**4.3.1 Glucocorticoids**

In addition to leading to lung maturation in the preterm infant, administration of glucocorticoids has been favourably reported to accelerate renal maturation thus establishing an adequate GFR and efficient tubular reabsorption (Ervin et al., 1996; Ervin et al., 1998; Petershack et al., 1999). However, the question remains: 'Does this acceleration in renal maturation lead to an abnormal and rapid cessation of nephrogenesis which would ultimately affect nephron endowment? In support of this, a number of experimental studies (conducted in animal models) have shown that exposure of the fetus to maternal glucocorticoids can lead to reduced nephron endowment in the offspring (Celsi et al., 1998; Ortiz et al., 2001; Moritz et al., 2002). As follow up to these studies, in a carefully controlled study in our baboon model we have examined the effect of administration of antenatal betamethasone (intramuscular injection of 6mg at 48 hours and 24 hours prior to preterm delivery) on nephrogenesis in the neonatal baboon kidney (Gubhaju et al., 2009). We found that although there was acceleration of glomerular maturation in the betamethasone-treated baboons, the total number of nephrons was within the normal range and importantly we demonstrated that fetal exposure to maternal glucocorticoids was not the cause of the glomerular abnormalities associated with preterm birth.

## **4.3.2 Antibiotics**

The use of antibiotics is often essential in the treatment of the mother during pregnancy and of the preterm infant after birth. Alarmingly, it has been shown that antibiotics, such as the aminoglycosides, can be nephrotoxic in the newborn with the preterm infant most vulnerable (Giapros et al., 2003). This is of concern, given that aminoglycosides are not metabolised in the body and thus accumulate in the kidney where they are eventually

ongoing after birth in the preterm infant, this provides a window of opportunity whereby early postnatal nutrition in the intensive care unit may be able to directly influence the number of nephrons formed within the kidney. Hence optimising nutrition in the neonatal period, with an aim to maximising nephron endowment in the preterm newborn, is an important area for future research. At this stage, there is no known maternal nutrient supplementation that can improve renal outcomes in the fetus; it is critical to

There are a number of medications routinely administered to women during pregnancy and to preterm infants. Some of the most commonly used are: 1) antenatal glucocorticoids which are routinely administered either to the mother 'at risk' of preterm delivery (Vidaeff et al., 2003) or to the preterm infant immediately after delivery to accelerate lung maturation in the infant, 2) antibiotics, often administered to the mother with chorioamnionitis and to the infant with postnatal conditions such as necrotising enterocolitis (Gortner et al., 1991) 3) non steroidal anti-inflammatory drugs (such as ibuprofen and indomethacin) which are often administered to close a patent ductus arteriosus (Ellison et al., 1983) and 4) inotropes (such as dopamine and dobutamine) which are administered in cases of hypotension and poor blood flow (Osborn et al., 2002). Importantly, and of concern, all these medications have the

In addition to leading to lung maturation in the preterm infant, administration of glucocorticoids has been favourably reported to accelerate renal maturation thus establishing an adequate GFR and efficient tubular reabsorption (Ervin et al., 1996; Ervin et al., 1998; Petershack et al., 1999). However, the question remains: 'Does this acceleration in renal maturation lead to an abnormal and rapid cessation of nephrogenesis which would ultimately affect nephron endowment? In support of this, a number of experimental studies (conducted in animal models) have shown that exposure of the fetus to maternal glucocorticoids can lead to reduced nephron endowment in the offspring (Celsi et al., 1998; Ortiz et al., 2001; Moritz et al., 2002). As follow up to these studies, in a carefully controlled study in our baboon model we have examined the effect of administration of antenatal betamethasone (intramuscular injection of 6mg at 48 hours and 24 hours prior to preterm delivery) on nephrogenesis in the neonatal baboon kidney (Gubhaju et al., 2009). We found that although there was acceleration of glomerular maturation in the betamethasone-treated baboons, the total number of nephrons was within the normal range and importantly we demonstrated that fetal exposure to maternal glucocorticoids was not the cause of the

The use of antibiotics is often essential in the treatment of the mother during pregnancy and of the preterm infant after birth. Alarmingly, it has been shown that antibiotics, such as the aminoglycosides, can be nephrotoxic in the newborn with the preterm infant most vulnerable (Giapros et al., 2003). This is of concern, given that aminoglycosides are not metabolised in the body and thus accumulate in the kidney where they are eventually

**4.3 Pharmacological treatments to the mother prior to birth and / or the infant** 

investigate this.

**4.3.1 Glucocorticoids** 

**4.3.2 Antibiotics** 

potential to adversely impact on nephrogenesis.

glomerular abnormalities associated with preterm birth.

**after birth** 

eliminated (Nagai and Takano, 2004). In experimental studies antibiotics are also linked with impairment of nephrogenesis (Gilbert et al., 1990; Gilbert et al., 1994; Cullen et al., 2000; Nathanson et al., 2000). For instance, it has been shown that incubation of metanephroi in culture with gentamicin leads to decreased branching morphogenesis of the ureteric tree; this is a likely mediator of the reduction in the number of nephrons formed (Cullen et al., 2000). Given that antibiotics can readily cross the placenta, plus their wide use in the neonatal care of the preterm infant, it is imperative in future studies to gain a more precise understanding of the dose, duration and class of antibiotic treatment that leads to adverse effects in the neonatal kidney; such information would likely influence the care in the neonatal intensive care unit.
