Fetal Growth Restriction in Preterm Infants and Cardiovascular Function at Five Years of Age

Mikkola, Kaija; Leipälä, Jaana; Boldt, Talvikki; Fellman, Vineta

doi:10.1016/j.jpeds.2007.04.030

Cited by 56 publications

(49 citation statements)

References 34 publications

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“…Our findings are similar those reported in a smaller cohort of 5‐year‐old children 25. Many participants suffered from postnatal growth restriction in infancy, and this has been explained by suboptimal neonatal nutrition.…”

Section: Discussionsupporting

confidence: 90%

The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6‐Year‐Old Survivors of Periviable Births

Mohlkert

Hallberg

Broberg

et al. 2018

JAHA

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BackgroundPreterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start.Methods and ResultsIn total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22–26 weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off‐line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance.ConclusionsSix‐year‐old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same‐aged children born at term.

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Section: Discussionsupporting

confidence: 90%

The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6‐Year‐Old Survivors of Periviable Births

Mohlkert

Hallberg

Broberg

et al. 2018

JAHA

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“…Baseline echocardiographic results were similar to those in previously published studies [14,15] which revealed smaller heart (LV, RV and LA) dimensions in the group of ELBW children than in the control group. After expressing the results as z-scores for BSA, statistically significant differences were observed for diastolic diameters of both ventricles and the volume of the left one.…”

Section: Discussionsupporting

confidence: 89%

From a Regional Cohort of Extremely Low Birth Weight Infants: Cardiac Function at the Age of 7 Years

et al. 2013

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Background: The long-term impact of prematurity on cardiac structure and function has not yet been fully discovered. Objectives: To assess long-term cardiac complications in the regional cohort of extremely low birth weight (ELBW) children born in 2002-2004. Material and Methods: Eighty-one children born as ELBW infants (91% of the available cohort) with a median birth weight of 890 g (25-75th percentile: 760-950) were evaluated at the mean age of 6.7 years. The control group included 40 children born full-term, selected from one general practice in the district. Echocardiography and 24-hour ambulatory blood pressure measurements (ABPM) were performed. The primary outcome variable was the presence of cardiac complications such as left ventricular hypertrophy (LVH), diastolic dysfunction or systolic dysfunction. Results: LVH was diagnosed in 4/81 ELBW children and 2/40 control children (p = 1.0). Concentric remodeling was detected in 8 (10%) subjects from the ELBW group and in 2 (5%) from the control group (p = 0.49). There were no patients with diastolic or systolic dysfunction in either group. After having expressed the results of M-mode echocardiography as z-scores for body surface area (BSA), statistically significant differences were observed for right-ventricle dimension in diastole (-1.49 ± 1.25 vs. -0.31 ± 0.91; p < 0.001), LV inner dimension in diastole (-0.53 ± 1.26 vs. 0.13 ± 0.94; p = 0.01) and left atrium (-0.93 ± 1.07 vs. -0.15 ± 1.02; p < 0.01). Heart rate (HR) was significantly faster in ELBW children (92.9 ± 8.4 vs. 86.7 ± 7.4 bpm; p = 0.01 adjusted for BSA) and they also had significantly higher night-time blood pressure [mean (z-score): 1.15 vs. 0.2; p = 0.02] without nocturnal dipping (night-time dipping <10%: 13 (16.7%) vs. 2 (5.2%), p = 0.13). Conclusions: No differences were found between the groups in the occurrence of cardiac complications. Ex-preterm ELBW children at age 6 may have a faster HR, smaller cardiac dimensions on echocardiography and higher nocturnal blood pressure. The clinical relevance of these findings is unknown.

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“…36,37 To our knowledge, however, very few studies have evaluated the cardiac repercussions of preterm birth itself. Mikkola et al 38 reported increased interventricular septum thickness and decreased LV end-diastolic diameter in 5-year-olds born at 28 weeks of gestation as compared with values of a reference population. Thus, current data corroborate clinical and epidemiological data suggesting that neonatal high O 2 exposure in an immature individual could be a risk factor for cardiac disease at adult age.…”

Section: Discussionmentioning

confidence: 97%

Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin–Angiotensin System

et al. 2014

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Abstract-Perinatal conditions (such as preterm birth) can affect adult health and disease, particularly the cardiovascular system. Transient neonatal high O 2 exposure in rat in adulthood (a model of preterm birth-related complications) leads to elevated blood pressure, vascular rigidity, and dysfunction with renin-angiotensin system activation. We postulate that neonatal hyperoxic stress also affects myocardial structure, function, and expression of renin-angiotensin system components. Sprague-Dawley pups were kept with their mother in 80% O 2 or in room air (control) from days 3 to 10 of life. Left ventricular function was assessed in 4-, 7-, 12-week-old (echocardiography) and in 16-week-old (intraventricular catheterization) male O 2 -exposed versus control rats. At 16 weeks, hearts from O 2 -exposed rats showed cardiomyocyte hypertrophy, enhanced fibrosis, and increased expression of transforming growth factor-β1, senescence-associated proteins p53 and Rb, upregulation of angiotensin II type 1 (AT1) receptor expression (protein and AT1a/b mRNA), and downregulation of AT2 receptors. At 4 weeks (before blood pressure increase), the expression of cardiomyocyte surface area, fibrosis, p53, and AT1b was significantly increased and AT2 decreased in O 2 -exposed animals. After 4 weeks of continuous angiotensin II infusion (starting at 12 weeks), O 2 -exposed rats developed severe heart failure, with impaired myocardial mechanical properties compared with saline-infused rats. Transient neonatal O 2 exposure in rats leads to left ventricular hypertrophy, fibrosis and dysfunction, and increased susceptibility to heart failure under pressure overload. These results are relevant to the growing population of individuals born preterm who may be at higher risk of cardiac dysfunction when faced with increased peripheral resistance associated with hypertension, vascular diseases, and In cardiovascular disease, RAS plays a major role in vascular dysfunction, cardiac hypertrophy, and fibrosis through Ang II acting predominantly on its type I receptor (AT1) 10,11 triggering downstream mechanisms such as the profibrotics transforming growth factor-β1 (TGF-β1) and hypoxic-inducible factor-1α (HIF-1α), 12 as well as senescence-associated pathways. 13Activation of the RAS in the kidneys, brain, and systemic vasculature plays a key role in the elevation and maintenance of BP in experimental models associated with deleterious perinatal conditions including transient neonatal high O 2 exposure. 6,14 However, the effect of neonatal pro-oxidant conditions on cardiac RAS components has not been reported. To determine whether neonatal hyperoxia exposure impaired cardiac development and predisposed to cardiac dysfunction, myocardial structure, and function, expression of cardiac RAS components, as well as TGF-β1, HIF-1α, and senescenceassociated proteins, was determined in young, 4-week-old, and adult, 16-week-old rats infused or not with Ang II. Materials and MethodsSprague-Dawley pups were kept with their mother in 80% O 2 using an oxyc...

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Fetal Growth Restriction in Preterm Infants and Cardiovascular Function at Five Years of Age

Cited by 56 publications

References 34 publications

The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6‐Year‐Old Survivors of Periviable Births

The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6‐Year‐Old Survivors of Periviable Births

From a Regional Cohort of Extremely Low Birth Weight Infants: Cardiac Function at the Age of 7 Years

Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin–Angiotensin System

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