asfiksia perinatal

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Birth asphyxiaDefinition and Causes

PETER G.J. NIKKELSDept. of Pathology UMC Utrecht,

the Netherlands

21st European Congress of PathologySeptember 08-13, 2007Istanbul, 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 > 5 minutes)

– arterial cord blood pH (pH < 7.0)

– base deficit (> -12 -16 mmoll/l)

– late decelerations on foetal monitoring or meconiumstaining

– 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 > 12 mmoll/l 2%Umbilical artery base deficit > 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 asphyxiaA disturbed delivery of oxygen is often caused by placental

and/or umbilical cord pathology

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Perinatal asphyxiaDelivery 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 asphyxiaDisturbed oxygen delivery, acute and/or chronic

1. Not enough or loss of placental parenchyma

2. Diffusion distance too large between maternal and foetal circulation

3. Disturbance in the connection between foetus and placenta, umbilical cord pathology

4. Miscellaneous, e.g. blood loss

Increased demand , acute and/or chronic

1. Diabetes mellitus

2. Infection

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Disturbed oxygen delivery


• 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 pathologyAccelerated 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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Distal villous hypoplasia

31 weeks GA

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NRBC

31 weeks GA

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

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CD 3CD 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 aftertreatment 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]

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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 placenta’s 2%

– Placenta’s with overcoiled cord 20%

– Pre-eclampsia 20-30%

– Macrosomia without DM 30-40%

• Occasionally in association with CMV or trombophiliadisorder

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CMV

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Perinatal asphyxiaDisturbed oxygen delivery:





Increased demand


2. Infection

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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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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-vascularmembranes

• 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.

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

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Increased demand


2. Infection

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• 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: 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

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Umbilical cord withundercoiling

Umbilical cord withovercoiling

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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.

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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.

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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

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Cord coiling and maturationIn some cases increased coiling was associated with

insufficient formation of terminal villi with vascular membranes.

Pediatr Dev Pathol. 2007;10(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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Increased demand


2. Infection

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Increased demand


2. Infection

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Increased demandDiabetes 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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Increased demand


2. Infection

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HAVE FUN WITH YOUR PLACENTASPETER NIKKELS

asfiksia perinatal

Documents

perinatal asphyxia criteria

asphyxia definition

duration of asphyxia

foetal circulation blood

severe metabolic acidosis

foetal monitoring

foetal circulation3

different criteria