Sanne Hoeks

Chapter 1 16 PERINATAL TO ADULT IMMUNE DEVELOPMENT Most research on the neonatal immune system has been performed with cord blood (CB) cells as a representative for the neonatal immune system. Though, this approach ignores the dynamic changes after birth but several ethical issues hamper research on children and especially neonates since withdrawal of blood is invasive, painful and a relatively large volume of the blood is required for functional immunological tests (10 ml of blood is 3,5% of the total blood volume in a term born baby). Therefore blood of (healthy) new-born babies and infants must be proportional to these issues, especially in repetitive blood sampling, which is needed to address questions on (functional) immune maturation. In this thesis, we describe two alternative methods to address these questions on immune maturation. First, we followed newborns with a lip and/or palate cleft into their first year of life. This diagnosis is usually antenatally made and these infants need repetitive surgery at fixed time points in their first year of life. Therefore we were able to draw blood from the cord and subsequently three preoperative samples when the intravenous line was placed before surgery. We hypothesized that these infants represent healthy infants since their immune system is considered healthy. Despite some unsolved questions like the influence of anesthetics and perioperative antibiotics on immune maturation, this method generated new data about physiological immune maturation. Subsequently, we evaluated functional immune maturation in newborns with a viral infection. In this group of infants we generated ex vivo data of immune characteristics as a model for ultimate stress on the immune system.