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Spectrophotometric determination of meconium concentration in amniotic fluid.

When a fetus is acutely distressed, for example as a result of strangulation by the umbilical cord, the bowel content, meconium, may be passed into the amniotic fluid. Assessment of meconial contamination of the amniotic fluid is important in the management of late pregnancy. Fresh or increasing meconium content is an indication for urgent delivery. 'Old' meconium is usually distinguished from 'new' by visual inspection of the stained amniotic fluid; a more objective method could have advantages. We consider the effects of meconium staining of amniotic fluid on the spectrophotometric properties of the liquor. The absorption spectra of meconial amniotic fluids reveal an excess absorption band, centred around 410 nm. Quantification of the band height is proposed and it is shown that the height is linearly related to meconium concentration, with a proportionality factor, or sensitivity, of 0.046 +/- 0.009 (mean +/- s.d.) proportionality factor, or sensitivity, of 0.046 +/- 0.009 (mean +/- s.d.) optical density (OD) units per g l-1. This sensitivity factor may be used to estimate meconium concentration in samples of amniotic fluid.

Amniotic Fluid↗

Interaction of P-fimbriated Escherichia coli with human meconium.

The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.

Adhesins, Escherichia coli↗

Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the "Meconium Project".

For the first time in Europe, the "Meconium Project" aimed to estimate the prevalence of drug use by pregnant women and the effects of exposure to illicit drugs during pregnancy on the fetus and infant. Between October 2002 and February 2004, 1151 (79%) dyads among the 1439 mother-infant dyads from the Hospital del Mar, Barcelona, Spain, met eligibility criteria and agreed to participate in the study. We present preliminary results on the first 830 meconium samples and 549 mother-infant dyads, for which statistical analysis of socio-economic and demographic characteristics and newborn somatometry was completed. The meconium analysis showed an overall 7.9% positivity for drugs of abuse, with 6-monoacetylmorphine and cocaine being the analytes, most frequently found in samples positive for opiates and cocaine. Structured interview disclosed 1.3, 1.8 and 1.3% of mothers exposed to opiates, cocaine and both drugs, while only one mother declared ecstasy consumption. Meconium analysis showed that prevalence of opiates, cocaine and combined drugs exposure was 8.7, 4.4 and 2.2%, respectively, and confirmed the case of ecstasy use. Arecoline, the main areca nut alkaloid, was found in meconium specimens from four Asiatic newborns, whose mothers declared beetle nut consumption during pregnancy. Parental ethnicity was not associated with drug use, nor was the social class, although a higher tendency toward drug consumption was observed in professional and partly skilled mothers. Drug consuming mothers showed a higher number of previous pregnancies and abortions (p<0.05) when compared to non-consumer mothers (meconium negative test), probably due to a lack of family planning. Consumption of opiates and cocaine during pregnancy was associated with active tobacco smoking, a higher number of smoked cigarettes and cannabis use. Exposure status and smoking behavior correlated with significantly lower birth weight in newborns from mothers exposed only to cocaine and to opiates and cocaine simultaneously. Of the four newborns exposed to arecoline, one showed a low birth weight, low intrauterine growth, hyporeflexia and hypotonia.

Abortion, Induced↗

Intrapartum fetal heart rate monitoring. III. Association of meconium with abnormal fetal heart rate patterns.

Fetal heart rate (FHR) tracings of 284 fetuses with meconium-stained amniotic fluid (MSAF) and 1,672 fetuses without meconium staining were compared to investigate the significance of meconium associated with normal and abnormal FHR patterns. MSAF was found to be associated with significantly more low 1- and 5-minute Apgar scores and higher neonatal mortality rates than the control group without meconium. An increase in abnormal FHR patterns in the MSAF group over the control group as well as the postpartum sequelae of meconium itself was likely responsible for the unfavorable outcome. It is concluded that the presence of meconium should be viewed as a warning sign of fetal distress which warrants close intrapartum observation of the patient.

Amniotic Fluid↗

A selective aggressive approach to the neonate exposed to meconium-stained amniotic fluid.

OBJECTIVE: We attempted to determine the effect on meconium aspiration syndrome from a selective approach of neonatal endotracheal intubation in meconium-exposed fetuses. STUDY DESIGN: All pregnancies delivered at the Medical College of Virginia in 1990 were included. Meconium was noted at membrane rupture and qualified as thick, moderate, or thin. Neonates underwent suctioning with a DeLee device at delivery. They were observed without endotracheal intubation if they fulfilled the following criteria: vaginal delivery, gestational age > 37 weeks, birth weight > 2500 gm, and anticipated Apgar score > or = 8 at 1 minute. RESULTS: Of 4289 deliveries, 659 were exposed to meconium and 48% of infants were intubated. Birth weights, gestational ages at delivery, and umbilical arterial pH were similar between intubated and nonintubated neonates. Neonatal intensive care unit admissions were significantly higher in intubated neonates. All 9 neonates diagnosed with meconium aspiration syndrome were intubated at birth. CONCLUSIONS: Utilization of this protocol resulted in reduction of neonatal intubation. Meconium aspiration syndrome did not occur in the nonintubated group.

Amniotic Fluid↗

Meconium has no lecithin or sphingomyelin but affects the lecithin/sphingomyelin ratio.

OBJECTIVE: Although a few studies have evaluated the effect of meconium on the lecithin/sphingomyelin ratio for testing of fetal lung maturity, to date these studies have assessed only the lecithin-sphingomyelin ratio of amniotic fluid contaminated with meconium. The purpose of this study was (1) to determine whether meconium by itself has a lecithin/sphingomyelin ratio and, if so, (2) to determine whether the lecithin/sphingomyelin ratio is constant. STUDY DESIGN: A lecithin/sphingomyelin ratio was obtained by standard thin-layer chromatography on the first meconium stool of 20 neonates between 31 weeks and term. A quantitative assay was then performed on a sample from each gestational age (7 samples ranging from 31 weeks to term) to confirm the presence of lecithin and sphingomyelin. RESULTS: The 20 samples had atypical thin-layer chromatographic migratory patterns in the zones for lecithin and sphingomyelin. The presumed lecithin/sphingomyelin ratios ranged from 1.1 to 3.6, with no correlation with gestational age. However, the quantitative assay did not detect the presence of lecithin or sphingomyelin in any of the analyzed samples. CONCLUSIONS: Meconium does not appear to contain lecithin or sphingomyelin but has an unidentified moiety whose migratory pattern, as shown by qualitative standard thin-layer chromatography, is similar to that of lecithin with sphingomyelin. Therefore the presence of meconium in amniotic fluid may falsely raise or lower the lecithin/sphingomyelin ratio and confuse fetal lung maturity interpretations.

Chromatography, Thin Layer↗

Meconium ileus: is a stoma necessary?

During the 15 years from 1970 to 1984, 38 infants, all with cystic fibrosis, were treated for meconium ileus at The Montreal Children's Hospital and Ste-Justine Hospital for Children. Thirteen patients (34%) had complicated meconium ileus that included 7 perforations (2 colon, 5 ileum), 4 volvulus, and 2 atresia with meconium pseudocyst. In this group, various operations were done: resection with primary anastomosis for atresia, or resection with enterostomy for peritonitis or volvulus. One died shortly after surgery. Of 25 patients with uncomplicated meconium ileus (66%), one died shortly after arrival from respiratory distress, leaving 24 patients available for study. Gastrografin enema was attempted on 20 patients with eight successes (40%). Of the remaining 16 patients with unresolved meconium ileus, nine were treated with laparotomy and ileostomy, and one with laparotomy and T-tube irrigation. Six patients were treated by laparotomy and enterotomy for irrigation with N-acetylcysteine and evacuation by Fogarty catheter, a technique not widely used. No one succumbed in this group. This latter method of management is recommended for patients with simple uncomplicated meconium ileus.

Cystic Fibrosis↗

Neonatal abdominal calcification: is it always meconium peritonitis?

Intraluminal meconium calcifications are a rare cause of neonatal abdominal calcifications and can easily be misinterpreted as meconium peritonitis. We report three patients with anorectal anomalies, rectourethral fistula, and intraluminal calcified meconium. Intestinal stasis and mixing of urine and meconium may be predisposing factors for the calcification of meconium. Intraluminal calcifications appear as discrete punctate flecks within the distribution of the bowel, in contrast to meconium peritonitis, where the calcifications are linear and plaque-like, occurring anywhere in the abdominal cavity and scrotum. Careful differentiation of abdominal calcifications will allow more appropriate planning of the need and timing of surgery and can suggest the possibility of other anomalies that may not be suspected initially.

Abdomen↗

Is it necrotizing enterocolitis, microcolon of prematurity, or delayed meconium plug? A dilemma in the tiny premature infant.

Failure of a small premature newborn to adequately evacuate meconium for days or weeks has been attributed to "probable necrotizing enterocolitis (NEC)" or "microcolon of prematurity." The authors present an unusual type of "meconium plug syndrome" with the same clinical picture, seen in tiny premature babies (500 to 1,500 g), which required a contrast enema or Gastrografin upper gastrointestinal (UGI) series to evacuate the plugs. The obstruction resolved. Twenty babies (480 to 1,500 g) presented with the same clinical picture without any x-ray suggestion of NEC; contrast enemas were performed because of the suspicion of meconium plug syndrome. All 20 had extensive meconium plugs that were evacuated by the enema or by a Gastrografin UGI series. Most of them improved after the plugs were passed. These infants differ from typical full-term babies with meconium plug syndrome in a number of ways: (1) many of the mothers were on magnesium sulfate (MgSO4) or had eclampsia; (2) the plugs were diagnosed late rather than shortly after birth; and (3) the plugs were significant, extending to the right colon. The authors believe that when a tiny premature baby has findings consistent with meconium plug syndrome, the baby should be transported to radiology, for a Gastrografin enema, despite the difficulties involved. Delay postpones the start of feedings, and increases the number of radiographic studies.

Contrast Media↗

Meconium-induced umbilical vascular necrosis in abortuses and fetuses: a histopathologic study for cytokines.

OBJECTIVE: To show that meconium causes fetal morbidity and death at earlier gestations than reported previously. METHODS: We searched for specimens from 1997 and 1998 with pathologic diagnosis of meconium-induced umbilical vascular necrosis in placentas of nonmalformed fetuses and newborns. Because intra-amniotic infection is known to activate cytokines, and blood pigment is often microscopically indistinguishable from meconium, we removed those confounding considerations by excluding placentas with chorioamnionitis and signs of intra-amniotic bleeding. Light microscopic identification of vacuolar amniotic epithelial degeneration was used to select specimens with meconium because blood does not cause that histopathologic abnormality. We used histochemical procedures to show absence of hemosiderin and presence of bilirubin, and immunocytochemical labeling with interleukin-1beta to show cytokine. RESULTS: Four cases had meconium-induced umbilical vascular necrosis. The gestational ages were 16, 19, 29, and 38 weeks. Two cases were abortuses, the third was stillborn, and the fourth was a small-for-gestational-age liveborn, delivered by cesarean because of repetitive variable decelerations. Luna-Ishak staining showed bilirubin in macrophages between umbilical vascular myocytes and in the Wharton's jelly. Immunocytochemical methods showed interleukin-1beta in those same macrophages. CONCLUSION: Cytokines and other meconium-associated factors may contribute to the pathogenesis of fetal death. Survivors may suffer intraventricular hemorrhage, periventricular leukomalacia, and other morbidity.

Adult↗

Prevalence of fetal exposure to environmental toxins as determined by meconium analysis.

OBJECTIVE: The primary objective was to determine whether environmental pollutants, specifically lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As) and organochlorine and organophosphate pesticides can be detected in meconium. STUDY DESIGN: Prospective, cohort study. Infants were randomly recruited from the nurseries of five hospitals in Manila, Philippines. Their stools (meconium) were collected and analyzed for heavy metals by atomic absorption spectrophotometry and for pesticides by gas chromatography/mass spectrometry (GCMS). RESULTS: A total of 426 infants were studied. The exposure rate (based on meconium analysis) and the median concentration of the pollutants in the positive samples were as follows: lead (26.5%; 35.77 microg/ml), cadmium (8.5%; 13.37 microg/ml), mercury (83.9%; 3.17 ng/ml), chlordane (12.7%; 22.48 microg/ml), chlorpyrifos (11.0%; 8.26 microg/ml), diazinon (34.3%; 12.96 microg/ml), DDT (26.5%; 12.56 microg/ml), lindane (73.5%; 2.0 microg/ml), malathion (53.0; 6.80 microg/ml), parathion (32.0%; 2.30 microg/ml) and pentachlorphenol (16.1%; 90.00 microg/ml). Some maternal and neonatal factors that were significantly associated with the presence of environmental toxins in meconium included multi-gravidity, multiparity, multiple gestation, meconium stained fluid, smoking, gestational age, low birth weight and infant gender. CONCLUSION: Meconium analysis is a new and sensitive tool to detect fetal exposure to environmental toxins and its clinical use awaits further investigation.

Environmental Monitoring↗

Differential expression of interleukin-1 beta and interleukin-6 in human fetal serum and meconium-stained amniotic fluid.

The study was designed to investigate the expression of the inflammatory cytokines interleukin-1 beta and interleukin-6 in meconium-stained amniotic fluid and in fetal cord serum. Amniotic fluid and fetal cord serum specimens were collected from 10 and 9 women with meconium-stained and clear amniotic fluid, respectively, during Caesarean operation at labor The mean concentrations of interleukin-1 beta found in clear and meconium-stained amniotic fluid were 10.0 and 54.5 pg/ml, respectively, and the difference was not statistically significant. On the other hand, the concentrations of interleukin-6 in meconium-stained amniotic fluid (774 pg/ml) was significantly higher than that found in clear amniotic fluid (149 pg/ml) (P = 0.0036). The differences of levels of both interleukin-1 beta and interleukin-6 in fetal cord serum specimens were not significant between neonates born to mothers with either clear or meconium-stained amniotic fluid (P = 0.8702 and 0.2987, respectively). The results of this study suggest that the production of at least one of the inflammatory cytokines, interleukin-6, is associated with the meconium found in amniotic fluid.

Amniotic Fluid↗

Vasoconstrictive activity of oxytocin in meconium impregnated human placentas.

OBJECTIVE: The aim of our study is to determine whether oxytocin acts differently on the fetal-placental vascular bed of normal and meconium impregnated placentas. STUDY DESIGN: Isolated placental cotyledons (n=10) were dually perfused with fetal perfusion pressure used as an index of vascular resistance. As perfusion medium we used lactated Ringer salt solution, containing polyvinylpyrolidone (25 g/l), bovine serum albumin (0.1 mg/ml), glucose (1.0 g/l), heparin (20 IU/ml) and gentamycin (48 microg/ml). The pH of the medium was adjusted to 7.4 with bicarbonate. The maternal site was gassed with 95% O(2):5% CO(2) and in the fetal site with 95% N(2):5% CO(2) at 37 degree C. Perfusion rates were 4-6 and 10-12 ml/min in the fetal and maternal circulation, respectively. TNF-alpha and IL-beta1 levels in the fetal-placental perfusate were evaluated using specific commercial ELISA kits. RESULTS: No significant changes in the amount of TNF-alpha release were observed after injection of oxytocin into the fetal circulation (31+3pg/ml; P=0.5). No IL-beta1 activity was observed in the fetal perfusate of normal and meconium impregnated placentas during the experiments. No significant difference was seen in basal perfusion pressure in normal and meconium impregnated placentas, however, a bolus injection of oxytocin (10U/ml) resulted in a significant increase in perfusion pressure in meconium impregnated placentas from basal pressure of s45+5 to 88+4 mm Hg after injection of oxytocin, (P=0.004, ANOVA). CONCLUSION: Vasoconstrictive effect of oxytocin was observed only in meconium impregnated placentas and no vascular effect of oxytocin was documented in normal placentas. The clinical implication of our findings is that one should use oxytocin for stimulation of labor with caution in the presence of meconium stained amniotic fluid.

Case-Control Studies↗

Placental apoptosis in pregnancies with intrauterine meconium passage.

In this study we investigated the presence of placental apoptosis in pregnancies with intrauterine meconium passage. Placental tissue samples at term were obtained from 15 normal and 15 pregnancies with intrauterine meconium passage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method was applied to confirm apoptosis in all placental samples. The mean apoptotic ratio was significantly higher in placentas of pregnancies with intrauterine meconium passage when compared with normal ones (0.37 +/- 0.06% and 0.29 +/- 0.07%, respectively; p < 0.01). The mean apoptotic ratios in trophoblastic and stromal cells were significantly higher in placentas of pregnancies with intrauterine meconium passage than normal placentas (0.47 +/- 0.10% and 0.36 +/- 0.11% [ p < 0.05] and 0.29 +/- 0.07% and 0.22 +/- 0.07% [ p < 0.05], respectively). Increased placental apoptosis in pregnancies with intrauterine meconium passage could be a causative factor in the pathophysiology of the disorder or a direct effect of meconium on placental cells.

Adult↗

Meconium-stained amniotic fluid is associated with puerperal infections.

OBJECTIVE: The purpose of this study was to determine whether meconium-stained amniotic fluid is associated with puerperal infection and whether the quality of the meconium is further associated with this risk. STUDY DESIGN: We designed a retrospective cohort study of all deliveries beyond 37 weeks gestational age from 1992 to 2002 at a single community hospital. Data were collected on rates of chorioamnionitis, endomyometritis, quality of amniotic fluid, and length of labor and analyzed with bivariate and multivariate analyses. RESULTS: We found that, among the 43,200 women who were delivered at term, 18.9% of the women had meconium staining (8.8% thin, 5.5% moderate, 4.6% thick). Compared with deliveries with clear amniotic fluid, those with meconium-stained amniotic fluid had higher rates of chorioamnionitis (2.3% vs 4.1%, P<.001) and endomyometritis (1.0% vs 1.7%, P<.001). Further, the severity of meconium staining was associated with increased rates of infection. CONCLUSION: We found that the presence and severity of meconium-stained amniotic fluid is associated with puerperal infection even when being controlled for confounders.

Adult↗

Endothelin-1, atrial natriuretic peptide and pathophysiology of pulmonary hypertension in porcine meconium aspiration.

To evaluate the role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in the development of meconium aspiration-induced pulmonary hypertension, plasma ET-1 and ANP levels were measured serially for 6h after meconium instillation in juvenile pigs. Eleven 10-week-old, anaesthetized and catheterized pigs received intratracheally a bolus of 3 ml kg(-1) 20% human meconium, and five of them were premedicated with 30 mg kg(-1) methylprednisolone i.v. Another six pigs served as controls and were given 3 ml kg(-1) sterile saline intratracheally. Meconium instillation resulted in an increase in plasma ET-1 levels with a significant correlation to the simultaneously increasing PVR (r = 0.72). Methylprednisolone had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the second phase (1-6 h) rise with a concomitant attenuation of the progressive pulmonary hypertension. ANP concentrations were higher in the meconium than in the control group throughout the study and further increased after steroid treatment with a good correlation to ET-1 (r = 0.86). Thus, the postinjury rise in circulating vasoactive peptides, together with the pulmonary hypertensive response, and modulation of the peptide balance and pressor reaction by steroids, suggest a contributory role for ET-1 and ANP in the development of pulmonary hypertension after meconium aspiration.

Animals↗

Meconium hydrocele in a female newborn: an unusual cause of a labial mass.

Meconium peritonitis results from in utero perforation of the bowel and subsequent spillage of meconium into the peritoneal cavity. Free communication of the peritoneal space with the processus vaginalis during gestation permits formation of a meconium hydrocele. Meconium hydrocele has been reported in the newborn scrotum but to our knowledge there has been no previous report of meconium hydrocele in the labium of a female neonate. The predominance of meconium hydrocele in the male infant may be due to the obliteration of the processus vaginalis occurring later in the male than in the female fetus.

Female↗

Fetal exposure to alcohol as evidenced by fatty acid ethyl esters in meconium in the absence of maternal drinking history in pregnancy.

The detection of fatty acid ethyl esters (FAEE) in neonatal meconium has been proposed as a novel screening method for intrauterine exposure to alcohol. We investigated the potential use of meconium FAEE screening in a high-risk neonatal population in the absence of maternal drinking history. One hundred forty-two meconium samples of neonates suspected of intrauterine illicit substance exposure and referred to the Motherisk Laboratory were analyzed for the existence of drugs by enzyme-linked immunosorbent assay (ELISA) and FAEE by gas chromatography-flame ionization detection (GC-FID). A positive FAEE test was previously defined as a cumulative measurement of 7 individual FAEE > or = 2 nmol/g. Seventy-one percent of the samples tested positive for at least 1 illicit drug, with cannabis being the most prevalent (52.3%). Fourteen percent of all samples tested positive for prenatal alcohol exposure, as evidenced by cumulative meconium FAEE > or = 2 nmol/g. Ethyl oleate, linoleate, palmitate, and arachidonate were detected most often and at the highest levels. At least 3 individual FAEE were detected in 95% of all positive samples, and none could be identified by the use of 1 selected FAEE. Significantly elevated levels of FAEE above the baseline and the presence of multiple FAEE species in meconium are exclusive to neonates who have likely been exposed to excessive amounts of alcohol in utero. Babies born to mothers who are suspected to use illicit drugs in pregnancy are at elevated risk for exposure also to alcohol in utero. Meconium FAEE are emerging biologic markers that can potentially facilitate earlier diagnosis and intervention for less apparent forms of alcohol-related disabilities that cannot be confirmed in the absence of maternal drinking history.

Alcohol Drinking↗