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First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation

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Abstract

The first trimester combined screening, which analyzes fetal nuchal translucency and levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum, is routinely used to detect abnormal pregnancies associated with Down syndrome and other trisomy aneuploidies. Based on the hypothesis that major chromosomal translocations could lead to similar biochemical and developmental outcomes during early embryo development, we compared these markers among pregnancies with normal, balanced, or unbalanced fetal karyotypes. Among the parents, 71 (73%) carry balanced reciprocal translocation and 26 (27%) have Robertsonian translocation. Of the 97 pregnancies tested, 39 (40%), 37 (37%), and 22 (23%) fetuses had normal karyotype, balanced chromosomal translocations, and unbalanced chromosomal translocations, respectively. Importantly, we found that pregnancies with an unbalanced translocation had significantly higher free β-hCG multiple of the median (MoM) and larger nuchal translucency thickness than those with normal karyotype or balanced translocations. Analysis showed that the area under a receiver operating characteristic curve (AUC) is 0.716, 0.820, and 0.936 for free β-hCG MoM, PAPP-A MoM, and fetal nuchal translucency, respectively. When these 3 independent factors were combined, the AUC reached 0.976. In addition, logistic regression showed that the most optimal model for predicting an unbalanced chromosomal translocation is a combination of PAPP-A and nuchal translucency with an AUC of 0.980. Therefore, the first trimester combined screening is not only effective in the screening of Down syndrome and other trisomy abnormalities but also has high sensitivity for the detection of unbalanced chromosomal translocations in fetuses.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, 333, Taoyuan, Taiwan

    ShangYu Huang MD, ChiaLin Chang MD, PoJen Cheng MD & YungKuei Soong MD

  2. Department of Obstetrics and Gynecology, Taipei City Hospital, Women and Children Campus, Taipei, Taiwan

    ChingHua Hsiao MD

  3. Department of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan

    ChingHua Hsiao MD

  4. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

    Tao Duan MD

Authors
  1. ShangYu Huang MD
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  2. ChiaLin Chang MD
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  3. PoJen Cheng MD
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  4. ChingHua Hsiao MD
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  5. YungKuei Soong MD
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  6. Tao Duan MD
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Correspondence to PoJen Cheng MD.

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Huang, S., Chang, C., Cheng, P. et al. First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation. Reprod. Sci. 21, 594–600 (2014). https://doi.org/10.1177/1933719113508818

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