Stillbirth Management: The ACOG SMFM Consensus Document

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

  • 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
  • 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
    • Obesity: Prepregnancy BMI of 35.0 to 39.9, consider beginning weekly antenatal fetal surveillance by 37w0d | prepregnancy BMI ≥40, consider beginning weekly antenatal fetal surveillance by 34w0d (ACOG PB 230)
    • 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 230: Obesity in Pregnancy

COVID-19 and Risk for Stillbirth and Preterm Birth

PURPOSE:

  • Khalil et al. (JAMA, 2020) analyzed the association between COVID-19 and risk for stillbirth and preterm delivery        

METHODS:

  • Retrospective cohort study
    • St George’s University Hospital, London (UK)
  • Compared 2 time periods
    • Prepandemic: October 1, 2019, to January 31, 2020
    • Pandemic (following first reported cases in UK of COVID-19): February 1, 2020, to June 14, 2020
  • Outcomes
    • Stillbirth | Preterm birth | Cesarean delivery | NICU admission
    • Repeat analysis performed with exclusion of terminations for fetal anomalies (IN UK, stillbirth includes late termination ≥24 weeks)

RESULTS:

  • Prepandemic
    • 1681 births | 1631 singletons | 22 twins | 2 triplets
  • Pandemic period
    • 1718 births: 1666 singleton | 26 twins
  • Nulliparity was less common during the pandemic period (P < .001)
    • Prepandemic: 52.2%
    • Pandemic: 45.6%
  • Fewer pregnancies were complicated by hypertension during the pandemic period (P = .005)
    • Prepandemic: 5.7%
    • Pandemic period: 3.7%
  • Stillbirth incidence was increased during the pandemic period
    • Prepandemic: 2.38 per 1000 births (n=4)
    • Pandemic: 9.31 per 1000 births (n=16)
    • Difference: 6.93 per 1000 births (95% CI, 1.83-12.0; P = .01)
  • Stillbirth incidence remained elevated after exclusion of terminations for anomalies
    • Prepandemic: 1.19 per 1000 births
    • Pandemic: 6.98 per 1000 births
    • Difference: 5.79 (95% CI, 1.54-10.1; P = .01)
  • There were no significant differences identified for the following outcomes
    • Preterm deliveries (<37 weeks)
    • NICU admission
  • No cases of stillbirth were associated with COVID-19
    • None of the mothers had symptoms associated with COVID-19
    • No placental or postmortem exams suggested of COVID-19
    • Note: Universal testing for SARS-CoV-2 only began May 28, 2020

CONCLUSION:

  • Stillbirth rates were increased during the pandemic vs prepandemic period
    • One important limitation noted by authors is lack of data on cause of the stillbirth
  • Possible reasons for increase in stillbirth rate
    • Increase may still be due to SARS-CoV-2 infection in asymptomatic women (who would not have been tested)
    • Women may have deferred care due to COVID-19 concerns (e.g. delaying care to avoid infection)
    • Possible change in practice resulting in fewer antenatal visits or ultrasound assessments
    • Chance: Study time frame was short | If study was longer, difference perhaps would resolve
    • Hospital may have received more referrals 

Learn More – Primary Sources:

Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic