Stillbirth-Prof.Salah Roshdy

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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 1 National Center for Health Statistics

Definition and Incidence:

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:

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:

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:

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:

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:

Fetal conditions Multiple gestation IUGR Congenital anomaly Genetic abnormality Infection Hydrops

Placental Conditions:

Placental Conditions Cord accident Abruption PROM Vasa previa Fetomaternal hemorrhage Placental insufficiency

Maternal Risk Factors:

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:

Risk Factors in Developed Countries Non-Hispanic black race Nulliparity Advanced maternal age Obesity ACOG Practice Bulletin #102 March 2009

PowerPoint Presentation:

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:

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:

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:

Advanced Maternal Age Antepartum vs Intrapartum Maternal age (yrs) Rate per 1000 Saliu et al. J Obstet Gynaecol 2008;34:843

Obesity (BMI ≥ 30):

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:

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:

Chromosomal Abnormalities Method Success Rate Amniocentesis / CVS 85% Fetal tissue sampling 28% Korteweg et al 2008 Ob Gyn 111;865

Fetal Tissue:

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:

Chromosomal Abnormalities Korteweg et al 2008 Ob Gyn 111;865

Cord Accidents:

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 Re levant Co ndition at De ath Advantage-this system reduces the proportion of stillbirths currently categorised as unexplained.



Group A-Fetus :

Group A- Fetus





Group D-amniotic fluid:

Group D-amniotic fluid

Group E-Uterus:

Group E-Uterus

Group F-mother:

Group F-mother

Group G-Intrapartum:

Group G- Intrapartum

Group H-trauma:

Group H-trauma

Group I-unclassified:

Group I-unclassified

Wigglesworth Classification:

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 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:

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:

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:

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:

Antepartum Testing Protocol Weeks et al.

Antepartum Testing Protocol:

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 :

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:

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

PowerPoint Presentation:

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

Pregnancy after Stillbirth:

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”

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