Perinatal pathology

Perinatal pathology
Samantha Holden
Ta
ˇ
nia Fernandes
Caroline Gannon
Abstract
Perinatal post mortems are those performed on fetuses, stillborn in-
fants and infants who die in the neonatal period. The majority are per-
formed following consent being obtained from the parents. Performing
these cases requires special knowledge and equipment. The back-
ground to these cases and detailed information on what is undertaken
and how findings are interpreted will be covered in this review.
Keywords autopsy; fetal; neonatal; perinatal
Background
The World Health Organisation (WHO) definition of a perinatal
death is one occurring from 22 weeks gestation to the end of the
first week of neonatal life; there is no stipulation for weight,
although 500 g or more is suggested.1
According to this defini-
tion, more than 5 million perinatal deaths occur worldwide each
year. The United Kingdom (UK) does not follow this definition;
the stillbirth component is only collected from 24 weeks gesta-
tion onwards. There is no central registration for fetal demise
occurring below 24 weeks gestation which makes assessment of
numbers of miscarriages difficult. The Confidential Enquiry
system in the UK collates information regarding late fetal demise
(22 weeks onwards), stillbirth and neonatal death for the whole
country; the perinatal mortality rate in 2016 was 5.64 per 1000
total births, with a stillbirth rate (deaths after 24 weeks gestation
excluding live births) of 3.93 per 1000 total births. The rates for
stillbirth and neonatal death in the UK are relatively high
compared to similar countries.2
In 2015, the WHO published a
comparison table of stillbirth rates in 196 countries e using ba-
bies born at 28 weeks gestation or more, or weighing over 1000 g
e which showed the UK rate being 2.9 per 1000 births.3
The
range was from 1.3 per 1000 (Iceland) to 43.1 per 1000
(Pakistan). According to this, the UK was joint 23rd
in the list,
with many European Countries, Australia, New Zealand, Japan
and the Republic of Korea having a lower stillbirth rate. Of the
thirteen countries with a rate of 30 per 1000 or greater, with the
exception of Pakistan, all lie in Africa.
Authority for perinatal examinations
Perinatal pathology includes post mortem examinations per-
formed on stillborn infants and neonates but also earlier mis-
carriages and terminations for abnormality, in effect, from 12
weeks gestation onwards. Perinatal and paediatric pathologists
also perform post mortem examinations on infants and older
children, but the investigation of these cases is outside the remit
of this article. The vast majority of perinatal cases are performed
as a result of parental request with consent, rather than being a
medicolegal requirement, although there is some variation
throughout the regions of the UK.
In England and Wales, whilst HM Coroner’s power to inquire
into the circumstances of a death are wide ranging, they do not
have the power to investigate a stillbirth. A fetus or stillborn
infant is legally regarded as not achieving independent life, and
therefore cannot be subject to a coronial investigation currently
(this is part 1 of the Coroners and Justice Act 20094
). The
Coroner may have grounds for investigation if there is a possi-
bility that the infant achieved independent life before dying,
including concealed pregnancy or if there is a finding during the
post mortem suggestive of an iatrogenic cause of death.
Coronial legislation relating to the investigation of stillbirth
differs in Northern Ireland, where the Coroners Act (Northern
Ireland) 19595
includes a ‘fetus in utero capable of being born
alive’ as part of the definition of ‘deceased person’; this is
considered to explicitly permit the Coroner to investigate still-
births, i.e. babies >24 weeks gestation but who are subsequently
stillborn.
In Scotland, the Procurator Fiscal has powers to investigate
infant deaths that occur as a sudden, unexpected and unex-
plained perinatal death; where the body of a new-born is found
and it is unclear if the baby was live born or still born; and deaths
arising following a concealed pregnancy.
Currently, there is debate about expanding the role of the
Coroner in England and Wales in the investigation of stillbirth,
with a Bill proceeding through parliament.6
This is supported by
various charitable bodies including the UK Stillbirth and
Neonatal Death Charity (SANDS): there may be grounds for a
coronial investigation if the parental view is that hospital reviews
have been inadequate or not undertaken or whether there were
considered to be gaps in maternity care that could have resulted
in the stillbirth.
It is important that any perinatal post mortem, regardless of
the jurisdiction under which it is performed, is undertaken with
understanding of the need for additional investigations, as
described below.
The role of the Human Tissue Authority (HTA) is to ensure
that human tissue is used safely and ethically, and with proper
consent according to the Human Tissue Act 2004.7
The HTA
regulates, through licensing, the removal, storage and use of
human tissue for scheduled purposes. According to the HTA,
fetuses that have not exceeded the 24th
week of pregnancy are
considered to be the mother’s tissue as long as they have not
taken breath; they have produced guidelines for the sensitive
disposal of fetal tissues, although this is not legally covered by
the Act itself.
In most cases, consent is required from the parents prior to
performing the post mortem examination. The consent process is
Samantha Holden BSc MBBCh FRCPath Consultant Paediatric
Pathologist, Southampton General Hospital, Southampton, UK.
Conflicts of interest: none declared.
Ta
ˇ
nia Fernandes BSc LIBMS Paediatric Lead Anatomical Pathologist
Technologist, Southampton General Hospital, Southampton, UK.
Caroline Gannon MA MB BCh FRCPath Consultant Paediatric
Pathologist, Southampton General Hospital, Southampton, UK.
MINI-SYMPOSIUM: PAEDIATRIC PATHOLOGY
DIAGNOSTIC HISTOPATHOLOGY 25:9 350 Ó 2019 Published by Elsevier Ltd.

often undertaken by the clinicians who have been caring for the
parents prior to the baby’s death, although in some centres pa-
thologists may be involved in consent processes.
The consent form used currently in the UK is one written in
conjunction with SANDS,8
which included the thoughts of
bereaved parents when compiling the forms. The consent en-
compasses: the extent of examination permitted (full, limited to a
body cavity, laparoscopic autopsy with biopsy sampling or
external examination only9
); taking and examination of tissues
for histology, genetic investigations and other laboratory tests;
and whether images or tissues may be used for audit, research
and teaching. Unless the parents object, radiology and photog-
raphy are performed in every case.
The post mortem examination
The post mortem examination is performed according to the
guidelines produced by the Royal College of Pathologists.10,11
There are some similarities with adult post mortem examina-
tions, although there are significant differences (see Table 1 and
Figures 1, 2 and 3).
Radiology
Radiology in many centres is limited to plain x-rays in two di-
mensions (AP and lateral). CT and MRI post mortem examina-
tion is performed in some centres along with external
examination of the baby only or with additional sampling which
may include targeted biopsies, limited or full post mortem ex-
amination.9
It is likely this will increase in availability in the
future. Radiology is paramount in skeletal dysplasia, as diagnosis
requires radiological and histological assessment. An assessment
of fetal age can be made from measurement of long bone length
and appearance of ossification centres. Radiographs may also
identify trauma, bone disease, extra-skeletal mineralisation and
vascular calcification. Contrast radiology can be useful for ven-
triculomegaly and bladder outlet obstruction, the former espe-
cially if CT or MRI imaging is unavailable. MRI imaging has
potential but is not widely available - high resolution MRI can
delineate grey and white matter and may be a good option if
consent for an invasive examination is withheld. Also, neuro-
pathological assessment can be altered by autolysis and ante-
mortem MRI scans will provide more information.
Photography
Post mortem photography, assuming consent is given, is
invaluable as a record of findings and for teaching.
External examination
Measurements:
The following measurements are taken:
weight
Differences between adult and paediatric post mortems
Perinatal cases Adult cases
Jurisdiction Usually hospital
consented
Usually coronial
Purpose of post
mortem examination
To provide
information for the
family
Assessment of
anatomy
Confirmation of
anomalies seen on
scan
Identification of
anomalies/other
pathology not
previously identified
Recurrence risk
Obtain information for
future pregnancies
Stillbirths are
considered a serious
adverse incident/
serious incident
requiring full hospital
enquiry
To identify the cause
of death
NB normal anatomy
usually assumed
Size (see Figures 1, 2
and 3)
Smaller instruments
Class 2 scales (high
precision scale)
Magnifying lens/
dissecting microscope
Usual instruments
found in any mortuary
Radiology Always performed Very rarely performed
Pathology
encountered
Some adult style
pathology but wide
range of paediatric
pathology
Adult pathology
Pathologist
undertaking case
Specialist paediatric
pathologist
General pathologist
Location of services
(see Figures 1, 2 and
3)
Combination of
instrument
requirements and
specialist pathologist
results in centralised
service
Any mortuary
Organ retention Retention of,
especially, brain and
heart common e but
usually temporary
with return to body
following sampling
Uncommon
Additional samples
(eg histology,
microbiology,
cytogenetics e see
also Table 5)
Routine to take
histology and
additional samples
(part of consent and
normal practice)
Only taken with
coronial permission
for establishing the
cause of death
Follow-up Usually with
consultant
General practitioner or
at Inquest
Table 1 (continued)
Perinatal cases Adult cases
obstetrician/
paediatrician
Table 1

crown-heel, crown-rump and foot lengths
head, chest and abdominal circumference
inner canthal distance
length of any umbilical cord remaining attached to the
baby (with comment on appearance).
One of various tables which have been published (including
centile charts) should be consulted to assess the size of the baby
compared to that seen for the estimated gestational age. Body
weight may alter if there is delay between delivery and post
mortem or if the baby is wrapped in an absorbent cloth, which
may result in over diagnosis of growth restriction.12
The foot
length is the best-preserved parameter; if there is discrepancy
between the parameters, this will provide the best assessment of
fetal age. However, in the presence of fetal anomalies such as
talipes, the foot length may be less useful.
Maceration: in cases where the baby was born without signs
of life, an estimate of maceration is made. Maceration is the
special type of decomposition which occurs following death in
utero and the severity gives an indication of time from demise to
delivery. Changes include:
skin slippage
formation of bullae beneath the superficial epidermis
colour change (externally and internally)
laxity of soft tissues with movement of bones, especially
the skull
formation of blood-stained serous cavity effusions.
The extent of maceration, when present, must be taken into
account when comparing the growth parameters of the baby with
those expected; ligament laxity may result in increased length
following demise.
The examination is best performed in a systematic way
looking for congenital anomalies (developmental disorders of the
embryo and fetus) and other pathology. See Table 2 for further
external assessment.
Internal examination
Head: the skin incision is similar to that used in adult post
mortem examination, except in cases of posterior fossa abnor-
malities, intrapartum death or neural tube defect where an
Arnold Chiari malformation needs to be excluded, where the
back of the neck must be exposed also.
The cranial cavity is entered by opening the sutures between
the five skull bones resulting in a ‘petal’ effect. The cerebral
cleavage and gyral pattern is checked; the latter is a good marker
for gestational age. Performing this underwater is helpful as the
tissue is usually very soft. The brain can then be taken out from
water and, if needed, transferred into formalin using clingfilm.
Torso: in most cases, a central midline incision (similar to
adults) is used, although if the neck structures need to be
assessed (in cases with possible cord entanglement, intrapartum
death or neck pathology/abnormalities seen on scan) an addi-
tional curved incision may be required across the upper chest.
Other circumstances in which further incisions may be required
include bladder outlet obstruction (an inverted Y allows better
exposure of the bladder outlet) and skeletal dysplasia (curving
the lower aspect of the central incision onto the outer upper leg
will allow access to the upper part of the femur). After opening
the torso, the cartilaginous part of the ribs with sternum is
removed. Further detail on the internal examination, especially
concentrating on differences from adult post mortems, is
included in Tables 3 and 4; it should be noted this list is not
comprehensive. All organs and supporting structures are
assessed for congenital anomalies or other pathology.
All the organs are weighed following removal to allow accu-
rate assessment of intrauterine growth restriction, organomegaly
syndromes, for example, diabetes and disordered growth of
Figure 1 Dissection bench with specialist equipment.
Figure 2 Class 2 scales.

individual organs. They are then sampled for microscopy and
additional tests as required, see Table 5 for further information.
Histology
A combination of macroscopic (cerebral gyral pattern) and his-
tological appearances (particularly lungs and kidneys) is used to
aid assessment of gestational age and refine estimation of
gestational age and growth restriction. An extensive range of
fetal tissue is sampled during a full autopsy examination. Diag-
nosis of infection, assessment of hypoxic injury (particularly of
the brain and heart), and identification of many types of mal-
formation/dysplasia and metabolic disease are largely dependent
on histology. Factors such as hypoxia and physiological stress
can give rise to thymic lymphocyte depletion, pseudofollicular-
isation at the periphery of the adrenal glands, interstitial hae-
morrhage and neuronal changes, especially pontosubicular
necrosis (more usually seen in stillbirths) or watershed regions
such as the CA1 region of the hippocampus (more often in
neonatal deaths).
Placental examination
The post mortem examination is not complete unless the
placenta is also examined (although it may not be available for
neonatal deaths).
Placental lesions known to be associated with subsequent
neurological impairment include avascular villi, haemosiderin in
the chorionic plate, fetal vascular thrombosis and severe
inflammation.
These structures are part of the conceptus and it is often
overlooked that examining them can help establish the sequence
of events leading to perinatal death. For example, it may show
the cause (and give an estimate of the time of onset) of hypoxic/
ischaemic insults. There may be evidence of ascending or hae-
matogenous infection, and specific organisms can be identified
using special staining techniques, immunochemistry, and in situ
hybridisation. Assessment of chronicity is clearly important in
multiple pregnancy. Histological examination of the placenta
may give the first clue to an underlying inborn error of meta-
bolism. Fibroblasts prepared from placental tissue can be used
for metabolic studies as well as cytogenetic investigations, and
provide a source of DNA for molecular biological studies. His-
tological examination of the placenta may identify conditions,
such as chronic histiocytic intervillositis or villitis of unknown
aetiology, which may recur in subsequent pregnancies and
which may alter future obstetric management of the mother.
Therefore, after perinatal death (and also when infants are
born alive but in poor condition), the placenta and cord should
wherever possible be sent for pathological examination.
Increasingly, the findings are required to resolve issues raised
during medicolegal investigation.
Reconstruction
Any excess fluid and blood should be drained from all body
cavities to prevent leakage after reconstruction. The brain tissue,
within an appropriately sized, sealed plastic pouch, is placed in
the cranial cavity. In the rare case of brain retention place a
‘bolus’ of cotton wool of weight equivalent to the brain into the
skull. Align each petal of the skull bones to reform the cranial
shape. Gauze may be placed across the petal area to recreate this
and to prevent visible scalp irregularities. Cotton wool or
absorbent pads are placed in the neck and along the back of the
torso. The thoracic and abdominal organs and supporting tissue
are placed in sealable pouches and the skin replaced over them.
With an appropriately sized needle and twine, suture the scalp
or torso skin together as tightly as possible without tearing the
surrounding skin. The visible suture line should resemble a close
fitting zip in appearance and should create a clean and leak proof
theatre-type operational procedure site. If skin is too thin to be
able to hold suturing, skin glue should be used instead.
The baby is washed to remove any bio burden remaining from
the post mortem examination then a towel used to dry the baby.
Dressings are placed over the sutures and the baby dressed with
appropriate-sized clothing.
Care should be taken to ensure the head is slightly raised to
minimise leakage and the head is aligned with the torso to pre-
vent decolourisation of the face and soft tissues.
With appropriate reconstruction, parents may view their baby
following examination.
Interpretation of findings
As highlighted above, examination for the presence of congenital
anomalies and other pathology is paramount. Some examples of
common pathology and their causes are given in Table 6.
Figure 3 Instruments required; (left) over 16 weeks; (right) under 16 weeks.

Congenital anomalies
European derived data estimates the prevalence of perinatal
mortality with congenital anomaly to be 0.92 per 1000 births
(incidence cannot be given because many miscarriages occur
before pregnancy is confirmed).13
In general, chromosomal and
central nervous system defects account for more fetal deaths due
to termination (where this is allowed) whilst cardiac, urinary and
respiratory defects account for more early neonatal deaths. The
types of anomalies which give rise to infant death tend to be
those which either are not detected through screening (or
screening has not taken place) or do not cause death in utero and
have a high risk of early death due to the anomaly or compli-
cations of treatment, such as cardiac anomalies.14
In cases with anomalies, it is relevant to consider referring
families for clinical genetic advice. A clear and accurate record of
malformations compiled at post mortem examination is helpful
for genetic counselling, arranging targeted genetic testing and
predicting a recurrence risk for the family.
There is no universally accepted system of classification, but
anomalies are considered to fall within three main categories:
1. Malformations - due to intrinsically abnormal processes
during development. Includes chromosomal abnormalities
and single gene defects (see Table 7 for common chromo-
somal anomalies).
2. Disruptions - occur when there is interference with normally
developing processes, eg due to drugs, chemicals, viral
infection or ionising radiation.
3. Deformations - abnormal form, shape or position due to
mechanical forces.
Other terminology used includes the following:
Syndrome e a recognisable, consistent pattern of anoma-
lies due to a single aetiology, eg Trisomy 21/Down
syndrome;
Sequence e a pattern of anomalies due to a primary defect
in morphogenesis, eg, Potter sequence with classical
morphological features seen due to renal agenesis;
Association e a collection of features which frequently
occur together, eg VACTERL association, a combination of
three of vertebral defects, anal atresia, cardiac defects,
External examination
Anatomical structure Assessment to consider
Overall assessment Is maceration present?
Are the head, torso and limbs in proportion?
If not what is disproportional?
If limb shortening, which part of the limb is
affected (rhizomelia ¼ proximal segment
affected, mesomelia ¼ middle segment,
acromelia ¼ distal segment)
Is oedema, pallor or muscle wasting present?
Head Shape
Evidence of injury/bruising/forceps marks
(especially intrapartum demise and neonatal
deaths)
Eyes Normal size, symmetrical sizes
Petechial haemorrhages
Are there epicanthic folds? Sub-orbital
creases?
NB eyelids often fused until around 24 weeks
gestation
Coloboma may be difficult to assess in
stillbirth
Nose Probe nostrils for choanal patency
Assess shape of nose-is there depression of
the nasal bridge? Broad columnella? Flared
alar nasi?
Mouth Is the jaw of normal size (micrognathia is a
small jaw)
Are the lips and palate intact or clefted?
Are the corners of the mouth downturned?
Does the tongue protrude? Appear large
(macroglossia)?
Ears Position e examine the lateral view of the
head; the upper insertion should be on a line
from the outer angle of the eye to the occiput,
the lower insertion on a line from the outer
corner of the mouth to the occiput
The ears should be roughly vertical
NB ears may appear low-set or posteriorly
rotated in fetuses below 20 weeks gestation
Ear anatomy may be difficult to assess in the
presence of hydrops
Neck Any structural abnormalities such as cystic
hygroma, broad/webbed appearance
Torso Any body wall defects e examine the edge;
irregular edges raise the possibility of
artefactual change
Any neural tube defects e palpate the back of
the baby to exclude spina bifida occulta
External genitalia Can be difficult in young fetuses; any opening
separate to the anus is a strong suggestion
this is a female fetus
Anus Probe to assess patency
Limbs
Table 2 (continued)
Anatomical structure Assessment to consider
Assess for free movement/fixed flexion or
extension
Palmar skin creases
Fingers and toes Count the digits e polydactyly of a short
segment of finger or toe is easily seen but
duplication of a complete digit may be missed
if the digits are not counted individually
Separate digits to exclude syndactyly (fusion)
e maceration may hamper this
Palmar skin creases Check for normal creases vs single transverse
palmar crease e may be hampered by
maceration or young fetal age
Table 2

Macroscopic internal examination
Body cavity Structure Factors to assess
All cavities Soft tissue and bone Check for soft tissue and bone injuries including bruising and
oedema. Specific considerations for the head include: caput
succedaneum (bleeding within scalp); subgaleal haemorrhage
(beneath galeal fascia); cephalhaematoma (subperiosteal
haemorrhage)
Head Skull Normal suture formation, size of anterior fontanelle, fractures
Dura Whether intact, any injuries (especially intrapartum/neonatal
deaths), haemorrhage (if discoloured, a section submitted for iron
staining may be useful)
Brain Cleaving of cerebral hemispheres
Normal gyral appearance for gestational age
Normally sized cerebellum and brainstem
Any lesions on sectioning
Chest and neck Thymus gland (NB can extend into neck) Presence of gland (absence linked with some chromosomal
anomalies)
Presence of petechial haemorrhages
Heart (for more detail see Table 4) Assess and dissect in a sequence following the flow of blood
(sequential segmental analysis), starting with right atrium to right
ventricle to pulmonary artery, followed by opening the left side of
the heart
Assess anatomical and morphological sides of the chambers
Look for septal defects
Is the foramen ovale patent or closed?
Are the valves and cusps normal?
Are the atria and ventricles of similar sizes or one side smaller than
the other? If not valve and other anomalies should be considered
Great vessels Pulmonary artery should arise in front of and to the left of the aorta
(if not consider transposition of the great vessels)
Check the coronary artery ostia
Check the patency of the ductus arteriosus
Examine the branches of the aortic arch e does the right subclavian
artery arise from the first branch
Confirm the side of the descending aorta
Respiratory system Assess laryngeal and tracheal patency
Assess bronchial branching pattern
Exclude trachea-oesophageal fistula
Check lung lobation
Cut surface-any cystic lesion seen?
Oesophagus Check patency, exclude atresia
Ribs Count number of ribs if unclear on X-ray or any anomalies
Check for fractures in intrapartum or neonatal deaths
Abdomen and pelvis Umbilical vessels Check two arteries
Assess patency of umbilical vein
Stomach Check side and size, assess contents, meconium?
Intestines The appendix is a marker of intestinal rotation e if in the right flank
this is normal, elsewhere is usually a marker of malrotation,
although unreliable under 20 weeks gestation
As the intestine is removed check for atretic areas, Meckel’s
diverticulum, fistula formation (eg with bladder in cloacal
abnormalities)
Liver Check side, presence of gall bladder, patency of extra-hepatic biliary
tree (if meconium is green in colour, that means it is patent)
Pancreas Confirm presence and location-annular pancreas? NB Pancreas is
earliest tissue to undergo autolysis

trachea-oseophageal fistula, renal anomalies and limb
abnormalities;
Dysplasia e structural changes as a result of cellular dis-
organisation in a tissue, eg skeletal dysplasia.
Factors which increase the risk for anomalies (some of which
are mentioned above) include: alcohol, drug use, con-
sanguinuity, previous pregnancies with anomalies, parental age
(usually increasing age, although gastroschisis, an abdominal
wall defect, is linked with young maternal age), maternal dia-
betes or obesity.
It is important to remember the anomaly may not account for
demise e there may be iatrogenic causes or other natural disease
present, such as infection.
The negative autopsy
Knowing the cause of a stillbirth is important to parents, and a
full autopsy examination generally offers the best chance to
explain why their baby was stillborn. However, some stillbirths
(around 1 in 7) remain unexplained even after a full autopsy
examination. The value of a negative observation cannot be
underestimated; this may still provide useful information that
can help plan and manage future pregnancies and provide reas-
surance for parents.
Negative findings allow clinicians to refine their plan of
management for future pregnancies, for example, by excluding
inheritable conditions, and provides an audit of ultrasonographic
diagnosis, obstetric and neonatal intensive care.
Negative findings are important because of national themes
and trends associated with perinatal deaths:
national lessons may be learned via review
allow assessment of whether maternal care was
appropriate
provide professional learning and training.
For the family, negative findings may:
exclude a chromosomal or genetic aberration - reassurance
for future pregnancies
provide confirmation there was no overlooked or un-
treated clinical issue
provide reassurance of normal fetal growth and placental
function
exclude the possibility of infection or other issues which
may impact on future pregnancies
contribute to scientific research
reduce fear for future pregnancies.
It is not uncommon in stillbirth autopsies for there to be a
range of anomalies that, when taken as isolated findings, would
not have caused the death of the baby, but when considered as
part of a wider whole, may have contributed towards death. The
idea that routine histology is of little value is utterly wrong.
Whilst it is correct that histology alone infrequently provides the
Table 3 (continued)
Body cavity Structure Factors to assess
Spleen Check side, whether single or polysplenia, look for splenunculi
Adrenal glands Larger than in adults, usually similar size to kidneys
Assess presence, shape (should be pyramidal-flat adrenals usually
indicates abnormality of the kidneys) any haemorrhage
Kidneys Normal fetal lobulation seen
Assess presence, any enlargement or cystic appearance
Ureters Check for dilation or tortuous appearance
Bladder Check for any distension, if so examine outflow by removing the
pubic symphysis if required to get access
Internal genitalia Look to see if female or male genitalia present - the testes may have
descended into the scrotum during the third trimester
Table 3
Detailed cardiac examination
Anatomical structure Morphologically right Morphologically left
Atrium Triangular atrial appendage with wide opening
Crista terminalis present
Pectinate muscles in appendage extending
around atrioventricular junction
Hook like atrial appendage with narrow
opening
Pectinate muscles confined to appendage
Atrioventricular valve Tricuspid valve has septal and papillary
muscle attachment
Mitral valve has papillary muscle attachment
only (no septal attachment)
Ventricle Coarse apical and septal trabeculations Fine trabeculations
Membraneous tissue adjacent to aorta
Table 4

cause of death, it routinely provides important information about
the antecedent events (even where the death remains ’unex-
plained’). For example the pattern, severity and timing of
hypoxic-ischaemic brain injury, the extent of meconium aspira-
tion, and the presence of unexpected renal vein thrombosis are
all valuable pieces of information when trying to understand
what has happened. Negative findings are as important as posi-
tive ones. There is a massive difference between ’it wasn’t there’
and ’we didn’t look’.
Of course there is a need to try to develop new tests to
(ideally) predict rather than explain stillbirth, but it is far too
early to write off what is still a central part of the investigation.
In summary, a well-performed perinatal post mortem exami-
nation is one which can provide significant information
regarding the infant and the pregnancy, but will highlight
possible recurrence risks and scope for further investigation
(including genetic testing) for future pregnancies or screening of
other family members. It is important to emphasise the needs of
the family being central to the manner in which perinatal post
mortem examinations are delivered, due to the difficult and
sensitive nature of the cases. This includes flexibility over the
extent and timing of the autopsy, which allows parents to decide
when they feel ready for their baby to be released for the autopsy.
The pathologist may be involved in direct communication with
the family and may provide lay reports e family friendly version
of the report (one author used to give the family a copy of the
formal report and a lay interpretation with a glossary so they
received the same as the clinician).
Perinatal pathology: not in the textbooks
Crown-rump measurement generally equal to head
circumference in a non-macerated baby - a difference
means something is wrong.
Radiographs - look for calcification in the liver, common in
aneuploidy, hypoxia or infection.
Calcification in the intestines - stasis, obstruction, meco-
nium peritonitis, chromosomal abnormality e and normal
babies.
Meconium staining - look between the toes, behind the
ears, in the mouth and throat. Babies may be bathed on the
ward after delivery, and meconium staining may be very
Further investigations which may be undertaken
Type of test Situations required Samples taken
Neuropathology [NB will depend on local practice]
Brain abnormalities
Arthrogryposis/other movement disorders
Brain
For arthrogryposis/other movement disorders
e consider spinal cord, muscle and nerve
Cytogenetics Any abnormalities
Stillbirths
Neonatal deaths
Recurrent (more than 3) miscarriage
Skin
Placenta
Other tissues as required
Microbiology Stillbirths
Neonatal deaths
Heart swab/blood cultures
Lung
Cerebrospinal fluid in neonates
Other as required especially if lesions seen
Virology Termination for brain abnormalities
Fetal hydrops
Stillbirths
Neonatal deaths
Liver
Other tissues as required, eg respiratory tract
in neonatal death
Biochemistry Neonatal deaths Consider: Blood and bile spots for
acylcarnitine analysis
Urine for organic acid analysis if clinical
suspicion
Frozen tissue (two samples may be required,
one to retain for further testing, the other for
ORO staining for fat)
Fetal hydrops
Neonatal deaths
Any suspicion of metabolic disorder
Heart
Kidney
Liver
Skeletal muscle
Spleen
Placenta
Lung if neonatal respiratory disorder
Electron microscopy Renal cystic disease
Suspicion of metabolic disorder
Lung disorder
Tissue as required depending on underlying
pathology
Table 5

subtle, but provides a good marker of possible fetal
hypoxia.
Desiccation - in mid-trimester fetuses, there is rapid
desiccation of the extremities and scalp. Gently soaking the
scalp skin with damp cotton wool for a short time may
permit the skin to loosen sufficiently to allow removal of
the brain without tearing the skin.
In macerated infants, tissue fluid effluxes into the body
cavities: this is usually red-brown in colour and can
obscure the appearances. Remove the fluid using slightly
damp cotton wool -dry cotton wool sticks to the tissues.
Measuring effusions: effusions in fetuses are obviously far
less in volume than effusions in adults. These can be
measured by suctioning via a syringe or weigh a wad of
slightly damp cotton wool, then mop up effusions and re-
weigh (1 ml of fluid is equivalent to 1 g).
Maceration can cause significant alternation of the facial
features. Usually, there is considerable cosmetic improve-
ment after reconstruction; it is always worthwhile looking
at the baby again after reconstruction to compare before
and after appearances.
Look at the x-rays before you start - if there is a skeletal
dysplasia you will need to sample more bones for diag-
nostic purposes than in babies without skeletal dysplasia
Ratios - there are lots of useful ratios:
o Brain weight to liver weight ratio 3:1 at any gestation.
In macerated fetuses, it can elevate a little due to fluid
loss, but anything over 4:1 indicates growth
restriction.
o Lung weight to body weight ratio to help determine the
presence of pulmonary hypoplasia.
Cerebral tissue frequently liquefies as a result of severe
maceration, but the cellular features of HIE can still be
Common post mortem findings and possible causes
Finding Possible causes
Pallor Fetomaternal haemorrhage
Viral infection
Oedema (hydrops fetalis) Chromsomal anomaly
Viral infection
Congenital anomaly, especially
heart, urogenital tract
Immune (eg Rhesus incompatibility)
Idiopathic
Small size Growth restriction/small for
gestational age
Placental issue
Constitutional
Skeletal dysplasia
Maternal diabetes
Large size (macrosomia) Maternal diabetes
Beckwith Wiedemann syndrome or
other hypertrophy syndromes
Head disproportionately
large
Intracranial abnormality
Triploidy
Congenital anomalies Isolated anomaly may be sporadic
If multiple anomalies, consider
syndromes and associations (see
text)
Maternal diabetes or obesity
Table 6
Common chromosomal anomaly and associated findings
Chromosomal anomaly Common findings
Trisomy 21 (Down
Syndrome)
Growth restriction
Fetal hydrops
Epicanthal folds
Protruding tongue
Single transverse palmar crease
Sandal gap between great and
second toes
Congenital heart defect, especially
atrioventricular septal defects
Duodenal atresia/stenosis
Trisomy 18 (Edwards’
Syndrome)
Growth restriction
Micrognathia (small jaw)
Cleft lip and palate
Clenched hands with overlapping
fingers
Rocker-bottom feet (rounded soles)
Cardiac abnormalities
Oesophageal atresia
Renal tract anomalies
Trisomy 13 (Patau
Syndrome)
Growth restriction
Microphthalmia (small eyes),
anophthalmia (absence of one or
both eyes),
Hypotelorism (reduced distance
between eyes
Cleft lip and palate
Holoprosencephaly
Exomphalos
Polydactyly
Monosomy X (Turner
Syndrome)
Growth restriction
Fetal hydrops
Cardiac abnormalities including
coarcation of the aorta
Triploidy Growth restriction with head
disproportionately large compared
to the body, which is often thin
Hypertelorism
Syndactyly of the middle and ring
fingers of the hands and second
and third toes of the feet
Cardiac abnormalities
Placental examination important
due to risk of partial molar
pregnancy
Table 7

seen so it is still worthwhile submitting some cerebral
tissue for histology.
Estimation of timing of death can be made using the degree
of maceration and the microscopic appearance of various
tissues (principally renal tissue) - useful from a clinical
point of view to correlate with maternal fetal movement
observation.
Cord coiling: hypo and hyper coiled cords are associated
with poor fetal outcome. Frequently the cord has already
been cut and the full length not submitted, but it is
worthwhile assessing the cord attached to the baby as well
as that attached to the placenta, looking at diameter,
coiling and any areas of stricture.
Skirting sign e hold up the thoracic pluck; the lungs
should reach to the base of the heart - if they skirt above,
consider pulmonary hypoplasia and look for causes
Footballer’s line up sign - to decide if upper limbs are
normal length - the hands should cross over the groin e if
not, the arms are short and skeletal dysplasia should be
excluded.
Kidneys and adrenal glands e if the adrenals are pyrami-
dal, at one point, the kidneys were normally positioned
and shaped, even if they are now cystic and distorted. If
the adrenals are flat and plate like, the kidneys were never
normally shaped or positioned
Iatrogenic lesions - photograph any lines in situ prior to
removal. A
REFERENCES
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2 Draper ES, Gallimore ID, Kurinczuk JJ, et al. on behalf of the
MBRRACE-UK Collaboration. MBRRACE-UK perinatal mortality
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