Placenta pathology associated with maturation abnormalities and late intra uterine foetal death'

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Placenta pathology associated with maturation
abnormalities andlate intra uterine foetal death.

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

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Anatoom Frederick Ruysch, J. van Neck 1683
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Perinatal death

• Perinatal death occurs in 1,5 of all birth
• Frequency of stillbirth in western Europe
  approximately 2,2-4,4 / 1000 life birth
• Riskfactors
• multiple pregnancy, prematurity, first or second
  pregnancy, hypertension or pre-eclampsia of the
  mother, congenital abnormalities (20-40) and
  inflammation

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Causes of IUFD

• Placenta or umbilical cord pathology 62
• Congenital abnormalities 17
• Intra-uterine infection 2
• Trauma 1
• Miscellaneous (tumors, storage disorder) 3
• Unexplained (12/47 no placenta) 15
• Horn et al. Identification of the causes of
  intrauterine death during 310 consecutive
  autopsies. European Journal of Obstetrics
  Gynaecology and Reproductive Biology 113 (2004),
  134-8.
• University Hospital Leipzig, IUFD from 22-42 6/7
  weeks.

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Causes of IUFD

• Placenta or umbilical cord pathology 62
• Utero-placental pathology 38
• Dysmaturity of parenchym 23
• Inflammation 14
• Umbilical cord 22
• (Compression, bleeding, haematoma)
• Miscellaneous 3
• (TTTS, chorangioma etc.)
• Horn et al. Identification of the causes of
  intrauterine death during 310 consecutive
  autopsies. European Journal of Obstetrics
  Gynaecology and Reproductive Biology 113 (2004),
  134-8.
• University Hospital Leipzig, IUFD van 22-42 6/7
  weeks.

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Main cause of IUFD

• Disturbance in delivering oxygen to the foetus
• Not enough or loss of parenchyma
• Small placenta
• Placental infarcts
• Chronic inflammation
• Foetal thrombosis
• Diffusion distance too long
• Fibrin deposition
• Abnormal maturation
• Umbilical cord pathology

Placental bed pathology
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Normal development of the placenta parenchyma

• Placenta the fastest growing organ of the human
  body
• from 1 tot 5 x 1010 cells in 38 weeks

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Placental weight Ratio of placental weight and
foetal weight
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Normal development of placental parenchyma

• FIRST TRIMESTER
• In first 12 weeks only mesenchymal villi
• Development of immature intermediate villi with
  two layers of trophoblast
• Development of stem villi with central fibrous
  core

Amniotic cavity
Yolk sac
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Normal 13 weeks
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Normal 13 weeks
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Normal maturation of placental parenchyma

• SECOND TRIMESTER
• Parenchyma consists of immature intermediate
  villi, there is some development of mature
  intermediate villi
• Largest variation in villus shape and diameter
• Mesenchymal stroma alongside stem villi
  disappears and occasionally some fibrinoid
  material can be seen

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Normal 23 weeks
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Normal 23 weeks
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Normal 25 weeks
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Normal 25 weeks
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Normal 31 weeks
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Normal 31 weeks
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Normal maturation of the placental parenchyma

• THIRD TRIMESTER
• Development of terminal villi
• At 40 weeks 40 of the villous volume are
  terminal villi
• Terminal villi have syncytio-vascular membranes
• Stem villi are covered with fibrinoid material

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Normal 35 weeks
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Normal 35 weeks
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Normal 40 weeks
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Normal 40 weeks
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Abnormal maturation of the placenta parenchyma

• Accelerated maturation
• Delayed maturation and dysmaturity

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Accelerated maturation

• Utero-placental pathology
• decreased blood flow to the placenta due to
  abnormalities in spiral arteries
• maternal hypertension or pre-eclampsia
• Sometimes also abnormalities in vessels in the
  membranes or in the decidua (acute atherosis)
• Multiple pregnancy placenta (two or more)
• Recipient of the twin-transfusion syndrome

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Normal spiral arteries
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Multinucleated trophoblast
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Spiral artery
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Acute atherosis in artery of membranes
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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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NRBC
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Other abnormalities of utero-placental /
placental bed pathology

• Infarcts
• (partial) solutio
• (Massive) subchorionic haematoma
• Intervillus thrombi / haematoma

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Recent infarct
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Old infarct with central hemorrhage
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Accelerated maturation

• Recipiënt of twin-twin transfusion syndrome
• CS at 30 weeks because of worsening foetal
  condition after multiple amniotic drainage

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recipiënt 30 weeks donor
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Delayed maturation and dysmaturity

• Less terminal villi as expected.
• From 30 weeks onwards terminal villi
  recognisable.
• At 40 weeks 40 of the villi are terminal villi.
• Maternal diabetes
• Macrosomia without diabetes
• Chronic villitis
• Defective placental maturation
• Congenital and / or chromosomal abnormality
• Donor of twin-twin transfusion syndrome
• Foetal anaemia of low colloid osmotic pressure
• Foetal cardiac decompensation

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Delayed maturation, maternal diabetes

• Small groups of immature villi and hydropic villi
• Chorangiosis
• Fibrinoid necrosis of the villous stroma
• Increase of NRBCs

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NRBC
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Variable maturation example 1
Bichorionic twin placenta at 38 weeks Small
placental part heavy placental part
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Main cause of IUFD

• Disturbance in delivering oxygen to the foetus
• Not enough or loss of parenchyma
• Small placenta
• Placental infarcts
• Chronic inflammation
• Foetal thrombosis
• Diffusion distance too long
• Fibrin deposition
• Abnormal maturation
• Umbilical cord pathology

Placental bed pathology
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Loss of parenchyma, chronic inflammation

• Severe villitis of unknown etiology
• Destruction of villi, less mature
• Infiltrate with macrophages and T-cells
• High recurrence risk of IUGR and IUFD
• Recently some case reports with 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 3
CD 68
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Loss of parenchyma, chronic inflammation

• 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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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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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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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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Other placental causes of IUFD

• Haemorrhage feto-maternal transfusion
• Usually no abnormalities visible in the placenta
• Inflammation
• Ascending infection e.g. bacterial
• Chorioamnionitis and funisitis
• Acute villitis and microabscesses
• Haematogenous infection e.g. viral,
  toxoplasmosis
• Chronic villitis

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Placenta abnormalities and time of death
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IUFD 6-36 hr
Nuclear dust
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IUFD 12 hr -
Degeneration of smooth muscle
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IUFD 12 hr -
granulocytes
Degeneration of smooth muscle cells
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IUFD 2 days - weeks
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IUFD 2 days - weeks
Loss of basophilia in smooth muscle cells
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IUFD 2 days - weeks
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IUFD 2 days - weeks
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Umbilical cord pathology

• Too short, too long
• Knots
• Strangulation
• Thrombosis
• Haemangioma
• Meconium induced necrosis
• Coiling

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placenta
umbilical cord
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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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HAVE FUN WITH YOUR PLACENTAS PETER NIKKELS