Human Meconium Research Articles

Efficacy of synthetic surfactant (CHF5633) bolus and/or lavage in meconium-induced lung injury in ventilated newborn rabbits.

The pathogenesis of neonatal meconium aspiration syndrome (MAS) involves meconium-induced lung inflammation and surfactant inactivation. Bronchoalveolar lavage (BAL) with diluted surfactant facilitates the removal of meconium. CHF5633, one of the most promising synthetic surfactants, is effective in neonatal respiratory distress syndrome. Here we investigated its efficacy via BAL in an experimental MAS model. Experimental MAS was induced at birth in near-term newborn rabbits by intratracheal instillation of reconstituted human meconium. First, undiluted CHF5633 was compared with a porcine-derived surfactant (Poractant alfa) via intratracheal bolus (200 mg/kg). Second, the efficacy of BAL with diluted CHF5633 (5 mg/mL, 20 ml/kg) alone, or followed by undiluted boluses (100 or 300 mg/kg), was investigated. Meconium instillation caused severe lung injury, reduced endogenous surfactant pool, and poor survival. CHF5633 had similar benefits in improving survival and alleviating lung injury as Poractant alfa. CHF5633 BAL plus higher boluses exerted better effects than BAL or bolus alone in lung injury alleviation by reversing phospholipid pools and mitigating proinflammatory cytokine mRNA expression, without fluid retention and function deterioration. CHF5633 improved survival and alleviated meconium-induced lung injury, the same as Poractant alfa. CHF5633 BAL plus boluses was the optimal modality, which warrants further clinical investigation. To explore the efficacy of a synthetic surfactant, CHF5633, in neonatal lung protection comparing with Poractant alfa in a near-term newborn rabbit model with meconium-induced lung injury. Similar effects on improving survival and alleviating lung injury were found between CHF5633 and Poractant alfa. Optimal therapeutic effects were identified from the diluted CHF5633 bronchoalveolar lavage followed by its undiluted bolus instillation compared to the lavage or bolus alone regimens. Animals with CHF5633 lavage plus bolus regimen exerted neither substantial lung fluid retention nor lung mechanics deterioration but a trend of higher pulmonary surfactant-associated phospholipid pools.

The Human Meconium Metabolome and Its Evolution during the First Days of Life.

Meconium represents the first newborn stools, formed from the second month of gestation and excreted in the first days after birth. As an accumulative and inert matrix, it accumulates most of the molecules transferred through the placenta from the mother to the fetus during the last 6 months of pregnancy, and those resulting from the metabolic activities of the fetus. To date, only few studies dealing with meconium metabolomics have been published. In this study, we aimed to provide a comprehensive view of the meconium metabolic composition using 33 samples collected longitudinally from 11 healthy newborns and to analyze its evolution during the first 3 days of life. First, a robust and efficient methodology for metabolite extraction was implemented. Data acquisition was performed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), using two complementary LC-HRMS conditions. Data preprocessing and treatment were performed using the Workflow4Metabolomics platform and the metabolite annotation was performed using our in-house database by matching accurate masses, retention times, and MS/MS spectra to those of pure standards. We successfully identified up to 229 metabolites at a high confidence level in human meconium, belonging to diverse chemical classes and from different origins. A progressive evolution of the metabolic profile was statistically evidenced, with sugars, amino acids, and some bacteria-derived metabolites being among the most impacted identified compounds. Our implemented analytical workflow allows a unique and comprehensive description of the meconium metabolome, which is related to factors, such as maternal diet and environment.

Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice

SummaryPreterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32–37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.

Corynebacterium matruchotii Demography and Adhesion Determinants in the Oral Cavity of Healthy Individuals.

Corynebacterium matruchotii may be key in tooth biofilm formation, but information about demographics, bacterial partners, and binding ligands is limited. The aims of this study were to explore C. matruchotii’s demography by age and colonization site (plaque and saliva), in vitro bacterial–bacterial interactions in coaggregation and coadhesion assays, and glycolipids as potential binding ligands in thin-layer chromatogram binding assays. C. matruchotii prevalence increased from 3 months to 18 years old, with 90% and 100% prevalence in saliva and tooth biofilm, respectively. C. matruchotii aggregated in saliva in a dose-dependent manner but lacked the ability to bind to saliva-coated hydroxyapatite. In vivo, C. matruchotii abundance paralleled that of Actinomyces naeslundii, Capnocytophaga sp. HMT 326, Fusobacterium nucleatum subsp. polymorphum, and Tannerella sp. HMT 286. In vitro, C. matruchotii bound both planktonic and surface-bound A. naeslundii, Actinomyces odontolyticus, and F. nucleatum. In addition, C. matruchotii exhibited the ability to bind glycolipids isolated from human erythrocytes (blood group O), human granulocytes, rabbit intestine, human meconium, and rat intestine. Binding assays identified candidate carbohydrate ligands as isoglobotriaosylceramide, Galα3-isoglobotriaosylceramide, lactotriaosylceramide, lactotetraosylceramide, neolactotetraosylceramide, and neolactohexaosylceramide. Thus, C. matruchotii likely uses specific plaque bacteria to adhere to the biofilm and may interact with human tissues through carbohydrate interactions.

Effects of intravenous phosphodiesterase inhibitors and corticosteroids on severe meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is a major cause of severe respiratory failure in near- and full-term neonates. Alleviating inflammation is key to successfully treating severe MAS. Phosphodiesterase (PDE) inhibitors are known to play a role in airway smooth muscle relaxation and alveolar inflammation inhibition. This study aimed to investigate the effects of various intravenous (IV) PDE inhibitors and corticosteroids on MAS. MAS was induced in newborn piglets by instilling human meconium in them. The piglets were randomly divided into five groups (n = 5 in each group): (1) control (sham treatment); (2) dexamethasone (Dex) (IV 0.6 mg/kg of dexamethasone); (3) aminophylline (Ami) (IV 6 mg/kg of aminophylline, followed by continuous infusion of 0.5 mg/kg/h of aminophylline; (4) milrinone (Mil) (IV 50 μg/kg of milrinone, followed by continuous infusion of 0.75 μg/kg/h of milrinone); and (5) rolipram (Rol) (IV 0.8 mg/kg of rolipram). The duration of the experimental period was 4 hours. Compared to the control group, all the four treatment groups revealed better oxygenation 3 hours and more after the start of treatment. The Rol group had a significantly elevated heart beat (p < 0.05) and relatively lower blood pressure compared to the other groups during the first 2 hours of the experiment. The Dex group had significantly lower interleukin (IL)-1β levels in the lung tissue compared to the other groups (p < 0.05) and significantly lower IL-6 levels compared to the Ami and Mil groups (p < 0.05). Lung histology showed slightly less inflammation and atelectasis in the Dex group compared to the other groups, but lung injury scores showed no significant between-group differences. Using IV corticosteroids or any type of PDE inhibitors has some beneficial effects in improving oxygenation in MAS. PDE inhibitors are not superior to IV corticosteroids; in fact, adverse cardiovascular effects occur with the phosphodiesterase type 4 (PDE4) inhibitor. Further investigations are required before using IV corticosteroids and PDE inhibitors in future clinical application.

Effects of intratracheal captopril on severely meconium-injured piglet lungs.

Severe meconium aspiration syndrome (MAS) may cause intractable respiratory failure in neonates. Targeting the renin-angiotensin system may be an effective way to treat such pulmonary dysfunction. Captopril has the potential to mitigate the severity of lung injury by inhibiting angiotensin-converting enzyme. Twelve newborn piglets were intratracheally instilled with human meconium to induce severe MAS and were randomly treated with IT administration of captopril (0.5 mg/kg) (IT-Cap group, n = 6), or sham air instillation (Control group, n = 6). Cardiopulmonary profiles were monitored for a total of 5 hours. Pulmonary history was examined to compare lung injury severity between groups. There were no significant differences between the two study groups in gas exchange and lung compliance, peak inspiratory pressure, heart rate, and mean arterial blood pressure over the 5-h experimental period, but there were trends toward lower blood pressure and pH in the IT-Cap group. Histopathological examinations revealed significantly higher lung injury scores in the dependent site of the control group than in the nondependent site of the control group and both sites of the IT-Cap group. Intratracheal captopril did not present significant beneficial effects on severe meconium-injured lungs within 5 hours after injury. Further studies with different disease severities and dosing strategies are required.

The human primordial microbiome hosts complex bacterial and fungal interkingdom ecologies that vary with gestational age

Commensal microbial communities play important roles in human development. While microorganisms appear to be predominately transmitted from mother to child, the timing of transmission remains controversial. Meconium, the first stool passed after birth, was traditionally considered sterile because it originated from a sterile uterine environment. Following advances in next‐generation sequencing (NGS) techniques, more recent evidence suggests bacterial communities may exist in the gut prior to birth, however, the presence of primordial fungal communities has not been described. Here, we demonstrate the presence of multi‐kingdom microbial communities in meconium immediately following birth based on NGS. To describe the ecology of the primordial microbiome, we prospectively enrolled premature (gestational age &lt; 32 weeks') very low birthweight (VLBW &lt; 1500 g) and full term (FT, gestational age 37–41 weeks') newborns and collected the initial meconium. We examined the interkingdom community structure using 16S and ITS rDNA‐based amplicon sequencing followed by culture‐based techniques. We prospectively enrolled 57 VLBW and 35 FT newborns and collected a stool sample at &lt; 48h of life from 34 infants in each group. Bacteria were found in meconium of 90% of VLBW and 82% of FT samples (χ2P=0.325) and fungi in 93% of VLBW and 62% of FT samples (χ2P=0.003). The bacterial and fungal communities differed significantly between VLBW and FT (bacteria: PERMANOVA P=0.006, fungi: PERMANOVA P=0.013). Fungal communities of VLBWs were dominated by Ascomycota, including Candida, while FT meconium contained greater Basidiomycota and taxonomic diversity. Bacterial communities in VLBW meconium were also less diverse and contained on average a third as many taxa compared with FT. These results demonstrate human meconium contains complex interkingdom microbial communities that develop with gestational age, suggesting host‐microbe interkingdom relationships may exist in the uterine environment. Intriguingly, fungi are 50% more commonly observed in premature meconium than in full term neonates which could suggest a pathological association with preterm birth.Support or Funding InformationThe Marshall Klaus Perinatal Research Award from the American Academy of PediatricsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Preliminary results of identification and quantification of paclitaxel and its metabolites in human meconium from newborns with gestational chemotherapeutic exposure

ObjectiveCancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.Study designMeconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.ResultsMean (standard deviation) levels of paclitaxel in positively screened samples were 399.9 (248.6) pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3’-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel mean levels were 105.2 (54.6) and 113.4 (48.9) pg/mg meconium, respectively.ConclusionIntact paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.

Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors

Earlier work form this laboratory showed that exposure of alveolar epithelial cells (AECs) to meconium caused significant cell detachment and that meconium-induced detachment of cells was prevented by a protease inhibitor cocktail. Therefore, it was hypothesized that protease inhibitors might protect AEC monolayers against meconium-induced collapse of epithelial barrier function both in vitro and in vivo. To investigate this theory in vitro, albumin flux was measured across cultured, confluent monolayers of human type II derived cell line A549 on microporous filter inserts. Human meconium was collected from seven healthy full-term neonates and the samples were pooled and diluted prior to analysis. Exposure of AECs to 5% human meconium increased albumin flux across the cultured AEC monolayers, but the increase was significantly blocked by protease inhibitors (P<0.001). In C57/BL6 mice, intratracheal instillation of 5% human meconium increased the passage of Evans Blue Dye (EBD) from the vascular compartment into the alveolar spaces, measured in bronchoalveolar lavage (BAL) fluid after intravenous injection of EBD. Moreover, intratrachial coinstillation of protease inhibitors prevented the meconium-induced increase in EBD passage into BAL fluid (P<0.01). The data presented herein clearly demonstrate that protease inhibitors protect AEC barrier function against meconium-induced injury, and suggest the future possibility of using protease inhibitors in the treatment of meconium aspiration syndrome.

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs.

To evaluate the combined effects of surfactant lavage and intratracheally instillation of budesonide on meconium-injured piglet lungs. A prospective, randomized, animal model study. An experimental laboratory. Twenty-four anesthetized and mechanically ventilated newborn piglets. Human meconium slurry was intratracheally instilled into piglet lungs to induce lung injury. The injured piglets were randomly assigned to either the sham treatment group (control) or one of the three therapeutic groups: the intratracheally instilled budesonide (Bud) group, the bronchoalveolar lavage with diluted surfactant (dsBAL) group, and the combination therapy of Bud and dsBAL (dsBAL + Bud) group. Cardiopulmonary profiles were measured hourly. Proinflammatory cytokine (interleukin-1β, interleukin-6, and interleukin-8) levels in bronchoalveolar lavage fluid were measured. Finally, the pulmonary histology of the experimental subjects was examined at the end of experiments. Both of the lavaged groups (dsBAL and dsBAL + Bud) showed significantly better oxygenation than those that had not undergone lavage (control and Bud) (p < 0.05). The dsBAL + Bud group showed a significantly higher lung compliance and required a significantly lower peak inspiratory pressure during the experimental periods than the other three groups (p < 0.05). All treatment groups had significantly lower concentrations of interleukin-1β concentration in the bronchoalveolar lavage fluid than the control group (p < 0.05). The dsBAL + Bud group also had a significantly lower interleukin-6 concentration in the bronchoalveolar lavage fluid (p< 0.05), as well as a significantly lower lung injury score based on pulmonary histology than the control group (p < 0.05). Therapeutic bronchoalveolar lavage with diluted surfactant followed by intratracheal instillation of budesonide has a synergistic and beneficial effect when treating severe meconium-injured newborn piglet lungs.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome

ABSTRACTBackground: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). Purpose of the Study: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. Materials and Methods: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. Results: Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1β, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). Conclusion: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.

CAPACIDAD ANTIOXIDANTE DEL MECONIO EN RECIÉN NACIDOS DE MADRES CON PREECLAMPSIA

OBJETIVO: Determinar la capacidad antioxidante del meconio en recién nacidos de mujeres preeclámpticas. MATERIAL Y MÉTODOS: Se obtuvo el primer meconio de los recién nacidos de embarazos normales y con preeclampsia (PE) leve, y antes de las doce horas fue llevado a liofilización, por un promedio de siete horas. RESULTADOS: En un total de 60 embarazos, el meconio humano resultó tener elevada capacidad de captar radicales libres, con 64,5% ± 19,0 en embarazos normales y 43,6% ± 24,0 en el grupo de PE, lo que da una diferencia significativa (a &lt; 0.01). Con relación al contenido de glutatión, los resultados fueron 15,6 ± 3,8 umol/g y 10,8 ± 3,2 umol/g de meconio para el grupo normal y con preeclampsia, respectivamente; y, con respecto a bilirrubina, 26,9 ± 12,3 en el grupo normal y 20,1 ± 7,0 en el grupo con PE. CONCLUSIÓN: El meconio parece ser un poderoso antioxidante, pero esta capacidad disminuye en embarazos complicados con preeclampsia.

Ventilator „Chirana Aura V“ In Two Models Of Neonatal Acute Lung Injury - A Pilot Study

Abstract In severe respiratory insufficiency, neonatal and pediatric patients should be ventilated artificially by a ventilator. Aim of this experimental study was to evaluate whether the newly developed ventilator Chirana Aura V may effectively ventilate the lungs of animals with two different models of acute lung injury: acute respiratory distress syndrome (ARDS) induced by repetitive saline lavage and meconium aspiration syndrome (MAS) induced by intratracheal instillation of neonatal meconium. The experiments were performed on 10 adult rabbits (New Zealand white). In ARDS group (n=5), the lungs were repetitively lavaged with saline (30 ml/kg) until partial pressure of oxygen (PaO2) in arterial blood was under 26.7 kPa at inspiratory fraction of oxygen FiO2=1.0. In MAS group (n=5), animals were instilled 4 ml/kg of suspension of human meconium (25 mg/ml). When the model of acute lung injury was developed, animals were ventilated for additional 2 hours with pressure control ventilation (PCV) regime by ventilator Chirana Aura V. Ventilatory parameters, blood gases, acid-base balance, end-tidal CO2, O2 saturation of hemoglobin, oxygenation indexes, ventilation efficiency index, dynamic lung compliance, and right-to-left pulmonary shunts were measured and calculated in regular time intervals. In both experimental groups, used ventilatory settings provided acceptable gas exchange within the period of observation. Thus, the results indicate that ventilator Chirana Aura V might be suitable for ventilation of animal models of acute lung injury. However, further pre-clinical investigation is needed before its use may be recommended in neonatal and/or pediatric patients with acute lung injury.

Field Study on the Attraction and Development of Insects on Human Meconium and Breast‐fed‐Infant Feces

Urogenital myiasis of newborn infants, although rare, is usually considered to indicate neglect due to attraction of flies to feces; however, infant feces have not been determined to attract insects. Human meconium and breast-fed-infant feces were used to determine attractiveness to insects and to examine subsequent colonization and growth patterns of insect larvae. Despite small amounts of fecal material present, adults of Lucilia sericata arrived at breast-fed-infant feces within five minutes; insects were rarely observed on meconium. Oviposition and growth of L.sericata larvae occurred only on breast-fed-infant feces; however, the larvae did not progress beyond the second instar. These data suggest that urogenital myiasis by L.sericata in newborn human infants within the first few days postpartum would not be expected, but desiccation and depletion of infested feces may provide a possible pathway for urogenital myiasis in older newborn infants.

The use of mass spectrometry in obstetric and gynecology

Abstract The present review shows the utility of using mass spectrometry (MS) in obstetrics and gynecology. In this review different gas chromatography / mass spectrometry and liquid chromatography / mass spectrometry methods developed before to be used in obstetrics and gynecology are described. These methods are very useful to determine different hormones in pregnancy, fatty acids esters (related to the use of ethanol) in human meconium and toxic compounds in umbilical cord (as ethanol, steroids, morphine, cocaine, methadone and other drugs). It is also shown in this review the progress during last decades in the field of using mass spectrometry in obstetrics and gynecology (for screening in utero exposure of the child to alcohol, drugs and other toxic compounds). In the field of using mass spectrometry in obstetrics and gynecology are still many problems to solve. For example, the detection of fatty acids esters in meconium has several limitations, which affects the results. One limitation is multiple births. Also in fetal distress, meconium may be passed before birth, and in this case, the collection is impossible. Moreover the meconium is formed starting from the fourth month of pregnancy, so the fetal exposure at any toxic compounds during the first three months cannot be detected at all. To solve all of these, the best would be to combine the results obtained from meconium, with other results obtained from pregnancy serum, placenta or umbilical cord. The main reason for using MS in obstetrics and gynecology is that MS is a noninvasive and a complementary method. It offers the results at a very early point in time, even before the act of birth. Sometimes the use of mass spectrometry is the only alternative. This shows that these methods are of great interest for the future and need to be developed further.

Norovirus GII.4 virus-like particles recognize galactosylceramides in domains of planar supported lipid bilayers.

A sticky situation: Domain-dependent recognition of the glycosphingolipid galactosylceramide by norovirus-like particles (see picture; red/yellow) is shown using supported lipid bilayers (purple) as model membranes. Optimal ligand presentation is found to promote strong binding to GalCer. This presentation can be found at the edges of the glycosphingolipid-enriched domains (green) and binding is repressed in the absence of these domains.

The effects of pentoxifylline on lung inflammation in a rat model of meconium aspiration syndrome

ABSTRACTTo examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord

Objective To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. Study design We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. Results Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. Conclusions Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Total liquid ventilation efficacy in an ovine model of severe meconium aspiration syndrome

To test the hypothesis that total liquid ventilation enables a more effective and better tolerated lavage than a bronchoalveolar lavage performed with diluted surfactant in a newborn ovine model of severe acute meconium aspiration syndrome. Prospective, randomized, interventional study. Animal research laboratory at the Faculté de médecine et des sciences de la santé de l'université de Sherbrooke, Sherbrooke, Canada. Twenty-three newborn lambs, <4 days, 2.5-4.0 kg in weight. Animals were intubated, anesthetized, and paralyzed. Catheters were placed in the femoral artery and jugular vein. Severe meconium aspiration syndrome was obtained by instillation of a 25% dilution of human meconium in saline (1 mL/kg × 2). Lambs were then randomized in 12 total liquid ventilation-bronchoalveolar lavage (minute ventilation of 160 mL/kg/min with perfluorodecalin) vs. 11 bronchoalveolar lavage performed with diluted surfactant (conventional ventilation + 30 mL/kg in two aliquots bronchoalveolar lavage with 5 mg/mL BLES surfactant). Surviving lambs were ventilated for a total of 4 hrs and euthanized. Arterial blood gases, systemic and pulmonary hemodynamic parameters using the thermodilution method, percentage of recovered meconium, and lung histologic scores. Total liquid ventilation bronchoalveolar lavage enabled a significantly higher PaO2 throughout the experiment. PaCO2, pH, and hemodynamic parameters were comparable for both groups except for an increase in mean pulmonary arterial pressure during total liquid ventilation. Total liquid ventilation bronchoalveolar lavage allowed for 43 ± 14% of the instilled meconium to be removed vs. 28 ± 10% for bronchoalveolar lavage performed with diluted surfactant (p = .022). Lung histologic analysis showed no difference between total scores. Total liquid ventilation bronchoalveolar lavage is well tolerated and more effective in terms of meconium washout and gas exchange than bronchoalveolar lavage performed with diluted surfactant in this experimental model of severe meconium aspiration syndrome. These positive results open the way to further experiments in our ovine model, ultimately aiming at a clinical trial with total liquid ventilation bronchoalveolar lavage to treat severe meconium aspiration syndrome.