Antenatal infection in the rabbit impairs postnatal growth and lung alveolarization

¹ Dépt de Périnatologie, Hôpital Mère Enfant, CHU de Nantes, Nantes, France; and UPRES EA 3826, Université de Nantes, Nantes Atlantique Universités, Thérapeutiques Cliniques et Expérimentales des Infections, EA3826, UFR Médecine, Nantes, France
² Dépt de Périnatologie, Hôpital Mère Enfant, CHU de Nantes, Nantes, France
³ INSERM U841, Institut Mondor de Recherche Biomédicale, Equipe 6, Créteil, France; and premUP, Paris, France
⁴ INSERM U539, Faculté de Médecine de Nantes, Nantes, France
⁵ INSERM U841, Institut Mondor de Recherche Biomédicale, Equipe 6, Créteil, France; Université Paris 12, Faculté de Médecine, IFR10, Créteil, France; and premUP, Paris, France
⁶ premUP, Paris, France; and INSERM U767, Faculté de Pharmacie, Paris, France

	Abstract

Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. We hypothesized that in the rabbit, antenatal infection may impair lung development after birth despite effective maternal antibiotic therapy.

Pregnant rabbits received an intrauterine inoculation of 10³ Escherichia coli CFU 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 alveolarization for the first two weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently.

Intrauterine 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.