The impact of intrauterine growth retardation on glomerular filtration rate

Introduction: Intrauterine growth retardation (IUGR) is a multifactorial, pathological entity, resulting in small-for-gestational-age (SGA) newborns. These neonates have higher mortality and morbidity rates in perinatal life and are at risk for the development of adult hypertension and related cardiovascular diseases. Congenital oligonephropathy has been postulated as the primary mechanism.

Objective: To determine whether IUGR is a predisposing factor for reduction of glomerular filtration rate (GFR) at birth.

Methods: Clearance of amikacin (Cl) was used since clearance of aminoglycosides reflects GFR. Clinical characteristics (gestational age, weight) and amikacin pharmacokinetics were retrospectively collected in a cohort of 305 preterm infants [<34 weeks gestational age (GA), early neonatal life] in whom paired amikacin samples were collected for therapeutic drug monitoring before and following administration of the second dose.(1,2) Pharmacokinetics were calculated assuming a one-compartment model with instantaneous input and first order output. Amikacin Cl (ml/kg/min) and distribution volume (l/kg) was compared between appropriate-for-GA (AGA) and SGA infants (<10th percentile for GA) (Mann-Whitney U).

Results: 262 infants were AGA, 43 infants were SGA. No significant differences were observed in Cl and in distribution volume (Vd) between both groups.

• AGA (n=262) SGA (n=43) p

• Birth weight (g) 1281 (SD 436) 714 (SD 226) <0,001

• GA (weeks) 29 (SD 2.3) 28 (SD 2.2) NS

• Vd (l/kg) 0.59 (SD 0.35) 0.56 (SD 0.29) NS

• Cl (ml/kg/min) 0.49 (SD 0.2) 0.48 (SD 0.45) NS

Conclusions: These retrospective data fail to support the hypothesis that neonates with IUGR already have impaired GFR at birth. Hence, prenatal growth does not appear to contribute to interindividual variability in amikacin clearance.

References: (1) Ped Nephrol 2005;20:740–3. (2) Br J Clin Pharmacol 2006;61:34–41.