Copy number variants and fetal growth in stillbirths.
chromosomal microarray
copy number changes
copy number variants
growth restriction
karyotype
large for gestational age
placental insufficiency
small for gestational age
stillbirth
Journal
American journal of obstetrics and gynecology
ISSN: 1097-6868
Titre abrégé: Am J Obstet Gynecol
Pays: United States
ID NLM: 0370476
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
27
04
2022
revised:
30
10
2022
accepted:
02
11
2022
pmc-release:
01
05
2024
medline:
1
5
2023
pubmed:
11
11
2022
entrez:
10
11
2022
Statut:
ppublish
Résumé
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. This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36356697
pii: S0002-9378(22)02162-7
doi: 10.1016/j.ajog.2022.11.1274
pmc: PMC10149588
mid: NIHMS1855953
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
579.e1-579.e11Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002539
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD045953
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD045954
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD045925
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD045952
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD045955
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD045944
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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