San Gabriel Valley Perinatal Medical Group
  Specialists in High Risk Pregnancy
  Evaluation of the Stillbirth
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The purpose of this guideline is to help identify high risk populations and aid in the development of risk-reducing interventions. In addition it is hoped that families will be provided with information about the cause of death, as well as emotional guidance.

Gundersen Lutheran Medical Foundation in La Crosse, Wisconsin

Stillbirth may be suspected when the mother ceases to feel fetal movement, and the obstetrician is unable to hear fetal heart tones.  When the question of fetal death arises during labor, an internal fetal monitor can be applied to the presenting part. Maternal cardiac electrical activity can be transmitted through a dead fetus, however, so the rate and rhythm on the tracing should be compared with those of the mother.

BACKGROUND

Data from the National Center for Health Statistics showed a fetal mortality rate of 6.5 per 1000 births in 2001 [1].

     Risk factors associated with stillbirth [1,2-4]

  • Maternal age (both high and low)
  • Unmarried status
  • Male fetal sex
  • Multiple gestation.
  • Multiparity ( > 5)
  • Nonvertex presentation

     Maternal diseases associated with increased risk to the fetus [2,21,22]

  • Chronic hypertension
  • Preeclampsia
  • Metabolic diseases (especially uncontrolled diabetes mellitus)
  • Viral infections
    • Parvovirus B19,  cytomegalovirus, and Coxsackie virus
  • Bacterial infections
    • Listeria monocytogenes, Escherichia coli, group B streptococci, and Ureaplasma urealyticum
  • Other
    • Toxoplasma gondii

     Other Causes [3,5-8]

  • Congenital malformations (up to 35%)
  • IUGR
  • Placental abruption
  • Placental pathology
  • Nuchal cord or knotted cord
  • Oligohydrmanios
  • PROM

EVALUATION [3,9,10]

Approximately one fourth of stillbirths will remain unexplained despite an adequate evaluation [1].

  • Fetal death should be confirmed by ultrasound.
  • Consideration should be given to obtaining amniotic fluid for cytogenetics if not already done [11]. Obtain 15-25 ml of amniotic fluid into 2-3 sterile tubes.
  • Review relevant maternal and family history to help identify specific risk factors:
    • History of current pregnancy, specifically:
      Family history, particularly pregnancy losses, consanguinity, mental retardation, diabetes, congenital anomalies

     Maternal laboratories

  • On all mothers draw random glucose, CBC with platelet count, PT, PTT, fibrinogen, antibody screen, VDRL, urine toxicology screen.
  • The value of nonselective (TORCH) viral cultures and serologies varies. Parvovirus, syphilis, or CMV serologies may be useful depending on the population [12, 13].
  • Although an ANA is not very useful (the rate of + ANA can be expected to be 14.4% in otherwise healthy pregnant controls), anticardiolipin antibody (ACA) and lupus anticoagulant (LA)are specific and identifiable causes of fetal death.[14]

  • A Kleihauer-Betke (fetal cell count) may be drawn for evaluation. Fetal-maternal hemorrhage sufficient to cause fetal death has been reported in 10-15% of otherwise unexplained fetal deaths and in 3-5% of all fetal deaths (7,8)
  • Draw other laboratories as indicated by clinical history and exam.
    See sample orders

     Induction [15-23]
     Overall, 80-90% of patients enter spontaneous labor within 2 weeks of fetal death [3].

  • The patient may be induced if not already in labor.
    • Concentrated intravenous oxytocin, high dose Prostin E2 suppositories ,and misoprostol are effective for achieving delivery prior to 28 weeks [15-20]. However these agents should be used with caution in patients with a history of previous cesarean delivery, because of the increased risk for uterine rupture and blood transfusion associated in with midtrimester pregnancy termination in this group of women [19-21].
    • High dose Prostin E2 suppositories are contraindicated > 28 weeks gestation [23] as is misoprostol in patients with a uterine scar after 24 weeks [15] .

     

     Postpartum [3,24-26]

  • After delivery, the stillborn infant and placenta should be examined by someone experienced in the examination of the newborn and placenta.
     
  • The table below may be helpful in dating of the intrauterine fetal demise [27-29].
     

    Grade of Maceration

    		 Features Duration of Intrauterine Demise

    0

    		 • "parboiled" reddened skin < 8 hours

    I

    		 • skin slippage and peeling > 8 hours

    II

    		 • extensive skin peeling 
    • red serous effusions in chest and abdomen due to hemoglobin staining    		 2-7 days

    III

    		 • liver yellow-brown 
    • turbid effusion 
    • may be mummified    		 >= 8 days

    Additional datings

    • Bullae in epidermis (leading to peeling): appear at about 24 hours
    • Hemoglobin staining of internal viscera (loss of normal color): 24-48 hours
    • Separation of dura from calvarium bone: 5+ days
     

  • Cord blood or infant cardiac blood may be sent for culture and cytogenetic studies
    • Draw at least 1 ml for bacterial culture.
    • Draw 1- 5 ml for STORCH [syphilis, toxoplasma, other (e.g. parvovirus), rubella, CMV, HSV] serology ( 1-5 ml in red top tube).
    • Cord blood; Cytogenetics. Send 1 –10 ml in green top tube (sodium heparin). Store in the refrigerator until shipped. Do not freeze.

  • The Placenta should be sent for pathological evaluation accompanied by Fetal Death/Stillborn Autopsy Request [30]
    • Gross and microscopic examination of the placenta should be included. Clinically relevant findings may be expected in ~ 30% of studied placentas [12, 13]. Findings such as microinfarcts suggest a hypertensive disorder or APS.
    • Cultures for bacteria or viruses ideally should be done in the delivery. Cultures are obtained by separating amnion from chorion, and using a sterile swab beneath the amnion [30].
    • Placenta cytogenetics. Near the insertion of the cord, peel away the membranous covering. Using clean technique cut a ½ centimeter square piece of placenta 2-3 mm deep from beneath membranes. Wash in sterile saline and place in a sterile container with sterile saline. Seal the container and label. Store in the refrigerator until shipped. Do not freeze.
    • Amnion cytogenetics
      • Take a 1 cm. X 1 cm. sample of the amnion from the fetal surface of the placenta next to the insertion of the cord. Wash in sterile saline and place in a sterile container with sterile saline. Seal the container and label. Store in the refrigerator until shipped. Do not freeze.
  • Obtain permission to obtain samples of fascia .
    • Fascia sample cytogenetics (Macerated or non-macerated fetus)
      • Clean the inguinal crease with sterile saline> Make a scalpel incision above the inguinal crease and tease down to thin glistening fascia. take about a 1 centimeter square piece of fascial tissue. Place in a sterile container with sterile saline. Seal the container and label. Store in the refrigerator until shipped. Do not freeze.
  • Obtain parental permission to take clinical photographs and x-rays [3,12]
    • Photographs of unclothed infant should include:
      • View of the whole body including the limbs; include frontal, dorsal and lateral views
      • Profile views of the head
      • Close-up frontal view of the face •
       Additional photographs of any abnormal part
    • A single AP plain radiograph of the whole body (including hands and feet) is obtained with limbs extended and in the anatomic position if possible (limbs can be held in place by non-radiopaque tape): obtain lateral views if abnormalities are noted on the AP film or to define bones suspected or known to have a structural anomaly • If dwarfism is present, additional AP and lateral views of the infant limbs, head and spine should be obtained
  • Request and obtain written consent for an autopsy
      • Autopsy is often  useful step in identifying the cause of fetal death A recent retrospective review at LAC/USC by Incerpi et al. showed that autopsy reduced the number of unexplained stillbirths by 10% [12]
      • If consent is not given for a full autopsy, ask the parent to consider a limited autopsy such as external examination by pathologist/clinical geneticist or internal examination limited to brain and/or spinal cord; chest organs or abdominal organs as appropriate
      • OR MRI. [31]

COUNSELING THE FAMILY

  • Explain that results of all investigations may take 2 or 3 months for completion.
  • Explain that despite extensive evaluation a cause of death may not be found.
  • In addition to investigating the medical aspects of a stillbirth, it is important to consider the psychological effects on the family. Grief counseling should be initiated prior to discharge from hospital.
  • Bereavement programs and materials are available from: Gundersen Lutheran Medical Foundation in La Crosse, Wisconsin


SEE ALSO: Pregnancy Loss
                       Assessment of Intrauterine Death of One Twin

 REFERENCES


    1. Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System: Arias E, Anderson RN, Kung HC, Murphy SL, Kochanek KD. Deaths: Final data for 2001. National vital statistics reports. vol 52 no 3. Hyattsville, Maryland: National Center for Health Statistics. 2003.
    2. Froen JF, et al. Risk factors for sudden intrauterine unexplained death: epidemiologic characteristics of singleton cases in Oslo, Norway, 1986-1995. Am J Obstet Gynecol;184:694-702 MEDLINE
    3. ACOG: Diagnosis and management of fetal death. ACOG Technical Bulletin Number 176-January 1993. Int J Gynaecol Obstet 1993; 42: 291-9
    4. Oron T, Sheiner E, Shoham-Vardi I, Mazor M, Katz M, Hallak M. Risk factors for antepartum fetal death. J Reprod Med. 2001 Sep;46(9):825-30. PMID: 11584485
    5. Froen JF, Vege A, Ormerod E, Stray-Pedersen B [Finding the cause of death in intrauterine death--which examination should be done?]Tidsskr Nor Laegeforen. 2001;121(3):326-30. PMID: 11242876
    6. Goldenberg RL, Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol 2003;189:861–73.PMID: 14526331
    7. Laube DW, Schauberger CW. Fetomaternal bleeding as a cause for "unexplained" fetal death. Obstet Gynecol 1982;60:649-651
    8. Owen J, Stedman CM, Tucker TL. Comparison of predelivery versus postdelivery Kleihauer-Betke stains in cases of fetal death. Am J Obstet Gynecol 1989; 161:663-666
    9. Guidelines and Statements. Investigation Of Stillbirths The College of Physicians and Surgeons of Manitoba
    http://www.umanitoba.ca/colleges/cps/Guidelines_and_Statements/609.html Accessed: 3/13/03
    10. ACOG: ACOG committee opinion. Genetic evaluation of stillbirths and neonatal deaths. Number 178, November 1996. Committee on Genetics. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 1997 Mar; 56(3): 287-9
    11. Brady K, Duff P, Harlass FE, Reid S. The role of amniotic fluid cytogenetic analysis in the evaluation of recent fetal death. Am J Perinatol 1991;8:68-70
    12. Incerpi MH, Miller DA, Samandi R, Settlage RH, Goodwin TM. Stillbirth evaluation:what tests are needed. Am J Obstet Gynecol 1998;178:1121-5
    13. Ahlenius I, Floberg J, Thomassen P. Sixty-six cases of intrauterine fetal death. A prospective study with an extensive test protocol.Acta Obstet Gynecol Scand. 1995 Feb;74(2):109-17. PMID: 7900505
    14. Lockwood CJ, Rand JH. The immunobiology and obstetrical consequences of anti-phospholipid antibodies. Obstet Gynecol Surv 1994;49: 432-41
    15. ACOG: Induction of labor. ACOG Practice Bulletin Number 10-November 1999.
    16. Jain JK, Mishell DR. A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second trimester pregnancy. N Engl J Med 1994;331:290-3.
    17.  Bugalho A, Bique C, Machungo F, Bergstrom S. Vaginal misoprostol as an alternative to oxytocin for induction of labor in women with late fetal death. Acta Obstet Gynecol Scand1995 ; 74: 194-8.
    18. Dickinson JD, Evans SF. The optimization of intravaginal misoprostol schedules in second trimester pregnancy termination.Am J Obstet Gynecol 2002; 186 : 470-4.  PMID: 11904609
    19. le Roux PA, Pahal GS, Hoffman L, Nooh R, El-Refaey H, Rodeck CH. Second trimester termination of pregnancy for fetal anomaly or death: comparing mifepristone/misoprostol to gemeprost. Eur J Obstet Gynecol Reprod Biol. 2001 ;95:52-4. PMID: 11267720
    20. Dickinson JE, Evans SF. A comparison of oral misoprostol with vaginal misoprostol administration in second-trimester pregnancy termination for fetal abnormality. Obstet Gynecol. 2003 Jun;101(6):1294-9.
    PMID: 12798539
    21. Chapman SJ, Crispens M, Owen J, Savage K.Complications of midtrimester pregnancy termination: the effect of prior cesarean delivery. Am J Obstet Gynecol. 1996;175:889-92.PMID: 8885742
    22. Levrant SG, Wingate M. Midtrimester uterine rupture. A case report. J Reprod Med. 1996;41:186-90. PMID: 8778419
    23. PROSTIN E2 ® Vaginal Suppository package insert, 2002
    24. Guidelines and Statements. Investigation Of Stillbirths The College of Physicians and Surgeons of Manitoba
    http://www.umanitoba.ca/colleges/cps/Guidelines_and_Statements/609.html Accessed: 3/13/03
    25. ACOG: ACOG committee opinion. Genetic evaluation of stillbirths and neonatal deaths. Number 178, November 1996. Committee on Genetics. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 1997 Mar; 56(3): 287-9
    26. Lindsey JL, Evaluation of Fetal Death (Medical College of Virginia
    www.emedicine.com/med/topic3235.htm
    http://www.emedicine.com/med/images/Large/28782878efd_table2a.pdf Accessed: 3/13/03
    27. Bain AD. The perinatal autopsy, pages 820-834. IN: Cockburn F, Drillien CM (editors). Neonatal Medicine. Blackwell Scientific Publications. 1974.
    28. Langley FA. The perinatal postmortem examination. J Clin Pathol. 1971; 24: 159-169.
    29. Wigglesworth JS. Perinatal Pathology, Second Edition. WB Saunders. 1996. Chapter 6: The macerated stillborn fetus. pages 78-86.
    30. Practice Guideline for Examination of the Placenta: Developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med, 1997;121:449-476.
    31. Woodward PJ, Sohaey R, Harris DP, et al. Postmortem fetal MR imaging: comparison with findings at autopsy. AJR Am J Roentgenol. 1997;168(1):41-46.

    Created: 11/2/2002  Mark Curran,M.D.
    Updated: 11/20/2004 Mark Curran,M.D.

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