The post mortem: new developments in understanding causes

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The post mortem new developments in
understanding causes

• Phil Cox
• Birmingham Womens Hospital

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Objectives

• Incidence and importance of Stillbirth
• Classification of Stillbirth
• Causes of Stillbirth
• IUGR in Stillborn babies
• Areas of interest/controversy in the pathology of
  stillbirth

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Definition of Stillbirth

• Stillbirth
• A child issued forth from its mother after the
  24th complete week of pregnancy which did not at
  any time after being completely expelled from its
  mother breathe or show any other signs of life
• Before labour - Antepartum
• During labour - Intrapartum

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Incidence of Stillbirth

• England, Wales Northern Ireland
• 5.0/1000 total births (1998)
• 3347 losses
• W Midlands
• 6.2/1000 (2002)
• 383 losses

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Causes of Explained Stillbirth (antepartum)

• Infection
• Bacterial
• Viral
• Abruption
• Chromosomal
• Malformation
• Feto-Maternal Haemorrhage
• Hydrops

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Placenta - CMV
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Stillborn infant with Trisomy 21
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Classification of Stillbirth

• Wigglesworth
• Congenital malformation
• Infection
• Intrapartum events
• Other specific causes
• Unexplained
• Unclassifiable

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Classification of Stillbirth

• Wigglesworth
• Congenital malformation 12.2
• Infection 3.5
• Intrapartum events 9.2
• Other specific causes 4.6
• Unexplained 69.9
• Unclassifiable 0.6

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Classification of Stillbirth

• Aberdeen (Obstetric factors)
• Antepartum haemorrhage
• Maternal disorder
• Pre-eclampsia
• Mechanical
• Miscellaneous
• Unexplained

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Classification of Stillbirth

• Aberdeen (Obstetric factors - Unexplained
  Wigglesworth)
• Antepartum haemorrhage 15.7
• Maternal disorder 7.2
• Pre-eclampsia 5.4
• Mechanical 1.9
• Miscellaneous 0.5
• Unexplained 69.4

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ReCoDe

• Relevant Condition at Death
• Records any condition present at the time of
  death which may have contributed to outcome
• Does not have to be THE CAUSE only a FACTOR
• Reduces unexplained from 70 to 14

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IUGR in stillborn babies

• What is IUGR?
• Failure of a fetus to reach its optimum size and
  birth weight

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Incidence of IUGR in stillborn infants

• CESDI 5th Annual Report
• W Midlands Antepartum stillbirth study - BLR gt4
  or lt5th centile
• 22/86 (26)
• Froen JF et al (2004)
• 52 of stillbirths lt10th centile
• OR 7 (95 confidence interval 3.3-15.1)

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Patterns of IUGR

• 2 classical patterns
• Symmetrical
• Early onset
• Associated
• Infection e.g. rubella
• Chromosomal / Genetic
• Teratogens
• Impaired cell division
• No catch -up
• Rare

• Asymmetrical
• 3rd trimester
• Associated
• Uteroplacental insufficiency
• Smoking
• Chronic disease
• Multiple pregnancy
• Impaired nutrition
• Post natal catch-up
• Common

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Identification of IUGR

• Birth weight (and other growth) centiles
• Crude (Population based)
• Customised (for main maternal and fetal growth
  determinants)
• Maternal height and weight
• Parity
• Ethnic group
• Fetal sex

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Pathological diagnosis of IUGR (at post mortem)

• Weight
• Crude/customised centile
• Problems
• Gain of weight in agonal phase
• Hydrops
• Loss of fluid after birth
• Dependent on correct gestation
• Interval between death and delivery

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Pathological diagnosisAsymmetrical IUGR

• Markers of maintained brain growth
• Head circumference centile gt weight centile
• Brain weight appropriate for gestation but other
  organs appropriate for body weight
• Brain weight liver weight ratio

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Pathological diagnosisAsymmetrical IUGR

• Brain weight liver weight ratio
• Normal ratio 2.81 (Gruenwald 1969)
• gt4 indicates impaired nutrition
• gt6 indicates severe IUGR
• May be as high as 201 in severe, longstanding
  IUGR

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Pathological diagnosisAsymmetrical IUGR

• Brain weight liver weight ratio
• Problems
• ? Effect of maceration
• Hepatic engorgement may mask elevation
• Exsanguination may give false elevation
• Limited post mortem

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Pathological diagnosisAsymmetrical IUGR

• Other markers of fetal stress / impaired growth
• Small thymus and / or adrenals
• Thymus histology
• Adrenal histology

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• Thymus - Chronic stress
• Prominent Hassalls corpuscles
• Cortical atrophy

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• Adrenal - Chronic stress
• Fatty change in definitive cortex

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BWH Study of IUGR in Stillbirths

• Aim
• To examine the relationship between customised
  birth weight centile and BLR
• To examine the value of each in assessing fetal
  nutrition and growth in stillborn babies
• To identify other markers of IUGR

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Materials and methods

• PM reports 1999-2002
• Stillbirths gt 24 weeks gestation
• Exclusions
• Congenital malformations
• Known chromosomal abnormality
• Limited post mortem
• Incomplete data

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Materials and methods

• Data collection
• Mother
• Parity
• Ethnicity
• Fetus
• Sex
• Gestation
• Birth weight
• Organ Weights

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Materials and methods

• Calculation
• Brainliver ratio (BLR)
• (partially) customised weight centile
• (Centile calculator)

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Results

• 225 stillbirths
• Customised centile
• 105/225 (46.7) ? 3rd centile
• 120/232 (53.3) lt10th centile
• Brainliver ratio
• 110/225 (48.7) ? 4.0
• 46/225 (20.4) ? 6.0

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Results
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Results
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• Group A (N centile, N BLR)
• Normally grown and nourished
• Group D (low centile, high BLR)
• Asymmetrical IUGR
• Group B (low centile, N BLR)
• ? Incomplete customisation
• Weight loss post delivery / prolonged retention
  ? gest
• Concealed IUGR (liver congestion)
• Symmetrical IUGR
• Group C (N centile, high BLR)
• ? Early IUGR - fetal malnutrition
• ? Artefactual e.g. exsanguination
• Incomplete customisation

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Conclusion

• 37 of stillbirths show IUGR by both centile and
  BL ratio and in a further 19 one or the other
  is abnormal
• Assessment of multiple parameters is essential
  when analysing fetal growth at post mortem

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Next steps

• Analysis of groups B C
• Value of other ratios e.g. brainthymus in
  assessing IUGR
• Centile calculator and ReCoDe are available from
  www.perinatal.co.uk

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Areas of interest/controversy in the pathology of
stillbirth

• Placental villous dysmaturity
• Umbilical cord coiling
• Fetal thrombotic vasculopathy

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Placental villous dysmaturity

• Abnormal villous maturation leading to large
  villi with excess loose stroma and poorly formed
  vasculosyncytial membranes

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Placental villous dysmaturity
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Placental villous dysmaturity
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Placental villous dysmaturity

• Theory
• The abnormal villi allow transfer of nutrients
  from maternal to fetal circulation
• Poor gas exchange
• Results in normal growth but death due to hypoxia
• results in death in 3 per 1000 pregnancies.
  Detection helps to minimise recurrence in
  subsequent pregnancies Stallmach Hebisch, 2004

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Placental villous dysmaturity

• Questions
• Is this really a significant lesion?
• Is this an effect of fetal compromise rather than
  a cause?
• Is this a post mortem change?
• But rescue by birth
• Is it a marker of recurrence risk?
• What is the cause?

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Umbilical Cord Coiling

• Role of umbilical cord coiling in adverse
  perinatal outcome (including Stillbirth)
• Overcoiling and undercoiling
• Normalcoiling index 3 coils/10cm
• Range - 1-4 coils/10cm

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Umbilical Cord Coiling
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Umbilical Cord Coiling

• Increased/decreased coiling index associated
  with
• Stillbirth (37 /29)
• Fetal distress (14/21)
• IUGR (10/15)
• Chorioamnionitis (10/29)
• (Machin et al, 2000)

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Umbilical Cord Coiling

• Coiling abnormalities also associated with
• Premature delivery
• Cocaine abuse
• Old and young mothers
• Gestational Diabetes
• Pre-eclampsia
• Chromosome abnormality

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Umbilical Cord Coiling

• Significance?
• Extreme cord hypercoiling may impair cord blood
  flow (-fetal vascular thrombosis)
• For lesser degrees of hypercoiling and
  undercoiling case is unproven
• Biomechanics would suggest increased coiling does
  not interfere with blood flow

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Fetal Thrombotic Vasculopathy

• Thrombosis in the fetal circulation during fetal
  life
• Reported association with
• Stillbirth
• IUGR
• Brain injury
• Thrombophilia

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Fetal Thrombotic Vasculopathy
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Fetal Thrombotic Vasculopathy

• Problems
• Differentiation from post mortem vascular changes
  in fetal vessels in S/B
• Downstream changes (avascular villi)

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Fetal Thrombotic Vasculopathy
Avascular villi
Thrombosed stem vessel
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Fetal Thrombotic Vasculopathy

• Problems
• Significance of mural (non-occlusive thrombi)
• Significance of minor focal changes
• Significance of fresh thrombi
• Sampling

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Conclusions

• Stillbirth remains a common problem
• Improved classification methods may aid in
  understanding the factors leading to stillbirth
• IUGR is a frequent factor in stillbirth
• Villous dysmaturity, cord coiling abnormalities
  and fetal thrombotic vasculopathy may be a factor
  in some cases, but their importance remains to be
  proven.