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Morphology and function of pulmonary surfactant inhibited by meconium.

The pathophysiology of neonatal meconium aspiration syndrome (MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. It has also been suggested that meconium causes inhibition of surfactant function. To assess its in vitro effect on surfactant function and morphology, we used a pulsating bubble surfactometer to measure the dynamic surface tension of meconium-surfactant mixtures and observed their electron microscopic structures. The mixtures were prepared by adding serial dilutions of human meconium to various concentrations of Surfactant-TA (Surfacten) that had been used for the prevention and treatment of neonatal respiratory distress syndrome. Inhibition of the surface tension-lowering properties of Surfactant-TA was caused by the addition of meconium and depended on the concentration of the surfactant; the inhibition could be overcome by increasing the surfactant concentration. When meconium was added to Surfactant-TA, the characteristic ultrastructural features of the latter, the loosely stacked layers, changed to a spherical lamellar structure and folded linear structures. These results suggest that meconium inhibits surfactant function by altering surfactant morphology. Our morphologic and functional findings support the new concept that surfactant inhibition may play a role in the pathophysiology of MAS.

Biological Products↗

Polymyxin B/pulmonary surfactant mixtures have increased resistance to inactivation by meconium and reduce growth of gram-negative bacteria in vitro.

Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl2) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0-5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl2/PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.

Animals↗

Effect of meconium ileus on the clinical prognosis of patients with cystic fibrosis.

The objective of the present study was to determine the possible prognostic factors which may explain the difference in the survival of patients with cystic fibrosis (CF) with and without meconium ileus. Over a period of 20 years, 127 patients with CF, whose diagnosis was confirmed by typical clinical characteristics and altered sweat chloride levels, were studied retrospectively. The patients were divided into two groups: group 1 consisted of patients who presented CF and meconium ileus (N = 9), and group 2 consisted of patients with CF without meconium ileus (N = 118). The characteristics studied were based on data obtained upon admission of the patients using a specific protocol. Demographic, clinical, nutritional and laboratory data were obtained. The genotype was determined in 106 patients by PCR. Survival was analyzed using the Kaplan-Meier method. The median follow-up period was 44 months. A statistically significant difference was observed between the groups studied regarding the following variables: age at diagnosis and weight and height z scores. The presence of meconium ileus was associated with an earlier diagnosis; these patients had greater deficits in height and weight at the time of diagnosis and at the end of the study. The estimated probability of survival for patients with CF without meconium ileus was 62 +/- 14% and for those with meconium ileus 32 +/- 18%. Patients with CF and meconium ileus presented a poor nutritional status at diagnosis and a lower survival rate compared to the general CF population.

Chi-Square Distribution↗

Meconium peritonitis in stillbirths.

Meconium peritonitis is a sterile, chemical peritonitis resulting from perforation of the bowel in perinatal life. In stillbirths meconium peritonitis is extremely rare. We report the autopsy findings in three fetuses ranging from 21-39 weeks gestation in which meconium peritonitis was identified. Maternal history in two cases was suggestive of possible fetal hypoxia. No family history of cystic fibrosis was discerned. One fetus was hydropic and abdominal calcifications were noted on postmortem radiograph. Gross evidence of meconium in the peritoneal cavity, visceral adhesions, and serosal nodules were noted in two fetuses. Nodules of calcified meconium seen by microscopy were the only clues to diagnosis in the third fetus. The discovery of meconium peritonitis at autopsy may be the only residual evidence of antecedent bowel perforation. We suggest that intrauterine hypoxia may play a role in the development of meconium peritonitis in some cases.

Adult↗

Meconium aspiration syndrome: pathophysiology and prevention.

BACKGROUND: Despite the common occurrence of intrauterine meconium passage and resultant meconium aspiration syndrome (MAS), controversies regarding the pathophysiology and use of appropriate preventive strategies abound. METHODS: Databases from MEDLINE, MD Consult, and the Science Citation Index were searched from 1964 to the present to find relevant sources of information. RESULTS AND CONCLUSIONS: Meconium passage occurs by three distinct mechanisms: (1) as a physiologic maturational event, (2) as a response to acute hypoxic events, and (3) as a response to chronic intrauterine hypoxia. Meconium passage might merely be a marker of chronic intrauterine hypoxia or can predispose to aspiration of meconium and resultant inflammatory pneumonitis, surfactant inactivation, and mechanical airway obstruction. Aspiration can occur in utero with fetal gasping, or after birth with the first breaths of life. Many cases of MAS can be prevented by the strategies addressed in this article, but some will occur despite appropriate preventive techniques. There is not enough evidence to support the use of amnioinfusion as a standard of care for all pregnancies complicated by meconium. Pharyngeal suctioning before delivery of the shoulders is an effective preventive intervention, as is the combination of pharyngeal suctioning followed by intubation and tracheal suctioning. Suctioning of the trachea may be done on a selective basis depending on fetal vigor and consistency of meconium.

Humans↗

In vitro effect of meconium on the physical surface properties and morphology of exogenous pulmonary surfactant.

The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.

Humans↗

Meconium-stained amniotic fluid activates polymorphonuclear leukocytes ultrastructural and enzyme-cytochemical evidence.

The purpose of the present study was to demonstrate morphological evidence that meconium-stained amniotic fluid activates polymorphonuclear leukocytes. We used Boyden chamber techniques to determine the chemotactic activity of meconium-stained amniotic fluid for leukocytes, and ultrastructural enzyme-cytochemistry for peroxidase and alkaline phosphatase to characterize the leukocyte features induced by contact with meconium-stained amniotic fluid. Amniotic fluid with meconium staining enhanced migration of leukocytes. These leukocytes exhibited more numerous cytoplasmic processes and more prominent phagosomes compared to peripheral blood leukocytes. Peroxidase and alkaline phosphatase activity were evident on the phagosomal membranes. Our results indicate that meconium-stained amniotic fluid activates or stimulates polymorphonuclear leukocytes. Meconium-stained amniotic fluid induced leukocyte activation might play important roles in the pathophysiology of initiation of term labor or of the meconium aspiration syndrome.

Alkaline Phosphatase↗

The design and development of a biosensor to measure the concentration of meconium in amniotic fluid.

Meconium aspiration syndrome occurs in 0.2% to 1% of all deliveries and has a mortality rate as high as 18%. The disease is responsible for 2% of all perinatal deaths. Meconium may be classified as being thick or thin, but this assessment is normally performed visually by clinicians. A "meconiumcrit" analysis has been developed to objectively define the concentration of meconium. However, this analysis does not provide real-time continuous readings. This study focused on the design and development of a sensor to provide an objective, continuous, real-time assessment of meconium thickness. Meconium has an absorption spectrum centered at 410 nm and observes Beer's law. Blue light centered at 430 nm was delivered through meconium solutions, and a photodiode translated the strength of the incoming light into a voltage. This voltage was analyzed by a microcontroller to determine the concentration of meconium.

Amniotic Fluid↗

[Meconium and postnatal neurologic handicaps].

OBJECTIVE: A review of meconium pathophysiology and its contribution to the incidence of postnatal neurological handicap. DESIGN: Reviewed article. SETTING: Department of Gynaecology and Obstetrics, Charles University and Faculty Hospital Plzen, Czech Republic. SUBJECT AND METHOD: Meconium can be a cause of infant neurological handicap. Two main pathogenetic pathways are mentioned. 1. Meconium (and its components: bile acids) may have a direct vasoconstrictive effect on umbilical and placental vessels. This way still remains controversial. 2. Meconium as a possible cause of intraamniotic infection results in a release of fetal cytokines (TNF alpha, IL-1 beta, IL-6), which can damage myelinogenesis in periventricular white matter. RESULTS: Meconium in premature labour is a higher risk factor compared to term delivery. 41% of premature infants were diagnosed as having CP when meconium was present compared to 10% in the same group with clear amniotic fluid. The incidence in term pregnancy with meconium present is 0.4% compared to 0.3% in a population without any obstetrical risk. CONCLUSION: Ultrasonographically found periventricular leukomalacia is the most reliable sign of subsequent cerebral palsy or other neurological sequelae.

Amniotic Fluid↗

[A new method for diagnosis of amniotic fluid embolism by means of monoclonal antibody TKH-2 that recognizes mucin-type glycoprotein, a component in meconium].

Five monoclonal antibodies (moABs TKH-2, MA54, MA61, B72.3, and CC49), directed toward the O-linked mucin-type glycoprotein, showed signs of specific reactivity with human meconium. The reactivity of these moABs with meconium extract was examined by solid-phase ELISA with different native and sialidase-treated glycoproteins. All moABs react with meconium extract, whereas the reactivities of TKH-2, MA54, and MA61 are sialidase sensitive and the reactivity of TKH-2 with meconium extract was only inhibited by ovine submaxillary mucin (OSM), indicating that TKH-2 is the most sensitive and specific antibody clearly directed to the sialyl Tn antigen in meconium. The possible application of TKH-2 to diagnose amniotic fluid embolism (AFE) has been prelimiarily investigated. We demonstrated that the concentration of sialyl Tn antigen in the serum of patients with AFE was significantly increased, indicating that meconium was released into the maternal circulation. Our method for detecting sialyl Tn antigen in the serum of AFE patients is a direct way to demonstrate the release of meconium into the maternal circulation, and is a simple, rapid, non-invasive and sensitive method for the diagnosis of AFE.

Amniotic Fluid↗

Meconium-induced umbilical cord vascular necrosis and ulceration: a potential link between the placenta and poor pregnancy outcome.

The literature lacks epidemiologic study of pregnancy outcome with light-microscopic meconium-related lesions. We recently described previously unreported meconium-induced necrosis of placental and umbilical cord vessels and hypothesized that the lesions represent preceding vasocontraction and fetal hypoperfusion. Preliminary experiments then confirmed that meconium produces vasocontraction in isolated umbilical venous tissue. In the present study, we examined whether clinically meaningful abnormalities occur with these vascular signs of remote fetal meconium discharge. In a light-microscopic review of 1100 meconium-stained placentas, we found ten with meconium-induced vascular necrosis. In six of these ten cases, fetal distress necessitated cesarean delivery. Seven newborns had Apgar scores of 3 or less at 1 minute, and each of the seven cases tested had umbilical arterial pH less than 7.19. Because seven of the ten infants were born after December 1, 1989, clinical follow-up was limited. One died, another has neurodevelopmental deficiency, and a third has experienced enlargement of head circumference from the 50th percentile at birth to the 95th percentile at 10 months of age. Two placentas had umbilical cord ulceration, a lesion that has rarely been reported in the literature. We conclude that meconium-induced vascular necrosis seems to be a meaningful, detrimental lesion.

Amniotic Fluid↗

Bilirubin pigments in the first meconium of newborn infants.

OBJECTIVE: To determine the pattern of excretion of total bilirubin IXa and IXb in the first meconium of newborn infants. METHODS: First two newborns of varying gestational age were selected every week through random sampling from the neonatal unit. Of the 41 newborn infants selected 8 expired before meconium passage, hence the results are from 33 newborns. Meconium was collected and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with equal amount of dimethyl-sulfoxide, centrifuged, and analyzed by HPLC. RESULTS: Unconjugated Bilirubin-IXalpha and -IXbeta were identified and quantitative estimation of Bilirubin-IXa done. Bilirubin-IXb was greater than 50% of the total, in the first meconium of the newborn. Amount of bilirubin excreted in meconium was 29.2 - 90.8 mg [0.051 - 0.155 mmol] per sample of meconium passed. Amount was 9.7 mg/ Kg of body weight in term newborn and 12 mg/kg in preterm. CONCLUSION: The amount of bilirubin -IXb decreases and bilirubin-IXa increases with increasing gestational age. Newborns with birth asphyxia (BA) had significantly greater quantity of bilirubin in meconium, compared to infants without BA.

Bile Acids and Salts↗

Relationship between meconium staining, umbilical cord plasma motilin level and infantile colic.

OBJECTIVE: To assess the effects of meconium-stained amniotic fluid and umbilical cord plasma motilin levels on the development of infantile colic. STUDY DESIGN: One hundred forty pregnant women referred to our department for labor care were enrolled in the study. All subjects were laboring women with singleton, vertex-presenting fetuses, with a gestational age of > or = 36 weeks. After each infant with meconium-stained amniotic fluid was born, the following 2 infants without meconium were selected as controls. Umbilical cord plasma motilin levels were measured in 47 infants with meconium-stained amniotic fluid and 93 infants with no meconium. At the end of the third month of the infants' lives, the development of infantile colic was evaluated. Umbilical cord serum specimens were collected from 45 infants with colic and 95 infants without colic. Statistics included Student's t, chi2 and Mann-Whitney U tests, as appropriate. Multivariate analysis was performed. RESULTS: There was no correlation between the presence of meconium-stained amniotic fluid and the development of infantile colic. No association was found between umbilical cord plasma motilin levels and the development of infantile colic. Neonatal intensive care unit admission was found to be a significant risk factor for the development of infantile colic. CONCLUSION: Meconium-stained amniotic fluid and umbilical cord plasma motilin levels do not affect the development of infantile colic.

Amniotic Fluid↗

[Study on the specific diagnosis of meconium aspiration syndrome (MAS) with fluorometry].

Porphyrins are found in fetal urine, neonatal urine, amniotic fluid, and meconium. Zn-coproporphyrin (Zn-CP), which we identified in meconium, has two fluorescent peaks at 580 nm and 630 nm, and Coproporphyrin (CP), found in fetal urine, has one fluorescent peak at 620 nm, when both porphyrins are excited at 405 nm. In this study, the fluorescent peak at 580 nm was used to detect Zn-CP in neonatal urine, using the new index, that is the Urinary Fluorescence Meconium Index (UFMI); UFMI = F580-(F580 + F600)/2 [F: fluorescence intensity]. We obtained urine samples from neonates in these three groups: Group-I: Meconium Aspiration Syndrome (MAS; n = 3), Group-II: non-MAS with meconium stained amniotic fluid at delivery (n = 18), and Group-III: non-MAS with clear amniotic fluid at delivery (n = 25). The UMI (Urinary Meconium Index) was also measured by conventional optical absorbance. The results show that many false positive cases were observed in UMI, and that no false positive cases were observed in UFMI. These results lead one to speculate that Zn-CP, which is specific in meconium, is used in UFMI measurement, while UMI measurement by absorbance cannot exclude contamination by CP in neonatal urine, so Zn-CP and CP are measured all together. UFMI values reflected the clinical course of neonates. It is concluded that UFMI is a more sensitive method than UMI for the diagnosis of MAS.

Coproporphyrins↗

The prevention of meconium aspiration in labor using amnioinfusion.

In an effort to improve maternal and fetal outcome in patients laboring with thick meconium, 85 patients presenting with thick meconium were randomized to receive either amnioinfusion with 1000 mL normal saline initially and every 6 hours until delivery, or routine care. Meconium was discovered on initial examination during labor, after artificial rupture of membranes, through the use of an intrauterine pressure catheter, or on amniocentesis. Labor management was otherwise routine. Forceps operations and cesarean sections were for distress or failure to progress, as indicated. Patients receiving amnioinfusion had significantly fewer low 1-minute Apgar scores, less meconium below the cords, and a significantly lower incidence of operative delivery. The only three cases of meconium aspiration syndrome occurred in infants delivered of patients receiving routine management. No adverse side effects of amnioinfusion were detected. Amnioinfusion is a simple, inexpensive, and safe technique that reduces the incidence of meconium below the cords and improves obstetric outcome in patients laboring with thick meconium.

Adult↗

Urinary beta 2-microglobulin in full-term newborns: evidence for proximal tubular dysfunction in infants with meconium-stained amniotic fluid.

Urinary concentrations of beta 2-microglobulin (beta 2M) and creatinine were measured in normal term infants and in those born with meconium-stained amniotic fluid. None of the infants or their mothers had conditions known to modify beta 2M excretion. Measurements of beta 2M were made on urines collected by bagging; urines obtained from diapers were not satisfactory. Urinary beta 2M concentrations increased significantly (P less than .02) in the normal infants from the first day (0.36 +/- 0.29 mg/L: n = 29) to the third day (0.60 +/- 0.43 mg/L: n = 21) postpartum. Compared with the normal infants, values for the infants with meconium-stained amniotic fluid were increased significantly on days 1 (1.64 +/- 2.16 mg/L: n = 25: P less than .005) and 3 (2.12 +/- 2.04 mg/L: n = 23: P less than .005). Levels exceeded two standard deviations above the normal mean in 12 of the 26 infants with meconium-stained amniotic fluid on postpartum day 1, and 12 of the 23 infants with meconium-stained amniotic fluid on day 3. Urinary creatinine levels were similar in both the normal infants and those with meconium-stained amniotic fluid. All infants with meconium-stained amniotic fluid with a one-minute Apgar score of 6 or less had an elevated urinary beta 2M concentration. The elevated levels of urinary beta 2M in infants with meconium-stained amniotic fluid indicate the existence of tubular dysfunction, probably mild acute tubular necrosis secondary to hypoxia.

Amniotic Fluid↗

Late meconium passage in labor--a sign of fetal distress?

Although the passage early in labor of thick amniotic fluid heavily stained with meconium is recognized as an indication of potential fetal asphyxia, the significance of late passage of meconium-stained fluid in labor is less certain. One hundren twenty-eight patients with late passage of meconium in labor and 134 control patients were examined, using chi 2 and discriminant analysis, to determine if any relationships existed between fetal heart rate (FHR) patterns, late passage of meconium in labor, and neonatal morbidity. In the group with late meconium passage, adequate baseline FHR variability and nonperiodic accelerations were predictive of high Apgar scores, and repeated (over 20) variable decelerations were predictive of low Apgar scores. In the control group, none of the FHR patterns examined were predictive of Apgar score. Thus, the combination of late passage of meconium in labor with other intrapartum signs may indicate a fetus at risk for asphyxia when neither sign alone is predictive. The presence of late meconium passage demands close observation of the patient in labor, including assessment by electronic FHR monitoring.

Apgar Score↗

Meconium ileus--a rare cause of neonatal intestinal obstruction in Malaysia.

Meconium ileus, rare in Malaysia, accounts for 3.7% of all neonatal intestinal obstructions (excluding imperforate anus) seen in the University Hospital, Kuala Lumpur, from 1980-1990. This paper retrospectively reviews our clinical experience with 5 cases of meconium ileus seen over a 12-year period from 1980-1991 in the University Hospital, Kuala Lumpur. Three of the neonates were Malays, and two were Punjabis. Four of them were full-term and one preterm. The birth weights ranged from 1900 to 3700 g, with a mean of 2670 g. One of them also had a sibling with meconium ileus. Two of them were found to have foetal ascites and one had intestinal obstruction, antenatally by ultrasonography. The remaining two were symptomatic soon after birth. Extensive calcification was observed on plain abdominal radiographs in three babies and dilated bowels in the other two. All of them underwent laparotomy and uncomplicated meconium ileus was confirmed in two cases, meconium peritonitis in two and one meconium pseudocyst in addition to meconium peritonitis. There was one intraoperative death, and one long-term survivor who did not have cystic fibrosis. The remaining three did not have additional features suggestive of cystic fibrosis, and finally succumbed to respiratory infection. Sweat test was not done to confirm the diagnosis for logistic reasons. The management of such patients proved to be a challenge to clinicians because of the rarity of this condition.

Female↗