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Cardiac dysfunction is associated with altered sarcomere ultrastructure in intrauterine growth restriction

Presented at the 31st annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 6-11, 2011.
https://doi.org/10.1016/j.ajog.2014.01.023Get rights and content

Objective

The purpose of this study was to assess whether abnormal cardiac function in human fetuses with intrauterine growth restriction (IUGR) is associated with ultrastructural differences in the cardiomyocyte sarcomere.

Study Design

Nine severe early-onset IUGR fetuses and 9 normally grown fetuses (appropriate growth for gestational age) who died in the perinatal period were included prospectively. Cardiac function was assessed by echocardiography and levels of B-type natriuretic peptide and troponin-I. Heart sections were imaged by second harmonic generation microscopy, which allowed unstained visualization of cardiomyocyte's sarcomere length.

Results

Echocardiographic and biochemical markers showed signs of severe cardiac dysfunction in IUGR fetuses. Second harmonic generation microscopy demonstrated a significantly shorter sarcomere length in IUGR as compared with appropriate growth for gestational age fetuses.

Conclusion

IUGR is associated with changes in the cardiomyocyte contractile machinery in the form of shorter sarcomere length, which could help to explain the cardiac dysfunction previously documented in IUGR.

Section snippets

Study groups

The study population included 9 severe early-onset IUGR and 9 AGA fetuses from 19-33 weeks of gestation who died in the perinatal period because of perinatal complications or medical termination of pregnancy. Cases were singleton pregnancies with IUGR that had been included in a large prospective cohort that evaluated cardiac dysfunction in IUGR.9 AGA fetuses were selected among women who underwent termination of pregnancy because of severe maternal disease or noncardiac malformations.

Study populations

Table 1 displays perinatal and Doppler data of the study groups. All included cases were very severe early-onset IUGR cases with a birthweight that ranged from 169-900 g. As expected, IUGR cases showed signs of placental insufficiency and hemodynamic redistribution by Doppler ultrasound evaluation and a lower birthweight percentile. The percentage of cardiac arrest with potassium chloride was similar among the study groups. Pregnancy termination in AGA was performed because of maternal

Comment

This study provides evidence that IUGR is associated with cardiac dysfunction and ultrastructural cardiomyocyte changes in the form of shorter sarcomere length.

In the present study, IUGR fetuses showed signs of severe hemodynamic deterioration and cardiac dysfunction by echocardiography and cord blood BNP. This finding was expected because all cases were early-onset severe IUGR fetuses, and it is consistent with previous studies that demonstrated cardiac dysfunction in IUGR, which correlates

Acknowledgments

We thank Anna Bosch and Dr Maria Calvo from the Advanced Optical Microscopy Unit from Scientific and Technological Centres from the University of Barcelona for their support and advice with second harmonic generation and confocal techniques. The samples used in this project were provided by the Hospital Clínic-IDIBAPS Biobank with appropiate ethical approval.

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    Supported in part by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (FIS-PI11/01709, FIS PI11/00051, PI12/00801, and SAF2012-37196) cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa” and Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, Spain (P.G.C.); an IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) predoctoral fellowship (A.G.T.); and the Programa de Ayudas Postdoctorales Sara Borrell (CD08/00176) from the Instituto de Salud Carlos III, Spain (I.T.).

    The authors report no conflict of interest.

    Cite this article as: Iruretagoyena JI, Gonzalez-Tendero A, Garcia-Canadilla P, et al. Cardiac dysfunction is associated with altered sarcomere ultrastructure in intrauterine growth restriction. Am J Obstet Gynecol 2014;210:550.e1-7.

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