Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep.

Objective: Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that Ureaplasma colonization of amniotic fluid would modulate chorioamnionitis induced by Escherichia coli lipopolysaccharide (LPS).

Study Design: Sheep received intraamniotic (IA) injections of media (control) or live Ureaplasma either 7 or 70 days before delivery.

High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome.

Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments.

Antenatal glucocorticoids counteract LPS changes in TGF-β pathway and caveolin-1 in ovine fetal lung.

Inflammation and antenatal glucocorticoids, the latter given to mothers at risk for preterm birth, affect lung development and may contribute to the development of bronchopulmonary dysplasia (BPD). The effects of the combined exposures on inflammation and antenatal glucocorticoids on transforming growth factor (TGF)-β signaling are unknown. TGF-β and its downstream mediators are implicated in the etiology of BPD.

Intraamniotic lipopolysaccharide exposure changes cell populations and structure of the ovine fetal thymus.

Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure.

Methods: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days).

The MANDATE model for evaluating interventions to reduce postpartum hemorrhage.

Objective: To create a comprehensive model of the comparative impact of various interventions on maternal, fetal, and neonatal (MFN) mortality.

Methods: The major conditions and sub-conditions contributing to MFN mortality in low-resource areas were identified, and the prevalence and case fatality rates documented. Available interventions were mapped to these conditions, and intervention coverage and efficacy were identified.

Physiology of transition from intrauterine to extrauterine life.

The transition from fetus to newborn is the most complex adaptation that occurs in human experience. Lung adaptation requires coordinated clearance of fetal lung fluid, surfactant secretion, and onset of consistent breathing. The cardiovascular response requires striking changes in blood flow, pressures, and pulmonary vasodilation.

Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner.

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d).

Moderate tidal volumes and oxygen exposure during initiation of ventilation in preterm fetal sheep.

Background: Preterm infants often receive mechanical ventilation and oxygen at birth. Exposure to large tidal volumes (V(T)s) at birth causes lung inflammation, and oxygen may amplify the injury. We hypothesized that normal V(T) ventilation at birth causes lung injury that is exacerbated by 95% oxygen.

Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol.

Background: Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries.

LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung.

Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally but disrupt late-gestation lung development. Because Sonic Hedgehog (Shh) signaling is a major pathway directing lung development, we hypothesized that chorioamnionitis and antenatal corticosteroids modulated Shh signaling, resulting in an altered fetal lung structure. Time-mated ewes with singleton ovine fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) and/or maternal intramuscular betamethasone 7 and/or 14 days before delivery at 120 days gestational age (GA) (term = 150 days GA).

Effects of chorioamnionitis on the fetal lung.

Very preterm infants are commonly exposed to a chronic, often asymptomatic, chorioamnionitis that is diagnosed by histologic evaluation of the placenta only after delivery. The reported effects of these exposures on fetal lungs are inconsistent because exposure to different organisms, durations of exposure, and fetal/maternal responses affect outcomes. In experimental models, chorioamnionitis can both injure and mature the fetal lung and cause immune nodulation.

Sex differences in lung gas volumes after lipopolysaccharide-induced chorioamnionitis in fetal sheep.

Background: Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival.

Objective: Given the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses.

Methods: Time-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days).

The Maternal and Newborn Health Registry Study of the Global Network for Women's and Children's Health Research.

Objective: To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Women's and Children's Health Research sites in Asia, Africa, and Latin America.

Methods: The Global Network sites began a prospective population-based pregnancy registry to identify all pregnant women and record pregnancy outcomes up to 42 days post-delivery in more than 100 defined low-resource geographic areas (clusters). Pregnant women were registered during pregnancy, with 42-day maternal and neonatal follow-up recorded-including care received during the pregnancy and postpartum periods.

An MRI system for imaging neonates in the NICU: initial feasibility study.

Background: Transporting premature infants from a neonatal intensive care unit (NICU) to a radiology department for MRI has medical risks and logistical challenges.

Objective: To develop a small 1.5-T MRI system for neonatal imaging that can be easily installed in the NICU and to evaluate its performance using a sheep model of human prematurity.

Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids.

Rationale: Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown.

Neonatal death in low- to middle-income countries: a global network study.

Objective: To determine population-based neonatal mortality rates in low- and middle-income countries and to examine gestational age, birth weight, and timing of death to assess the potentially preventable neonatal deaths.

Methods: A prospective observational study was conducted in communities in five low-income countries (Kenya, Zambia, Guatemala, India, and Pakistan) and one middle-income country (Argentina). Over a 2-year period, all pregnant women in the study communities were enrolled by trained study staff and their infants followed to 28 days of age.

Intra-amniotic administration of E coli lipopolysaccharides causes sustained inflammation of the fetal skin in sheep.

Preterm birth is associated with in utero infection and inflammation. Although the fetal membranes and fetus contribute to the intra-amniotic inflammatory profile, the relationships between a proinflammatory exposure to the fetal compartment and cytokine expression in the fetal skin are unknown. Using an ovine model, we asked whether the fetal skin would generate an extended response to inflammatory stimuli.

Antenatal exposure to chorioamnionitis affects lipid metabolism in 7-week-old sheep.

Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism.

The role of the multiple banded antigen of Ureaplasma parvum in intra-amniotic infection: major virulence factor or decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep.