Clinical Review


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New approaches to the genetic evaluation, risk assessment, and classification of stillbirth contribute to understanding and management of this troubling phenomenon



Three important areas of research into stillbirth have evolved over the past year, furthering our understanding of the phenomenon and our ability to provide comprehensive, evidence-based care:

  • Genetic studies. Karyotype analysis is useful in determining the cause of stillbirth, especially when analysis is based on a sample of amniotic fluid that was obtained before delivery. And array-based comparative genomic hybridization, which yields information on the chromosome count as well as micro-duplications and deletions, can be performed on nondividing cells.
  • Risk factors. Further investigation implicates advanced maternal age, obesity, and African-American race.
  • Classification. Paring down the more than three dozen systems that exist for classification of stillbirth was the main challenge addressed by an international consensus group in 2009 and the focus of a separate analysis.

The individual studies that contribute to our knowledge base in these areas are discussed in more detail in the articles that follow.

Stillbirth is broadly defined as fetal demise after 20 weeks’ gestation and with a fetal weight exceeding 350 g. In the United States, stillbirth occurs in 1 of every 160 live births (6 stillbirths for every 1,000 live births). Although the rate of neonatal demise has decreased over the past decade, the rate of stillbirth has declined less strikingly.

For an analysis of karyotype, amniotic fluid is best

Korteweg FJ, Bouman K, Erwich JJ, et al. Cytogenetic analysis after evaluation of 750 fetal deaths: proposal for diagnosis workup. Obstet Gynecol. 2008;111:865–874.

ACOG Practice Bulletin #102: Management of stillbirth. Obstet Gynecol. 2009;113:748–760.

When stillbirth occurs, determination of the cause of death fulfills several goals:

  • It informs counseling of the parents, who must come to terms with the loss
  • It aids in determining the risk of recurrence, which informs family planning
  • It furthers research into stillbirth and facilitates the comparison of national and international data.

Chromosomal anomaly is one potential cause of stillbirth. Its frequency depends on the presence of structural malformation. For example, Korteweg and colleagues found a rate of chromosomal anomaly of 4.6% among stillbirths involving fetuses without structural abnormality, but the rate rose to 38% when anatomic malformation was present. The distribution of chromosomes among stillbirths mirrored the pattern seen in live births, including 45, X and trisomies of chromosome 21, 13, and 18.

The utility of karyotype assessment when ultrasonography (US) has not identified structural malformation has been debated. Given the 5% incidence of chromosomal anomaly in the absence of structural abnormality, and the limitations of US in detecting subtle dysmorphology, a karyotype seems advisable to assess all stillbirths.

Comparison of methods points to superiority of amniocentesis

Because fewer than 20% of skin biopsies result in a useful culture, postmortem skin biopsy for karyotype assessment is unreliable. Korteweg and colleagues evaluated other methods of obtaining cells for examination and found that a successful karyotype is most likely with predelivery amniocentesis (85%), followed by umbilical cord culture (32.1%). A karyotype of cells from fascia lata and skin biopsy yielded poor results, especially in the setting of maceration. Placental biopsy is likely to provide an adequate karyotype (71% probability) but findings may be confounded by confined placental mosaicism.1

ACOG also advocates predelivery amniocentesis

In its 2009 practice bulletin, ACOG supported inclusion of amniocentesis in the assessment of stillbirth and preparation for delivery. Once an epidural is placed, amniocentesis provides cells for karyotype assessment, polymerase chain reaction (PCR) for viral studies, and any other metabolic or specific genetic studies that may be indicated by fetopsy.

If amniocentesis is not performed, ACOG recommends umbilical cord culture as an alternative. Because nondividing cells can be utilized in fluorescence in situ hybridization (FISH) for chromosome 13, 18, 21, X, and Y, this method should be considered in any case involving culture failure (TABLE).2


Genetic components of stillbirth assessment

Type of assessmentSteps
Inspection of fetus and placentaMeasure head circumference and length of fetus
Weigh fetus and placenta
Photograph fetus and placenta, including frontal and profile shots of whole body, face, extremities, palms, and any abnormality
Document findings
Cytologic analysisObtain consent from parents
Obtain acceptable specimens using one of the following sterile techniques:
• Amniocentesis at the time of prenatal diagnosis of demise
• Placental block (1 x 1 cm) taken from below the cord-insertion site on the unfixed placenta
• Umbilical cord segment (1.5 cm)
• Internal fetal tissue specimen, e.g., costochondral junction or patella (not skin)
Preserve specimens in a sterile culture medium of lactated Ringer’s solution at room temperature during transfer to laboratory
FetopsyObtain parental consent; if no consent is given, send placenta for pathologic analysis
Perform autopsy and pathologic assessment of the placenta
Consider whole-body fetal radiographs
Source: ACOG Practice Bulletin #102


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