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PubMed2006

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography--flame ionization detection and confirmed by gas chromatography--mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n=3 fetuses). For meconium of the ethanol offspring (n=25 fetuses) compared with the sucrose offspring (n=23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium total FAEE concentration and both body weight and brain weight.

Animals↗
PubMed1989

Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins.

The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. This approach resulted in 50 neutral and 30 acidic oligosaccharides. The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides.

Binding Sites↗
PubMed1987

Meconium aspiration--role of obstetric factors and suction.

Meconium aspiration occurred in 66 of 120 infants with meconium-stained liquor admitted to a Neonatal Unit. Four of the 66 infants died, whilst 17 other required ventilatory support. Meconium aspiration syndrome, especially when severe, was more likely if the mother was a smoker, hypertensive, anaemic, Maori or the pregnancy was greater than 42 weeks' gestation. Meconium aspiration was also associated with thick meconium, prolonged labour, late fetal heart decelerations and inadequate suctioning of the airway at birth. Although meconium-stained liquor is a common occurrence in labour, a bad neonatal outcome will only be obviated by vigilant intrapartum care and active suctioning of the infant's airway at birth. Once aspiration has occurred, intensive treatment is often required and sometimes fails.

Ethnicity↗
PubMed2005

Meconium aspiration induces neuronal injury in piglets.

AIM: Meconium aspiration-induced hypertensive lung injury, especially when connected with perinatal asphyxia, has been associated with brain damage. We aimed to determine the neuronal injury induced by pulmonary meconium contamination alone and with concurrent asphyxia. METHODS: 36 anaesthetized and ventilated newborn piglets were haemodynamically monitored for 6 h. Seven piglets without concurrent asphyxia and seven piglets with asphyxia were instilled with a bolus of human meconium intratracheally. Seven piglets had only asphyxia and 15 piglets served as controls. The brains were studied histologically. RESULTS: Meconium aspiration did not change systemic haemodynamics acutely, while its combination with asphyxia diminished the abrupt postasphyxic systemic hypertensive peak and resulted in a transient increase in carotid artery flow, not seen after isolated asphyxia. Systemic pressure declined after 4 h in all insulted groups, but only isolated asphyxia was associated with a sustained decrease in carotid artery flow. Arterial oxygenation remained normal, except during the acute insults. Brain examination after meconium instillation indicated neuronal injury, especially in the CA3 region of the hippocampus. Asphyxia resulted in neuronal injury in the cortical, cerebellar and hippocampal hilus regions. CONCLUSION: Severe meconium aspiration itself may result in hippocampal neuronal injury.

Animals↗
PubMed1979

Screening for cystic fibrosis in the newborn by meconium analysis.

During a 4-year routine screening programme for cystic fibrosis (CF) 15 464 specimens were examined for raised meconium albumin levels by a test strip method and by electroimmunoassay. The incidence of false-positive results was about 5 per 1000 specimens in either test. This could be reduced by 90% by determining the ratio of albumin : alpha-1-trypsin inhibitor (a ratio below 2.0 being considered as a negative result), and it could be reduced to zero by determining the ratio in subsequent faecal specimens. Three of 12 meconium specimens from infants with proved CF gave false-negative results in all 3 tests. The other 9 specimens had greater than 100 mg albumin/g dry weight and albumin: alpha-1-trypsin inhibitor ratios of greater than 3.0; in subsequent faecal specimens the ratios were over 4.0. 176 meconium specimens from elsewhere in the UK were examined and these included 23 from infants who were subsequently proved to have CF. Six of these 23 CF specimens gave false-negative results, the other 17 being strongly positive. The origins of meconium serum protein suggest that infants with CF in whom meconium gives false-negative results have normal pancreatic functions at birth. The specificity of current meconium tests therefore cannot be improved as they depend on pancreatic dysfunction.

Albumins↗
PubMed2002

Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model.

Meconium aspiration syndrome is a cause of significant morbidity and mortality in the perinatal period and has been implicated in the pathogenesis of airway dysfunction. In this study, we developed a murine model to evaluate the effects of meconium aspiration on airway physiology and lung cellular responses. Under light anesthesia, BALB/c mice received a single intratracheal instillation of meconium or physiological saline. Respiratory mechanics were measured in unrestrained animals and expressed as percent increase in enhanced pause to increasing concentrations of methacholine (MCh). Furthermore, we assessed the changes in cells and cytokines into the bronchoalveolar lavage fluid (BALF). We found meconium aspiration produced increased airway responsiveness to MCh at 7 days. These functional changes were associated with lymphocytic/eosinophilic inflammation, goblet cell metaplasia, and increased concentrations of IL-5 and IL-13 in the BALF. Our findings suggest meconium aspiration leads to alterations of airway function, lung eosinophilia, goblet cell metaplasia, and cytokine imbalance, thus providing the first evidence of meconium-induced airway dysfunction in a mouse model.

Animals↗
PubMed2000

Detection of cytomegalovirus in the meconium of infected newborns by polymerase chain reaction.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a leading cause of hearing loss and mental retardation throughout the world. Detection of the CMV DNA by polymerase chain reaction (PCR) offers a sensitive, rapid, and specific means of identification. Meconium, the stool formed in utero, may be an ideal specimen for CMV detection. The objective of this study was to develop a PCR-based methodology for the detection of CMV in the meconium of neonates. METHODS: Meconium was collected from 10 newborn infants (seven with positive viral cultures and three uninfected infants born to CMV-seropositive mothers). For each, DNA was isolated from meconium by organic extraction and attachment to a DNA-binding matrix, and PCR was performed using amplimers specific for the major intermediate early (MIE) and late antigenic (LA) regions of CMV. RESULTS: Gel electrophoresis demonstrated an anticipated PCR product of 250 base pairs (bp) corresponding to the MIE region of CMV in all infected and positive control meconium samples. Furthermore, a single band of 150 bp corresponding to the LA region of CMV was also amplified in several of the infected infants. Conversely, no amplification of these antigenic regions was noted in either uninfected infants born to CMV-seropositive mothers or negative controls. CONCLUSIONS: CMV is present within the meconium of infected neonates and is readily detectable by PCR.

Cytomegalovirus↗
PubMed2002

Meconium enhances the release of nitric oxide in human airway epithelial cells.

Meconium aspiration syndrome (MAS) is a cause of significant morbidity and mortality in the perinatal period. Despite the clinical relevance of MAS, its pathogenesis is poorly understood and the role played by epithelial-derived metabolites not well defined. In this study, we evaluated whether exposure to meconium affects the release of nitric oxide production in human airway epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell line, were incubated with various concentrations of meconium. Control cells were incubated with serum-free medium in a similar manner. The supernatant fluid was removed at various time points and assayed for nitrite production. In selected experiments, the effects of dexamethasone (10(-6) M), L-nitroarginine methyl ester (L-NAME, 10(-6) M) and indomethacin (10(-6) M) on nitrite release were evaluated. Results were obtained in terms of pmol/mg protein and expressed as % control (mean +/- SE). We found exposure to meconium produced a significant release of nitrite from A549 cells. Dexamethasone, L-NAME and indomethacin inhibited meconium-induced release of nitrite. Our findings demonstrate meconium enhances the production of nitric oxide from A549 cells suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Intravenous immunoglobulin g attenuates pulmonary hypertension but induces local neutrophil influx in meconium aspiration in piglets.

BACKGROUND: Pulmonary hypertension and inflammation are well-identified pathogenetic features in meconium aspiration syndrome of newborns, but current approaches to their treatment or prevention are still often unsatisfactory. OBJECTIVES: To investigate the possible protective effects of human intravenous immunoglobulin G (IVIG) on the hypertensive and inflammatory lung injury in severe neonatal meconium aspiration. METHODS: Eleven newborn (10-12 days old) ventilated and catheterized piglets that received an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium were studied for 6 h. IVIG was infused in 5 piglets 30 min before meconium administration, and 6 piglets served as controls and received the vehicle only. RESULTS: Meconium instillation induced a biphasic pulmonary hypertensive response, which was significantly diminished by IVIG pretreatment. Similarly, IVIG improved the oxygenation of the piglets, but the intrapulmonary shunt fraction or systemic hemodynamic parameters did not differ between the study groups, except of a minor decrease in the mean arterial blood pressure caused by IVIG. The blood leukocyte count was comparable in the 2 groups. The lung tissue ultrastructural and histological changes, number of apoptotic cells and phospholipase A2 activity were similar in the 2 groups. The amount of neutrophil accumulation, assessed by myeloperoxidase activity, was however significantly increased in macroscopically damaged lung tissue after IVIG administration. CONCLUSIONS: Our results thus indicate that IVIG treatment of newborns with severe meconium aspiration significantly diminishes the pulmonary hypertensive response and improves oxygenation, but the effects do not extend to protection of lung cellular injury.

Animals↗
PubMed1997

Effects of timing, dosage, and duration of morphine intake during pregnancy on the amount of morphine in meconium in a rat model.

Meconium drug analysis is a new and sensitive test for detecting the intrauterine exposure of infants to drugs of abuse. To explore other potential, diagnostic use of the test, we studied, in timed pregnant rats, the relationship between timing, dosage, and duration of morphine administration to the dam and the concentration of morphine, analyzed by radioimmunoassay, in their pups' meconium. The term 'meconium' refers to both the intestine and its contents. Due to the minute size of the pups' intestines, the intestinal contents were not separated from the intestines. The mean morphine concentration in meconium was found to be significantly (p < 0.05) higher in the groups treated with a higher morphine dose (10 vs. 5 mg/ kg/day), longer duration of treatment (7-20 vs. 18-20 days), or treated during the last week of gestation (14-20 vs. 1-6 or 7-13 days). We conclude that the concentration of a drug in the meconium is related to amount, timing, or duration of the drug exposure of the fetus, in utero. The quantitative analysis of drugs in the meconium, therefore, provides added information which enhances the diagnostic use of the test.

Animals↗
PubMed1997

Methylprednisolone attenuates the pulmonary hypertensive response in porcine meconium aspiration.

Severe neonatal aspiration of meconium is frequently complicated by fatal pulmonary hypertension. The protective effect of an i.v. bolus of methylprednisolone on meconium aspiration-induced hypertensive lung injury was studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator settings were adjusted to keep arterial PO2 above 8 kPa and arterial PCO2 below 5 kPa. Meconium insufflation induced a biphasic pulmonary pressor response during the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h) increase in pulmonary artery pressure and inhibited significantly the second phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary vascular resistance. This inhibition of resistance increase was most profound in the postarterial segment of the lung circulation, as determined by pulmonary artery occlusion. Additionally, the methylprednisolone pretreated group demonstrated a significant decrease in venous admixture together with improved oxygenation during the late phase after the insult, and further showed evidence of diminished lung edema formation. Although meconium aspiration-induced fall in blood leukocyte concentration was inhibited by methylprednisolone pretreatment, no histologic difference was found in pulmonary leukocyte sequestration. Our results thus show that in adapted porcine lungs methylprednisolone pretreatment improves oxygenation and attenuates the meconium aspiration-induced pulmonary hypertensive response by preventing the increase in the postarterial resistance.

Animals↗
PubMed1998

Involvement of thromboxane A2 and prostacyclin in the early pulmonary hypertension after porcine meconium aspiration.

Severe perinatal aspiration of meconium is frequently complicated by unsuccessful neonatal adaptation with associated pulmonary hypertension. This vascular complication is supposedly related to pulmonary release of vasoconstrictory agents, including metabolites of arachidonic acid. Thus, to investigate the role of prostanoids on these meconium-induced circulatory changes in the lungs, the hemodynamic response to meconium instillation was studied in acetylsalicylic acid-pretreated juvenile pigs. Twelve 10-wk-old pigs with adapted lung circulation received 3 mL/kg of 65 mg/mL human meconium via the endotracheal tube. Six of them were medicated with 10 mg/kg acetylsalicylic acid 30 min before meconium insufflation. Hemodynamic parameters and urinary excretion of stable metabolites of thromboxane A2 and prostacyclin were measured serially for 6 h after the insult. Meconium administration induced a biphasic increase in mean pulmonary artery pressure and pulmonary vascular resistance, and a rapid rise in urinary levels of prostanoid metabolites. Acetylsalicylic acid pretreatment prevented the initial (0-1 h) pulmonary hypertensive response and increase in prostanoid excretion. During the second phase (1-6 h), acetylsalicylic acid did not attenuate the progressive increase in mean pulmonary artery pressure and pulmonary vascular resistance nor did it affect the longitudinal distribution of the pulmonary resistances. Our results thus show that in adapted porcine lungs, arachidonic acid metabolites contribute to the early hypertensive response, but have only minor effects during the second phase vascular hypertension.

Adaptation, Physiological↗
PubMed2001

Newborn piglets with meconium aspiration resuscitated with room air or 100% oxygen.

We investigated whether newborn piglets exposed to hypoxemia and severe meconium aspiration could be reoxygenated with room air as efficiently as with 100% O(2). Twenty-one 2- to 5-d-old piglets were randomly divided into three groups: 1) the room air group: hypoxemia, meconium aspiration, and reoxygenation with room air (n = 8); 2) the O(2) group: hypoxemia, meconium aspiration, and reoxygenation with 100% O(2) (n = 8); and 3) the control group: meconium aspiration, and reoxygenation with room air (n = 5). Hypoxemia was induced by ventilation with 8% O(2) until the mean blood pressure reached <20 mm Hg or the base excess reached <-20 mM. At this point, reoxygenation was started with either room air or 100% O(2). Three milliliters per kilogram of meconium 110 mg/mL was instilled into the trachea immediately before the start of reoxygenation. The O(2) tension in arterial blood was significantly lower in the room air group; at 5 min of reoxygenation it was 9.1 +/- 0.5 kPa versus 43.5 +/- 6 kPa in the O(2) group (p < 0.05). At 5 min of reoxygenation the tidal volume per kilogram was 12.1 +/- 0.7 mL/kg in the room air group and 13.1 +/- 0.9 mL/kg in the O(2) group (NS). There were no significant differences between the room air and the O(2) groups during 120 min of reoxygenation in mean arterial blood pressure, pulmonary arterial pressure, cardiac index, base excess, or plasma hypoxanthine. In conclusion, hypoxic newborn piglets with meconium aspiration were found to be reoxygenated as efficiently with room air as with 100% O(2).

Animals↗
PubMed2003

Prevalence of fatty acid ethyl esters in meconium specimens.

BACKGROUND: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs), and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the result of maternal alcohol consumption during pregnancy. Facial characteristics are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose. Fetal exposure to alcohol can cause central nervous system dysfunction, pre- and postnatal growth problems, cardiac defects in neonates, and attention deficit disorders and mental retardation in older children. To date, diagnosis of fetal alcohol effect has depended largely on maternal interview, although clinical tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed in the body by esterification of ethanol with free fatty acids and trans-esterification of glycerides and have been detected in the meconium of newborns. This report estimates the prevalence of fetal alcohol exposure in two populations by detecting FAEEs in meconium. METHODS: We analyzed the prevalence of FAEEs in the meconium of two separate groups of neonates by use of solid-phase extraction and analysis by gas chromatography-mass spectrometry in the chemical ionization mode. In the first study, meconium samples were taken anonymously from babies born in a large, regional perinatal center in Hawaii. In the second study, specimens were obtained from infants admitted to six different newborn intensive care units within the state of Utah. RESULTS: In the first study, 73 of 436 (16.7%) meconium specimens tested were considered positive for FAEEs. When broken down into quartiles, the mean total FAEEs measured were 1,059, 3,133, 6,628, and 62,115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered positive. When broken into quartiles, the mean total FAEEs were 1,139, 3,067, 7,674, and 50,143 ng/g. The overall FAEE profiles of the two study sets were remarkably similar. CONCLUSION: In an adequate meconium specimen, a total FAEE concentration >10,000 ng/g may indicate that the newborn has been exposed to significant amounts of alcohol during pregnancy.

Biomarkers↗
PubMed1990

Significance of meconium staining of the amniotic fluid.

The study was conducted to determine the significance of meconium staining and more specifically its association with fetal heart rate patterns. Five hundred and one patients in labor were examined, 106 of whom had meconium stained amniotic fluid. A multivariate analysis of the data was performed by logistic regression analysis using meconium staining as the dependent variable. The determinants of meconium in the amniotic fluid were gestational age, base deficit, calcified placenta, late decelerations and placental weight. The following variables had no effect on the occurrence of meconium: maternal age, type of risk, parity, fetal sex, duration of labor, duration of the second stage of labor, entanglement of the umbilical cord, FHR variability, variable decelerations, oxytocin usage, type of anesthesia, maternal smoking and alcohol consumption habits. In conclusion, meconium in the amniotic fluid seems to be associated with placental rather than with umbilical insufficiency.

Amniotic Fluid↗
PubMed2001

The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report.

OBJECTIVE: The objective of this study was to describe drug use by pregnant women participating in the 4-site Maternal Lifestyle Study of in utero cocaine and/or opiate exposure. METHODS: Meconium specimens of 8527 newborns were analyzed by immunoassay with GC/MS confirmation for metabolites of cocaine, opiates, cannabinoids, amphetamines, and phencyclidine. Maternal self-report of drug use was determined by hospital interview. RESULTS: The prevalence of cocaine/opiate exposure in the 4 sites was 10.7% with the majority (9.5%) exposed to cocaine based on the combination of meconium analysis and maternal self-report. However, exposure status varied by site and was higher in low birth weight infants (18.6% for very low birth weight and 21.1% for low birth weight). Gas chromatography/mass spectrometry (GC/MS) confirmation of presumptive positive cocaine screens was 75.5%. In the cocaine/opiate-exposed group, 38% were cases in which the mother denied use but the meconium was positive. There was 66% agreement between positive meconium results and positive maternal report. Only 2% of mothers reported that they used only cocaine during pregnancy and mothers were 49 times more likely to use another drug if they used cocaine. CONCLUSION: Accurate identification of prenatal drug exposure is improved with GC/MS confirmation and when the meconium assay is coupled with a maternal hospital interview. However, the use of GC/MS may have different implications for research than for public policy. We caution against the use of quantitative analysis of drugs in meconium to estimate the degree of exposure. Our study also highlights the polydrug nature of what used to be thought of as a cocaine problem.

Adolescent↗
PubMed2002

Newly developed mecometer method for objective assessment of meconium content.

We developed a new method for an objective assessment of the meconium content in amniotic fluid. By establishing a standard scale through a serial dilution of a known amount of meconium into the amniotic fluid, we developed a new method "mecometer" that can objectively measure the meconium content in meconium-stained amniotic fluid samples. The objectivity and reliability of this mecometer were verified by 300 student volunteers. At least 70% of the volunteers could objectively measure and digitally describe the meconium content in meconium-stained amniotic fluid samples. We believe our newly developed mecometer is a very simple, reliable, and portable method, not requiring any instruments.

Amniotic Fluid↗
PubMed2003

Disappearance of meconium pigment in placental specimens on exposure to light.

CONTEXT: Meconium discharge has been associated with fetal distress and poor neonatal outcome; thus, its presence is of clinical importance. OBJECTIVE: Loss of meconium pigment in histologic sections from light exposure has been described. We sought to confirm this finding and to measure this loss quantitatively. DESIGN: Sections of umbilical cord, fetal membranes, and fetal surface from 11 grossly meconium-stained placentas were processed swiftly to minimize light exposure. Two serial sections from each block were cut and stained; one set was reviewed immediately, and the other was exposed to 8 hours of direct fluorescent lighting. Each site and exposure was scored for pigment intensity (0, no staining; 1, weak expression; and 2, moderate/strong expression) and number of meconium-laden macrophages per 10 high-power fields (HPF). Results were compared on the same specimen using the chi(2) and the paired-samples t test. RESULTS: The maximum meconium macrophage count was 13.2/10 HPF in the unexposed sections versus 6.1/10 HPF in the exposed sections (P <.001). Unexposed sections varied from 1+ to 2+ intensity, while exposed sections were all 1+ or negative (P <.001). CONCLUSION: Exposure to fluorescent laboratory lights for 8 hours resulted in a significant loss in the intensity and number of identifiable meconium macrophages in histologic sections. These findings have important implications in the handling of placental specimens, and we recommend that care be taken to minimize exposure to laboratory lights during processing.

Extraembryonic Membranes↗