Tamara van Donge

Chapter 2 30 corticotrophin-releasing hormone (CRH) levels. 33-35 The ability to diagnose the exposure during pregnancy after birth by neonatal hair has evolved. In neonates, hair grows during the last trimester of pregnancy. A positive neonatal hair test (for opioids, cannabinoids, etc.) can reflect fetal exposure, even long after the pregnant woman became aware of her pregnancy, making hair an easily available carrier for biomarkers of maternal drug dependence. 24,34 Assessing the CRH levels during the third trimester of pregnancy can provide insights on the risk of obesity later in life. Elevated placental CRF has been shown to be associated with catch-up growth, which has been shown to be a prognostic factor for increased metabolic activity and, therefore, obesity. 33 Neonatal life and pharmacotherapy: do we need new dosing strategies? From a pharmacological point of view, neonates are considered as a separate subpopulation, different from small children and adults. 2 In order to provide evidence-based and tailored dosing recommendations, it is clear that we first need to have a clear understanding of the physiological changes that occur during the neonatal period (first 28 days of life). Levels of gastric pH after birth are unclear because of contradicting information. 2,36,37 An acidic gastric pH has been observed in preterm neonates, but oral ingestion of acid- buffering milk might result in an increase in gastric pH values. Gastric emptying is an important factor for intestinal drug absorption and appears not to be driven by age, but by type of food intake. 38 The extracellular and total-body water compartments differ vastly between newborns, infants, children, adolescents and adults. 2,39 This causes water-soluble drugs (e.g. aminoglycosides) to distribute into a larger physiological (extracellular) space in neonates; in order to reach effective drug exposure, they require higher dosages (Figure 1). The distribution of drugs in the central nervous system is different in newborns versus children and adults. Due to decreased protein binding, a higher ratio of cerebral to systemic blood flow and a higher relative brain weight, the concentrations in brain are likely to be higher in newborns. 39,40 Drug- metabolizing enzymes play an important role in the transformation of xenobiotics. Overall, three different developmental trajectories can be observed according to the ontogeny of drug-metabolizing enzymes. 27 During gestation, group 1 of these drug- metabolizing enzymes become highly active but are only expressed at low levels after birth (e.g. CYP3A7). The second group consists of enzymes which are expressed at constant levels during gestation and after birth. In the last group, the enzymes are present which expression is observed within the first two years of life. 27 The renal clearance increases with advancing gestational age, postnatal age and body weight. 2 The creatinine clearance remains the best measurement of the assessment of GFR in this population, although it is widely known that assessment of serum creatinine levels during the first days after birth is rather a reflection of the mother’s renal function