Original Investigation
Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants

https://doi.org/10.1016/j.jacc.2023.03.423Get rights and content

Abstract

Background

In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges.

Objectives

Normative reference intervals and z-scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed.

Methods

The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components.

Results

Infants in the study population (48.5% were female) had a median body surface area of 0.23 m2 (IQR: 0.22-0.25 m2) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals.

Conclusions

This study provides normative reference intervals and z-scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists.

Section snippets

Data source

The CBHS is a prospective population-based cohort study of cardiac structure and function from infancy onward. Enrollment in the CBHS was open to all infants born in the 3 main maternity wards in the Copenhagen metropolitan area of Denmark between April 2016 and October 2018. Detailed descriptions of the CBHS’s design and baseline characteristics have previously been published.15,16 Parents were informed about the study at the routine ultrasound scan offered to all pregnant women during

Results

The study population included 13,454 newborns (Figure 1). Maternal and newborn characteristics of the study population are presented in Table 1. Median age at TTE was 12 days for both boys and girls (IQR: 8-15 days and 8-12 days, respectively); the distribution of age at examination was similar for both sexes (Supplemental Figure 2). Overall, 17.4% (n = 2,342) of the study cohort were 0 to 6 days of age at TTE, 49.8% (n = 6,699) were 7 to 13 days old, 21.8% (n = 2,931) were 14 to 20 days old,

Discussion

We estimated BSA- and age-specific reference intervals and z-scores for 10 echocardiographic measures of LV dimensions and function based on >13,000 healthy newborns. Sex-specific differences in estimated parameters were minimal. In contrast, we found that differences between LV parameters measured in the first week of life and those measured in subsequent weeks were so large that separate reference intervals were required for these 2 periods. The Central Illustration presents an example of z-

Conclusions

We present reference intervals and z-scores for 10 LV echocardiographic parameters based on a cohort of 13,454 healthy children examined in the first 30 days of life, filling a pressing need for echocardiographic reference material for infants. Normative data are crucial to the evaluation and optimal management of patients with heart disease, and our results provide a useful tool for evaluating LV echocardiographic measurements in newborns.

COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS:

Funding Support and Author Disclosures

This work was supported by the Danish Heart Foundation, the Lundbeck Foundation, King Christian X’s Foundation, Carl and Ellen Hertz’s Foundation for Danish Medical and Natural Sciences, and The Hede Nielsen Family Foundation. The funders played no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of manuscripts; or in decisions to publish results. The authors have reported that they have no relationships relevant to the contents of this

References (34)

  • S.D. Colan et al.

    The ventricular volume variability study of the pediatric heart network: study design and impact of beat averaging and variable type on the reproducibility of echocardiographic measurements in children with chronic dilated cardiomyopathy

    J Am Soc Echocardiogr

    (2012)
  • K. Ichihashi et al.

    Changes in ventricular and muscle volumes of neonates

    Pediatr Int

    (1999)
  • A.J. Rein et al.

    Left ventricular mechanics in the normal newborn

    Circulation

    (1987)
  • H. Popat et al.

    Noninvasive assessment of the early transitional circulation in healthy term infants

    Neonatology

    (2012)
  • S.L. Lindstedt et al.

    Use of allometry in predicting anatomical and physiological parameters of mammals

    Lab Anim

    (2002)
  • J.M. Tanner

    Fallacy of per-weight and per-surface area standards, and their relation to spurious correlation

    J Appl Physiol

    (1949)
  • T.G. Neilan et al.

    Derivation of a size-independent variable for scaling of cardiac dimensions in a normal paediatric population

    Eur J Echocardiogr

    (2009)
  • Cited by (0)

    Listen to this manuscript's audio summary by Editor-in-Chief Dr Valentin Fuster on www.jacc.org/journal/jacc.

    The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

    Drs Boyd and Bundgaard share last authorship.

    View full text