stillbirth prof.salah roshdy

Work-Up of Stillbirth

An Evidence Review

Salah Roshdy,MD Professor of Obstetrics & Gynecology

Qassim College of Medicine,KSA

Sohag University , Egypt

Definitions • Fetal death

• Death prior to the complete expulsion of a product of

human conception, irrespective of the duration of

pregnancy .1

• Delivery of a fetus showing no signs of life

• Absence of breathing, heart beat, umbilical cord

pulsations, definitive voluntary movements

1National Center for Health Statistics

Definition and Incidence

• Birth of a baby who shows no evidence of life

• Heartbeat or breathing

• Definition varies from place to place

• In Australia from 20w or 400g

• WHO 500g- 22 w

• In the UK from 24w

• >350g in some states of US

• Rate varies from 5 per 1000 resource rich countries to 32 per 1000 in South Asia & Sub-Saharan Africa

Incidence

• > 3 million stillbirths each year worldwide

• 2007 rate of 6-7/1000 total births in US

• Rate of early stillbirth has remained stable

• Rate of late fetal loss has decreased by 29% since

1990

• African Americans have 2x stillbirth rate as

Caucasians

•DM, HTN, abruption, PPROM

Types of Stillbirth

• Macerated stillbirth

•Skin peeling implies that intrauterine fetal death has occurred >24 hours prior to delivery

• Fresh stillbirth

•Implies that fetal death occurred after the onset of labour and is perhaps a reflection of intrapartum care

•Better referred to as intrapartum death

Diagnosis of Stillbirth • Absence of fetal movements is the usual symptom

• Diagnosis requires real-time ultrasound

• Which should be available at all times

• Diagnosis based on absence of fetal heart motion will be wrong up to 20% of the time

• Both false positives and false negatives can occur

• Scalp clip ECG is a dramatic example

• Some mothers feel passive fetal movements

• So repeat ultrasound may be required

• May require colour Doppler in some cases

• Severe oligohydramnios

• Gross obesity

• Spalding’s sign & intrafetal gas sometimes

Work-Up of Stillbirth

An Evidence Review

Etiology

• Unknown in 25 – 60% of cases

• Identifiable causes can be attributed to

•Maternal conditions

•Fetal conditions

•Placental conditions

Maternal Conditions

• Prolonged pregnancy

• Diabetes (poorly controlled)

• SLE

• APAS

• Infection

• HTN

• Preeclampsia

• Eclampsia

• Hemoglobinopathy

• Rh disease

• Uterine rupture

• Maternal trauma or death

• Inherited thrombophilia

Fetal conditions

• Multiple gestation

• IUGR

• Congenital anomaly

• Genetic abnormality

• Infection

• Hydrops

Placental Conditions

• Cord accident

• Abruption

• PROM

• Vasa previa

• Fetomaternal hemorrhage

• Placental insufficiency

Maternal Risk Factors Developed Countries Developing Countries

Congenital and karyotypic anomalies Obstructed prolonged labor and

associated asphyxia, infection, injury

Growth restriction/placental anomalies Infection – syphilis and gram-negative

infection

Medical disease – diabetes, SLE, renal

disease, thyroid, cholestasis

Hypertensive disease – complications of

preeclampsia and eclampsia

Hypertensive disease, preeclampsia Congenital anomalies

Infection – Parvovirus B19, syphilis,

GBS, listeria Poor nutritional status

Smoking Malaria

Multiple gestation Sickle cell disease

Risk Factors in Developed Countries

• Non-Hispanic black race

• Nulliparity

• Advanced maternal age

• Obesity

ACOG Practice Bulletin #102 March 2009

24 - 27 weeks 28 - 37 weeks 37+ weeks

Infection (19%) Unexplained (26%) Unexplained (40%)

Abruptio placenta

(14%)

Fetal malnutrition

(19%)

Fetal malnutrition

(14%)

Anomalies (14%) Abruptio placenta

(18%)

Abruptio placenta

(12%)

Most Frequent Types of Stillbirth According to GA

Fretts and Usher. Contem Rev Ob Gyn 1997;9:173-9

Infection • Most common cause of stillbirth 24 – 27 weeks

• Contribution to stillbirth rate is difficult to define

• Some pathogens are clearly causally related

• Parvo B-19

• CMV

• Toxoplasmosis

• Some are associated with stillbirth but absent evidence of

causal relationship

• Ureaplasma urealyticum

• Mycoplasma hominis

• GBS

Infection • Most stillbirths occur in premature fetuses

• 19% of stillbirths < 28 weeks

• 2% of stillbirths at term

• No change despite widespread use of antibiotics

• Viral pathogens are the most common source of

hematogenous infection of the placenta

• Fetal death resulting from maternal infection is rare

• Diagnostic criteria are not well defined

Multiple Gestations • 19.6 / 1,000 stillbirth rate (4x singletons)

• Complications specific to multiple gestations

•TTTS

• Increased risk of common complications

• Placental abruption

•Fetal anomalies

•Growth restriction

• PET Cord accident

Advanced Maternal Age

• Lethal congenital and chromosomal anomalies

• Medical complications associated with age

•Multiple gestations

•HTN

•DM

• Unexplained fetal demise is the only type that

is statistically more common (late pregnancy)

Advanced Maternal Age

Antepartum vs Intrapartum

4.4

3.6

0.8

3.63.2

0.6

4.4

3.7

0.6

6.3

5.3

1

10.5

9.3

1.2

0

2

4

6

8

10

12

20 - 24 25 - 29 30 - 34 35 - 39 > 40

Stillbirth

Antepartum

Intrapartum

Maternal age (yrs)

Rat

e p

er 1

00

0

Saliu et al. J Obstet Gynaecol 2008;34:843

Obesity (BMI ≥ 30)

• Increased risk

• Behavioral, socioeconomic and obstetric factors

• Smoking, diabetes, preeclampsia

• Risk remains even after controlling for above

• Theories

• Perception of fetal movements

• Hyperlipidemia

• Apnea – hypoxia events

Obesity

BMI Stillbirth Rate per 1000

< 30 5.5 / 1000

30 – 39.9 8 / 1000

≥ 40 11 / 1000

Chromosomal Abnormalities • Abnormal karyotype found in 8 – 13% stillbirths

• > 20% with anatomic abnormalities or growth restriction

• 4.6% with normally formed fetuses

• Most common abnormalities

• Monosomy X (23%)

• Trisomy 21 (23%)

• Trisomy 18 (21%)

• Trisomy 13 (8%)

• Karyotypic analysis underestimates risk

Chromosomal Abnormalities

Method Success Rate

Amniocentesis / CVS 85%

Fetal tissue sampling 28%

Korteweg et al 2008 Ob Gyn 111;865

Fetal Tissue

• Umbilical cord – 32.1%

• Fascia lata – 29.9%

• Cartilage – 24.2%

• Fetal blood – 22.2%

• Pericardium – 0%

• Other tissue – 19.2%

•Placenta, skin, unknown

Chromosomal Abnormalities

Korteweg et al 2008 Ob Gyn 111;865

Cord Accidents

• 30% of normal pregnancies

• Account for only 2.5% of stillbirths in autopsy

case series

• Attribution requires

•Cord occlusion and hypoxic tissue on autopsy

•Exclusion of other causes

• Actual proportion remains uncertain

Thrombophilia

• Relationship with late fetal death is more consistent than

with early losses

• Have been associated with late loss but lack of evidence

of causal relationship

• Inconsistent studies

• OR range from 1.8 to 12

• Thrombophilias are not uncommon

• 15 – 25% of Caucasian populations

Thrombophilia

• Some but not all studies show a relationship with

adverse outcomes

• Most are retrospective or case-controlled

•Prospective longitudinal studies are needed

• Inappropriate or no controls

• No evaluation for other causes

• At least one type of thrombophilia is seen in 30%

of normal controls

Thrombophilia

Gonen R et al. Absence of association of inherited thrombophilia

with unexplained third-trimester intrauterine fetal death. AJOG

2005;192:742-6

Types

• Wigglesworth classification

• Aberdeen

• ReCoDe

• Fetal neonatal classification

ReCoDe

• Relevant Condition at Death

• Advantage-this system reduces the proportion

of stillbirths currently categorised as

unexplained.

ReCoDe

Catergories

Group A-Fetus

Group B-Umbilical cord

Group C-Placenta

Group D-Amniotic fluid

Group E-Uterus

Group F-Mother

Group G-Intrapartum

Group H-Trauma

Group I-unclassified

Group A-Fetus

Group A-Fetus

5.fetomaternal haemorrhage

6.GROWTH RESTRICTION

7.FETAL GROWTH RESTRICTION

1.lethal congenital abnormality 2.infection

2.1 acute

2.2 chronic

3.non-immune hydrops

4.isoimmunisation

Group B-UMBILICAL CORD

B-UMBILICAL CORD

1-PROPLAPSE

2-CONSTRICTING LOOP OR KNOT

3-VELAMENTOUS INSERTION

4-OTHER

Group C-PLACENTA

C-PLACENTA

1-ABRUTIO

2-PRAEVIA

3-VASA PRAEAVI

4-Other placental insuffiency

5-Other

Group D-amniotic fluid

D-amniotic fluid

1-chorioamnionitis

2-oilgohydramnios

3-polyhrdramnios

4-other

Group E-Uterus

E-Uterus

1-rupture

2-uterine anomalies

3-other

Group F-mother

Mother

1-diabetes

2-thyroid disorders

3-essential hypertension

4-hypertensive diseases in pregnancy

5-lupus or antiphospolipid syndrome

6-cholestasis

7-drug misuse

8-other

Group G-Intrapartum

G-Intrapartum

1-asphyxia

2-Birth trauma

Group H-trauma

H-trauma

1-External

2-iatrogenic

Group I-unclassified

I-unclassified

1-no relevant condition identified

2-no information available

Wigglesworth Classification

• Pathophysiological approach

• Category 1

Congenital defect/malformation (lethal or severe):

• Only lethal or potentially lethal congenital malformation should be included here.

• Category 2

Unexplained antepartum fetal death:

EXTENDED WIGGLESWORTH CLASSIFICATION

•Category 3’ Death from intrapartum ‘asphyxia’, ‘anoxia or ‘trauma’:

• This category covers any baby who would have survived but for some catastrophe occurring during labour.

•These babies will tend to be • normally formed, stillborn

• or with poor Apgar scores, • possible meconium aspiration

• or evidence of acidosis.

EXTENDED WIGGLESWORTH CLASSIFICATION

• Category 4 Immaturity:

•This applies to live births only,

•who subsequently die from

•structural pulmonary immaturity,

•surfactant deficiency,

• intra ventricular haemorrhage,

• or their late consequences - including chronic

lung damage.

EXTENDED WIGGLESWORTH CLASSIFICATION

•Category 5 Infection:

• This applies where there is clear microbiological evidence of infection that could have caused death

e.g. maternal infection with

G B S,

rubella,

parvovirus B19,

syphilis etc

EXTENDED WIGGLESWORTH CLASSIFICATION

• :Category 6 Other specific causes • Use this if there is a specific recognisable

• fetal,

• neonatal or

• paediatric condition not covered under the earlier categories.

• Examples include:

(1) fetal conditions; twin-to-twin transfusion and hydrops fetalis;

(2) neonatal conditions; • pulmonary haemorrhage,

• pulmonary hypoplasia

(3) paediatric conditions;

malignancy

acute abdominal catastrophe ( volvulus )

EXTENDED WIGGLESWORTH CLASSIFICATION

• Category 7 :

• Accident or non-intra partum trauma:

• Category 8 :

• Sudden infant death, cause unknown:

• Category 9 :

• Unclassifiable: To be used as a last resort. Details must be given if this option is ticked

Evaluation

Evaluation

• Fetal autopsy

• Single most useful test

• Examination of placenta, cord and membranes

• Karyotype evaluation

• 8 – 13% of stillbirths

• Comparative genomic hybridization

• Useful when fetal cells cannot be cultured

Infection • Autopsy and histologic evaluation of placenta,

membranes, and cord provide best evidence of infectious

etiology

• Value of routine cultures and serology is controversial

• Parvovirus serology

• Screening for syphilis

• TORCH titers questionable utility

• Placental culture problematic

• Incidence in live birth is unknown

• DNA test associated with false positives

Hematologic Etiology

• Fetal – maternal hemorrhage

•Kleihauer-Betke test

•Typically underestimates fetal cell count with

large FMH

• Red cell alloimmunization

•Indirect Coombs’ test

•Autopsy and placenta assessment useful

Thrombophilia

• Routine testing is controversial

• Evidence to support limited testing

•Evidence of placental insufficiency

•IUGR

•Placental infraction

•Recurrent fetal loss

•Personal or family history of thrombosis

Medical Complications

• Exclude clinically overt diabetes and thyroid

dysfunction

•GDM has stillbirth rate similar to normal

•Subclinical thyroid disease has not been

proven as cause of still birth

• Screening for subclinical disease is of unproven

benefit

Ante partum Surveillance

• Little evidence-based data to guide testing with

previous unexplained stillbirth

•32 – 34 weeks

•2 – 4 weeks before gestational age of

previous still birth

• Most subsequent pregnancies have a favorable

outcome

• Increased risk of iatrogenic prematurity

Antepartum Testing Protocol

Weeks et al.

• Protocol may not be appropriate for all previous stillbirths

•Nonrecurring conditions

•Perinatal infection

•Fetal anomalies

•Maternal trauma

•Stillbirths following OB complications that can recur but cannot be predicted

•Abruption

•Prolapse

•Uterine rupture

Antepartum Testing Protocol

ACOG Practice

• Little evidence-based data to guide antepartum

surveillance with prior unexplained stillbirth

• Antepartum testing may be initiated at 32 – 34 weeks

• Associated with potential morbidity and costs

•16.3% delivery at or before 39 weeks

•1% delivery before 36 weeks

Management of Stillbirth March 2009

ACOG Practice

• Antenatal testing before 37 weeks gestation

•1.5% rate of iatrogenic prematurity for

intervention based on false-positive test

• Excess risk of infant mortality due to late

preterm birth

•8.8 / 1000 at 32 – 33 weeks gestation

•3 / 1000 at 34 – 36 weeks gestation

Silver et al. Work-up of stillbirth: a review of the evidence. AJOG 2007;196:433-444.

Pregnancy after Stillbirth

• Early booking & careful dating

• Obstetric consultation

• Screen for gestational diabetes

• Monitor fetal growth if previous loss was associated with IUGR

• Large studies indicate an increased risk of stillbirth ≈12-fold independent of known recurrent causes

• Timing of delivery needs to take into account

• Risks to the baby

• Potential mode of delivery

• The time of the previous fetal loss

• The wishes of the patient

Prevention

• Early prenatal care

• Screen for

congenital

anomalies

• Optimize health,

weight gain

• Reduce multiples

• Improve awareness and

management of

decreased fetal

movement

• Individualize risk

assessment late in

pregnancy, include

race, age, obesity,

parity on treating a

women when she is

“post-dates”

THANK YOU