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

Abstract

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.

Keywords: Adolescence; Angiotensinogen; Fetal growth restriction; Kidney function; Kidney parenchyma; Kidney volume; Renal cortical volume; Renal medullary volume; Very preterm.

A higher resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

MR images with delineations for renal cortical and medullary volumes (A), and for renal parenchymal T1 (B) and T2* (C) values. A transaxial image of the left kidney for volume measurements without delineations (A; left), and with cortical (A; middle) and medullary delineations (A; right). A coronal image of the left kidney for T1 mapping measurements without delineations (B; left), and with cortical (B; middle) and medullary delineations (B; right). A coronal image of the left kidney for T2* measurements without delineations (C; left), and with cortical (C; middle) and total parenchymal delineations (C; right). Renal parenchymal borders are depicted by black lines, and non-parenchymal tissue removed from volume (A) are depicted by white lines. For T1 and T2* values delineations were placed to avoid partial volume effects. Both left and right kidneys were delineated

Fig. 2

Kidney volumes normalized for body surface area. Total kidney volumes (left column), cortical volumes (middle column), and medullary volumes (right column) are shown for both sexes combined (upper row), boys (middle row), and girls (lower row) in adolescents born preterm with fetal growth restriction (preterm FGR), preterm with birth weight appropriate for gestational age (preterm AGA), and born at term (term AGA). Girls born preterm due to FGR had smaller BSA-adjusted parenchymal volumes compared to girls born term AGA. FGR, fetal growth restriction; AGA, appropriate for gestational age