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. Graphical abstract

Second Trimester Amniotic Fluid Angiotensinogen Levels Linked to Increased Fetal Birth Weight and Shorter Gestational Age in Term Pregnancies

“…A recently published study has explored the correlation between FGR, including SGA cases and preterm birth, and kidney size and kidney function by measuring several biochemical markers, such as the renin-angiotensin-aldosterone system (RAAS), in adolescents. Although the researchers observed that FGR and preterm birth were associated with smaller total kidney volume, no statistical difference in the biochemical markers of kidney function or RAAS components, including angiotensinogen, was found in this study, which is in accordance with our own angiotensinogen findings [46]. Moreover, these findings were consistent with the previous results of research into fetal growthrestricted sheep wherein the researchers reported significant reductions in the sheep's kidney weight but no evidence of alteration in the renal RAS components [47].…”

Placental Nanoparticle-mediated IGF1 Gene Therapy Corrects Fetal Growth Restriction in a Guinea Pig Model

“…The abnormal growth and development of these organs from FGR are what lead to childhood and adulthood morbidities that increase risks associated diseases such as fatty liver disease, obesity, and cardiovascular disease 6,7,32 . Studies identifying the precise malperfusions and functional consequences have been and continue to be investigated for these various organ systems [48][49][50][51][52][53] . We are the first to show a treatment correcting fetal growth and one of the most prominent and significantly disordered features of FGR.…”

Placental Malaria Induces a Unique Placental Methylation Profile Associated with Fetal Growth Restriction

“…Early onset FGR (<32 weeks gestation) and severe FGR (<3 rd percentile) are associated with up to 1.5-fold increased risk of stillbirth and a 2 to 5-fold risk of perinatal death (9). Long term complications of FGR include increased childhood morbidity, and even cardiovascular, metabolic, and neuropsychiatric diseases in adulthood (2,4,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Non-malarial etiologies of FGR include maternal comorbidities, placental dysfunction, genetics, and environmental exposures (e.g.…”