**3.1 Effects on the lung**

The inflammatory cytokines that reach the amniotic fluid will have an effect on the development of the fetal lung. Chorioamnionitis is an important risk factor for bronchopulmonary dysplasia. In neonates whose mothers had increased cytokine levels in the amniotic fluid: IL-8, IL-8, IL-1β and TNF-α, severe forms of bronchopulmonary dysplasia were more frequent. The pathological examination of the placenta can provide important information about the placental inflammatory process. Among our cases, we had a patient with a severe form of bronchopulmonary dysplasia, with oxygen requirements until the age of 4 months, without a history of severe respiratory distress, but with abscess areas, extensive inflammation evidenced by the pathological examination of the placenta and umbilical cord (**Figures 1** and **2**). The mother showed no clinical symptoms, but inflammatory syndrome and premature rupture of membranes were evidenced 14 days prior to labor [11].

Although there are meta-analyses showing a weak association between inflammation and bronchopulmonary dysplasia, animal studies have revealed significant inflammation in the lungs after endotoxin injection in preterm lambs [12]. Inflammatory mediators have effects on the regulation of angiogenesis, morphogenesis and cell growth in the lungs [13].

Bronchopulmonary dysplasia is more frequent in extreme preterm neonates. It may have a long-term effect on respiratory function during childhood or even adulthood. These children at school age will have an increased risk to develop asthma phenotype. Treatments used in bronchopulmonary dysplasia can also have adverse effects that will be validated in the medium or long term. Thus, prolonged use of corticoids in severe disease forms can have an impact on neurological

**Figure 1.** *Amniotic membrane inflammation [11].*

**Figure 2.** *Inflammation in the umbilical cord [11].*

development; prolonged use of diuretics may influence auditory bone development in the newborn [11]. Studies have shown airway obstruction in prematurely born children or adults with a history of BPD [14]. Other factors favoring the development of the disease in preterm infants are delivery by cesarean section, infections, antibiotic therapy. The risk of infections increases with the decrease of gestational age. Humoral and cellular immunity is not prepared for extrauterine life in newborns with small gestational age.

Recent research has highlighted a correlation between microbiota and immunity, i.e. the presence of a lung - intestine axis regarding mucosal status.

Multivariate logistic regression analysis of a neonatal cohort (2527 neonates with BPD and 12826 unaffected controls) revealed that neonatal sepsis is a risk factor for BPD. Breast milk and probiotics play a role in reducing BPD incidence in preterm infants [15].

In BPD, there are changes in pulmonary vascularization, the number of alveoli, the reduction of septation, the simplification of alveolar structure with an impact on gas exchanges.

In the lungs, there is an inflammatory process mediated by pro-inflammatory cytokines, inflammation being maintained by mechanical ventilation, oxygen administration and infection. The cytokine level will depend on the duration of mechanical ventilation, tidal volume and the type of ventilation used.

Preterm neonates with BPD have in their cord blood a high level of Th17 compared to unaffected newborns [16]. A study analyzing the serum of newborns with BPD revealed high levels of Il-6, IL-8 and granulocyte–colony stimulating factor (G-CSF) in the first week of life [17].
