Elsevier

Obstetrics & Gynecology

Volume 96, Issue 2, August 2000, Pages 281-286
Obstetrics & Gynecology

Features
Comparative genomic hybridization for cytogenetic evaluation of stillbirth

https://doi.org/10.1016/S0029-7844(00)00879-6Get rights and content

Abstract

Objective: To ascertain the feasibility and reliability of comparative genomic hybridization for cytogenetic evaluation of macerated stillbirths.

Materials: We examined ten stillborn fetuses above 15 weeks’ gestation whose karyotypes were unknown because of tissue culture failure. Sixteen fetuses that were successfully karyotyped using prenatal or postnatal tissues were also examined as controls, including five pregnancy terminations with autosomal aneuploidy, one with sex chromosome aneuploidy, one with a chromosomal deletion; five macerated fetuses with normal karyotypes, three with autosomal aneuploidy, and one with sex chromosome aneuploidy and discrepancy between chorionic villi and fetus.

Results: All comparative genomic hybridization analyses in fresh and macerated tissues were successful except for one. All normal karyotypes and aneuploidies were confirmed. Comparative genomic hybridization failed in one fetus with a deletion of the short arm of chromosome 18. In the stillborn fetuses without known karyotypes, one aberrant profile was found; however, the results were not confirmed with interphase fluorescence in situ hybridization. In one fetus triploidy was diagnosed with DNA flow cytometry.

Conclusion: Comparative genomic hybridization is a valuable backup technique for aneuploidy screening in tissues from macerated stillborn fetuses when tissue culture fails. Gains or losses can subsequently be confirmed by fluorescence in situ hybridization, using DNA probes that focus on specific loci of a chromosome.

Section snippets

Materials and methods

We studied tissues of two groups of fetuses of various gestational ages. The first group (n = 16) comprised fetuses whose karyotypes had been determined before or after birth, including seven cases of pregnancy termination for genetic reasons (fresh tissues) and nine stillborn fetuses (macerated tissues). The second group (n = 10) were stillborn fetuses without known karyotypes because of tissue culture failures. All material was taken with patients’ consent either to confirm antenatal

Results

Tissues from the 16 fetuses with known karyotypes were used to ascertain reliability of comparative genomic hybridization in fresh (n = 7) and macerated (n = 9) specimens at various gestational ages (Table 1). Gestational ages ranged from 12–3427 weeks. Comparative genomic hybridization results were obtained in all samples but one. Five fetuses had normal karyotypes (all female) and were correctly identified by comparative genomic hybridization, including their sexes (Figure 1). Ten fetuses

Discussion

In liveborn infants, postnatal karyotyping usually succeeds. However, in stillborn fetuses there is an overall success rate of only 60%, and even less with increased time since death. In our study, eight of 18 (44%) macerated stillborn fetuses were karyotyped successfully. Until now only a few studies have described the usefulness of comparative genomic hybridization in perinatal medicine. Bryndorf et al15 studied 11 fetal samples. Four were prenatal cases with unidentifiable material that was

References (23)

  • R.M Pitkin

    Fetal deathDiagnosis and management

    Am J Obstet Gynecol

    (1987)
  • G.V.N Velagelati et al.

    Primed in situ labeling for rapid prenatal diagnosis

    Am J Obstet Gynecol

    (1998)
  • F Forozan et al.

    Genome screening by comparative genomic hybridization

    Trends Genet

    (1997)
  • B Levy et al.

    Clinical applications of comparative genomic hybridization

    Genet Med

    (1998)
  • G.R Sutherland et al.

    Cytogenetic studiesAn essential part of the paediatric necropsy

    J Clin Pathol

    (1983)
  • R.R Angell et al.

    Chromosome variation in perinatal mortalityA survey of 500 cases

    J Med Genet

    (1984)
  • G.B Feldman

    Prospective risk of stillbirth

    Obstet Gynecol

    (1992)
  • R.M Pauli et al.

    Wisconsin stillbirth service programII. Analysis of diagnoses and diagnostic categories in the first 1000 referrals

    Am J Med Genet

    (1994)
  • R.F Mueller et al.

    Evaluation of a protocol for postmortem examination of stillbirths

    N Engl J Med

    (1983)
  • T.A McPherson et al.

    Predicting in vitro tissue culture growth for cytogenetic evaluation of stillborn fetuses

    Eur J Obstet Gynecol Reprod Biol

    (1985)
  • G Stetten et al.

    New cytogenetic technology and its application in maternal-fetal medicine

    J Maternal Fetal Invest

    (1997)
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    Supported by the Wim Schellekens Foundation.

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