Oral docosahexaenoic acid given to pregnant mice increases the amount of surfactant in lung and amniotic fluid in preterm fetuses

Blanco, Paola G.; Freedman, Steven D.; López, M.C. Medina; Ollero, Mario; Comen, Elizabeth; Laposata, Michael; Álvarez, Juan G.

doi:10.1016/j.ajog.2003.11.001

Cited by 21 publications

(9 citation statements)

References 14 publications

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“…Potential candidate drugs are proposed (Blanco et al, 2004), but the most important known endogenous surfactant stimulator is mechanical stretching of the lung (Wirtz and Dobbs, 1990). Our previous data suggest that monotonous cyclic stretching of surfactant secreting cells in culture down-regulates surfactant secretion (Arold et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs

et al. 2017

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Preterm infants often require mechanical ventilation due to lung immaturity including reduced or abnormal surfactant. Since cyclic stretch with cycle-by-cycle variability is known to augment surfactant release by epithelial cells, we hypothesized that such in vivo mechanotransduction improves surfactant maturation and hence lung physiology in preterm subjects. We thus tested whether breath-by-breath variability in tidal volume (VT) in variable ventilation (VV) can be tuned for optimal performance in a preterm lamb model. Preterm lambs were ventilated for 3 h with conventional ventilation (CV) or two variants of VV that used a maximum VT of 1.5 (VV1) or 2.25 (VV2) times the mean VT. VT was adjusted during ventilation to a permissive pCO2 target range. Respiratory mechanics were monitored continuously using the forced oscillation technique, followed by postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV in blood gas parameters (pH, SaO2, cerebral O2 saturation). However, only VV2 lowered PaCO2 and had a higher specific respiratory compliance than CV. VV2 also increased surfactant protein (SP)-B release compared to VV1 and stimulated its production compared to CV. The production and release of proSP-C however, was increased with CV compared to both VVs. There was more SP-A in both VVs than CV in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly increased in CV in both the lavage and lung. Compared to CV, the cytokines IL-1β, and TNFα decreased with both VVs with less inflammation during VV2. Additionally, VV2 lungs showed the most homogeneous alveolar structure and least inflammatory cell infiltration assessed by histology. CV lungs exhibited over-distension mixed with collapsed and interstitial edematous regions with occasional hemorrhage. Following VV1, some lambs had normal alveolar structure while others were similar to CV. The IgG serum proteins in the lavage, a marker of leakage, were the highest in CV. An overall combined index of performance that included physiological, biochemical and histological markers was the best in VV2 followed by VV1. Thus, VV2 outperformed VV1 by enhancing SP-B metabolism resulting in open alveolar airspaces, less leakage and inflammation and hence better respiratory mechanics.

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Section: Introductionmentioning

confidence: 99%

Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs

et al. 2017

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“…For example, in murine models of hyperoxia-induced lung injury, DHA supplementation reduced inflammatory responses and improved lung growth [ 19 – 21 ]. Separate studies have also demonstrated that exposure to high DHA increased the production of dipalmatoylphosphtidylcholine, the major surfactant lipid in the fetal and neonatal lung [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation

et al. 2016

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BackgroundBronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation.Methods/designThis is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05).DiscussionDHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants.Trial registrationAustralia and New Zealand Clinical Trial Registry: ACTRN12612000503820. Registered 09 May 2012.

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“…Very low birthweight babies have difficulty in establishing enteral feeds, and standard parenteral nutrition does not usually contain long‐chain omega‐3 fatty acids. Animal studies suggest that DHA increases surfactant production, and therefore, adequate provision may decrease the initial RDS. In addition, the inflammatory cascade contributing to CLD starts in the first month of life when minimal DHA is provided.…”

Section: Discussionmentioning

confidence: 99%

Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates

Atwell

Collins

Sullivan

et al. 2012

J Paediatrics Child Health

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Oral docosahexaenoic acid given to pregnant mice increases the amount of surfactant in lung and amniotic fluid in preterm fetuses

Cited by 21 publications

References 14 publications

Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs

Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation

Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates

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