**4.1 Adverse factors in the** *in utero* **environment**

Two potential factors in the *in utero* environment that may render the preterm kidney vulnerable are IUGR and/or exposure to chorioamnionitis.

### **4.1.1 Intrauterine growth restriction**

IUGR (growth below the 10th percentile for gestational age) is often a co-morbidity of preterm birth. Certainly, it is well described in both human and experimental models that IUGR leads to a reduced nephron endowment at birth (Hinchliffe et al., 1992a; Merlet-Benichou et al., 1994; Manalich et al., 2000; Zimanyi et al., 2004; Zohdi et al., 2007). This is likely due to the reduced growth of the fetal kidney (with the number of nephrons directly proportional to kidney size). In this regard, there is often redistribution of blood flow in the growth-restricted fetus, leading to preferential blood flow to the brain (termed brain sparing) and reduced blood flow to organs such as the kidneys (Behrman et al., 1970; Gunnarsson et al., 1998). To our knowledge the impact of reduced blood flow to the formation of nephrons in the IUGR fetal kidney has not been investigated. Given the dramatic change in hemodynamics at the time of birth (elevation in blood pressure and increased renal blood flow) it is conceivable that the recently formed glomeruli in the IUGR kidney (with a reduced renal blood flow prenatally) may be particularly vulnerable to the haemodynamic transition at birth. This is an important area of research that needs to be thoroughly investigated.
