weeks OR
fetus < 400 grams
Stillbirth = IUFD (intrauterine fetal demise)
death after gestation of 20 weeks or more (by LMP)
OR fetus > 400grams
…know your own State’s definition
5 CDC: 1997 State Definitions and Reporting Requirements
Is this a...
Stillbirth: General Statistics
~26,000 per year
0.6% of all births
nearly equal to infant mortality infant mortality = death prior to 1st birthday
stillbirth rates ”stable” for several decades
Detailed analytical study is limited
state-to-state variability in definitions and reporting requirements
risk factor assessment a challenge
6
Certificate
of Fetal
Death
7 NCHS Fetal Death Manual - 2012
State Reporting of Fetal Death
8
All products of human
conception = fetal death:
American Samoa
Arkansas
Colorado
Georgia
Hawaii
New York City
New York State
Northern Mariana Islands
Rhode Island
Virginia
Virgin Islands
The 1992 Revision of the Model State Vital Statistics Act and
Regulations:
‘‘Each fetal death of 350 grams or more, or if weight is
unknown, of 20 completed weeks gestation or more,
calculated from the date last normal menstrual period began
to the date of delivery, which occurs in this state shall be reported
within 5 days after delivery to the (Office of Vital Statistics) or as
otherwise directed by the State Registrar.’’
Eleven areas report all periods of gestation as a fetal death;
25 20 weeks or more; [Montana]
13 350 grams or more or >20 weeks;
1 400 grams or more or >20 weeks; [Michigan]
1 500 grams or more or >20 weeks;
1 350 grams or more;
3 500 grams or more;
1 >16 weeks; and
1 > 5 months.
CDC: 1997 State Definitions and Reporting Requirements
Montana Definitions
(15) (a) "Stillbirth" means a fetal death occurring
after a minimum of 20 weeks of gestation.
(b) The term does not include an abortion, as
defined in 50-20-104.
http://codes.lp.findlaw.com/mtcode/50/15/1/50-15-
101#sthash.rTOoFjNf.dpuf
9
Case – Suspected
Abortifacient Poisoning
23 y/o woman, G1P0, 17 weeks gestation
Extreme abdominal cramping and nausea
following alleged administration of “morning
after pill” by disinterested boyfriend
presents to emergency room
No fetal heart tones on admission
ß-hCG: 73,000 IU/ml
10
Case (cont’d)
D&C one day later
Case reported to Medical Examiner
Maternal and fetal toxicology samples
collected with fetal remains & placenta
11
Case: Placenta
Fragmented placenta
with “grape-like”
vesicles
Three vessel cord
12
Case: Autopsy
Fragments of:
calvarium
left hand, portion right hand
rib cage and shoulder girdle…
Not enough to make a morphological
assessment, but tissue sent for “genetic
analysis”
13
14
15
16
Case: Atypical villous morphology
Variable size and shape of villi
Villous scalloping and notching
Trophoblastic inclusions
trophoblastic hyperplasia
17
Case: Results
Toxicology
Maternal and fetal blood negative for
mifepristone and norgestrel
Chromosome analysis
69XXX
Diagnosis…
18
Case: Diagnosis?
Partial hydatidiform mole
Conclusions:
miscarriage/abortion imminent
later presentation than usual
no association with “purposeful” administration
of abortifacient
19
Initial : All Stillbirths
Inspection of fetus and
placenta
photographs
document any anomalies
weights
trimmed placenta weight
fetal measurements
HC, CR, Foot length
Consent for cytologic
specimens, may include:
amniotic fluid if delivery is
not imminent
fresh placental tissue
1x1cm below cord insertion
umbilical cord segment
internal fetal tissue
chondroid or patella
not skin
collect sterilely store in LR
at room temp 20 ACOG Practice Bulletin #102, May 2009
Initial Evaluation: All Stillbirth (cont’d)
Maternal History
smoking, drugs
diabetes, autoimmune
FH: hereditary conditions
Ob Hx: recurrent AB,
prior demise, SGA babies
Current Pregnancy
AMA, HTN, TTTS, bleeding
alloimunization
Maternal Laboratory Eval
Kleihauer-Betke
(immediate)
parvovirus
syphilis (RPR/VDRL)
MTHFR gene mutation
anti-cardiolipin antibodies
thrombophilias
Factor V Leiden, Protein C
or S
antithrombin III
21 ACOG Practice Bulletin #102, May 2009
Fetal Autopsy in Stillbirth
Obtain parental
consent, unless
deemed indicated by
Medical Examiner
Placental exams
covered by insurance
extremely valuable in
identifying underlying
etiologies
Despite
recommendations of
both fetal and
placental exam, only
15-40% are done
<50% of parents
consent for fetal
autopsy
22
ACOG Practice Bulletin #102, May 2009
Etiology of Stillbirth
Unknown in 25 – 60% of cases
Cause of Stillbirth can be related to one or more
of the following:
Maternal conditions
Fetal conditions
Placental conditions
23
Partial Hydatidiform Mole
triploid fetal
morphology 24
dispermy fertilization
triploid chromosome
25-45% of molar gestations
Normal to elevated hCG
GTN?
persistent HCG <5%
choriocarcinoma NO!
Case: Questions…
Fetal Death?
but not at the hand of another
Miscarriage or “stillbirth”?
Reportable case?
How would you Classify this pregnancy loss?
classification of stillbirth… have you heard about this?
25
Difficulties in Stillbirth Classification Systems
not utilized nor easy to use
definition of stillbirth varies
investigators, states,
countries, and systems
no International approach
“unexplained” ranges from
15-71%
Two “Best”:
ReCoDe (Relevant
Condition at Death)
PSANZ-PDC
(Perinatal Society of
Austrailia-New
Zealand Perinatal
Death Classification)
26 BMC Pregnancy & Childbirth 9: 24-37, 2009
both stillbirth & neonatal
death have overlapping, but
distinct sets of disease
ReCoDe:
relevant conditions @ death
Fetal lethal anomaly
infection
hydrops
F-M hemorrhage
IUGR
Umbilical cord prolapse
constricting loop/knot
Maternal diabetes
hypertension
cholestasis
drugs
Idiopathic
Placenta abruption
placenta previa
vasa previa
insufficiency
Amniotic Fluid infection
oligo- or poly-
Uterus
Intrapartum “asphyxia”
birth trauma
External trauma
Unclassified
27 BMC Pregnancy and Childbirth 2013, 13:182
http://www.biomedcentral.com/1471-2393/13/182
Next case…
28
Case: IUFD after “kick” in abdomen
21 y/o G2P1:24 weeks decreased fetal movement
5 year old child kicked her in the abdomen days earlier
noted leaking of “greenish” fluid AM of admission
NO signs of maternal trauma noted
U/S: no fetal movement or cardiac activity
DIAGNOSIS: Intrauterine fetal demise (IUFD) 29
Case: IUFD (cont’d) Antenatal history:
chlamydia 1st trimester
ER visit one month earlier for abdominal cramps
declined pelvic or cervical exam
marijuana use twice a day since age 17
did not stop after discovery of this pregnancy
DID cut back from 8 cigarettes to 2-3/day
PMH:
cholecystectomy – age 15
SVD at term – age 16
30
Case IUFD
Clinical Course:
delivery of a non-viable female infant
further details of fetal demise not provided
autopsy refused by mother
placenta pale and edematous (weight not given)
31
Pale edematous placenta:
appears “large” for 24 weeks
32
33
34
35
36
Numerous Erythroblasts with
Eosinophilic Nuclear Inclusions
37
Parvo B19 Immunohistochemistry
38
Human parvovirus B19
commonly infects children
causing erythema infectiosum (fifth disease)
TORCH: it’s the “other” or the 5th disease
a significant adult population has not been
exposed to the virus
many adults are non-immune
susceptible to infection
30-50% of pregnant women have not been exposed
39 BJOG 118:175-86, 2011
Human Parvovirus B19 in Pregnancy
Maternal Acute Infection
~1-2% incidence in pregnancy
50% asymptomatic
vertical transmission may still occur
fetal effects:
anemia
edema (hydrops)
congestive heart failure
myocarditis
fetal demise
40 BJOG 118:175-86, 2011
Fetal Effects from Parvo Infection Consequences of Infection
3% of all spontaneous AB
fetal death ≈ age at infection
1st trimester – 19%
2nd trimester – 15%
3rd trimester – 6%
no increase in malformations
over background incidence
IgM positive infants imply
resolution of infection
Mechanism of injury
primarily anemia due to
red cell destruction
evidence of virus in cell
eosinophilic nuclear
inclusion
also…
myocarditis
hepatitis
hypoalbuminemia
placentitis/villitis
most prominent injury
noted in 2nd trimester
41
Case Summary Based upon placental evaluation alone:
marked increase in NRBCs
eosinophilic intranuclear inclusions
parvovirus b19 infection (confirmed with IHC).
immature, enlarged, hypercellular villi with increased stromal histiocytes and edema
red-cell destruction and other adverse fetal effects cannot be assessed in the absence of fetopsy (hydrops etc)
Conclusions: the claim “a kick in the stomach” by the 5 year old caused the
demise is not possible
it may indeed be true that the child exposed the patient to parvovirus infection that did ultimately result in IUFD
42
Differential Diagnosis: Pale ± Heavy Placenta
Immune-hydrops
RhD antigen (most common)
ABO incompatibility
lesser common blood group
antigens
Non-immune hydrops
15-35% genetically transmitted disease
~10% alpha-thalassemia chronic blood loss (occasionally acute blood loss)
trauma: massive or chronic fetal-maternal hemorrhage
large chorangiomas
cystic adenomatoid malformation
congenital malformations
congenital heart disease
congenital nephrotic syndrome
infectious parvovirus
adenovirus
43
Hydrops=ascites + generalized edema + hydramnios (+/-) + fluid accumulation (i.e. pleural)
24 - 27 weeks 28 - 37 weeks 37+ weeks
Infection
(19%)
Unexplained
(26%)
Unexplained
(40%)
Abruptio placenta
(14%)
Fetal growth
restriction (19%)
Fetal growth
restriction (14%)
Anomalies
(14%)
Abruptio placenta
(18%)
Abruptio placenta
(12%)
Most Frequent Types of Stillbirth
Based on Gestational Age
Fretts et al. Ob Gyn 1992;79:35-9
Fretts and Usher. Contem Rev Ob Gyn 1997;9:173-9
44
SCRN: Causes of Death Among Stillbirths
(n=663)
75% agreed to fetal autopsy (best in literature)
racial disparity: 2.3 risk for non-Hispanic black
Placental Disease (26%)
maternal decidual vasculopathy (8%)
uteroplacental insufficiency (5%)
umbilical cord abnormalities (10%)
vasa previa, cord entrapment (prolapse) &
occlusion (nuchal cord alone not a cause)
more common after 32 weeks
46 JAMA 306(22):2459-2468, 2011
N.B.: Fetal Death Following Maternal
Trauma
Maternal Trauma
with maternal death
medical examiner
case
post-mortem emergent
cesarean
autopsy
mother
placenta
…and baby
Maternal Trauma
with maternal survival
placental examination
?medical examiner?
…fetal autopsy?
informed consent
or, a medical examiner
case
?fetal homicde?
47
Evaluation of Stillbirth: Conclusions
Understanding Requires:
diligent protocols for
evaluation
with or without concurrent
maternal death/trauma
the fetal “cause of death”
increased knowledge risk
reduction
standardize reporting is
desirable, but not likely
Team Approach
medical examiners
and investigators
maternal-fetal
specialist
perinatologists
placental pathology
48
References for Stillbirth Evaluation:
Stillbirth Collaborative Research Network
Postmortem Evaluation
Am J Perinatology 29(3):187-202, 2012
Placenta and Umbilical Cord
Am J Perinatology 28(10):781-792, 2011
Neuropathological Examination
Am J Perinatology 28(10):793-802, 2011
49
50
The
“Scream”
of the
Placenta
Assorted Causes of Fetal
Demise – Stillbirth
Cord Anomalies
Two Vessel Cord
Three Vessel Cord
False Knot in Cord
True Knot in Cord 52
Cord: “Loss of Spiral”
Growth Delayed small placenta
small baby decreased fetal
movement
Possible Etiologies
drugs & EtOH
smoking
congenital
infection
anomalies
etc…..
54
Placental Insufficiency
Umbilical Coiling: Too many or too few
Umbilical coiling index
Defined: 1 /(over the) #coils
per length of cord
Hypercoiled > 0.31 coils/ cm
Hypocoiled < 0.065 coils/ cm
Controversial association
with poor outcome
55
Hint: Photograph cord fully extended;
you can count the coils later as needed.
Stillbirth: Umbilical Cord Stricture
56
True “Cord Accident”
57
Cord Accidents Nuchal cord present in 25% of normal pregnancies
~2.5% of stillbirths in autopsy case series
Strict criteria for “causation”
Cord occlusion and hypoxic tissue
placenta with compensatory mechanisms (chorangiosis…)
fetal ischemic changes (hard to differentiate from post-mortem)
Exclusion of other causes
Actual proportion remains uncertain
58
Placental
Variations
Abnormal Shapes lobar variations
number, shape
cord implantation location on disc
membranous implant
membrane anomalies circumvallate
amnionic bands
59
Velamentous Insertion & Vasa Previa
60
Placenta Percreta ~
“Chronic” Rupture of LUS
61
Multifetal Gestation
62
Twin-Twin Transfusion
Syndrome
63
Monoamnionic Twin Gestation
64
Placental Infarction
65 from www.pathguy.com
…and one more
66
Ectopic Pregnancy
67
Where life imitates art… Placental Histopathology
Gromit (from Wallace & Gromit)
Ultrasound
68
Case: Placenta
69
Retroplacental
hematoma
Three vessel cord
Maternal Surface… clot doesn’t appear significant
70
Traumatic Uterine Rupture,
2nd Trimester
71