An unusual diagnostic sign in meconium peritonitis: vaginal drainage of meconium.
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OBJECTIVE: We sought to use an in vitro approach to determine relationships between meconium and fetal lung liquid production and to relate meconium to possible problems in lung liquid removal at birth. STUDY DESIGN: Near-term fetal guinea pigs were divided according to the level of spontaneously occurring meconium (no meconium, light meconium, or heavy meconium). Their lungs were maintained in vitro in Krebs-Henseleit saline solution for 3 hours. Lung liquid production or reabsorption was measured by a dye-dilution method, and loss of lactate to the lung liquid and outer Krebs-Henseleit solution was monitored. Reabsorptions were investigated by activating powerful responses with dinitrophenol during the middle hour. RESULTS: During the first hour, lungs from meconium-free fetuses produced liquid at 1.25 +/- 0.12 mL/kg(-1) body weight. h(-1); rates from light or heavy meconium groups were not significantly different (n = 18). Similarly, total lactate loss was not significantly different between the meconium-free and light-meconium groups but was twice as high in heavy-meconium preparations (73.68 +/- 10.60 micromol/L. g(-1) dry lung tissue. h(-1); P <.025, analysis of variance). The meconium-free and heavy-meconium groups continued to produce fluid, with no significant change throughout the 3 hours of incubation; lactate losses fell slightly. Therefore there were no problems with fluid production with meconium present, but the high-lactate losses with heavy meconium suggested long-term intrauterine hypoxia. Dinitrophenol produced powerful reabsorptions in lungs from meconium-free fetuses (-0.85 +/- 0.35 mL. kg(-1) body weight. h(-1); P <.005, analysis of variance; P <.0005, regression analysis) but failed to do so in heavy-meconium fetuses (n = 36). Lactate losses rose 2-fold in both groups (P <.005 to P < 0.0005, analysis of variance and regression analysis), despite already elevated losses with heavy meconium (n = 12). Therefore, in heavy-meconium fetuses, dinitrophenol affected metabolic pathways but did not activate fluid reabsorption, suggesting damage to reabsorptive mechanisms. CONCLUSION: Unless major airways are blocked, meconium is not associated with reduced fetal lung liquid production, which can cause poor lung development, but there may well be poor fluid removal after birth because of compromised reabsorptive mechanisms, which are unlikely to be helped by possible hormonal intervention.
OBJECTIVE: It is unclear whether children with cystic fibrosis (CF) who present with neonatal meconium ileus have a different long-term outcome from those presenting later in childhood with pulmonary complications or failure to thrive. We examined a cohort of patients with meconium ileus, and compared their long-term outcome with children who had CF without meconium ileus and neonates who had meconium obstruction without CF (meconium plug syndrome). STUDY DESIGN: Comparative study using retrospective and follow-up interview data. PATIENTS: Group 1 consisted of 35 surviving CF patients who presented with meconium ileus between 1966 and 1992. Two control groups were also studied: 35 age- and sex-matched CF patients without meconium ileus (group 2), and 12 infants presenting with meconium plug syndrome during the same time period (group 3). OUTCOME MEASURES: Pulmonary, gastrointestinal, nutritional, and functional status were reviewed, and surgical complications were recorded. RESULTS: Mean follow-up was 12.6 +/- 6, 12.6 +/- 6, and 9. 3 +/- 4 years in groups 1, 2, and 3, respectively. Patients without CF (group 3) demonstrated better growth and functional status, and had a lower incidence of pulmonary and gastrointestinal problems. Although the presence of meconium ileus among CF patients was associated with an earlier diagnosis, there were no significant differences between groups 1 and 2 with respect to hepatobiliary, nutritional, functional, or respiratory status. Meconium ileus was associated with a higher risk of meconium ileus equivalent (20% vs 6%), although this difference was not statistically significant. Long-term surgical complications (adhesive small bowel obstruction and blind loop syndrome) were seen in 27% of children with meconium ileus; there were no long-term surgical complications in groups 2 or 3, because these infants did not have any neonatal surgical procedures. Children presenting with complicated meconium ileus had a higher rate of long-term surgical complications than those with uncomplicated meconium ileus (36% vs 17%), and those managed with resection or enterostomy had more complications than those treated by enterotomy and lavage (33% vs 0%). CONCLUSIONS: Long-term outcome is similar in CF patients who present with meconium ileus and those who do not, except for a slightly higher incidence of meconium ileus equivalent, and a significantly higher rate of surgical complications. The risk of surgical complications is highest in those presenting with complicated meconium ileus and those undergoing resection or enterostomy. Patients with meconium obstruction who do not have CF have an excellent long-term prognosis. This information will be useful in counseling the families of infants presenting with neonatal meconium obstruction.
BACKGROUND/PURPOSE: Contact with amniotic fluid causes intestinal damage in gastroschisis, and intraamniotic meconium has been shown to be responsible. Meconium has been shown to contain a significant amount of IL-8, which may be the responsible cytokine for harmful effects of meconium. Neonatal urine contains high amount of urinary trypsin inhibitor (UTI) compared with adult human urine. Urinary trypsin inhibitor has been shown to exert inhibitory effects on IL-8. Therefore, far from being destructive, presence of fetal urine in the amniotic fluid might be beneficial because human urine contains UTI. An experimental study has been performed to investigate whether presence of intraamniotic human urine (consequently UTI) besides meconium is beneficial on intestines of chick embryo with gastroschisis. METHODS: Five-day-old fertilized chick eggs were used. Gastroschisis was created through amniotic cavity without opening the allantoic cavity. Sterile urine and meconium were obtained from newborn humans. Study was conducted in 2 stages. In the first stage, gastroschisis was created, and meconium suspensions at minimal harmful meconium concentration were prepared using natural and denatured human neonatal urine and instilled into the amniotic cavity. In the second stage of study, various concentrations of UTI plus meconium suspension at minimal harmful meconium concentration was instilled into the amniotic cavity. RESULTS: Serosal thickening, inflammation, and focal fibrin deposits were observed in intestines of the groups with meconium and meconium in denatured urine. Histopathologic features of intestines of the group with meconium in natural urine did not differ from the intestines of the control group. Histopathologic examination of intestines of groups with meconium and meconium plus 50 U/mL UTI showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic features of intestines of the groups with 1:400 intraamniotic meconium plus 100 and 200 U/mL UTI did not differ from the intestines of control group. CONCLUSION: Urinary trypsin inhibitor 100 U/mL prevented the intestinal damage via inhibiting IL-8, which is contained by 1:400 concentration of meconium. Therefore, besides the existence of threshold level of meconium, the existence of UTI, which is capable of inhibiting IL-8 contained by threshold level of meconium, may be a factor in the occurrence of intestinal damage in gastroschisis.
We set out to determine if the clinical course or genetic profiles of patients with cystic fibrosis who had meconium ileus differed from those of other patients with cystic fibrosis. Since 1950 we have followed 158 patients with meconium ileus among 1175 patients with cystic fibrosis (13.4%). Patients with meconium ileus had lower birth weight (3026 +/- 610 gm) than patients with no meconium ileus (3169 +/- 534 gm; p less than 0.008); the deficit was especially evident in female patients. Survival in the first year of life increased from 55% in those born between 1958 and 1972 to 96% in those born between 1973 and 1987. Since 1973 the median survival of male and female patients with meconium ileus was similar to that in female patients with no meconium ileus (21 years), whereas 78% of males with no meconium ileus survived to this age (p less than 0.0001). Patients with meconium ileus born before 1972 had lower weight and height percentiles at age 13 years compared with patients with no meconium ileus, but this difference was not as apparent in patients born after 1973. There were no differences between the two groups in forced vital capacity, forced expiratory volume in 1 second, or forced expiratory flow in the middle half of forced vital capacity. Patients with meconium ileus acquired Pseudomonas aeruginosa at a younger age than did patients with no meconium ileus (4.20 +/- 4.67 vs 7.18 +/- 5.19 years), but there was no difference in age of acquisition of P. cepacia. In families in which the first child had meconium ileus, 29% of subsequent siblings with cystic fibrosis had meconium ileus, compared with 6% of siblings born to families in which the first child did not have meconium ileus. Allelic frequencies and haplotypic variants for cystic fibrosis chromosomes with respect to DNA markers closely linked to the cystic fibrosis locus were similar in families with cystic fibrosis with meconium ileus and those with no meconium ileus. These findings suggest that patients with cystic fibrosis and those without meconium ileus do not have major intrinsic differences and that the previously poor outlook in patients with meconium ileus has improved greatly.
BACKGROUND: ACOG states meconium stained amniotic fluid (MSAF) as one of the historical indicators of perinatal asphyxia. Thick meconium along with other indicators is used to identify babies with severe intrapartum asphyxia. Lactate creatinine ratio (L:C ratio) of 0.64 or higher in first passed urine of babies suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic Encephalopathy (HIE). Literature review shows that meconium is passed in distress and thin meconium results from mixing and dilution over time, which may be hours to days. Thin meconium may thus be used as an indicator of antepartum asphyxia. We tested L:C ratios in a group of babies born through thin and thick meconium, and for comparison, in a group of babies without meconium at birth. METHODS: 86 consecutive newborns, 36 to 42 weeks of gestation, with meconium staining of liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of these 27 had thick meconium and 25 had thin meconium at birth. 42 others, who did not have meconium or any other signs of asphyxia at birth provided controls. Lactate and creatinine levels in urine were tested by standard enzymatic methods in the three groups. RESULTS: Lactate values are highest in the thin MSAF group followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF, followed by thick MSAF and controls. Normal babies had an average L:C ratio of 0.13 (+/- 0.09). L:C ratio was more among thin MSAF babies (4.3 +/- 11.94) than thick MSAF babies (0.35 +/- 0.35). Median L:C ratio was also higher in the thin MSAF group. Variation in the values of these parameters is observed to be high in the thin MSAF group as compared to other groups. L:C ratio was above the cutoff of 0.64 of Huang et al in 40% of those with thin meconium. 2 of these developed signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital stay. One had L:C Ratio of 93 and the other of 58.6. A smaller proportion (20%) of those with thick meconium had levels above the cutoff and 2 developed HIE and convulsions with L:C ratio of 1.25 and 1.1 respectively. CONCLUSION: In evolving a cutoff of L:C ratios that would be highly sensitive and specific (0.64), Huang et al studied it in a series of babies with severe intrapartum asphyxia. Our study shows that the specificity may not be as good if babies born through thin meconium are also included. L:C ratios are much higher in babies with thin meconium. It may be that meconium alone is not a good indicator of asphyxia and the risk of HIE. However, if the presence of meconium implies asphyxia then perhaps a higher cut-off than 0.64 is needed. L:C ratios should be tested in a larger sample that includes babies with thin meconium, before L:C ratios can be applied universally.
To investigate the effects of aspirating different meconium concentrations on the pulmonary circulation in 10- to 12-day-old piglets, 30 catheterized animals were studied. The piglets received an intratracheal bolus of 3 ml/kg of a mixture of human meconium in saline with concentrations of 20 mg/ml (light, n = 7), 40 mg/ml (moderate, n = 6), or 65 mg/ml (thick, n = 10) meconium in saline. Control piglets (n = 7) received 3 ml/kg of intratracheal saline. Pulmonary and systemic pressures were measured and vascular resistances calculated at baseline and serially for 4 hours after instillation. Four of the piglets died early and were excluded from the study. In addition, 23 samples of human meconium-stained amniotic fluid were collected at delivery for determination of their meconium concentration. After an initial rise in pulmonary artery pressure and vascular resistance after meconium and saline instillation, pulmonary artery pressure and resistance increased progressively and concentration-dependently in the meconium groups, but returned to baseline in the control group. The saline and meconium-induced initial increases, and the subsequent meconium-stimulated progressive rise in vascular resistance occurred mainly in the postarterial segment. There were no significant changes in systemic hemodynamics. Mean airway pressure increased and oxygenation deteriorated after meconium instillation. The impairment of oxygenation depended on the meconium concentration in the instilled bolus and persisted throughout the study after moderate and thick meconium instillation. Similarly, the intrapulmonary shunt fraction increased initially and remained elevated in the moderate and thick meconium groups. Meconium concentrations in the human amniotic fluid samples were in the same range as concentrations used in the present experimental study. These results indicate that aspirated meconium at concentrations found in light to moderate meconium-stained human amniotic fluid has significant effects on pulmonary hemodynamic and oxygenation in newborn piglets.
To identify the fetus and newborn at risk for meconium aspiration syndrome the perinatal characteristics of 238 infants delivered through meconium-stained amniotic fluid were prospectively examined. All infants with meconium-stained amniotic fluid were routinely suctioned with a DeLee apparatus before tracheal intubation and suctioning. The type and presence of meconium in the trachea, neonatal breathing before intubation, and Apgar scores were recorded in the delivery room. Intrapartum fetal monitoring data were collected for 80% (190/238) of the mothers and umbilical artery pH for 74% (177/238) of the newborns. Despite suctioning with a DeLee apparatus and endotracheal suctioning, meconium was present in the trachea in 87/238 (37%) and meconium aspiration syndrome developed in 22 (9.2%). A total of 73% of newborns who had meconium aspiration syndrome were delivered through thick meconium. Thick meconium, the presence of fetal tachycardia, and absence of intrapartum fetal cardiac accelerations identified the fetus at high risk for meconium aspiration syndrome. The presence of these monitoring findings and thick meconium should alert obstetricians to the possibility of a fetus that requires intervention. Low umbilical artery pH, Apgar scores less than 5, and meconium in the trachea further characterized the newborn at high risk for meconium aspiration syndrome. The combination of these findings may best identify the infant delivered through meconium-stained amniotic fluid who requires close observation for meconium aspiration syndrome.
Meconium staining of the skin is a common event associated with fetal hypoxia, stillbirths, weak-born piglets, and neonatal mortality. Aspiration of meconium leads to meconium aspiration syndrome (MAS). This study was undertaken to assess the relationship between the degree of meconium staining of the skin at birth, meconium aspiration, and pulmonary changes in porcine neonates. A total of 353 farrowing sows and 3,693 born piglets were monitored during parturition and for 15 days after delivery. Umbilical cords were classified as normal or ruptured. Meconium staining in the skin was graded as nonstained, mildly, moderately, and severely stained. Mortality from birth to 15 days of age was 8.4%. The lungs from 60 meconium-stained piglets and 60 lungs from nonstained piglets were collected and microscopically examined for meconium aspiration and inflammation. Rupture of the umbilical cord was significantly higher (P < 0.01) in meconium-stained piglets. Microscopically, 32% and 40% of the lungs had evidence of meconium for the stained and nonstained groups, respectively. The microscopic grade of meconium aspiration and inflammatory cells was not different between nonstained and meconium-stained piglets. Aspiration of meconium induced a granulomatous response in the lungs. It was concluded that the grade of meconium staining is a good indicator of fetal hypoxia, but not a good predictor for meconium aspiration and MAS in piglets.
OBJECTIVE: We attempted to determine the impact of "early" (before delivery of the chest) oronasopharyngeal DeLee suctioning at the perineum in the prevention of meconium aspiration syndrome and to confirm that meconium aspiration syndrome is a postnatal event. STUDY DESIGN: We compared infants with meconium-stained fluid who underwent "early" oronasopharyngeal DeLee suctioning with a similar group of infants whose airways were suctioned "late" (after chest delivery). Practicing obstetricians did not know the study was being conducted by the pediatric staff, and an independent observer documented whether obstetricians performed "early" or "late" oronasopharyngeal DeLee suctioning. Immediate postnatal tracheal suctioning was performed in both groups. The study was conducted in a private tertiary care center averaging 5800 deliveries annually. A consecutive sample of 438 infants with meconium-stained fluid was analyzed. Of these infants, 221 received "early" oronasopharyngeal DeLee suctioning, while 217 infants were suctioned "late". RESULTS: Of the 438 infants with meconium-stained fluid, meconium aspiration syndrome developed in 38 (9%). These infants had higher rates of fetal distress (i.e., abnormal fetal heart rates) and lower Apgar scores (< or = 6) than infants without meconium aspiration syndrome (58% vs 17% and 65% vs 13%, respectively; p < 0.001). Forty-five percent of the infants with meconium aspiration syndrome had renal failure during the first 20 hours of life. In spite of "early" oronasopharyngeal DeLee suctioning, 53% of the infants in this group had meconium below the vocal cords and meconium aspiration syndrome developed in 7%. The time of oronasopharyngeal DeLee suctioning did not affect the rate of meconium aspiration syndrome or the presence of meconium below the vocal cords. CONCLUSIONS: We concluded that "early" oronasopharyngeal DeLee suctioning at the perineum does not affect the rate of meconium aspiration syndrome. We speculate that meconium aspiration syndrome is predominantly an intrauterine event associated with fetal distress and that meconium in the airways is merely a "marker" of previous fetal hypoxia.
Inflammation plays an important role in the pathogenesis of meconium aspiration syndrome, and pneumonitis is one of the major characteristics. We have previously shown that meconium has chemotactic properties because of the presence of IL-8. We hypothesize that IL-8 and other proinflammatory substances in meconium may amplify inflammation in meconium aspiration syndrome, inducing endogenous cytokine production by lung epithelial cells. We measured proinflammatory substances in first-pass meconium from healthy newborns and evaluated the effect of sterile meconium on cytokine production in cultured A549 alveolar epithelial cells in vitro. IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha were measured by ELISA, and heme was measured spectrophotometrically. After incubation of meconium samples with A549 cells, cytokine concentrations in the supernatant were measured. Meconium samples contained variable amounts of IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and heme. On stimulation of A549 cells with meconium, the IL-8 concentration in the culture supernatant significantly increased above baseline measurements, whereas tumor necrosis factor-alpha showed a variable pattern and IL-1beta or IL-6 remained unchanged. There was no quantitative relationship between the concentration of the measured cytokines and heme in meconium and cytokine release by the A549 cells after meconium exposure. Meconium contains proinflammatory substances. All samples induced IL-8 release and some induced tumor necrosis factor-alpha release in cultured A549 epithelial cells. We speculate that proinflammatory substances in meconium can induce lung inflammation in meconium aspiration syndrome in two ways: directly via cytokines and heme present in meconium and indirectly by inducing cytokine release by the epithelial lung cells.
OBJECTIVES: To compare the indicators and levels of mercury (Hg) exposure in the mother with those in the fetal compartments, and determine its effects on the newborn. METHODS: Hg levels using atomic absorption spectrophotometry were determined in maternal blood, breast milk, cord blood, infants' hair, and meconium of 78 consecutive mother-infant pairs in a community with high Hg pollution. The prevalence and levels of Hg both in meconium and in cord blood were correlated with maternal and infant risk factors. RESULTS: The prevalence of Hg in the fetal compartments was higher than in the maternal fluid compartments. Hg was present in 6.4% of maternal blood and 6.4% of breast milk, as compared with 16.7% of cord blood, 31.6% of infants' hair, and 46.1% of meconium. Forty-six percent of infants with Hg in cord blood had none in meconium, whereas 80.6% with Hg in meconium had none in cord blood. Hg was not present in the maternal blood of all infants (n = 36) with Hg in their meconium. Among those with detectable Hg, the mean levels were: mothers' blood 24 parts per billion +/- 5.47, cord blood 53.3 parts per billion +/- 37.49, and meconium 48.6 +/- 43.48. Quantitative measurement in hair was not done because of insufficient sample. Paired comparisons were all significant between Hg levels in the mothers' blood and meconium, mothers' blood and cord blood, and cord blood and meconium. Regression analysis showed Hg levels in meconium to be correlated with prevalence of Hg in infants' hair, length of stay in Tagum, and meconium-stained amniotic fluid. Fisher's Exact probability test showed that the prevalence of Hg in meconium was significantly related to the prevalence of Hg in the mothers' blood and length of stay in Tagum. The prevalence of Hg in cord blood was significantly related to the prevalence in the mothers' blood. Regression analysis of levels of Hg in cord blood showed a significant relation to levels in mothers' blood (.0001), prevalence in infants' hair (.0126), gestational age (GA) (.0091), and head circumference (HC) (.0469). By quadrant analysis of weight against HC in 66 full-term infants all of 4 infants weighing an average of >3000 g at birth and with HCs lower than the fifth percentile had Hg in meconium. CONCLUSION: The higher prevalence and levels of Hg in the fetal compartments reflect the ease of placental transfer with fetal trapping. Hg determinations in the mothers' blood underestimate the degree and extent of fetal exposure. There is a significant difference in each compartment's ability to reflect Hg exposure of the fetus. A small HC may be associated with the presence of Hg in meconium. Hg in meconium should be measured in addition to cord blood to determine the load of fetal Hg.
The fetus discharges meconium (its bowel contents) into the amniotic fluid during labour in approximately 10% of pregnancies. In about 10% of cases where meconium is passed, the fetus gasps, inhaling the sticky meconium into the upper respiratory tract. After birth, the meconium blocks the air passages in the lungs, impairing gas exchange (meconium aspiration syndrome, MAS). Up to 20% of infants suffering from MAS die and recently published studies have shown a long-term effect of MAS in causing cough and wheeze. At present, meconium is only noticed at birth or occasionally when amniotic fluid leaks past the presenting part of the fetus. We have developed a system to monitor meconium continuously during labour, using a flexible intrauterine probe. The system provides a measurement of the meconium concentration of amniotic fluid during labour every 2 min, with a 60% prediction interval of +/- 10 g l-1, and a 99% prediction interval of +/- 30 g l-1 (clinically 'thick meconium' contains around 100 g l-1). The noise of the measurement is of the order of +/- 10 g l-1, and the response to changes in the meconium concentration is from 40 to 120 s, depending on its configuration. The system also provides other obstetric variables such as fetal heart rate and uterine activity measurement, obtained from a fetal monitor. Preliminary clinical results indicate that this system can measure meconium not apparent to the attending staff; the system can detect changes in the meconium concentration of amniotic fluid; the measurements are confirmed by visual observation at delivery; and changes of meconium concentration seem to correlate with known stressful stimuli. The system therefore provides a new tool from which new variables are obtained, which can greatly enhance clinical research into the pathophysiology of meconium passage and aspiration.
OBJECTIVE: We evaluated the published literature on the effectiveness of amnioinfusion in reducing meconium below the vocal cords and meconium aspiration syndrome among infants born to women presenting with more than trace meconium-stained fluid. STUDY DESIGN: A literature search was conducted to evaluate clinical trials of amnioinfusion and meconium aspiration. Trials meeting certain basic design criteria (n = 5), which included a prospective study design and blinded assessment of newborn outcome, were selected for statistical analyses estimating the average effect's size and direction. In total, 247 women with meconium-stained fluid receiving amnioinfusion and 260 women with meconium-stained fluid not receiving amnioinfusion were represented by these trials. RESULTS: Infants born to women with meconium-stained fluid receiving amnioinfusion were less likely to have meconium below the vocal cords (odds ratio 0.13, 95% confidence interval 0.08 to 0.20) and were less likely to have meconium aspiration syndrome (odds ratio 0.20, 95% confidence interval 0.08 to 0.48) than were infants born to women with meconium-stained fluid not receiving amnioinfusion. DISCUSSION: Amnioinfusion appears to be an effective intrauterine intervention for the prevention of meconium aspiration. Clinicians should consider implementing amnioinfusion in women presenting with thick meconium to prevent intrapartal meconium aspiration in newborns.