Perinatally acquired organ injury affects both term and preterm infants. Depending on the timing of injury and/or delivery, infants need to cope with different challenges. In the developing brain of a preterm infant, the spectrum of injury suggests that the underlying pathophysiology is not due to a single lesion but consists of white and gray matter disturbances [
1]. Thus, a comprehensive multidimensional assessment of potential contributing factors such as maternal medical history, obstetric antecedents, intrapartum factors (including fetal heart rate monitoring results and issues related to the delivery itself), and placental pathology is recommended [
2]. In the term-born infants, perinatal insults such as birth asphyxia or perinatal stroke affect 1 to 3 newborns out of 1000 [
3,
4]. In contrast, in preterm-born infants morbidity and mortality strongly relate to the gestational age. While preterm birth before 37 weeks of gestation occurs in 5–8 % of all pregnancies, very low gestational age (VLGA) before 32 weeks of gestation occurs in about 1 % of singletons and 9 % of twin pregnancies [
5]. Mortality of VLGA infants ranges between 7.3 and 21.4 % at 30 days and 9.0 and 22.7 % at 1 year [
6]. Additionally, a large number of survivors suffer significant long-term disabilities including cerebral palsy (CP), epilepsy, increased hyperactivity, and developmental disorders [
7]. For example, the risk to develop CP is 30 times higher in infants born before 33 weeks of gestation compared to term-born infants [
8]. Moreover, injury in these infants is frequently exacerbated by fetal inflammation and preferentially affects cerebral white matter resulting in periventricular leukomalacia and germinal matrix hemorrhage [
1]. Currently, the only intervention known to reduce the burden of perinatal brain injury in the term population is hypothermia. Several large clinical trials confirmed that hypothermia in infants with neonatal hypoxic-ischemic encephalopathy is associated with a significant reduction in death and disability [
9]. However, 40–50 % of infants treated with hypothermia still die or develop significant neurological disability [
10]. In the preterm population, therapeutic options are lacking as hypothermia is contra-productive. Antenatal magnesium sulfate prior to birth at less than 30 weeks of gestation reduces CP and combined CP and mortality rate at 2 years of age. However, randomized control trials do not demonstrate long-term neurological benefits [
11,
12]. Approximately 25 % of VLGA infants will develop BPD with long-lasting consequences such as chronic respiratory impairment and neurodevelopmental delay [
13]. Changes in clinical management reduced the incidence of BPD significantly with a shift from VLGA to extreme low gestational age newborns developing BPD. Not surprisingly, the current pathogenesis of BPD is based on immaturity with disordered alveolar and capillary development and represents a developmental disorder [
14]. The plasticity of the developing lung after preterm birth is poorly understood. Long-term follow-up studies suggest an incomplete regeneration of the lung growth in survivors with BPD. Current treatment options for BPD include vitamin A and caffeine in addition to supportive therapies, but their results often remain unsatisfactory [
15].