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. 2017 Jul;82(1):36-46.
doi: 10.1038/pr.2017.96. Epub 2017 May 24.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

Christina Y L Aye  1 , Adam J Lewandowski  1 , Pablo Lamata  2 , Ross Upton  1 , Esther Davis  1 , Eric O Ohuma  3 , Yvonne Kenworthy  1 , Henry Boardman  1 , Samuel Wopperer  1 , Alice Packham  1 , Satish Adwani  4 , Kenny McCormick  4 , Aris T Papageorghiou  5 , Paul Leeson  1
Affiliations

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

Christina Y L Aye et al. Pediatr Res. 2017 Jul.

Abstract

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

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Conflict of interest statement

The authors declare no conflict of interest.

Supplementary material is linked to the online version of the paper at http://www.nature.com/pr

Figures

Figure 1
Figure 1
Flow diagram of study recruitment. A total of 392 individuals took part in the study for echocardiography imaging. One hundred and ninety two individuals were recruited during gestation (fetal studies) to undergo echocardiography scans, with n=55 (n=10 preterm; n=45 term, shown in teal) going on to take part in the postnatal studies. An additional n=200 individuals were recruited at birth (shown in dark blue) to take part in birth and 3-month postnatal age echocardiography scans (total n=255 postnatal studies, n=121 preterm; n=134 term).
Figure 2
Figure 2
Ventricular mass in preterm versus term-born infants. (a) (i) Left and (ii) right ventricular mass index change between birth and 3 months increases with degree of prematurity (P-value relates to one-way ANOVA). (b) Trajectories of (i) left and (ii) right ventricular mass from 15 weeks of gestation through to 3 months of postnatal age for term (red with gray points) and preterm (blue with blue points) infants, and (c) trajectories indexed for head circumference demonstrate the preterm postnatal cardiac hypertrophy. Dashed lines indicate 3rd, 50th, and 97th centiles. LV indicates left ventricular; RV right ventricular; HC head circumference. **P<0.05; **P<0.01; †P<0.001.
Figure 3
Figure 3
Ventricular function in preterm versus term-born infants. (a) Image demonstrates contoured four-chamber view on TomTec Image Arena 4.6 with figure that demonstrates a significantly higher ejection fraction in term (green) compared with preterm (blue) infants at birth that is no longer evident by 3 months of age. (b) Examples of M-mode measurements of tricuspid annular plane systolic excursion (TAPSE) that is significantly reduced in preterm (right) compared with term (left) infants at both birth and 3 months of age. (c) Examples of lateral mitral valve annular Tissue Doppler Imaging measures of early diastole velocities (E′) in term (left) and preterm (right) infants with corresponding pulsed-wave Doppler mitral valve inflow (E/A ratio). Lateral E′ is decreased and lateral E/E′ increased in preterm infants at 3 months of age. Error bars represent the standard error of the mean. *P<0.05; **P<0.01; †P<0.001.
Figure 4
Figure 4
Ventricular shape in preterm versus term-born infants. (a) Significant shape differences between term (green) and preterm (blue) infants at birth are mainly accounted for by ventricular size (mode 1 in principal component analysis) with convergence by 3 months of age. (b) Linear discriminant analysis (LDA) identifies five further modes (modes 2–6), which account for the majority of shape variation independent of size between term and preterm infants. These describe variation between a “globular” and “conical”-shaped ventricle. Further modes did not significantly increase the area under the curve (AUC), confirmed by cross-validation (leave one out). Blue arrows indicate combination of modes 2–5 and red arrows 2–6. (c) Shape variations (mode 2–6) at birth between term and preterm infants persist after size adjustment and, again, are reduced by 3 months of age. Brown and purple contours demonstrate ±3 SDs from mean. Colored dots indicate relative placing of groups within shape range (term—green, preterm—blue). *P<0.05; **P<0.01; †P<0.001.
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