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The perinatal autopsy and

placental pathology
Drucilla Roberts
djroberts@partners.org

Millennium Development Goals


Goal 4: Reduce child mortality ratesTarget
4A: Reduce by two-thirds, between 1990 and
2015, the under-five mortality rate
Goal 5: Improve maternal healthTarget 5A:
Reduce by three quarters, between 1990 and
2015, the maternal mortality ratio*
*Maternal Mortality Ratio is the ratio of the number
of maternal deaths per 100,000 live births

Problem
To affect improvement in maternal and childhood
deaths one has to know
The NUMBERS
Vital statistics

The CAUSES
Autopsy
Social
Verbal
Anatomical

The Social Autopsy


Definition: The examination of a
social error to discover the cause
of the error and to prevent it from
occurring again.

Evaluation and Program PlanningVolume 29, Issue 1, February 2006, Pages 44-54,
Organizational Learning

Verbal autopsy
Mechanism to determine events
surrounding the death by interview

Verbal Autopsy
Verbal autopsy questionnaires and
algorithms need to distinguish between
different possible causes of death using
only information that can be recalled by
caregivers.

Verbal autopsy technique


assumptions
Causes of death have distinct symptom
complexes which can be recognized,
remembered, and reported
It is possible to classify deaths into useful
categories based on symptom complexes

Verbal Autopsy
Trained but non-medical interviewers
Notification by town/village elders
Home visits between 1-21 months after
deaths
30-90 minute interview of respondant
Family member generally head of household

Interpretation
Algorithms
Physicians

YES
Pregnant < 7 months + vaginal bleeding

abortion

NO
Pregnant >6 months + convulsions
or
Delivered < 15 days + convulsions

eclampsia

Pregnant > 8 months + heavy bleeding before delivery +


Labor pains < 24h
OR
hemorrhage
Delivered <4d + heavy bleeding after delivery
Labor pains > 24 hours

obstructed labor

Delivered < 15 d + fever + abdominal pain


puerperal sepsis

Validation
Since verbal autopsies rely solely on information recalled by the
next-of-kin for determining the cause of death, and are not
based on clinical or laboratory evidence, they may be subject to
relatively high misclassification errors. (Although, even
diagnoses based on clinical and laboratory evidence may have
substantial misclassification.) This can have a profound effect
on the verbal autopsy estimate of the proportion of deaths due
to a specific cause.

Confirmation studies
NONE with autopsy
Validation by physician review of answers
Occasionally by correlation with hospital or
medical records

Discrepancies between clinical


diagnosis and autopsy findings

26% Medical ICU deaths - USA


17% Community hospital - USA
16% (Major) Tertiary care hospital - Brazil
15% Military hospital - Pakistan
No maternal mortality data on discrepancies
Internal Massachusetts death report reviews
found >10%

Confirmatory studies
By culture
Interviewer, respondant, time

By diagnosis
<30% renal

<50% malaria, cirrhosis, pneumonia


~90% direct maternal
Lowest were combined causes, eg. AIDS and TB

If we are basing huge


expenditures for public health
measures on reports of
causes of death we ought to do better than that!

Perinatal autopsy
Definitions
Death of the infant within first 2 weeks of life
Death of a fetus before birth
Sometimes differentiated as
Previable - <20 weeks or <350g
Potentially viable - >20 weeks or >350g

Optimal procedure
Complete and unrestricted - histopathology,
microbiology
Placental examination

Minimalistic approach
Weights and measurements
Careful gross examination of body and placenta

APPROACH TO PATHOLOGIC
EVALUATION
Be honest, understand limitations - personal
and within the field
Be thorough and timely
Be respectful
Be available

Placental examination - WHY?


The placenta explains cause of death in
stillbirths in a large percentage of cases
Placental pathology explains the cause of
prematurity in a large percentage of cases

Gross Placental Examination

Umbilical Cord
Vessels
Length
50-70cm at term

Diameter
1.5-3cm at term

Twist/coils
3 in 10 cm

Insertion
Knots

Membranes
Completeness

Insertion

Rupture Site

Color

Placental Exam
Set up your materials
You need

Formalin in jar
Labels
Forceps
Scissors
Scale
Template and pen

Umbilical Cord

Cut off the cord


Take two samples (one from each end of the cord)
place both samples in formalin jar

Membranes

Cut a strip of membranes ~3cm wide and 10 cm long


Hold end with forceps and roll membrane around forceps
Place roll into formalin container

Disk

Cut membranes off the disk


Weigh disk and record
Measure greatest length and
record

GA

SINGLETONS
percentiles
10 - 25 - 50 -75 -90 %

TWINS (COMBINED WT)


percentiles
10 - 25 - 50 - 75 - 90 %

12

56

14

83

16

110

18

137.8

20

145

166-190-218-245-270

22

122-138-157-176-191

191-219-251-282-310

24

145-166-189-212-233

232-267-307-346-382

26

175-200-227-255-280

284-330-380-430-475

28

210-238-270-302-331

345-401-464-527-584

30

249-281-316-352-384

409-478-554-631-700

32

290-325-364-403-438

472-554-644-734-815

34

331-369-411-453-491

531-624-727-830-923

36

372-412-457-501-542

582-684-798-912-1014

38

409-452-499-547-589

619-728-850-972-1082

40

442-487-537-587-632

638-753-879-1005-1118

Disk Sampling
Lesion

Use scissors and cut through placenta in 4 cm strips


Measure greatest thickness and record
Look for lesions
Take at least two full thickness samples from the middle of the disk
and place in formalin jar
Take any lesions and place in formalin jar

Finish
Place the LABELED
placenta in the refrigerator
You should have in the
LABELED formalin
container:
Two sections of umbilical
cord
One membrane roll
2-3 sections of placenta

Template
PLACENTAL WORKSHEET

TEMPLATE FOR DICTATION

Placental Grossing and Sampling Template


Singleton or separate twin placentas
PATIENT ID NUM BER

____________________

The specimen was received fresh labeled with the patient's name and unit number and consists of
Date delivered _______________ a singleton placenta.

Singleton

Cord insertion _____________c m from margin (or _______ cm in membranes from margin)

Twin

Cord length ___________c m


Separate Placentas (use 2 forms)

Number of vessels ________

Fused Placenta (use twin placental form)

other cord findings ___________ (hypo or hyper twisted, abnormal color, nodules, masses, etc)

Other (send placenta(s) intact)

cord color __________ (white, yellow, green, brown, etc)


Membranes inserted ___________ % (marginally, circummarginately, circumvallate)

Liveborn

Membrane rupture site ________ cm to margin


Stillborn

Membrane color ____________


other membrane findings _______________ (nodu les, hemorrhage, membranous vessels, etc)

Neonatal death

The trimmed placental weight is ______________ g


Disk measurement _________c m in greatest diameter X _________ cm thick
Diameter ________________________ cm

Fetal surface findings _____________ (nodules, masses, chorionic vascular thromboses, etc)
Weight __________________________ gms

Maternal surface ______________ (complete, disrupted, masses, calcification, fibrin,


hematomas, indentations, etc)

Thickness _______________________ cm

Parenchyma _____________________ (normal = beefy, spongy, red ; lesions = number, size, %


of mass involved, location)

Findings: (describe)

Summary:

Cassettes:

Fetal Surface

Color

Vasculature

Fibrin

Blood

Maternal
Surface

Completeness
Clots
Color

Parenchyma

Color
Consistency

Blood clots
Infarcts

From Gross to Microscopic

Umbilical Cord

2 Arteries, 1 Vein
Amnionic
Epithelium
Whartons Jelly:

Polysaccharides
Macrophages
Myofibroblasts
Mast cells

Umbilical Cord- Unique Features


Arterial muscular coat: crossing spiraled fibers, no
internal elastic membrane, minimal elastica
Venous coat: separate layers of circular fibers,
possess elastic subintimal layer
Endothelial cells rich in organelles; interdigitating
extensions to adjacent muscle cells
(enotheliomuscular system)
No vasa vasorum
except intra-abdominal portion after 20 wks GA

No nerves within cord


placenta without neural supply

Membranes
Amnion
Chorion
Extravillous
Trophoblast

Decidua
Capsularis

Chorionic Plate

from Baergen, R.N. Manual of Benirschke and


Kaufmanns Pathology of the Human Placenta

Basal Plate

Parenchyma
Villous
Tree
Materna
l Blood
Fetal
Vessels

Villous Histology

Malarial Sequestration

FETAL RESPONSE
Fetal response to acute chorioamnionitis
includes:
Inflammatory cells migrating from fetal vessels
Umbilical cord
Chorionic plate

Vasculitis is a risk factor for


neurodevelopmental delay/cerebral palsy

Placental insufficiency

Small placenta (<10th, often <3rd %ile)


Decidual vasculopathy
Atherosis
Ischemic changes/pressure related injury
Infarcts
Hypermaturity
Small villi (1 capillary, smaller than free knots)
Many knots (usually 1/3-5 villi, here 1/1 villous and >10 nuclie per
knot!)
Lots of space between villi

Abruption

Severe decidual vasculopathy with atherosis

Normal vessels in decidua


capsularis

Decidual vasculopathy with


atherosis

Hypermature villi - distal villous hypoplasia

Regular type of infarct - maternal perfusion defect

Usual type infarct histology

Small sclerotic villi


Small, central, round infarct
Large syncytial knots
Usually multiple
Lots of intervillous space
watershed zone
Indication of global/chronic ischemia
HYPERMATURE VILLI

Chronic abruption

Chronic abruption histology

Acute abruption

Intravillous hemorrhage - acute abruption/cord accident

Fetal deaths
Deaths in utero
Prematurity related deaths
Delivery related deaths

SECOND TRIMESTER
LOSSES

Infections
Anomalies
Placental
Maternal

THIRD TRIMESTER LOSSES


PLACENTA PLACENTA PLACENTA
Abruption
Insufficiency

Uterine rupture
Other:
Consider micro and virology studies
Blood spot for metabolic studies
Lethal anomalies

STILLBIRTH/IUFD
PATHOLOGY
Difficult emotionally and professionally
50-80% failure rate to determine etiology of
death
Placental examination essential

APPROACH TO AUTOPSY
Pictures are critical no matter how disturbing.
Always XRAY
Eviscerate and fix organs in LARGE volume
formalin for 24 hours before dissection.
Save placental and skin tissue for special studies
Blood spot saved for metabolic screen

FETAL HISTOLOGY IN
STILLBIRTH/IUFD
Ghosts possible in most autolyzed tissue

CMV
HSV
Rhabdomyomata
Hematological disturbances
Tumors

PLACENTAL FINDINGS
Often best preserved of all tissues
Metabolic, hematological, infectious
etiologies easily identified.
Fetal vascular events
Anatomic findings
Cord insertions

FETAL VASCULAR EVENTS


Thromboemboli in fetal vasculature - in placental
or viscera
Loose or occlusive
Differential diagnosis:

Anatomic vascular damage


Endothelial damage
Sepsis
Primary thrombophilia
Maternal diabetes

COMPLETE EXAM
INCLUDES

Complete autopsy
Placental examination
Fetal X-Ray
Fetal labs- Hct,blood type, bacterial cultures
Maternal-blood type, KB, TORCH titers

Chorion Nodosum
Rupture of the amnion early in gestation
(before the middle of the second trimester)
Fetus develops between the amnion and
chorion
Differential diagnosis:
Iatrogenic
Maternal/fetal collagen defects
Limb-body wall syndrome

Limb-body wall syndrome:


short umbilical cord
chorion nodosum

Normal Progression of Autolysis


during retention of IUFD
6 hours: desquamation >/= 1cm
Brown-red discoloration of cord

12 hours: desquamation of face, abdomen or back


18 hours: desquamation >5% of body surface
24 hours: brown skin discoloration
Moderate to severe desquamation

2 weeks: mummification

Reporting

Liveborn/Stillborn
Male/female
Infant/fetus
Weight, crown-rump length, etc and EGA
based on these measurements
Placenta - weight, cord length, color
Findings with a focus on biology

Example
Liveborn female fetus (1320g, CRL = cm; EGA
based on autopsy measurements of wks), age at
death, 2 hours.
No congenital/structural anomalies
Placenta - 120g Immature placenta
Severe acute chorioamnionitis [maternal stage 2 grade
2; fetal stage 2 grade 2]
Massive acute villous edema

Cause of death: Extreme prematurity, pulmonary


immaturity, aspiration pneumonia
Cause of premature delivery: acute
chorioamnionitis (cultures of lung and placenta
grew GBS).