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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