Birth asphyxia Definition and Causes

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Birth asphyxiaDefinition and Causes

• PETER G.J. NIKKELS
• Dept. of Pathology UMC Utrecht,
• the Netherlands

21st European Congress of Pathology September
08-13, 2007 Istanbul, TURKEY Symposium Birth
Asphyxia and Birth Trauma
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Definition of perinatal asphyxia

• What is asphyxia
• Definition of the task force of the World
  Federation of Neurology Group in 1993
• Condition of impaired gas exchange leading, if
  it persists, to progressive hypoxemia and
  hypercapnia.
• Added suggestion in 1997
• with a significant metabolic acidosis.

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Perinatal asphyxia

• Criteria used in clinical practice
• Apgar score (0-3 for gt 5 minutes)
• arterial cord blood pH (pH lt 7.0)
• base deficit (gt -12 -16 mmoll/l)
• late decelerations on foetal monitoring or
  meconium staining
• delayed onset of respiration
• multiorgan involvement (brain, heart, kidney,
  etc.)
• necessity for resuscitation

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Perinatal asphyxia

• Many different criteria and different cut off
  points of the criteria are used to define
  perinatal asphyxia.
• Comparison between different studies difficult.
• Only severe acidemia has predictive value for
  long-term neurological injury
• A severe metabolic acidosis is associated with
  multiorgan complications (not a respiratory
  acidosis).
• Incidence
• Umbilical artery base deficit gt 12 mmoll/l 2
• Umbilical artery base deficit gt 16 mmoll/l 0.5

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Perinatal asphyxia

• However, metabolic acidosis determined at the
  time of sampling does not necessarily reflect the
  severity of asphyxial exposure to the foetus.
• Duration of asphyxia not known
• Nature of insult not known (continuous or
  intermittent)
• Foetal response influences the importance of the
  asphyxial exposure.
• Response centralization of the foetal
  circulation
• (blood to brain, heart and adrenals)
• If hypoxia sustains cardiovascular decompensation

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Perinatal asphyxia

• Sustained hypoxia cardiovascular decompensation
  more severe brain damage, cardiac and renal
  dysfunction and respiratory complications.
• 2 of newborns has been exposed to an asphyxial
  event
• Majority of events is mild to moderate with
  little or no long-term significance
• Criteria used cerebral, cardiac, renal and
  respiratory evaluation in first days after birth

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Perinatal asphyxia

• What is causing asphyxia?
• Disturbed delivery of oxygen or an increased
  demand, transient or continuous, acute and/or
  chronic.
• Maternal factors
• Maternal diseases
• Maternal anaemia
• Cigarette or drug abuse
• Multiple pregnancy (mono- or bichorionic)
• Foetal factors
• Placenta and umbilical cord problems

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Perinatal asphyxia

• A disturbed delivery of oxygen is often caused by
  placental and/or umbilical cord pathology

placenta
umbilical cord
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Perinatal asphyxia

• Delivery of oxygen in the placenta is by
  diffusion
• Dependent on
• Diffusion distance / Placental membrane distance
• Maternal blood flow
• Foetal blood flow
• Placental perfusion
• Surface area
• Metabolic activity of the placenta
• (placenta uses 50 of oxygen delivered to the
  foetus)

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Perinatal asphyxia

• Disturbed oxygen delivery, acute and/or chronic
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand , acute and/or chronic
• Diabetes mellitus
• Infection

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Disturbed oxygen delivery

• 1. Not enough or loss of placental parenchyma
• Placental bed pathology
• Severe chronic inflammation, chronic villitis
• Foetal thrombosis

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Placental bed pathology

• Placental bed pathology or insufficient formation
  of spiral arteries
• Placenta is too small / insufficient growth
• Infarcts
• (partial) abruption
• (Massive) subchorionic haematoma
• Accelerated maturation and distal villous
  hypoplasia
• Intervillus thrombi / haematoma

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Placental bed pathology

• Accelerated maturation histology
• Premature formation of terminal villi with
  syncytio-vascular membranes
• Stem villi with aspect normal for pregnancy
  duration
• Distal villous hypoplasia with long slender villi
  and increased space between villi
• Hyperchromasia of trophoblast
• Increased syncytial knotting

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31 weeks GA
Distal villous hypoplasia
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31 weeks GA
NRBC
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Disturbed oxygen delivery

• 1. Not enough or loss of placental parenchyma
• Placental bed pathology
• Severe chronic inflammation, chronic villitis
• Foetal thrombosis

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Loss of placental parenchyma

• Severe chronic villitis
• Destruction of villi, less mature villi
• Infiltrate with macrophages and T-cells
• High recurrence risk of IUGR and IUFD
• Recently some case reports with favourable
  outcome after treatment with corticosteroids and
  antithrombotics

Boog et al. J Gynecol Obstet Biol Reprod (Paris).
2006 Jun35(4)396-404. Combining corticosteroid
and aspirin for the prevention of recurrent
villitis or intervillositis of unknown etiology
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CD 3
CD 68
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Loss of placental parenchyma

• Chronic intervillositis
• Massive histiocytic infiltrate in maternal
  compartment
• Perinatal mortality 29, IUGR 77
• High recurrence risk of abortion, IUGR and IUFD
• Recently some case reports of favorable outcome
  after treatment with corticosteroids and
  antitrombotics

Boog et al. J Gynecol Obstet Biol Reprod (Paris).
2006 Jun35(4)396-404. Combining corticosteroid
and aspirin for the prevention of recurrent
villitis or intervillositis of unknown etiology
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CD 68
CD 3
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Disturbed oxygen delivery

• 1. Not enough or loss of placental parenchyma
• Placental bed pathology
• Severe chronic inflammation, chronic villitis
• Foetal thrombosis

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Loss of parenchyma, foetal trombosis

• Groups of avascular villi
• Histology similar as in IUFD
• Incidence
• Normal placentas 2
• Placentas with overcoiled cord 20
• Pre-eclampsia 20-30
• Macrosomia without DM 30-40
• Occasionally in association with CMV or
  trombophilia disorder

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CMV
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Perinatal asphyxia

• Disturbed oxygen delivery
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand
• Diabetes mellitus
• Infection

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Disturbed oxygen delivery

• 2. Diffusion distance too large between maternal
  and foetal circulation
• Massive perivillous fibrin deposition /gitter
  infarct
• Defective placental maturation

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Diffusion distance too long, fibrin

• Gitter infarct, maternal floor infarct
• Massive perivillous fibrin deposition
• High recurrence risk
• High risk of IUGR and IUFD
• Sometimes associated with VUE

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Disturbed oxygen delivery

• 2. Diffusion distance too large between maternal
  and foetal circulation
• Massive perivillous fibrin deposition /gitter
  infarct
• Defective placental maturation

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Diffusion distance too long, maturation

• Defective placental maturation
• Absence of terminal villi, no syncytio-vascular
  membranes
• Occurs after 35-36 weeks GA
• No IUGR
• Severe hypoxia and increase of NRBCs at the end
  of pregnancy

Stallmach et al. Rescue by birth defective
placental maturation and late fetal mortality.
Obstet Gynecol. 2001 Apr97(4)505-9.
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IUFD at 39 weeks GA IUFD at 40 weeks
GA Placenta with normal weight Placenta with low
normal weight
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Perinatal asphyxia

• Disturbed oxygen delivery
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand
• Diabetes mellitus
• Infection

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Disturbed oxygen delivery

• 3. Disturbance in the connection between foetus
  and placenta, umbilical cord pathology
• Too short, too long
• Knots
• Strangulation
• Thrombosis
• Haemangioma
• Meconium induced necrosis
• Coiling

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Too long with true knot
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strangulation
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Cord coiling

• Umbilical cord Whartons jelly, usually two
  arteries and a vein
• Whartons jelly hyaluronic acid, chondroitin
  sulphate, collagen
• Vessels form a helix,
• Normal coiling approximately between 1 and 3
  coils per 10 cm
• Abnormal coiling associated with severe perinatal
  morbidity and mortality

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Umbilical cord with undercoiling
Umbilical cord with overcoiling
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Cord coiling
Study of 885 placenta from UMCU, de Laat et al.
de Laat et al. Umbilical coiling index in normal
and complicated pregnancies. Obstet Gynecol. 2006
May107(5)1049-55.
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Cord coiling
Study of 885 placenta from UMCU, de Laat et al.
de Laat et al. Umbilical coiling index in normal
and complicated pregnancies. Obstet Gynecol. 2006
May107(5)1049-55.
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Cord coiling and mortality
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Cord coiling and maturation

• In some cases increased coiling was associated
  with insufficient formation of terminal villi
  with vascular membranes.

Pediatr Dev Pathol. 200710(4)293-9.
Hypercoiling of the umbilical cord and placental
maturation defect associated pathology? de Laat
MW, van der Meij JJ, Visser GH, Franx A, Nikkels
PGJ.
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Perinatal asphyxia

• Disturbed oxygen delivery
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand
• Diabetes mellitus
• Infection

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Perinatal asphyxia

• Disturbed oxygen delivery
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand
• Diabetes mellitus
• Infection

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Increased demand

• Diabetes mellitus
• Placental abnormalities associated with DM
• decreased maturation with decreased formation of
  terminal villi
• groups of immature villi and hydropic villi can
  be found
• increase of NRBCs
• other DM associated abnormalities are
  chorangiosis and fibrinoid necrosis of villous
  stroma
• (Less optimal delivery of oxygen by maternal
  hemoglobin)

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NRBC
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Perinatal asphyxia

• Disturbed oxygen delivery
• Not enough or loss of placental parenchyma
• Diffusion distance too large between maternal and
  foetal circulation
• Disturbance in the connection between foetus and
  placenta, umbilical cord pathology
• Miscellaneous, e.g. blood loss
• Increased demand
• Diabetes mellitus
• Infection

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HAVE FUN WITH YOUR PLACENTAS PETER NIKKELS