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The analysis of cocaine and benzoylecgonine in meconium.

We describe an assay for measuring cocaine and benzoylecgonine in meconium of infants born to mothers suspected of using cocaine during their pregnancy. The assay involves the use of fluorescence polarization immunoassay (FPIA) to screen for benzoylecgonine in a methanolic extract of the meconium. The FPIA is sensitive to 0.6 microgram benzoylecgonine per gram meconium. Confirmation of the presence (or absence) of benzoylecgonine and cocaine in meconium samples was performed by solid phase extraction of a second methanolic extract of the meconium, derivatizing using BSTFA, followed by a gas chromatographic/mass spectrometric (GC/MS) analysis, which can detect both cocaine and benzoylecgonine. The GC/MS confirmation was sensitive to less than 0.25 microgram cocaine or 0.5 microgram benzoylecgonine per gram meconium. FPIA, which is commonly used in many toxicology laboratories, is advantageous because it precludes the need to use radioimmunoassays for the initial screen. The confirmation step provides greater certainty for the presence of cocaine and/or benzoylecgonine in meconium.

Cocaine↗

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.

Amphetamine↗

High-frequency oscillatory ventilation versus conventional ventilation in a piglet model of early meconium aspiration.

OBJECTIVE: To compare the cardiopulmonary effects of high-frequency oscillatory ventilation (HFO) and conventional ventilation (CV) in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, randomized control study. SUBJECTS: Piglets 1 to 2 wks of age. INTERVENTIONS: Meconium aspiration was induced in 30 piglets. They were then randomized to CV, HFO at 10 Hz, or HFO at 15 Hz. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas, and systemic and pulmonary hemodynamics were measured serially. Airway opening pressure (P-Flex), static lung compliance (Crs), and trapped gas volume (TGV) were derived. Meconium instillation produced similar stable decreases in Crs (6.7 +/- 0.7 [SEM] to 4.7 +/- 0.4 mL/cm) and increases in pulmonary vascular resistance (68 +/- 6.4 vs. 91.9 +/- 8.5 mm Hg/mL/kg/min). A greater proportion of animals (40%, p< .007) remained hypercarbic during HFO at 15 Hz. Oxygenation indices were similar for all groups. In regards to high-frequency support, both power and deltaP were higher in the HFO at 15 Hz group (p< .001). When compared with both CV and HFO at 10 Hz, the TGV in the HFO at 15 Hz group was significantly higher following randomization to ventilator type. P-Flex was also greatest in the 15 Hz group, followed by the 10 Hz group and the CV group. Higher airway opening pressures, given identical compliance, suggest that HFO at 15 Hz resulted in greater large airway obstruction. With HFO's inherent low tidal volumes, progression of meconium to the distal airways may be delayed. CONCLUSIONS: Early institution of HFO at 15 Hz in meconium aspiration may exacerbate air trapping. HFO at lower rates may be the optimal method of respiratory support in meconium aspiration syndrome. HFO may extend the window of time available for removal of meconium.

Animals↗

Pancreatic function testing in meconium disease in CF: two case reports.

We report two infants with cystic fibrosis (CF), presenting with meconium ileus and meconium plug, who had no clinical or biochemical evidence of pancreatic insufficiency during infancy. They underwent pancreatic secretory function testing at 11 and 9 months of age, respectively. Both patients had sufficient lipase and colipase secretion to maintain normal digestion of fat, confirming that meconium disease in CF does not necessarily imply pancreatic insufficiency and the need for enzyme supplementation in infancy. Nonetheless, we documented markedly reduced enzyme secretion in both patients, implying a potential role for the pancreas in the pathogenesis of meconium disease, even when clinical pancreatic insufficiency is absent. In addition, our patient with meconium ileus had a severely limited fluid secretory capacity (10.3% of mean normal values). In contrast, the patient with the milder presentation of meconium plug had a far greater ability to secrete fluid (75% of mean normal), but had poorer pancreatic proteolytic activity. We suggest that impaired fluid secretion may be a very significant factor in the pathogenesis of meconium ileus, and we speculate that an inability to maintain sufficient intraluminal fluid relative to the degree of pancreatic proteolytic deficiency may more adequately explain the risk of occurrence and the severity of intestinal obstruction in CF than either factor alone.

Age Factors↗

Bilirubin-IXbeta is a marker of meconium, like zinc coproporphyrin.

BACKGROUND: Because meconium accumulates continuously in the fetal intestine, analysis of the postnatally excreted material could yield important information of intrauterine metabolism and maturation. Therefore, a study of the bilirubin pigments in meconium and in the first neonatal stools was carried out. METHODS: Meconium and stools from 37 neonates of various gestational ages were collected carefully, and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with an equal amount of dimethyl sulfoxide, centrifuged, and submitted to analysis by high-pressure liquid chromatography using newly developed methods to identify and to quantitate the bilirubin-IXalpha, -IXbeta, -IXgamma, and -IXdelta isomers. In addition, samples were also submitted to diazo coupling with ethyl anthranilate. Total coproporphyrins and zinc coproporphyrin were assayed for comparison. RESULTS: Unconjugated bilirubin-IXalpha and -IXbeta were detected in meconium but not the -IXgamma or the -IXbeta isomer. Bilirubin-IXbeta was the predominant pigment and comprised 63% to 96% of the unconjugated bilirubins in the first sample of meconium excreted. Its amount decreased rapidly during the first 5 days in full-term newborns, but this occurred more slowly in preterm neonates, especially in those with a gestational age less than 30 weeks. The decrease of bilirubin-IXbeta over time correlated with that of coproporphyrin. CONCLUSIONS: Bilirubin-IXbeta is the prevailing bile pigment in the first excreted sample of meconium. It gradually decreases after birth and can be considered a biochemical marker of meconium, like zinc coproporphyrin.

Bile Acids and Salts↗

ACOG Committee Opinion Number 346, October 2006: amnioninfusion does not prevent meconium aspiration syndrome.

Amnioinfusion has been advocated as a technique to reduce the incidence of meconium aspiration and to improve neonatal outcome. However, a large proportion of women with meconium-stained amniotic fluid have infants who have taken in meconium within the trachea or bronchioles before meconium passage has been noted and before amnioinfusion can be performed by the obstetrician; meconium passage may predate labor. Based on current literature, routine prophylactic amnioinfusion for the dilution of amnioinfusion for meconium-stained amniotic fluid should be done only in the setting of additional clinical trials. However, amnioinfusion remains a reasonable approach in the treatment of repetitive variable decelerations, regardless of amniotic fluid meconium status.

Amniotic Fluid↗

Population baseline of meconium fatty acid ethyl esters among infants of nondrinking women in Jerusalem and Toronto.

The detection of fatty acid ethyl esters (FAEE) in meconium may provide an objective estimate of prenatal alcohol exposure independent of maternal history. The authors report the results of the first population-based study conducted to investigate basal FAEE levels in the meconium of neonates not exposed to alcohol. Two hundred seven nondrinking women and their neonates were recruited from Toronto and Jerusalem. FAEE were extracted from meconium by solid-phase extraction and analyzed by GC/FID. Similar procedures were conducted in six neonates born to confirmed heavy drinkers. Low levels of meconium FAEE were detected from both cohorts (mean, 1.37 nmol/g vs. 2.08 nmol/g, Toronto vs. Jerusalem). Ethyl stearate, oleate, and linoleate were below the limit of detection in >80% of all samples, whereas ethyl laurate and palmitate were detected in >50% of the samples. Ethyl myristate was the FAEE most commonly detected (>80%). All six meconium samples with confirmed maternal drinking histories tested positive for FAEE at significantly higher levels (mean, 11.08 nmol/g). The use of 2 nmol total FAEE/g meconium as the positive cutoff, when lauric and myristic acid ethyl esters were excluded, yielded the greatest sensitivity (100%) and specificity (98.4%). The authors conclude that certain FAEE are present at measurable levels in the meconium of neonates not exposed to maternal drinking, and correction is needed to allow high specificity.

Adult↗

Evaluation of the effect of meconium on assessment of fetal lung maturity status by TDxFLM II testing.

OBJECTIVE: To evaluate the effect of meconium contamination on the TDxFLM II assay. METHODS: Amniotic fluid was collected from patients undergoing amniocentesis for obstetric indications between 31 and 40 weeks of gestation. A baseline TDxFLM II value was obtained and compared with amniotic fluid contaminated with 1%, 5%, and 10% meconium by weight. RESULTS: Twenty-one samples were studied, and in every case the TDxFLM II value decreased once the meconium was added. There was no consistent rate of decrease that correlated with the percentage of meconium added. CONCLUSION: Meconium contamination decreases the TDxFLM II value. A clinician who performs this test in the presence of meconium can be reassured that the contamination will not give an artificially elevated result. If the result is in the mature range, one can be confident that the result would only be higher if meconium were not present.

Adult↗

Assessment of the rectoanal inhibitory reflex in preterm infants with delayed meconium passage.

BACKGROUND: There is an inverse relationship between gestational age, birth weight and the time of first neonatal bowel movement. The authors hypothesized that delayed passage of meconium might result from a delayed maturation of the recto-anal inhibitory reflex (RAIR) in premature infants. OBJECTIVE: To evaluate whether the RAIR is absent in very preterm infants 28-32 weeks postmenstrual age with delayed meconium production. STUDY DESIGN: Anorectal manometry was performed in 10 preterm infants (seven male) with delayed meconium production (no meconium in the first 48 hours). Median postmenstrual age was 30 weeks (28-31 weeks). Birth weight ranged from 780 to 1930 g (median, 1395 g). A micromanometric assembly (outer diameter, 2.0 mm) was used which incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressure and relaxation. Four side-holes recorded anal and rectal pressures. Rectal distension was performed with direct air insufflation to elicit the RAIR. RESULTS: The time from birth to passage of meconium ranged from 48 to 105 hours (median, 82 hours). The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 22.0 +/- 5.0 mm Hg, 6.9 +/- 2.0 mm Hg, and 9.8 +/- 1.9/min, respectively. A normal RAIR was elicited in all infants. CONCLUSION: Anorectal manometry recordings in premature infants with delayed passage of meconium showed normal anorectal pressures and a normal RAIR, suggesting that delayed meconium passage is not related to the absence of a RAIR.

Anal Canal↗

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.

Animals↗

Meconium aspiration syndrome: the role of resuscitation and tracheal suction in prevention.

We reviewed our experience of meconium staining of liquor and meconium aspiration syndrome over a 33 month period. The clinical and radiological severity of disease was assessed in comparison with tracheal suction and resuscitation. Sixty (27%) of newborns with meconium stained liquor subsequently developed MAS. No association was found between the thickness of meconium or its presence on tracheal aspiration with subsequent severity of respiratory disease. However, the presence of meconium in the trachea was strongly associated with radiological abnormality. The severity of meconium aspiration syndrome and mortality were also related to the clinical stability of the infants at presentation. Our results indicate that intrauterine aspiration and pulmonary maladaptation may play a significant role in meconium aspiration syndrome rather than resuscitative events at delivery.

Humans↗

Meconium and neurotoxicants: searching for a prenatal exposure timing.

BACKGROUND: Exposure to organochlorine compounds (OCs) has been a subject of interest in recent years, given their potential neurotoxicity. Meconium is easily available and accumulates neurotoxicants and/or metabolites from the 12th week of gestation. AIMS: To determine whether neurotoxicants, specifically OCs, could be detected in serially collected meconium, and to compare the results with those obtained in cord blood samples. METHODS: A sample of cord blood and three serial stool samples were analysed in 10 newborns. Pentachlorobenzene (PeCB), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane (p,p'-DDT) and its metabolite dichlorodiphenyl dichloroethylene (p,p'-DDE), and hexachlorocyclohexane isomers (alpha-, beta-, gamma-, and delta-HCH) were analysed by gas chromatography. RESULTS: From serial stool collection and analysis in newborns, there was an increase in the concentrations of HCB, p,p'-DDE, PCBs, and beta-HCH between the first and last stools of the newborn. Levels of DDT diminished as pregnancy progressed. Concentrations in cord blood were positively associated with concentrations in meconium for p,p'-DDE and beta-HCH. CONCLUSIONS: Meconium is a very useful instrument for the investigation of fetal exposure to neurotoxicants; serial collection and analysis of meconium should estimate the timing and degree of in utero exposure of the fetus to neurotoxicants. Analysis and interpretation of neurotoxicants in meconium results is a complex process. Measurement in meconium of a wide range of neurotoxic substances should facilitate early identification of harmful exposures, and enable rehabilitation and instigation of preventive measures.

Adult↗

Ileal meconium plugs.

Eleven cases of neonatal intestinal obstruction associated with a white ileal meconium plug are described; 6 of these presented with complications--such as, giant meconium pseudocyst, perforation, volvulus, or atresia. Most of these complications are presumed to have arisen during the intrauterine period. Only one patient could be relieved of the ileal meconium plug by enemas. The condition of ileal meconium plug is not as benign as a meconium plug in the rectum or distal colon. A plea is made to restrict the name meconium plug syndrome to cases in which the meconium plug is white and chalky and the consequent intestinal obstruction can be relieved by enemas, without evidence of intestinal dysfunction in later life.

Enema↗

Hemodynamic effects of periodic G(z) acceleration in meconium aspiration in pigs.

The hemodynamic effects of periodic acceleration (pG(z)), induced in the spinal axis with noninvasive motion ventilation (NIMV), were studied in a piglet model of pulmonary hypertension associated with meconium aspiration. Animals (n = 12) were anesthetized, paralyzed, intubated, and supported by conventional mechanical ventilation (CMV). Thirty minutes after tracheal instillation of meconium solution (6 ml/kg), either CMV (n = 6) was continued or NIMV (n = 6) was initiated. Changes in systemic and pulmonary hemodynamics and arterial blood gases were tracked for 2 h after aspiration. Thermodilution, cardiac output, and heart rate were not significantly different after meconium aspiration in the pG(z) group relative to the CMV controls. Aortic pressure and systemic vascular resistance were significantly lower (approximately 30%) after meconium aspiration in NIMV animals relative to CMV animals. Pulmonary arterial pressure and pulmonary vascular resistance were also significantly lower, by 100%, after aspiration of meconium in the NIMV animals compared with the CMV controls. Meconium aspiration significantly decreased total respiratory compliance by approximately 50% and increased total respiratory resistance by approximately 100% in both CMV and NIMV animals, but such alterations did not differ between the two groups. Both CMV and NIMV satisfactorily supported ventilation in these paralyzed animals. In conclusion, NIMV through pG(z) in the spinal axis decreased systemic and pulmonary vascular resistance in piglets after meconium aspiration.

Acceleration↗

Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city.

OBJECTIVE: To investigate fetal exposure to toxic metals [lead (Pb), cadmium (Cd)] and fetal levels of trace elements [zinc (Zn), copper (Cu), and iron (Fe)] in newborns from an industrial city. Relationships between meconium mineral contents and parental occupation and location of residence were also tested. METHOD: The meconium mineral contents of 117 healthy newborn infants were measured by flame atomic absorption spectrophotometer. RESULTS: The median concentrations (interquartile range) of toxic metals and trace elements in the meconium were as follows: Pb: 46.5 (1,399) microg/g dry weight (wt), Cd: 2.3 (55.6) microg/g dry wt; Zn: 234 (3,049) microg/g dry wt; Cu: 11.8 (818.7) microg/g dry wt, and Fe 105 (2,980) microg/g dry wt. All the meconium samples contained both toxic metals and trace elements. The proportions of trace elements in the meconium samples with concentration higher than 100 microg/g dry wt of the substances tested were Zn 90%, Cu 64%, and Fe 53%. There were significantly positive correlations between the concentrations of toxic metals and trace elements. Also there were positive correlations between the levels of Zn, Fe, and parental occupations, and between the level of Fe and location of residence of the parents (proximity to the petroleum refinery or the dye industries). CONCLUSION: All the meconium samples were positive for toxic metals, and thus may reflect environmental pollution in the city. The occupation environments and the location of the family residence are linked with levels of trace elements in meconium.

Cadmium↗

Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic polymers, we added dextrans, polyethylene glycols (PEGs), or polyvinylpyrrolidones (PVPs) of various molecular weights to pulmonary surfactants. One to 3% human meconium or other inactivating substances were then added to the mixtures, which were tested in a modified pulsating bubble surfactometer. Polymers (3.3-500 kD) in 1-10% concentrations enhanced the ability of a commercial surfactant replacement (Survanta) to lower the minimum surface tension in the presence of meconium, serum, or lysophosphatidylcholine. Similar effects were seen when polymers were added after mixing of surfactant and meconium or other inhibitors, indicating that polymers are capable of reversing the inactivation. Results from rat experiments indicate that total lung capacity is increased when PEG is first added to the Survanta, then mixed with meconium and instilled into the lungs. We postulate that polymers separate meconium-surfactant complexes, permitting surfactant components better access to the air-liquid interface. Taeusch HW, Lu KW, Goerke J, Clements JA. Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

Animals↗

Intrapartum amnioinfusion for meconium-stained liquor in developing countries.

BACKGROUND: Intrapartum amnioinfusion (AI) has been reported to decrease perinatal mortality and morbidity in women with meconium-stained liquor. Such work has not previously been performed at King Edward VIII Hospital (KEH), in a developing country, where the incidence of meconium-stained liquor is said to be extremely high. OBJECTIVE: To establish whether AI during the intrapartum period for meconium-stained liquor decreases Caesarean section rates for fetal distress and decreases perinatal morbidity. METHOD: Informed consent was obtained from patients in labour who were 3-8 cm dilated, with meconium-staining of the liquor, grades I to III inclusive, and who had a normal cardiotocograph on presentation at term. Sixty patients were included in the trial; 30 had AI. The control group was managed by standard methods. The study group had an amnioinfusion of 0.9% normal saline at 15 ml/min under continuous cardiotocographic monitoring, until a volume of 11 was completed. This was repeated if delivery did not occur within 4 h. RESULTS: The mean pH of umbilical arterial blood was significantly higher in the AI group (7.30 versus 7.23; P = 0.0029). In addition fewer patients in this group developed hypoxic ischaemic encephalopathy (0 versus 2 controls) or meconium aspiration syndrome (1 versus 4 controls). This was not statistically significant. Caesarean section for fetal distress was performed on fewer patients in the AI group (3 versus 7 controls), although this was not statistically significant. CONCLUSION: These results demonstrate that amnioinfusion is an effective technique for improving the perinatal outcome of pregnancies complicated by meconium-stained liquor in labour. The decrease in Caesarean sections for fetal distress, though not statistically significant in this study, has clinical relevance. Furthermore, this study suggests that amnioinfusion is cost effective in a busy, high-risk labour ward unit and consequently should become standard practice in the management of meconium-stained liquor in labour.

Adult↗

Surfactant therapy and high-frequency jet ventilation in the management of a piglet model of the meconium aspiration syndrome.

In vitro data have shown a concentration-dependent inhibition of surfactant by meconium, while anecdotal reports demonstrate improved oxygenation after surfactant replacement in babies with meconium aspiration syndrome, particularly in conjunction with high-frequency jet ventilation. We randomized 70 newborn piglets to either conventional or high-frequency jet ventilation, followed by insufflation of 3 mL/kg of a 33% meconium solution. Each group was further randomized to one of five surfactant therapies: 1) control, 2) 4 mL/kg Survanta, 3) 8 mL/kg Survanta, 4) 5 mL/kg Exosurf, or 5) 10 mL/kg Exosurf. We followed arterial blood gases and ventilator requirements over 6 h of ventilation. Aspirates of airway fluids were obtained for surface tension measurements, as well as total protein and phospholipid concentrations. Using a previously established scoring system, a pathologist blinded to treatment evaluated four sections of lung per animal for histologic changes of meconium aspiration syndrome. There were no differences noted between groups in any physiologic parameter measured (mean airway pressure, arterial partial pressure of oxygen/alveolar partial pressure of oxygen ratio, etc.) during the 6 h of ventilation. Airway fluid aspirate total protein concentrations increased significantly after meconium instillation (4- to 5-fold, p < 0.007) and remained elevated in spite of surfactant therapy. There was an initial decline in airway phospholipid concentrations after meconium instillation followed by a rise to levels equal to or greater than premeconium levels. Surface tension measurements increased in all groups after meconium insufflation (p < 0.012) and did not decline thereafter, despite standard and twice-standard surfactant doses of both types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗