Background
Fetal growth abnormalities are associated with a higher incidence of stillbirth, with
small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased
risk, respectively. Although clinical risk factors such as diabetes, hypertension,
and placental insufficiency have been associated with fetal growth aberrations and
stillbirth, the role of underlying genetic etiologies remains uncertain.
Objective
This study aimed to assess the relationship between abnormal copy number variants
and fetal growth abnormalities in stillbirths using chromosomal microarray.
Study Design
A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth
Collaborative Research Network was performed. Exposure was defined as abnormal copy
number variants including aneuploidies, pathogenic copy number variants, and variants
of unknown clinical significance. The outcomes were small for gestational age and
large for gestational age stillbirths, defined as a birthweight <10th percentile and
greater than the 90th percentile for gestational age, respectively.
Results
Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal
copy number variants. The small for gestational age outcome was more common among
those with abnormal copy number variants than those with a normal microarray (29.5%
vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables.
In the final model, only abnormal copy number variants and maternal age remained significantly
associated with small for gestational age stillbirths, with an adjusted odds ratio
of 2.22 (95% confidence interval, 1.12–4.18). Although large for gestational age stillbirths
were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70–7.90), this finding
did not reach statistical significance.
Conclusion
Genetic abnormalities are more common in the setting of small for gestational age
stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype
make up approximately 50% of the genetic abnormalities in this population.
Key words
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Article info
Publication history
Published online: November 07, 2022
Accepted:
November 2,
2022
Received in revised form:
October 30,
2022
Received:
April 27,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
The authors report no conflict of interest or any substantial financial disclosures.
This work was supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10-HD045953 Brown University, RI; U10-HD045925 Emory University, GA; U10-HD045952 The University of Texas Medical Branch at Galveston, TX; U10-HDO45955 The University of Texas Health Sciences Center at San Antonio, TX; U10-HD045944 The University of Utah Health, UT; and U01-HD045954 RTI International, RTP. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Secondary analysis of the primary research was supported by salary support from the department of Obstetrics and Gynecology at the University of Utah Health, Salt Lake City, UT. Author T.W. is supported by grant funding from the National Center for Advancing Translational Sciences of the National Institutes of Health (grant 1UL01 TR002538 and KL2 TR002549).
This study was presented in part at the 68th annual Society for Reproductive Investigation Meeting, Boston, MA, July 6–9, 2021.
Cite this article as: Dalton SE, Workalemahu T, Allshouse AA, et al. Copy number variants and fetal growth in stillbirths. Am J Obstet Gynecol 2022;XX:x.ex–x.ex.
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