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Early structural cardiovascular changes on neonatal echocardiography after adverse intrauterine circumstances in identical twins

Pediatric Research volume 98, pages 1358–1365 (2025)Cite this article

Abstract

Background

Studies on cardiovascular changes after fetal growth restriction (FGR) are limited by their design in which growth-restricted neonates are compared to appropriately-grown neonates. We aim to investigate early structural cardiovascular remodeling after FGR in identical twins, controlling for confounding of genetic and maternal factors.

Methods

This study is part of a prospective cohort study including monochorionic twins from January 2019. Transthoracic echocardiography was performed within one week after birth. Z-scores for cardiac valve annuli diameters and left ventricle dimensions based on gestational age at birth were compared between smaller and larger twins. Z-score differences between birth weight and cardiac structure per twin were tested against the intercept.

Results

Median gestational age at birth of the 100 included twin pairs was 33.8 (interquartile range (IQR) 30.8–36.1) weeks, with birth weights of 1729 (IQR 1200–2115) grams for smaller twins and 2058 (IQR 1643–2500) grams for larger twins. Smaller twins had a lower z-score for all structures. Z-score differences in birth weight and cardiac structure were higher than the intercept.

Conclusion

While cardiac structures are generally smaller for the twin with the lower birth weight, the deviation in birth weight tends to be more pronounced than the deviation in cardiac structure.

Impact

  • Our study shows that in identical twins, the smaller twin at birth has a structurally smaller heart on neonatal echocardiography when compared to the larger twin. Yet, cardiac structures per individual twin are less affected than body size for their given gestational age at birth.

  • We have used a unique natural experiment by studying a population of identical twins with varying degrees of birth weight discordance, eliminating any confounding of genetic, maternal and obstetrical factors.

  • Our results are suggestive of early cardiovascular remodeling after adverse intrauterine circumstances. This provides insight into the fetal programming of cardiovascular disease.

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Fig. 1: Measurement of the aPWV based on two separate Doppler recordings of one single two-dimensional cross-section of the aorta.
Fig. 2
Fig. 3: Scatterplots of the relationship between the z-score of the birth weight (x-axis) and the z-score of the cardiac structures (y-axis), with the line depicting x = y.

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Data availability

Individual participant data (including data dictionaries) that underlie the results reported in this article will, after de-identification, be available beginning 3 months and ending 10 years following article publication. The study protocol will also be made available. The data will be shared with researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee identified for this purpose and the medical ethical committee of the Leiden University Medical Center. Proposals should be directed to s.g.groene@lumc.nl. To gain access, data requestors will need to sign a data access agreement.

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Acknowledgements

We wish to thank the parents and their twins participating in the Twinlife study for their time and efforts.

Funding

Supported by the Dutch Heart Foundation (grant number 2017T075).

Author information

Authors and Affiliations

  1. Neonatology, Willem-Alexander Children’s Hospital, Dept. of Pediatrics, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands

    Sophie G. Groene, Jeanine M. M. van Klink & Enrico Lopriore

  2. Molecular Epidemiology, Dept. of Biomedical Data Sciences, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands

    Sophie G. Groene & Bastiaan T. Heijmans

  3. Medical statistics, Dept. of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Albinusdreef 2, 2333ZA, Leiden, the Netherlands

    Erik W. van Zwet

  4. Pediatric Cardiology, Willem-Alexander Children’s Hospital, Dept. of Pediatrics, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands

    Arend D. J. ten Harkel & Arno A. W. Roest

  5. Fetal Therapy, Dept. of Obstetrics, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands

    Monique C. Haak

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Each author has met the Pediatric Research authorship requirements, including Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; Drafting the article or revising it critically for important intellectual content; and Final approval of the version to be published.

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Correspondence to Sophie G. Groene.

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Groene, S.G., van Zwet, E.W., ten Harkel, A.D.J. et al. Early structural cardiovascular changes on neonatal echocardiography after adverse intrauterine circumstances in identical twins. Pediatr Res 98, 1358–1365 (2025). https://doi.org/10.1038/s41390-025-03916-2

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