**2. Preterm birth and preterm neonate particularities**

Preterm birth according to the World Health Organization (WHO) is defined as birth before 37 completed weeks of gestation. In 2010, 14.9 million babies were born preterm, accounting for 11.1% of all births worldwide. In European countries, preterm birth represents approximately 5% of all births, while in certain African countries this ratio is around 18% [1]. Preterm birth represent the leading cause of childhood mortality in children under 5 years of age [2]. The high economic burden is generated by the neonatal intensive care, often followed by ongoing health care needs and a significant emotional impact experienced by families [3].

Preterm birth may occur spontaneously or based on a medical indication. About one third of all preterm births have a medical indication, determined by maternal or fetal risk factors, which are higher than the benefits generated by the continuation of pregnancy and include preeclampsia or diabetes mellitus [4]. Approximately 70% of preterm births are spontaneous, caused by premature rupture of membranes, preterm labor [4]. Preterm labor in about half of the cases is associated with inflammatory syndrome, with sustained inflammation. Preterm labor has a complex etiology; it can be induced by many factors: infection or inflammation, uteroplacental hemorrhage, placental ischemia, uterine overdistension or stress [5]. Maternal risk factors with a role in triggering preterm labor are numerous: extreme ages of the mother, high body mass index (BMI), multiple gestation, assisted reproductive technologies, history of preterm birth, and low socioeconomic status [4]. Race is also an important risk factor; African-Americans are at higher risk of preterm birth than other ethnic groups [5].

Preterm birth is an important cause of morbidity and mortality in the newborn. The pathologies induced by preterm birth are both acute and chronic. Chronic diseases may have a long-term impact on the health of preterm neonates, affecting their neurodevelopmental outcome in variable degrees.

The main acute disorders associated with preterm birth are: respiratory distress, cerebral hemorrhage, periventricular leukomalacia, necrotizing enterocolitis (NEC), while the most frequent chronic diseases with an impact on the development and long-term prognosis of newborns are: bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, and abnormal neurological development.

Prematurely born adults will have an increased risk of hypertension at adult age, diabetes mellitus and obesity [4].

The evolution of preterm infants is dependent on sex. Some studies showed that at the age of 2 years, chronic respiratory and neurological complications were more frequent among male compared to female preterm newborns [6].

Cytokines play an important role in initiating and regulating labor. Labor occurs under pro-inflammatory conditions with the participation of cytokines. In this pro-inflammatory environment, a three-step process takes place, which is characterized by uterine contractility, cervical ripening and membrane activation/ rupture [7].

There will be a considerable release of interleukin IL-1 β, IL-6 and IL-8, and tumor necrosis factor alpha (TNF-α). These pro-inflammatory substances will be released by stromal cells as well as monocytes and neutrophils that invade the myometrium and the cervix during labor. IL-1β and TNF-α will cause myometrial contraction through calcium influx in myometrial smooth muscle cells. Myometrial contraction is also stimulated by prostaglandins: PGF 2α and PGE 2.

Chemotactic activity and cytokine production differ in the case of premature rupture of membranes compared to term rupture of membranes. In the decidua, leukocyte infiltration occurs during labor. The number of neutrophils that infiltrate the decidua is much higher in the case of preterm labor with associated infection. In addition to neutrophils, the number of macrophages also increases, but this increase is present in both term and preterm labor [8].

Nuclear factor kB (NF-kB), which plays a role in the synthesis of prostaglandins and the regulation of matrix metalloproteinase (MMP) expression, thus influencing myometrial contraction and cervical ripening, should also be mentioned.

Chorioamnionitis is an inflammation caused by bacterial infections in the fetal membrane. This may induce different severe disorders in newborns, such as necrotizing enterocolitis, cerebral palsy or patent ductus arteriosus. These complications will have an immediate and long-term impact on the evolution of the neonate [9].

Inflammatory mediators will reach the fetus through the amniotic fluid or by transmission through the umbilical cord [10].
