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Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants
Abstract
Background: Congenital heart defects (CHDs) have been associated with placental anomalies. The nature and the consequences of this association remain poorly understood. We aimed to estimate the associations between all major subtypes of CHD and placental weight at birth, and the association between placental weight and measures of both overall and cerebral growth in fetuses with CHD, as well. Methods: We included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 7569. We compared mean differences in placental weight z score between newborns with CHD and newborns without CHD by multivariable linear regression adjusted for potential confounders. Results: CHD was associated with a mean z score difference of –0.04 (95% confidence interval, –0.07 to –0.02). Some subtypes were associated with smaller placental size at birth: tetralogy of Fallot, –0.45 (95% confidence interval, –0.58 to –0.31); double-outlet right ventricle, –0.48 (95% confidence interval, –0.87 to –0.10); major ventricular septal defects, –0.41 (95% confidence interval, –0.52 to –0.29). Placental weight z score was associated with birth weight and head circumference z scores in all subtypes. In the 3 mentioned subtypes, the mean deviations from the population mean head circumference and birth weight z scores were reduced by up to 66% with adjustment for placental weight z score. Conclusions: Three subtypes of CHD were associated with lower placental weight, and placental weight was associated with measures of both overall growth and cerebral growth in fetuses with all subtypes of CHD. In certain subtypes, the described deviations in fetal growth were reduced by up to two-thirds after adjustment for placental weight z score.
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“As a result of affected antenatal cerebral circulation, birth head circumferences and z-scores are decreased in CHD.31,32”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [31]
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Dehn, A. M., Sellmer, A., Vøgg, R. O. B., Dannesbo, S., Blixenkrone-Møller, E., Zingenberg, H., Boyd, H. A., Iversen, K. K., Bundgaard, H., & Hjortdal, V. E. (2025) · Cardiology in the Young · doi:10.1017/s1047951125110147
Self-citationRajagopalan, V., Rosas, V., Patel, R. M., Wang, S., Borzage, M., Detterich, J. A., Votava‐Smith, J. K., & Wood, J. (2025) · Magnetic Resonance in Medicine · doi:10.1002/mrm.70159
The Sooner, the Better: Neuroprotective Strategies in Fetuses With Congenital Heart Disease
Nijman, M., van der Meijden, M. E. M., Breur, J. M. P. J., Stegeman, R., Jansen, N. J. G., Bekker, M. N., Benders, M. J. N. L., & Claessens, N. H. P. (2026) · Prenatal Diagnosis · doi:10.1002/pd.70069
Prognostic value of fetal growth and prenatal functional echocardiography in tetralogy of FALLOT
Nogué, L., Bennasar, M., Guirado, L., Zölner, F., Reitz, J. G., Axt-Fliedner, R., Escobar-Diaz, M. C., Martínez, J. M., Gratacós, E., Crispi, F., et al. (2026) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.70137
Karakuş, E., Emin, M., Ağaoğlu, M. Ö., Karataş, E., & Sahin, D. (2026) · Pediatric and Developmental Pathology · doi:10.1177/10935266261419536
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Bonthrone, A. F., Cromb, D., Javed, S. A., Verdera, J. A., Pushparajah, K., Rutherford, M., Hutter, J., & Counsell, S. J. (2026) · Placenta · doi:10.1016/j.placenta.2026.05.027
Jacobwitz, M., Kapse, K. J., Ngwa, J. S., Asis‐Cruz, J. D., Wu, Y., Govindan, R. B., McDermott, C., Donofrio, M. T., du Plessis, A., Limperopoulos, C., et al. (2026) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd13060236
Cerebral autoregulation in congenital heart disease
van de Bunt, A., Breur, J. M. P. J., & van der Heyden, M. A. G. (2026) · Progress in Pediatric Cardiology · doi:10.1016/j.ppedcard.2026.101961
Placental pathology in fetuses with and without congenital heart defects
Doiron, T. E., Besmer, S., Guerrero, J. C., Salas, J., Fox, L., Zantow, E. W., & Chavan, N. R. (2026) · Pregnancy · doi:10.1002/pmf2.70439
Congenital heart disease in adults: evolving health systems and lifelong outcomes
Diller, G., Daniels, C. J., & Marelli, A. J. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag616
Fetal Ventricular-arterial Coupling: Development, Physiology, and Ultrasonographic Advances
Jiang, X., 方文伶, Hu, P., Yu, R., Ma, J., Wang, N., Wu, T., Ye, L., Ruan, W., Li, Z., et al. (2026) · Advanced ultrasound in diagnosis and therapy · doi:10.26599/audt.2026.250112
Metadata
- Authors
- Matthiesen, N. B., Henriksen, T. B., Agergaard, P., Gaynor, J. W., Bach, C. C., Hjortdal, V. E., & Østergaard, J. R.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Venue
- Circulation
- Published
- 2016-11-15
- Volume
- 134
- Issue
- 20
- Pages
- 1546-1556
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2531007892
- Cited by
- 112
- References
- 31
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 3
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Aarhus Universitet
- Aarhus Universitets Forskningsfond
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Congenital Heart Disease Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Cardiovascular Conditions and Treatments
- Keywords
- congenital heart disease, placental weight, fetal growth, head circumference, birth weight, tetralogy of Fallot, double outlet right ventricle, ventricular septal defect, placental abnormalities, liveborn infants
- MeSH terms
- Birth Weight, Female, Heart Defects, Congenital, Humans, Infant, Newborn, Male, Placenta, Pregnancy, Fetal Development
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