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

¹ Dept of Perinatology, Maternity and Paediatric Teaching Hospital, ² UPRES EA 3826, Nantes Atlantique University, School of Medicine, ⁵ INSERM U539, School of Medicine, Nantes, ³ INSERM U841, Mondor Institut of Biomedical Research, team 6, ⁶ Université Paris 12, School of Medicine, IFR10, Créteil, ⁴ premUP, Paris, and ⁷ INSERM U767, School of Pharmacy, Paris, France.

CORRESPONDENCE: C. Gras-Le Guen, Réanimation Pédiatrique, Hôpital Mère Enfant CHU Nantes, 38 Bd Jean Monnet, 44093 Nantes, France, Fax: 33 240083483E-mail: christele.grasleguen{at}chu-nantes.fr

Keywords: Bacterial infections, bronchopulmonary dysplasia

Received: February 14, 2008
Accepted July 23, 2008

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 10³ 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.