Uma apresem ntação muito boa sobre Patologia placentária, especialmente abordando alterações da maturação.

1. Placenta pathology associated with
maturation abnormalities and
late intra uterine foetal death.
PETER G.J. NIKKELS
Dept. of Pathology UMC Utrecht,
the Netherlands

2. Anatoom Frederick Ruysch, J. van Neck 1683

3. 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

4. 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.

5. 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.

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

7. 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

8. Placental weight
Ratio of placental weight and foetal weight

9. 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

10. Normal 13 weeks

11. Normal 13 weeks

12. 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

13. Normal 23 weeks

14. Normal 23 weeks

15. Normal 25 weeks

16. Normal 25 weeks

17. Normal 31 weeks

18. Normal 31 weeks

19. 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

20. Normal 35 weeks

21. Normal 35 weeks

22. Normal 40 weeks

23. Normal 40 weeks

25. Abnormal maturation of the placenta parenchyma
• Accelerated maturation
• Delayed maturation and dysmaturity

26. 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

28. Normal spiral arteries

29. Multinucleated trophoblast

30. Spiral artery

32. Acute atherosis in artery of membranes

33. 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

35. NRBC

37. Other abnormalities of utero-placental /
placental bed pathology
• Infarcts
• (partial) solutio
• (Massive) subchorionic haematoma
• Intervillus thrombi / haematoma

38. Recent infarct

39. Old infarct with central hemorrhage

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

41. recipiënt 30 weeks donor

42. 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

43. Delayed maturation, maternal diabetes
• Small groups of immature villi and hydropic villi
• Chorangiosis
• Fibrinoid necrosis of the villous stroma
• Increase of NRBCs

46. NRBC

48. Variable maturation example 1
Bichorionic twin placenta at 38 weeks
Small placental part heavy placental part

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

50. 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 Jun;35(4):396-404. [Combining corticosteroid and
aspirin for the prevention of recurrent villitis or intervillositis of unknown etiology]

52. CD 68 CD 3

53. 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 Jun;35(4):396-404. [Combining corticosteroid and
aspirin for the prevention of recurrent villitis or intervillositis of unknown etiology]

56. CD 68 CD 3

57. Loss of parenchyma, foetal trombosis
• Groups of avascular villi
• Histology similar as in IUFD
• Incidence
– Normal placenta’s 2%
– Placenta’s with overcoiled cord 20%
– Pre-eclampsia 20-30%
– Macrosomia without DM 30-40%
• Occasionally in association with CMV or
trombophilia disorder

63. CMV

64. 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

68. 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 NRBC’s at the
end of pregnancy
Stallmach et al. Rescue by birth: defective placental maturation and
late fetal mortality. Obstet Gynecol. 2001 Apr;97(4):505-9.

71. IUFD at 39 weeks GA IUFD at 40 weeks GA
Placenta with normal weight Placenta with low normal weight

72. 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

73. Placenta abnormalities and time of death
Time between death abnormalities in the placenta
and birth
6-36 hr Nuclear dust in foetal circulation and
villous stroma
12 hr Degeneration of smooth muscle cells
of the umbilical cord vessel wall
2 days Focal obliteration of vessels in the
placental parenchyma
2 weeks Extensive obliteration of vessels and
villous stromal fibrosis

74. IUFD 6-36 hr
Nuclear dust

75. IUFD 12 hr -
Degeneration of smooth muscle

76. IUFD 12 hr -
granulocytes
Degeneration of smooth muscle cells

77. IUFD 2 days - weeks

78. IUFD 2 days - weeks
Loss of basophilia in smooth muscle cells

79. IUFD 2 days - weeks

80. IUFD 2 days - weeks

81. Umbilical cord pathology
• Too short, too long
• Knots
• Strangulation
• Thrombosis
• Haemangioma
• Meconium induced necrosis
• Coiling

83. Too long with true knot

84. strangulation

85. Cord coiling
• Umbilical cord: Wharton’s jelly, usually two arteries and
a vein
• Wharton’s 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

86. Umbilical cord with Umbilical cord with
undercoiling overcoiling

87. Cord coiling
Study of 885 placenta from UMCU, de Laat et al.
Undercoiled cords
IUFD
Apgarscore < 7 after 5 minutes
Congenital / chromosomal abnormality
Trisomie (13 / 18 / 21)
Premature birth, not corrected
Premature birth corrected for amnionitis
Single umbilical artery
0.1 0.5 1 5 10 20 30
Odds Ratio (95% CI)
de Laat et al. Umbilical coiling index in normal and complicated pregnancies.
Obstet Gynecol. 2006 May;107(5):1049-55.

88. Cord coiling
Study of 885 placenta from UMCU, de Laat et al.
Overcoiled cords
IUFD
asfyxia
Umbilical arteriel pH < 7.05
IUGR
Trisomie (13 / 18 / 21)
Congenital / chromosomal abnormality
Single umbilical artery
0.1 0.5 1 5 10 20 30
Odds Ratio (95% CI)
de Laat et al. Umbilical coiling index in normal and complicated pregnancies.
Obstet Gynecol. 2006 May;107(5):1049-55.

90. Cord coiling and mortality
Perinatal Congenital Solutio, small Unknown
Mortality anomaly placenta or
prematurity
Undercoiled 44 % 48 % 40 % 12 %
(133) 58/133 28/58 23/58 7/58
Normal 22 % 46 % 49 % 5%
(492) 110/492 51/110 53/110 6/110
Overcoiled 38 % 39 % 24 % 37 %
(99) 38/99 15/38 9/38 14/38

93. HAVE FUN WITH YOUR PLACENTAS
PETER NIKKELS