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

PETER G.J. NIKKELS

Dept. of Pathology UMC Utrecht,

the Netherlands

Anatoom Frederick Ruysch, J. van Neck 1683

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

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.

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.

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

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

Placental weight

Ratio of placental weight and foetal weight

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 cavityYolk sac

Normal 13 weeks

Normal 13 weeks

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

Normal 23 weeks

Normal 23 weeks

Normal 25 weeks

Normal 25 weeks

Normal 31 weeks

Normal 31 weeks

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

Normal 35 weeks

Normal 35 weeks

Normal 40 weeks

Normal 40 weeks

Abnormal maturation of the placenta parenchyma

• Accelerated maturation

• Delayed maturation and dysmaturity

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

Normal spiral arteries

Multinucleated trophoblast

Spiral artery

Acute atherosis in artery of membranes

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

NRBC

Other abnormalities of utero-placental / placental bed pathology

• Infarcts

• (partial) solutio

• (Massive) subchorionic haematoma

• Intervillus thrombi / haematoma

Recent infarct

Old infarct with central hemorrhage

Accelerated maturation

• Recipiënt of twin-twin transfusion syndrome

• CS at 30 weeks because of worsening foetal condition after

multiple amniotic drainage

recipiënt 30 weeks donor

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

Delayed maturation, maternal diabetes

• Small groups of immature villi and hydropic villi

• Chorangiosis

• Fibrinoid necrosis of the villous stroma

• Increase of NRBCs

NRBC

Variable maturation example 1

Bichorionic twin placenta at 38 weeks

Small placental part heavy placental part

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

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]

CD 3CD 68

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]

CD 68 CD 3

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

CMV

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

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.

IUFD at 39 weeks GA IUFD at 40 weeks GAPlacenta with normal weight Placenta with low normal weight

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

Placenta abnormalities and time of death

Time between deathand birth

abnormalities in the placenta

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

Nuclear dust

IUFD 6-36 hr

Degeneration of smooth muscle

IUFD 12 hr -

Degeneration of smooth muscle cells

granulocytes

IUFD 12 hr -

IUFD 2 days - weeks

IUFD 2 days - weeks

Loss of basophilia in smooth muscle cells

IUFD 2 days - weeks

IUFD 2 days - weeks

Umbilical cord pathology

• Too short, too long

• Knots

• Strangulation

• Thrombosis

• Haemangioma

• Meconium induced necrosis

• Coiling

Too long with true knot

strangulation

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

Umbilical cord with undercoiling

Umbilical cord with overcoiling

Cord coiling

0.1 1 10

Single umbilical artery

Premature birth corrected for amnionitis

Premature birth, not corrected

Trisomie (13 / 18 / 21)

Congenital / chromosomal abnormality

Apgarscore < 7 after 5 minutes

IUFD

Odds Ratio (95% CI)

20 300.5 5

Undercoiled cords

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 May;107(5):1049-55.

Cord coiling

1 100.1

Single umbilical artery

Congenital / chromosomal abnormality

Trisomie (13 / 18 / 21)

IUGR

Umbilical arteriel pH < 7.05

asfyxia

IUFD

Odds Ratio (95% CI)

20 300.5 5

Overcoiled cords

de Laat et al. Umbilical coiling index in normal and complicated pregnancies.Obstet Gynecol. 2006 May;107(5):1049-55.

Study of 885 placenta from UMCU, de Laat et al.

Perinatal Mortality

Congenital anomaly

Solutio, small placenta or prematurity

Unknown

Undercoiled (133)

44 % 58/133

48 % 28/58

40 % 23/58

12 % 7/58

Normal (492)

22 % 110/492

46 % 51/110

49 % 53/110

5 % 6/110

Overcoiled (99)

38 % 38/99

39 % 15/38

24 % 9/38

37 % 14/38

Cord coiling and mortality

HAVE FUN WITH YOUR PLACENTASPETER NIKKELS