Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.

RATIONALE: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. Results of clinical trials with MSCs for many disorders do not yet match the promising preclinical studies. A lack of specific criteria to define functionally distinct MSCs persists. OBJECTIVES: To determine and correlate single-cell UC-MSC transcriptomic profile with therapeutic potential. METHODS: UC-MSCs from five term donors and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin) transcriptomes were investigated by single-cell RNA sequencing analysis (scRNA-seq). The lung-protective effect of UC-MSCs with a distinct transcriptome and control HNDFs was tested in vivo in hyperoxia-induced neonatal lung injury in rats. MEASUREMENTS AND MAIN RESULTS: UC-MSCs showed limited transcriptomic heterogeneity, but were different from HNDFs. Gene ontology enrichment analysis revealed distinct - progenitor-like and fibroblast-like - UC-MSC subpopulations. Only the treatment with progenitor-like UC-MSCs improved lung function and structure and attenuated pulmonary hypertension in hyperoxia-exposed rat pups. Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of non-therapeutic cells and associated with decreased lung retention. CONCLUSIONS: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Optimising homeothermy in neonates: a systematic review and clinical guidelines from the French Neonatal Society.

AIM: Thermal instability is harmful on the newborn infant. We sought to draw up practical guidelines on maintaining homeothermy alongside skin-to-skin contact. METHODS: A systematic analysis of the literature identified relevant studies between 2000 and 2021 in the PubMed database. Selected publications were evaluated, and their level of evidence were graded, in order to underpin the development of clinical guidelines. RESULTS: We identified 7 meta-analyses and 64 clinical studies with a focus on newborn infants homeothermy. Skin-to-skin contact is the easiest and most rapidly implementable method to prevent body heat loss. Alongside skin-to-skin contact, monitoring the newborn infant's body temperature with a target of 37.0°C is essential. For newborn infants <32 weeks of gestation, a skullcap and a polyethylene bag should be used in the delivery room or during transport. To limit water loss, inhaled gases humidification and warming is recommended, and preterm infants weighing less than 1600 g should be nursed in a closed, convective incubator. With regard to incubators, there are no clear benefits for single vs. double-wall incubators as well as for air vs. skin servo control. CONCLUSION: Alongside skin-to-skin contact, a bundle of practical guidelines could improve the maintenance of homeothermy in the newborn infant.

Two Novel Homozygous Mutations in Phosphoglucomutase 3 Leading to Severe Combined Immunodeficiency, Skeletal Dysplasia, and Malformations.

Phosphoglucomutase 3 (PGM3) deficiency is a rare congenital disorder of glycosylation. Most of patients with autosomal recessive hypomorphic mutations in PGM3 encoding for phosphoglucomutase 3 present with eczema, skin and lung infections, elevated serum IgE, as well as neurological and skeletal features. A few PGM3-deficient patients suffer from a more severe disease with nearly absent T cells and severe skeletal dysplasia. We performed targeted next-generation sequencing on two kindred to identify the underlying genetic etiology of a severe combined immunodeficiency with developmental defect. We report here two novel homozygous missense variants (p.Gly359Asp and p.Met423Thr) in PGM3 identified in three patients from two unrelated kindreds with severe combined immunodeficiency, neurological impairment, and skeletal dysplasia. Both variants segregated with the disease in the two families. They were predicted to be deleterious by in silico analysis. PGM3 enzymatic activity was found to be severely impaired in primary fibroblasts and Epstein-Barr virus immortalized B cells from the kindred carrying the p.Met423Thr variant. Our findings support the pathogenicity of these two novel variants in severe PGM3 deficiency.

Recommendation for hygiene and topical in neonatology from the French Neonatal Society.

We sought to establish guidelines for hygiene care in newborns based on a systematic review of the literature and grading of evidence using the Groupe de Réflexion et d'Evaluation de l'Environement des Nouveau-nés (GREEN) methodology. We examined 45 articles and 4 reports from safety agencies. These studies recommend a tub bath (rather than a sponge bath) for full-term infants and a swaddle bath for preterm newborns. They also recommend against daily cleansing of preterm infants. The literature emphasized that hygiene care must consider the clinical state of the newborn, including the level of awareness and behavioral responses. Hospitalized newborns treated with topical agents may also experience high exposure to potentially harmful excipients of interest. Caregivers should therefore be aware of the excipients present in the different products they use. In high-resource countries, the available data do not support the use of protective topical agents for preterm infants.Conclusions: We recommend individualization of hygiene care for newborns. There is increasing concern regarding the safety of excipients in topical agents that are used in neonatology. A multidisciplinary approach should be used to identify an approach that requires lower levels of excipients and alternative excipients. What is known: • Hygiene care is one of the most basic and widespread types of care received by healthy and sick newborns worldwide. • There is no current guideline on hygiene for preterm or hospitalized term newborn. What is new: • The French Group of Reflection and Evaluation of the environment of Newborns (GREEN) provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' behavioral responses to hygiene care, exposition to excipients of interest, and the potential risk of protective topical agents in a preterm infant. provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' possible behavioral responses to hygiene care, exposition to excipients of interest and the potential risk of protective topical agents in a preterm infant.

Severe Fetal Abnormality and Outcomes of Continued Pregnancies: A French Multicenter Retrospective Study.

Objectives To describe a population choosing to continue with their pregnancy despite being eligible to receive a medical termination of pregnancy (TOP). Methods Nine-year retrospective study of data (01/01/2006 to 31/12/2014) from three French prenatal diagnostic centers describing the perinatal outcomes of these pregnancies. Pregnancies were classified according to etiology and severity of its fetal pathology. Several perinatal parameters were described: maternal characteristics, parental prenatal choices and information on the pregnancy and neonatal outcomes. These parameters were classified in function of the severity of fetal pathology according to the classification proposed by Dommergues et al. (Prenatal Diagnosis 30(6):531-539, 2010) Results Overall, 155 pregnancies were continued; 140 have been included in our study. Pregnancy outcomes consisted of four TOPs (2.9%); 20 in utero deaths (14.3%); 110 live births (78.6%) of which 55.4% were still alive at 2 years old as the most recent information; and 6 (4.2%) with unknown outcomes. In 27 cases, perinatal palliative care was requested (an increase of 37% over 9 years). 36.4% of cases were classified as having a high mortality risk; 19.3% with a severe handicap risk; 11.4% with a risk of isolated intellectual disability; and 32.9% with an uncertain prognosis. The parental decisions to choose perinatal palliative care were significantly higher within the high mortality risk group as compared to other severity groups (p < 0.001); this group also had a significantly higher mortality (p < 0.001), with a survival rate of 26.3%. Conclusion Over the study period, in France, there was an increase in continued pregnancies, despite a diagnosis of severe fetal pathology in France. Therefore, it is essential that perinatal professionals are provided with a palliative care framework and training in their approach for this population which is heterogeneous in terms of etiology.

Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study.

Objectives: The study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants. Methods: This prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models. Results: Two hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693). Conclusion: In preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB.

Newborn Life Support course: does it make me more confident when resuscitating a newborn?

AIM: To describe the effectiveness of the Newborn Life Support (NLS) course in terms of attendees' knowledge, perceived self-efficacy, and clinical applicability. METHODS: We conducted an electronic survey of NLS course attendees (NLS + group). A control group (NLS-) was recruited via our regional perinatal network. The survey data were analyzed anonymously. Multiple linear regression analysis examined the following: NLS course, job tenure, maternity level, and profession. RESULTS: The survey completion rate was 62% (200/323) for the NLS + group. Among participants, 84% had participated in neonatal resuscitation since their course. The scores for positive perceived experience for neonatal resuscitation (fluency, security, and quality of care delivered) were higher in the NLS + group than the NLS- group (p<.006). After adjustment, the independent factors associated with a higher positive perceived experience were the NLS course, work in tertiary level maternity ward, and job tenure >5 years. The multiple-choice questions (MCQs) score (n = 10) was 8.2 ± 1.3 (NLS+) vs. 6.7 ± 1.5 (NLS-) (p<.0001). NLS course, medical degree, and work in a tertiary level maternity ward were independently associated with higher knowledge scores. CONCLUSIONS: The NLS course was associated with a positive perceived experience regarding neonatal resuscitation.Key notesNeonatal resuscitation training programs, like the Newborn Life Support (NLS), have been developed to improve the management and outcomes of newborns with poor adaptation at birth.The NLS course was associated with better knowledge of, and a positive perceived experience (fluency, safety, and quality of care delivered) regarding, neonatal resuscitation.Participation to the NLS course seems to strengthen the perceived self-efficacy in healthcare professionals, which is critical to performing neonatal resuscitation.

Definition and Characteristics of Mesenchymal Stromal Cells in Preclinical and Clinical Studies: A Scoping Review.

Mesenchymal stromal cells (MSCs) are widely used in preclinical and clinical research. Despite minimal criteria to define MSCs provided by the International Society for Cell and Gene Therapy (ISCT), concerns have been raised about inconsistent descriptions of cell products used. To address the question "How are MSCs currently defined and characterized?" we conducted a scoping review on original MSC preclinical and clinical studies published over a 3-month period. Selected studies identified from a systematic search of MEDLINE and Embase were categorized as follows: Clinical, Animal, Biology, or Biomaterial studies. Data were extracted from a randomly selected subsample of studies. We extracted information, including epidemiological characteristics of studies, study design, ISCT criteria, and MSC characterization and culture condition. A total of 1053 articles were included and among them, 318 articles were analyzed. Overall, 18% of the articles explicitly referred to the ISCT minimal criteria for MSC. MSC characteristics and culture conditions were inconstantly reported (eg, viability assay reported in only 18% of the articles). Only 20% of documents reported at least 1 functional assay. Clinical studies showed inconsistent completeness in reporting relevant information on the MSC characterization and cell manufacturing processes. These results suggest that further development and implementation of a consensus definition of MSCs and reporting guidelines are needed to enhance rigor, reproducibility, and transparency in MSC research.

Establishment of a consensus definition for mesenchymal stromal cells (MSC) and reporting guidelines for clinical trials of MSC therapy: a modified Delphi study protocol.

INTRODUCTION: Despite being more than two decades of research, mesenchymal stromal cell (MSC) treatments are still struggling to cross the translational gap. Two key issues that likely contribute to these failures are (1) the lack of clear definition for MSC and (2) poor quality of reporting in MSC clinical studies. To address these issues, we propose a modified Delphi study to establish a consensus definition for MSC and reporting guidelines for clinical trials of MSC therapy. METHODS AND ANALYSIS: We will conduct a three-round international modified Delphi survey. Findings from a recent scoping review examining how MSCs are defined and reported in preclinical and clinical studies were used to draft the initial survey for round 1 of our Delphi. Participants will include a 'core group' of individuals as well as researchers whose work was captured in our scoping review. The core group will include stakeholders from different research fields including developmental biology, translational science, research methods, regulatory practices, scholarly journal editing and industry. The first two survey rounds will be online, and the final round will take place in person. Each participant will be asked to rate their agreement on potential MSC definition characteristics and reporting items using a Likert scale. After each round, we will analyse the data to determine which items have reached consensus for inclusion/exclusion, and then develop a revised questionnaire for any new items, or items that did not reach consensus. ETHICS AND DISSEMINATION: This study received ethical approval from the Ottawa Health Research Network Research Ethics Board. To support the dissemination of our findings, we will use an evidence-based 'integrated knowledge translation' approach to engage knowledge users from the inception of the research. This will allow us to develop a tailored end-of-project knowledge translation plan to support and ensure dissemination and implementation of the Delphi results.

Benefits and obstacles to cell therapy in neonates: The INCuBAToR (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research).

Cell-based therapies hold promise to substantially curb complications from extreme preterm birth, the main cause of death in children below the age of 5 years. Exciting preclinical studies in experimental neonatal lung injury have provided the impetus for the initiation of early phase clinical trials in extreme preterm infants at risk of developing bronchopulmonary dysplasia. Clinical translation of promising therapies, however, is slow and often fails. In the adult population, results of clinical trials so far have not matched the enticing preclinical data. The neonatal field has experienced many hard-earned lessons with the implementation of oxygen therapy or postnatal steroids. Here we briefly summarize the preclinical data that have permitted the initiation of early phase clinical trials of cell-based therapies in extreme preterm infants and describe the INCuBAToR concept (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research), an evidence-based approach to mitigate the risk of translating advanced therapies into this vulnerable patient population. The INCuBAToR addresses several of the shortcomings at the preclinical and the clinical stage that usually contribute to the failure of clinical translation through (a) systematic reviews of preclinical and clinical studies, (b) integrated knowledge transfer through engaging important stakeholders early on, (c) early economic evaluation to determine if a novel therapy is viable, and (d) retrospective and prospective studies to define and test ideal eligibility criteria to optimize clinical trial design. The INCuBAToR concept can be applied to any novel therapy in order to enhance the likelihood of success of clinical translation in a timely, transparent, rigorous, and evidence-based fashion.

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage.

During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia with validation of some of the findings in lungs from BPD patients. We observe dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, stromal fibroblasts, capillary endothelium and macrophage populations. Pathway analysis and predicted dynamic cellular crosstalk suggest inflammatory signaling as the main driver of hyperoxia-induced changes. Our data provides a single-cell view of cellular changes associated with late lung development in health and disease.

Nasal high-frequency percussive ventilation vs nasal continuous positive airway pressure in newborn infants respiratory distress: A cross over clinical trial.

OBJECTIVE: To determine if nasal high-frequency percussive ventilation (nHFPV) to manage neonatal respiratory distress decreases the regional cerebral oxygen saturation (rScO2 ) compared to nasal continous positive airway pressure (nCPAP). STUDY DESIGN: A prospective, randomized, monocentric, open-label, noninferiority crossover trial. Newborns of gestational age (GA) ≥ 33 weeks exhibiting persistent respiratory distress after 10 minutes of life were treated with nHFPV and nCPAP, in succession and in random order. The primary endpoint was the mean rScO2 , as revealed by near-infrared spectroscopy (NIRS). RESULTS: Forty-nine newborns were randomized; the mean GA and birth weight was 36.4 ± 1.9 weeks and 2718 ± 497 g. The mean rScO2 difference during the last 5 minutes of each ventilation mode (nHFPV minus nCPAP) was -0.7 ± 5.4% (95% confidence interval (CI) -2.25; 0.95%). CONCLUSION: In our study on newborns of GA ≥33 weeks treated for respiratory distress, cerebral oxygenation via nHFPV was not inferior to nCPAP.

A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency.

Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis. Intratracheal administration of this vector delivering murine or human proSFTPB cDNA into SP-B deficient mice restores surfactant homeostasis, prevents lung injury, and improves lung physiology. Untreated SP-B deficient mice develop fatal respiratory distress within two days. Gene therapy results in an improvement in median survival to greater than 200 days. This vector also transduces human lung tissue, demonstrating its potential for clinical translation against this lethal disease.

Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: Identify measures to diagnose, prevent, and treat genital herpes infection during pregnancy and childbirth as well as neonatal herpes infection. MATERIALS AND METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: Genital herpes lesions are most often due to HSV-2 (LE2). The risk of HSV seroconversion during pregnancy is 1-5% (LE2). Genital herpes lesions during pregnancy in a woman with a history of genital herpes is a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In pregnant women with genital lesions who report they have not previously had genital herpes, virological confirmation by PCR and identifying the specific IgG type is necessary (professional consensus). A first episode of genital herpes during pregnancy should be treated with aciclovir (200 mg 5 times daily) or valaciclovir (1000 mg twice daily) for 5-10 days (Grade C), and recurrent herpes during pregnancy with aciclovir (200 mg 5 times daily) or valaciclovir (500 mg twice daily) (Grade C). The risk of neonatal herpes is estimated at between 25% and 44% if a non primary and primary first genital herpes episode is ongoing at delivery (LE2) and 1% for a recurrence (LE3). Antiviral prophylaxis should be offered to women with either a first or recurrent episode of genital herpes during pregnancy from 36 weeks of gestation until delivery (Grade B). Routine prophylaxis is not recommended for women with a history of genital herpes but no recurrence during pregnancy (professional consensus). A cesarean delivery is recommended if a first episode of genital herpes is suspected (or confirmed) at the onset of labor (Grade B) or if it occured less than 6 weeks before delivery (professional consensus) or in the event of premature rupture of the membranes at term. When a recurrence of genital herpes is underway at the onset of labor, cesarean delivery is most likely to be considered when the membranes are intact and vaginal delivery in cases of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most cases of neonatal herpes, mothers have no history of genital herpes (LE3). When neonatal herpes is suspected, various samples (blood and cerebrospinal fluid) for HSV PCR must be taken to confirm the diagnosis (professional consensus). Any newborn with suspected neonatal herpes should be treated with intravenous acyclovir (20 mg/kg 3 times daily) (grade A) before the PCR results are available (professional consensus). The duration of the treatment depends on the clinical form (professional consensus) CONCLUSION: There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes and the risk of recurrence at term, as well as cesarean rate because of herpes lesions.

Effect of high-frequency oscillation and percussion versus conventional ventilation in a piglet model of meconium aspiration.

BACKGROUND: Meconium aspiration syndrome (MAS) remains a frequent cause of morbidity and mortality in term newborns. Our objective was to compare two modes of high-frequency ventilation, high-frequency oscillation (HFOV), and high-frequency percussive ventilation (HFPV) with conventional mechanical ventilation (CMV) in a piglet model of MAS. METHODS: Fifteen newborn piglets were anesthetized, paralyzed, and intubated. Following the instillation of a 3 ml/kg solution of meconium diluted to 30%, the piglets were randomized to one of three groups: high-frequency oscillation (HFOV; Sensormedics®), HFPV (Percussionaire®), or CMV (Siemens®). Animals were ventilated for 6 hr to maintain arterial blood gases within a normal range, that is, pH 7.35-7.45, PaO(2) 10-16 kPa, PaCO(2) 4-6.6 kPa. Arterial blood gas measurements, dynCrs and dynRrs, ventilator settings, and vital signs (heart rate, arterial blood pressure, transcutaneous pulse oxygen saturation, and temperature) were collected at 30, 60, 90, 120, 180, 240, 300, and 360 min after meconium instillation. Oxygenation index (OI) ([(fraction of inspired oxygen)(mean airway pressure)(100)]/PaO(2) ), mean airway pressure, dynamic lung function, secretions cleared and histological alterations were studied in all groups. RESULTS: Mean airway pressure and OI were significantly lower in the CV and HFPV groups compared to the HFOV group (P < 0.05). There was no significant difference between groups regarding lung function, amount of secretions and histological alterations. CONCLUSION: In our model of MAS in piglets, whilst effective gas exchange with a lower mean airway pressure was possible with both CMV and HFPV compared with HFOV there was no apparent difference in lung histology or secretions.