SUMMARY:

Stillbirth is a devastating adverse pregnancy outcome, occurring in 1 out of 160 deliveries in the United States.  It is often associated with non-modifiable, but common, risk factors such as race and pre-existing co-morbidities. Even after thorough evaluation, often the underlying cause remains unknown.  ACOG has provided a comprehensive consensus document that addresses risk factors, causes, and management that includes bereavement support

• Background & Definition of Stillbirth
• Social and Demographic Factors Affecting Stillbirth
• Causes of Stillbirth
• Stillbirth Evaluation Algorithm
• Key Components of Stillbirth Evaluation
• Management of a Stillbirth
• Principles of Bereavement Care
• Recurrence Risk and Antepartum Surveillance

Background & Definition of Stillbirth

• Fetal death is defined by the US National Center for Health Statistics as the delivery of a fetus showing no signs of life
• Recommended to report all fetal deaths at ≥20 weeks or 350 grams (50%ile for GA 20 weeks) | Reporting varies among states
• Excluded from stillbirth statistics
  • Terminations of pregnancy for fetal anomalies
  • Pre-viable premature rupture of membranes
• From 2013
  • Overall rate 5.95 per 1,000 live births
  • Similar rate between early (3 per 1,000 for 20 to 27 weeks) and late (2.97 per 1,000 for >28 weeks)
• Rate calculation
  • Calculated via number of stillbirths per 1,000 live births plus stillbirths
  • Using a denominator of those pregnant at a given gestational age would provide clinically valuable ‘prospective fetal mortality rate’

Social and Demographic Factors Affecting Stillbirth

• Demographics
  • Race | Multiple Gestations | Past history of stillbirth | Male sex of fetus | Younger (<15) or Older (>35) maternal age
  • Older age: due to lethal congenital and chromosomal abnormalities | Increased risk if nulliparous and AMA
  • Younger age: Stillbirth rate for teenagers <15 is 15.88 per 1,000 (based on large US population-based cohorts)
  • Late-term pregnancies (vs 37 weeks)
    • Relative risk at 41 weeks: 2.9
    • Relative risk at 42 weeks: 5.1
• Co-morbidities
  • Diabetes (both pregestational and GDM | Hypertensive disorders | Obesity (BMI>30) and excessive weight gain | Substance abuse | IVF | Late-term & Post-term gestational age
  • Diabetes and hypertension account for 2 to 5x increased risk
  • Thrombophilia: Acquired thrombophilia (anti-phospholipid syndrome) associated with stillbirth but inherited thrombophilias generally are not
  • Substance abuse and smoking
    • Dose-related response, especially >10 cigarettes/day
    • Significantly associated with abruption and stillbirth

Note: Obesity is the most common modifiable risk factor | However, ACOG states that “There is no evidence showing a clear improvement in pregnancy outcome with antepartum surveillance, and a recommendation cannot be made for or against routine antenatal fetal surveillance in obese patients” (Practice Bulletin 156)

• Race: Non-Hispanic black women
  • Rate of stillbirth is approximately twice rate of other groups (10.53 per 1,000)
  • highest discrepancy at 20 to 27 weeks of gestation
  • Causes
    • Higher rates of co-morbidities (e.g. diabetes, hypertension)
    • PROM
    • Bias and racism
• Multiple Gestations
  • Risk approximately 2.5x that of singletons (14.07 vs 5.65 per 1000)
  • Risk of stillbirth with monochorionic > dichorionic
  • Triplets: 30.53 per 1,000
  • Causes
    • Complications unique to multiples such as twin transfusion
    • Congenital anomalies
    • FGR
• Past OB History
  • Increased risk in subsequent pregnancy: Approximately 5x
  • Previous adverse pregnancy outcomes such as preterm delivery, growth restriction, preeclampsia: Increases risk 1.7 to 2x
  • Not associated with prior cesarean section

Causes of Stillbirth

Perinatal Complications

• FGR: Especially <3%tile
• Abruption: 5 to 10% of stillbirths

Infection

• 10-20% of stillbirths
  • Most common: GBS, E.coli, Listeria monocytogenesis and syphilis
• Serology for toxoplasmosis, rubella, CMV, herpes not recommended

Umbilical Cord Events

• 10% of stillbirths
  • Examples: Vasa previa | Cord entrapment | Occlusion

Note: Nuchal cord not associated with increased risk of stillbirth

Genetics

• Chromosomal anomalies
  • 6 to 13% stillbirths | >20% if anatomic abnormalities are present
  • Most common chromosomal culprits: Trisomy 21 (31%) | Trisomy 18 (22%) | Trisomy 13 (8%) | Monosomy X (22%)
  • Because cells may no longer be viable at time of test, culture failure will often occur limiting utility of standard karyotyping | Amniocentesis or CVS prior to delivery can increase chance of obtaining a result because amniocytes and placental cells may still be viable (85% vs 28% yield)
  • Microarray analysis (preferred): Based on DNA technology and therefore does not require living tissue: Increases diagnostic yield to 41.9% of all stillbirths
• Single gene disorders: Some single gene disorders are associated with stillbirth
  • Routine testing not currently recommended
  • Clinical scenario and family history are used to guide molecular testing and workup
• Birth defects
  • Dysmorphic features and/or skeletal anomalies: 20%
  • Major malformations: 15 to 20%

Stillbirth Evaluation  Algorithm

• All stillbirths
  • Fetal autopsy (can include imaging) | Provides additional clinical information in approximately 30% of cases   
  • Placental pathology (gross and microscopic) including cord and membranes | Provides additional clinical information in approximately 30% of cases
  • Genetics | Abnormalities seen in 8% of cases
• If no other cause identified – add
  • Antiphospholipid antibody testing
  • Fetal-maternal hemorrhage testing
  • Other tests as indicated
• FGR or hypertensive disorder – add
  • Antiphospholipid antibody testing
  • Fetal-maternal hemorrhage testing
  • Other tests as indicated
• Suspected fetal anomaly – add
  • Other testing including molecular genetics based on findings
• Intrapartum stillbirth – add
  • Antiphospholipid antibody testing
  • Fetal-maternal hemorrhage testing
  • Other tests as indicated
• Preterm labor | Chorioamnionitis | PPROM | Other Clinical scenarios – add
  • Other tests as indicated based on clinical scenario
  • “Remaining tests of limited utility”

KEY POINTS:

Key Components of Stillbirth Evaluation

• Fetus & Placenta
  • Weight | HC | Fetal length | Placenta weight
  • Document abnormalities
• Obtain genetics consent: Collect ≥1 of the following specimens in sterile tissue medium of LR (not formalin fixative)   
  • Amniotic fluid (preferred if delivery not imminent)  
  • Placental block 1cm x 1cm taken from below cord insertion site
  • Umbilical cord segment of 1.5cm
  • Internal fetal specimen – costochondral junction or patella | Do not send skin (cells usually will not grow)
  • Obtain consent for fetal autopsy
    • If consent not given: Limit investigation to external evaluation (by trained perinatal pathologist)
    • May include photographs and imaging (X-ray, ultrasound)
  • Maternal evaluation
    • Obstetric history (previous and present)
    • Comorbidities
    • Exposures: Smoking | Alcohol | Drug or medication use
    • Genetics work-up including 3 generation pedigree
    • Personal or family history: Arrhythmias | Including sudden death (e.g. for for prolonged QT syndrome)
  • Lab testing
    • Kleihauer-Betke or flow cytometry at time of stillbirth
    • Syphilis  
    • Lupus anti-coagulant | Anticardiolipin | Beta-2 glycoprotein IgG and IgM antibodies (retest at 12 weeks if positive)
    • Based on clinical indication: Indirect Coombs | Glucose screening for LGA | Toxicology if abruption or suspected drug use

Management of a Stillbirth

• Method and timing of delivery depend upon gestational age and maternal preference
  • Timing of delivery is not critical because coagulopathies uncommon
• Second trimester
  • Medical induction of labor: D&C may be necessary for placental removal
  • D&E: May limit efficacy of autopsy
• <20 weeks
  • Mifepristone: 200 or 600mg PO plus misoprostol
    • Evidence limited between 24 and 28 weeks
• <28 weeks gestation
  • Vaginal misoprostol: 400 to 600mcg q3 to 6 hours | <400mcg associated with decreased efficacy
  • Addition of mifepristone 200 or 600mg PO 24 to 48 hours before misoprostol
    • <20 weeks: Good evidence to add  
    • 24 to 28 weeks: Evidence limited | reduces time to delivery but doesn’t improve overall efficacy compared to misoprostol alone
  • ≥28 weeks: Use standard obstetric induction protocols
• Prior uterine scar
  • < 24 weeks: Vaginal misoprostol
  • 24 to 28 weeks: Further research required to determine safety and optimum dose “in whom lower doses of misoprostol (200 micrograms per dose) may be preferred”
  • ≥28 weeks: Use standard obstetric induction protocols including cervical ripening with Foley
  • Women with increased risk of uterine rupture (e.g. classical): “Repeat cesarean delivery is a reasonable option” | Discuss risks and benefits

Principles of Bereavement Care

• Support services: Consider referral to a bereavement counselor, peer support group, or mental health professional
  • Feelings of guilt and/or anger are common
• Additional considerations
  • Good communication | Shared decision making | Recognition of parenthood | Acknowledge grief
  • Be aware of
    • Options including burials, cremation, and funerals | Emotional and practical support | Health professionals trained in bereavement care | Importance of self-care for health professionals

Recurrence Risk and Antepartum Surveillance

• Evidence is limited however appears to be increased risk for recurrence
• Antepartum surveillance
  • Comorbidities: Use recommended management guidelines
  • Previous stillbirth ≥32w0d: Once or twice weekly beginning  at 32w0d or 1 to 2 weeks prior to gestational age of last stillbirth
  • Previous stillbirth <32w0d:  Individualize | Consider potential morbidity and cost for delivery due to false positive results
  • Growth ultrasound at 28 weeks to screen for fetal growth restriction
• Fetal kick counts
  • Encourage awareness of fetal movement patterns
  • Shared decision making recommended due to lack of data to make specific recommendations
• Timing of delivery
  • 39w0d
  • If other comorbidities present: Time delivery as recommended for particular complication (see ‘Related ObG Entries’ below)
  • Maternal anxiety may warrant early term delivery (37 0/7 to 38 6/7) in women who are educated regarding increased fetal risks
  • Amniocentesis to confirm fetal lung maturity is generally not recommended

Note: While screening for acquired thrombophilia (lupus anticoagulant, IgG and IgM for both anticardiolipin and β2-glycoprotein antibodies) is recommended, routine aspirin use to prevent stillbirth is not advised due to lack of evidence for efficacy

Learn More – Primary Sources:

Obstetric Care Consensus No 10: Management of Stillbirth, March 2020

ACOG Practice Bulletin 156: Obesity in Pregnancy

Related ObG Topics:

How Many Stillbirths Could Be Prevented by Induction in Low-Risk Women at 39 Weeks?

Results from the MiNESS Trial: Does Supine vs Left-Sided Sleeping Position Impact Risk of Stillbirth?

Can Daughters Inherit a Predisposition Towards Stillbirth from Their Mothers?

Stillbirth Risks from 37 Weeks and Beyond

How Well Can Perceived Changes in Fetal Movements Predict Stillbirth?

Does Duration of Sleep in Late Pregnancy Impact Stillbirth Risk?

What Percentage of Stillbirths are Caused by Infection?

Has the Broad Adoption of the ‘39-Week Rule’ Impacted Stillbirth and Infant Mortality Rates?

ACOG Recommendations: When to Deliver Medically Complicated Pregnancies