Second-trimester cardiovascular biometry in growth-restricted fetuses: a multicenter cohort study

Julie Spang Frandsen*, Kasper Gadsbøll, Finn Stener Jørgensen, Olav Bjørn Petersen, Line Rode, Karin Sundberg, Helle Zingenberg, Ann Tabor, Charlotte Kvist Ekelund, Cathrine Vedel

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Background: Intrauterine growth restriction is associated with an increased risk of cardiovascular changes neonatally. However, the underlying pathways are poorly understood, and it is not clear whether the dysfunction is already present in the fetus. Objective: This study aimed to investigate fetal cardiac dimensions assessed from images at the second trimester anatomy scan from fetuses classified postnatally as small for gestational age and intrauterine growth restricted and compare them with appropriate for gestational age fetuses. Study Design: This was a substudy from The Copenhagen Baby Heart Study, a prospective, multicenter cohort study including fetuses from the second trimester of pregnancy in Copenhagen from April 2016 to October 2018. The mothers were recruited at the second trimester anatomy scan that included extended cardiovascular image documentation followed by consecutively measured heart biometry by 2 investigators blinded for the pregnancy outcome. The fetuses were classified postnatally as small for gestational age and intrauterine growth restricted according to the International Society of Ultrasound in Obstetrics and Gynecology 2020 guidelines using birthweight and with a retrospective assessment of Doppler flow. The mean differences in the cardiovascular biometry were adjusted for gestational age at the time of the second trimester scan and the abdominal circumference. The z-scores were calculated, and the comparisons were Bonferroni corrected (significance level of P<.005). Receiver operating characteristic curves were computed after performing backward regression on several maternal characteristics and biomarkers. Results: We included 8278 fetuses, with 625 (7.6%) of them being small for gestational age and 289 (3.5%) being intrauterine growth restricted. Both small for gestational age and intrauterine growth restricted fetuses had smaller heart biometry, including the diameter at the location of the aortic valve (P<.005), the ascending aorta in the 3-vessel view (P<.005), and at the location of the pulmonary valve (P<.005). The intrauterine growth restricted group had significantly smaller hearts with respect to length and width (P<.005) and smaller right and left ventricles (P<.005). After adjusting for the abdominal circumference, the differences in the aortic valve and the pulmonary valve remained significant in the intrauterine growth restricted group. Achievement of an optimal receiver operating characteristic curve included the following parameters: head circumference, abdominal circumference, femur length, gestational age, pregnancy associated plasma protein-A multiples of median, nullipara, spontaneous conception, smoking, body mass index <18.5, heart width, and pulmonary valve with an area under the curve of 0.91 (0.88–0.93) for intrauterine growth restricted cases. Conclusion: Intrauterine growth restricted fetuses had smaller prenatal cardiovascular biometry, even when adjusting for abdominal circumference. Our findings support that growth restriction is already associated with altered cardiac growth at an early stage of pregnancy. The heart biometry alone did perform well as a screening test, but combined with other factors, it increased the sensitivity and specificity for intrauterine growth restriction.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Obstetrics and Gynecology
Vol/bind227
Udgave nummer1
Sider (fra-til)81.e1-81.e13
ISSN0002-9378
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
O.B.P. holds a professorship funded by the Novo Nordisk Foundation; grant NNFSA170030576. None of the other authors report any conflict of interest concerning the content of this manuscript.

Funding Information:
C.V. received funding from the “Rigshospitalets Research Foundation” and the “Aase and Ejnar Danielsens Research Foundation” to carry out the study.

Funding Information:
We want to thank Professor Henning Bundgaard, MD, Department of Cardiology, Rigshospitalet, Denmark; Professor Kasper Iversen, MD, Department of Cardiology, Herlev Hospital, Denmark; and the rest of the Copenhagen Baby Heart steering committee for the collaboration that made this study possible.

Publisher Copyright:
© 2021 Elsevier Inc.

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