Bibian van der Voorn

20 CHAPTER 1 EARLY POSTNATAL CARE AND STRESS In animals, offspring subjected to maternal separation, or nonhandling, in early life exhibited dysregulation of the HPA axis, impaired cognitive capabilities, increased anxiety-like behavior and alterations in limbic structures 89 . Similarly, rat mothers that engaged in low amounts of licking and grooming with their pups had offspring that, as adults, were more responsive to stress 90 . This was associated with persistent alterations in DNA methylation and histone acetylation at the hippocampal GR 1 7 promotor, affecting nerve growth factor 1-A binding 90 . In humans, those who had experienced poor quality of parental care, such as neglect or emotional or physical maltreatment, early in childhood showed greater HPA axis activity and were at risk for mental illnesses, cardiovascular diseases and diabetes mellitus 91 . Furthermore, a study in hippocampal tissue from suicide victims showed that childhood abuse was associated with increased DNA methylation at the GR promotor and decreased expression of GR mRNA 92 . It is unknown whether these observations could be extrapolated to preterm babies, who are separated from their mothers after birth and, instead, are exposed to the stressful environment of the NICU. During admission to the NICU, exposure to stressors like invasive procedures, pain, interruption of sleep states and noise is common. Neonatal procedural pain-related stress after very preterm birth, however, has been associated with indices of cortisol production and HPA axis reactivity 72,93,94 . NEONATAL NUTRITION There is increasing evidence to suggest thatmetabolic signalsmodify theHPAresponse to maternal separation 95 . In suckling mice, along with an increase in HPA axis activity, maternal separation elicited alterations in glucose, leptin and ghrelin concentrations 96 . Pharmacological manipulation of glucose or ghrelin levels attenuated the HPA response to maternal separation 96 . As adults, offspring subjected to prenatal or early postnatal malnutrition displayed greater HPA axis activity 95 . Current nutritional recommendations for preterm newborns advocate early introduction and rapid advancement of protein and energy 97 . Evidence from randomized trials and observational studies showed that strategies providing early, increased energy and protein support reduce nutritional deficits and improve neonatal growth and neurodevelopmental outcome 97 . In the intervention groups, amino acids and lipids were initiated early and rapidly increased to 3.5 – 4 g/kg per day. Nevertheless, in clinical practice, nutritional goals are rarely achieved and nutritional deficits ensue 98 . It is unknown whether this has life-long effects on the preterm human’s HPA axis.