Early-Onset Fetal Growth Restriction Increases Left Ventricular Sphericity in Adolescents Born Very Preterm.

Left ventricular shape alterations predict cardiovascular outcomes and have been observed in children born preterm and after fetal growth restriction (FGR). The aim was to investigate whether left ventricular shape is altered in adolescents born very preterm and if FGR has an additive effect. Adolescents born very preterm due to verified early-onset FGR and two control groups with birthweight appropriate for gestational age (AGA), born at similar gestational age and at term, respectively, underwent cardiac MRI. Principal component analysis was applied to find the modes of variation best explaining shape variability for end-diastole, end-systole, and for the combination of both, the latter indicative of function. Seventy adolescents were included (13-16 years; 49% males). Sphericity was increased for preterm FGR versus term AGA for end-diastole (36[0-60] vs - 42[- 82-8]; p = 0.01) and the combined analysis (27[- 23-94] vs - 51[- 119-11]; p = 0.01), as well as for preterm AGA versus term AGA for end-diastole (30[- 56-115] vs - 42[- 82-8]; p = 0.04), for end-systole (57[- 29-89] vs - 30[- 79-34]; p = 0.03), and the combined analysis (44[- 50-145] vs - 51[- 119-11]; p = 0.02). No group differences were observed for left ventricular mass or ejection fraction (all p ≥ 0.33). Sphericity was increased after very preterm birth and exacerbated by early-onset FGR, indicating an additive effect to that of very preterm birth on left ventricular remodeling. Increased sphericity may be a prognostic biomarker of future cardiovascular disease in this cohort that as of yet shows no signs of cardiac dysfunction using standard clinical measurements.

Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction.

BACKGROUND: Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR). METHODS: Adolescents (14 (13-17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired. RESULTS: There were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1). CONCLUSIONS: Very preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR. IMPACT: Very preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys. In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness. In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness. Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence. Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.

Fetal growth restriction followed by very preterm birth is associated with smaller kidneys but preserved kidney function in adolescence.

BACKGROUND: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR. METHODS: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin-angiotensin-aldosterone system (RAAS) activation were analyzed. RESULTS: Sixty-four adolescents were included (13-16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups. CONCLUSIONS: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. A higher resolution version of the Graphical abstract is available as Supplementary information.

Pulse Wave Velocity Measurements by Magnetic Resonance Imaging in Neonates and Adolescents: Methodological Aspects and Their Clinical Implications.

Pulse wave velocity (PWV) by cardiovascular magnetic resonance (CMR) lacks standardization. The aim of this study was to investigate methodological aspects of PWV measurements by CMR in neonates and adolescents. A computer phantom was created to validate the temporal resolution required for accurate PWV. Fifteen neonates and 71 adolescents underwent CMR with reference standard 3D angiography and phase-contrast flow acquisitions, and in a subset coronal overview images. Velocity and flow curves, transit time methods (time-to-foot (TTF), maximum upslope, and time-to-peak (TTP)), and baseline correction methods (no correction, automatic and manual) were investigated. In neonates, required timeframes per cardiac cycle for accurate PWV was 42 for the aortic arch and 41 for the thoracic aorta. In adolescents, corresponding values were 39 and 32. Aortic length differences by overview images and 3D angiography in adolescents were - 16-18 mm (aortic arch) and - 25-30 mm (thoracic aorta). Agreement in PWV between automatic and manual baseline correction was - 0.2 ± 0.3 m/s in neonates and 0.0 ± 0.1 m/s in adolescents. Velocity and flow-derived PWV measurements did not differ in either group (all p > 0.08). In neonates, transit time methods did not differ (all p > 0.19) but in adolescents PWV was higher for TTF (3.8 ± 0.5 m/s) and maximum upslope (3.7 ± 0.6 m/s) compared to TTP (2.7 ± 1.0 m/s; p < 0.0001). This study is a step toward standardization of PWV in neonates and adolescents using CMR. It provides required temporal resolution for phase-contrast flow acquisitions for typical heartrates in neonates and adolescents, and supports 3D angiography and time-to-foot with automatic baseline correction for accurate PWV measurements.

Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes-A validation study.

BACKGROUND: Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. PURPOSE: To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. MATERIALS AND METHODS: Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13-16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5-97.5 percentiles. RESULTS: Agreement between MRI and ex-vivo quantification were -7 mL (-10-0 mL) for total parenchyma, -4 mL (-9-3 mL) for cortex, and -2 mL (-7-2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54-103 mL/m2 (boys) and 56-103 mL/m2 (girls) for total parenchyma, 39-62 mL/m2 and 36-68 mL/m2 for cortex, and 16-45 mL/m2 and 17-42 mL/m2 for medulla. CONCLUSION: The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.