Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation

Abstract

Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. The present authors hypothesised that, in the rabbit, antenatal infection may impair lung development after birth, despite effective maternal antibiotic therapy.Pregnant rabbits received an intra-uterine inoculation of 10 3 Escherichia coli colony forming units or vehicle at the end of gestation (day 29). Intravenous ceftriaxone therapy was initiated 8 h after inoculation for a period of 8 days. Pups born between 60 and 84 h after inoculation were kept with their mother until sacrifice on days 0, 1, 5, 8 and 15. Blood cultures from antenatally infected animals were sterile at birth. Postnatal growth was significantly impaired by day 8. Lung morphometry showed a significant decrease of alveolar surface density and interstitial density, with a significant increase of alveolar airspace volume, indicating impaired alveolarisation for the first 2 weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently.Intra-uterine infection in rabbits is, therefore, responsible for concomitant postnatal growth retardation and abnormal pulmonary development despite early and effective antenatal antibiotic therapy. This may constitute an alternative model to study the consequences of antenatal infection on postnatal growth and lung development.

Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin

“…Disrupted lung development has been demonstrated in animal models of chorioamnionitis (9,20,44,61,68), but other experimental studies showed that intra-amniotic inflammatory stimuli do not necessarily impair lung structure when assessed later during infancy (43,47). It has been suggested that the postnatal environment may interact with antenatal inflammation to further worsen late respiratory outcomes of preterm infants exposed to chorioamnionitis.…”

Forkhead box m1 mRNA expression of lung of preterm and term rabbits

“…In addition, reciprocal chromosome painting using human chromosomes showed complete homology in more than three chromosomes (7). Based on these observations, a rabbit seems to be a more appropriate model compared with other classical animal models for studying human lung development and various gene expressions during intrauterine and early neonatal life (11)(12)(13)(14).…”

The significance of E. coli treatment in perinatal period

“…However, the experimental studies on rabbits (animal model which resembles most the humans by chronological development of the alveoli) showed that untreated infection led to decreased respiratory alveolar surface (by 25%), leukomalacia, and postnatal retarded growth (by 60%) [14,15].…”

“…Th is may provide a window for pre-venting the white matter damage [14,25,26]. Screening for asymptomatic bacteriuria and treatment is recommended for selected groups such as pregnant women, where benefi t has been shown [2,3].…”