Tamara van Donge

Chapter 7 138 Table 4: Median [95% prediction interval] values for Scr concentration and creatinine clearance (CrCL) for various postnatal days for three different typical individuals of 24, 27 and 32 weeks of gestation, retrieved from simulations (n=1000), Volume of distribution is based on median weight (Wt) and fixed to 0.7 L/kg. Postnatal age 24 weeks GA Wt (g) Scr (mg/dl) CrCL (ml/min) Day 1 621 0.50 [0.31 - 0.81] 0.22 [0.14 - 0.37] Day 3 631 0.90 [0.58 - 1.24] 0.26 [0.15 -0.44] Day 7 658 0.79 [0.49 - 1.41] 0.33 [0.18 -0.52] Day 14 724 0.57 [0.38 - 1.11] 0.44 [0.23 -0.65] Day 21 795 0.49 [0.33 - 0.87] 0.51 [0.29 -0.74] Day 28 882 0.43 [0.31 - 0.69] 0.56 [0.36 -0.78] Day 35 992 0.41 [0.30 - 0.61] 0.60 [0.41 -0.82] Day 42 1132 0.39 [0.29 - 0.55] 0.63 [0.45 -0.84] Fifth, the effect of MOD on Scr concentrations and associated creatinine clearance in our analysis has not been shown before, but co-aligns with the AWAKEN study data, as these authors also observed a positive effect of C-section on the incidence of AKI. 22,24 It is known that MOD is one of many factors that can influence neonatal physiology, as the recent study by Charlton et al. showed that neonates who were born by scheduled C-section were subjected to a 30% lower probability of acute kidney injury. 24 As acute kidney injury was defined as a Scr increase (0.3 mg/dl), this finding is in accordance with our observations as higher Scr concentrations and lower creatinine clearances were observed for ELBW neonates who were born by vaginal delivery (Figure S2). It has been shown that infants delivered by C-section are subjected to a higher risk for pulmonary hypertension due to the blunted decrease of pulmonary vascular resistance compared to vaginal delivery. 25 Therefore, it might be probable that MOD modulates kidney (function) during early neonatal life since it depends on the vasoconstriction of renal vasculature and its postnatal adaptation pattern, although this hypothesis requires further investigation and more controlled studies. Besides neonatal physiology, maternal morbidities such as preeclampsia and hypertensive disorders are often underlying causes for performing C-section. Whether these maternal morbidities are the cause of lower creatinine concentrations during postnatal life needs to be investigated. However, it is reasonable to anticipate that such maternal morbidities would rather result in higher neonatal Scr concentrations in early neonatal life due to the higher maternal Scr associated with these morbidities. 3