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Prophylactic amnioinfusion for meconium-stained amniotic fluid.

OBJECTIVE: Previous studies have demonstrated reduced perinatal morbidity in patients receiving amnioinfusion for meconium-stained amniotic fluid compared with control patients receiving no amnioinfusion. Because amnioinfusion for variable fetal heart rate decelerations has become accepted care, we sought to determine the benefit of prophylactic amnioinfusion for meconium compared with standard care, incorporating therapeutic amnioinfusion for variable decelerations. STUDY DESIGN: Ninety-three term patients with moderate to heavy meconium and no variable fetal heart rate decelerations were randomized to immediate prophylactic amnioinfusion (600 ml saline solution bolus followed by 3 ml/min) or to standard care (including therapeutic amnioinfusion for variable decelerations developing later). All babies had DeLee suctioning on delivery of the head. Laryngeal cords were visualized and tracheal suctioning performed when meconium was seen below the cords. Statistical comparisons were performed using Student t test, Fisher's exact test, or chi 2 analysis. RESULTS: There were no significant differences in the incidence of operative delivery, fetal distress, or meconium below the cords or in newborn Apgar scores and umbilical artery gas values between the amnioinfusion (n = 43) and control (n = 50) patients. There were four cases of meconium aspiration, three in the amnioinfusion group, one in the standard care group. The rate of endometritis-chorioamnionitis was higher (p = 0.3) in the amnioinfusion (16%) than in the control group (8%), although time from ruptured membranes to delivery (8.5 hours vs 7.3 hours) and duration of intrauterine monitoring (6.1 hours vs 5.3 hours) were not different. CONCLUSIONS: Although amnioinfusion does dilute amniotic meconium, prophylactic amnioinfusion for meconium in the absence of variable decelerations remains controversial. Prophylactic amnioinfusion in term pregnancies did not improve perinatal outcome and increased the risk for chorioamnionitis-endometritis. Together with recent reports, the current data suggest that the benefit of amnioinfusion for meconium-stained amniotic fluid is a result of the alleviation of variable fetal heart rate decelerations rather than meconium dilution.

Adult↗

Meconium induces expression of inducible NO synthase and activation of NF-kappaB in rat alveolar macrophages.

Meconium aspiration causes intensive inflammatory reactions in the lungs, and may lead to neonatal respiratory disorder. Infiltrated inflammatory cells, particularly macrophages, play an important role in such an inflammation. A rat alveolar macrophage cell line (ATCC8383) was exposed to meconium alone or in combination with dexamethasone, budesonide, or interferon-gamma. Nitric oxide (NO) accumulation in the supernatant of the cell culture was detected by Griess reaction, and mRNA of inducible NO synthase (iNOS) expression was detected by reverse transcriptase-PCR. Nuclear factor-kappa B was analyzed by electrophoretic mobility shift assay, and iNOS location and nuclear factor-kappa B transactivation were determined by immunostaining. Our results showed that meconium was capable of inducing production of NO and expression of iNOS in alveolar macrophages in a dose- (1-25 mg/mL, p < 0.05) and time- (4-48 h, p < 0.05) dependent manner. This capability of meconium could be further enhanced in the presence of interferon-gamma (100 IU/mL, p < 0.05). Budesonide (10(-4)-10(-10) M) or dexamethasone (10(-4)-10(-6) M) effectively inhibited the meconium-induced NO production (p < 0.05). Using the protein synthesis inhibitor cycloheximide, we demonstrated that meconium directly induced iNOS in macrophages. Furthermore, meconium also triggered nuclear factor-kappa B activation, a mechanism possibly responsible for the iNOS expression. Our findings suggest that meconium is a potent inflammatory stimulus, resulting in iNOS expression, leading to overproduction of NO from the macrophages, which may be of pathogenic importance in meconium aspiration syndrome. In vitro steroids down-regulated the iNOS expression, thus suggesting a potential to down-regulate NO-mediated inflammation in neonates with meconium aspiration syndrome.

Animals↗

[The epidemiology of meconium stained amniotic fluid on hospital basis].

OBJECTIVE: To explore the epidemiology of meconium stained amniotic fluid pero-delivery. METHODS: 6,206 one-fetal delivery cases were divided into meconium stained amniotic fluid and normal amniotic fluid groups. Statistics were analysed on two groups using Cohort study. RESULTS: Incidence of meconium stained amniotic fluid was 16.4%. There was no significant difference on maternal medical complication between two groups. The percentage of parity, gestational week > or = 42 weeks and big birth weight were higher in meconium stained amniotic fluid group than that in normal amniotic fluid group (P < 0.001). The average Apgar score in meconium stained amniotic fluid group was lower than that in normal amniotic fluid group (P = 0.001). The percentage of stillbirth, low birth weight and transferred newborn care unit in meconium stained amniotic fluid group were higher than that in normal amniotic fluid group (P < 0.001). CONCLUSIONS: The relative factors on meconium stained amniotic fluid were maternal parity, gestational weeks > or = 42 weeks and big birth weight. No correlation between meconium stained amniotic fluid and maternal medical complication. Morbidity of newborn baby was higher in meconium stained amniotic fluid. Meconium stained amniotic fluid is a important clinical factor on evaluating pregnancy outcome.

Adult↗

Changing patterns of treatment and survival in neonates with meconium ileus.

This report describes 51 neonates with meconium ileus and emphasizes a changing pattern of treatment and improved survival. Twenty-four neonates had uncomplicated meconium ileus due to inspissated meconium obstructing the distal ileum. Twenty-seven neonates had 41 complications of meconium ileus including volvulus (18), bowel atresia (13), perforation (5), and giant cystic meconium peritonitis (5). Nine patients with uncomplicated cases responded to nonoperative clearing of meconium using a meglumine diatrizoate (Gastrografin) enema. Six of 7 patients with enema failures underwent laparotomy, purse-string enterotomy, and intraluminal irrigation. The remaining 9 patients with uncomplicated meconium ileus had resection and enterostomy. Complicated cases were managed by resection and anastomosis (13) or enterostomy (14). Survival at 1 year was 92% in patients with uncomplicated meconium ileus and 85% for those with complicated meconium ileus. Nonoperative Gastrografin enema or enterotomy-irrigation can relieve obstruction in uncomplicated meconium ileus and avoid an enterostomy in most cases.

Cystic Fibrosis↗

Meconium peritonitis--a leading cause of neonatal peritonitis in Kashmir.

Meconium peritonitis is a chemical reaction of peritonium to meconium which occurs due to leakage of meconium into peritoneal cavity as a result of perforation of intestines antinatally which gets subsequently sealed. In the present retrospective study, 39 cases of neonatal peritonitis were studied. Meconium peritonitis was diagnosed if a) abdominal X-ray showed diffuse calcifications (b) abdominal paracentesis showed meconium aspirate and c) leprotomy examination. Twenty (51.3%) out of 39 cases of neonatal peritonitis were found to have meconium peritonitis. These included 14 boys and 6 girls, birth weight ranged from 1500 gms to 3200 gms and mean age of presentation included abdominal distension in 100% cases, H/O not passing meconium in 50% cases, Ascites in 45% cases and vomiting in 40% cases, 30% presented with abdominal mass. Pseudocyst formation on X-ray was seen in 23% cases which was much higher than reported in world literature. Overall mortality in meconium peritonitis was 80%. The incidence of meconium peritonitis in this part of country in much higher than reported in Western and Indian literature. The high incidence may be due to underlying cystic fibrosis because Kashmir has a more homogenous population and consanguinity is very common. A prospective study including sweat chloride testing needs to be undertaken to look into the cause for proportionately higher occurrence of meconium peritonitis in Kashmir with particular reference to cystic fibrosis.

Female↗

Inhibition of neutrophil oxidative burst and phagocytosis by meconium.

OBJECTIVE: Meconium in amniotic fluid has been associated with an increased prevalence of chorioamnionitis. In an effort to delineate the mechanism of this association, we determined the effect of meconium on the neutrophil's capacity for phagocytosis and microbial killing by oxidative burst in vitro. STUDY DESIGN: Sterile meconium samples were obtained from four fetuses at the time of breech delivery and were then pooled and lyophilized. Neutrophils were purified from whole blood of each of 13 pregnant nonlaboring patients. Phagocytosis and the oxidative burst of neutrophils in the presence and absence of meconium were assessed by single-cell analysis with flow cytometry. Phagocytosis was measured as the mean fluorescence intensity produced after 30 minutes of incubation with fluorescein-labeled Escherichia coli. Oxidative burst was measured as the mean fluorescence intensity resulting from the oxidation of internalized reduced dichlorodihydrofluorescein after 15 minutes of stimulation with phorbol myristate acetate. Oxidative burst was expressed as the neutrophil oxidative index and the net fluorescence intensity. Neutrophil oxidative index was equivalent to the quotient of the mean fluorescence intensity for phorbol myristate acetate-stimulated and unstimulated cells. Net fluorescence intensity was equivalent to the absolute difference between stimulated and unstimulated cells. RESULTS: Exposure of neutrophils to light and very light meconium each resulted in significantly lower mean neutrophil oxidative index compared with unexposed controls (3.2 +/- 4.9 and 4.2 +/- 5.9 vs 16.2 +/- 7.5, p = 0.00002 and p = 0.0007, respectively) and significantly lower mean net fluorescence intensity than that of control cells (112 +/- 220 and 188 +/- 294 vs 613 +/- 328, p = 0.0001 and p = 0.005, respectively). Phagocytosis was significantly impaired in the presence of moderate meconium compared with control cells (2239 +/- 393 vs 4645 +/- 2071, p = 0.0001). Light meconium did not significantly affect phagocytosis. CONCLUSION: Meconium has significant effects on neutrophil function in vitro. Both light and very light meconium inhibit the oxidative burst. Moderate meconium inhibits phagocytosis.

Chorioamnionitis↗

Meconium-stained liquor during labor is associated with raised neonatal cord blood 8-iso-prostaglandin F2alpha concentration.

OBJECTIVE: The purpose of this study was to compare the umbilical arterial 8-iso-prostaglandin F2alpha, concentrations between pregnancies that were complicated by moderate or thick meconium-stained liquor and those with clear liquor. STUDY DESIGN: Umbilical cord arterial blood samples were collected from 247 singleton pregnancies with either moderate or thick meconium-stained liquor at any stage of labor or clear liquor at all stages of labor for the determination of the total 8-iso-prostaglandins F2alpha concentration. RESULTS: The median total 8-iso-prostaglandins F2alpha concentration of the meconium-stained liquor group was significantly higher than that of the control group (719.2 vs 115.8 pg/mL). Among the meconium-stained liquor group, those who had a change from "clear liquor" at early labor to "moderate/ thick meconium-stained liquor" at late first stage or at delivery (late meconium-stained liquor group) had higher 8-iso-prostaglandins F2alpha concentration, compared with those who had moderate/ thick meconium-stained liquor since early labor (early meconium-stained liquor group; 959.8 vs 499.9 pg/mL). With the use of multiple regression analysis, meconium-stained liquor, duration of second stage of labor, and abnormal fetal heart tracings were independent determinants of cord blood 8-iso-prostaglandins F2alpha concentration. CONCLUSION: Moderate or thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy.

Adult↗

Fetal oxygen saturation measured by pulse oximetry during labour with clear or meconium-stained amniotic fluid.

OBJECTIVE: To compare fetal oxygen saturation, scalp pH and arterial cord blood gases in cases of clear or meconium-stained amniotic fluid with and without meconium aspiration (MAS). STUDY DESIGN: Thirty-eight women in labour at term with abnormal fetal heart rate were included. Fetal oxygen saturation was continuously monitored using a Nellcor N-400 fetal pulse oximeter and FS-14 sensor. Fetal scalp blood samples were taken systematically at full dilatation or immediately before cesarean section. Arterial cord blood gases were analysed at birth. Fetal oxygen saturation, scalp pH and neonatal blood gases were compared between fetuses with clear amniotic fluid, meconium-stained amniotic fluid without MAS and meconium stained amniotic fluid with MAS. RESULTS: Moderate or thick meconium was observed in 13 cases during labour. Three newborns had a meconium aspiration defined as meconium below the vocal cords. No differences were observed in scalp pH, scalp base excess, umbilical arterial blood pH or base excess between groups. On the other hand, fetal oxygen saturation (fSpO2) obtained before birth was significantly lower in cases of MAS when compared to the other groups. This difference appears to be large compared to that which might be attributed to meconium and its direct effect on fetal pulse oximetry readings. Fetal oxygen saturation dropped dramatically in cases with meconium aspiration between the first stage of labour (44.7 +/- 8.0%) and the last measurement before birth (27.0 +/- 8.5%). CONCLUSION: Meconium aspiration is more likely to be associated with fetal hypoxemia than with fetal acidosis.

Adult↗

Influence of postdatism and meconium on fetal erythropoietin.

OBJECTIVE: To determine whether fetal erythropoietin (Epo) concentrations are increased in pregnancies extending beyond 41 weeks' gestation and whether this is influenced by the presence of meconium-stained amniotic fluid. METHODS: Epo concentrations were measured in 116 fetal umbilical cord blood samples from otherwise uncomplicated pregnancies between 37 to 43 weeks' gestation during the period of October 1996 to October 1997. An enzyme-linked immunosorbent assay kit was used to measure Epo. Maternal demographics and birth outcomes including Apgar score, cord blood pH, and base deficit were obtained. Fetuses born between 41 and 43 weeks' gestation (post-term) were compared with matched controls born between 37 and 40 weeks' gestation (term). In addition, both post-term and term fetuses with meconium-stained amniotic fluid were compared with matched controls without meconium. RESULTS: Post-term fetuses without meconium had significantly higher Epo levels compared with term fetuses (mean +/- SEM: 50.6 +/- 6.5 versus 29.5 +/- 3.3 mIU/ml, p = 0.002). When matched for gestational age, fetuses with meconium-stained amniotic fluid had significantly greater Epo concentrations compared with controls without meconium (post-term, 80.7 versus 50.6 mIU/ml; term, 61.4 versus 29.5 mIU/ml; p < 0.05). However, no significant difference in Epo levels was found between post-term fetuses with meconium and term fetuses with meconium (80.7 +/- 15.7 mIU/ml versus 61.4 +/- 12.8 mIU/ml, respectively). Mean cord blood pH and base deficit values for all groups were within normal clinical range. CONCLUSION: Cord blood Epo concentrations were significantly increased in pregnancies extending beyond 41 weeks. Irrespective of gestational age, meconium-stained amniotic fluid was associated with a significant rise in Epo. High Epo levels in these pregnancies imply subacute or chronic fetal hypoxia. Close clinical monitoring of post-term fetuses and those with meconium-stained amniotic fluid is warranted.

Adult↗

Significance of meconium-stained amniotic fluid in the preterm population.

OBJECTIVE: Numerous studies have assessed the significance of meconium-stained amniotic fluid (MSAF) at term. However, to date, there has been very little documentation on the incidence and significance of meconium in the preterm population. Our objective was to define the incidence of MSAF in patients delivering prematurely (<37 weeks) and examine its association with underlying fetal acidosis, Apgars and admission to the neonatal intensive care unit (NICU). METHOD: All patients delivering at a single tertiary care center between June 1994 and September 1997 were reviewed for the presence of meconium and gestational age <37 weeks at delivery. Maternal demographics and birth outcomes including cord gases, Apgar scores and admission to the NICU were collected. Exclusion criteria included multiple gestations, breech presentations, fetal anomalies and patients not in labor. RESULTS: Out of a total of 9570 patients there were 506 (5.3%) preterm births meeting the inclusion criteria, of whom 24 (4.8%) had MSAF noted either during labor or at delivery. Comparing the preterm group with and without meconium, there were no differences in maternal age, gravidity, rate of Cesarean section, or gestational age at delivery. Cord pH (7.27 meconium vs. 7.29 no meconium) and base excess (-5.1 meconium vs. -4.0 no meconium) were similar in both groups. There were no clinically significant differences in mean Apgar scores at 1 and 5 minutes. However, an increased number of NICU admissions were noted in the group with meconium (75% vs. 53%, p=0.04). CONCLUSION: The incidence of meconium staining of the amniotic fluid in labor in the preterm population is less than 5% and by itself is not a significant marker of fetal acidosis.

Acidosis↗

Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium.

OBJECTIVE: We assessed the agreement of testing for fetal exposure to illicit drugs contrasting paired specimens of meconium vs umbilical cord tissue. METHODS: We obtained paired samples of meconium and umbilical cord tissue from 118 pregnancies with high suspicion of illicit drug use by the mothers. Each specimen was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine using drug class-specific immunoassays. RESULTS: The agreement of drug screening results between cord and meconium was above 90% for all drugs tested. Meconium identified 21 cases as positive for amphetamines. The paired cord identified 20 of these, and in addition identified three other positives that the meconium labeled as negative. Gas chromatography-mass spectrometry confirmed these three cord samples as methamphetamine positive. Meconium identified 97 samples that were negative for amphetamines, while the cord identified 94 of these as negative but three as positive. Agreement of cord with meconium for amphetamines was 96.6%. The concordance for opiates was 94.9%, for cocaine was 99.2%, and for cannabinoids was 90.7%. CONCLUSIONS: Umbilical cord tissue performs as well as meconium in assessing fetal drug exposure to amphetamines, opiates, cocaine, and cannabinoids. Results of studies using the cord may have a more rapid return to the clinician, because waiting for meconium to be passed sometimes requires several days. Moreover, in some cases the meconium is passed in utero making collection impossible, whereas cord should always be available for drug testing.

Amphetamines↗

Intestinal damage in gastroschisis correlates with the concentration of intraamniotic meconium.

BACKGROUND/PURPOSE: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis, which has been shown to be caused by intraamniotic meconium. However, whether this intraamniotic meconium-induced intestinal damage is concentration dependent has not been investigated previously. The purpose of this study is to investigate the effects of intraamniotic human meconium at various concentrations on the intestines of chick embryo with gastroschisis. METHODS: Five-day-old fertilized chick eggs were used. Gastroschisis was created through the amniotic cavity without opening the allantoic cavity. Sterile meconium was obtained from newborn humans. Meconium suspensions at various concentrations were prepared using saline and instilled into the amniotic cavity. RESULTS: Intraamniotic 1:200 and 1:400 meconium was found to cause intestinal damage. Meconium concentrations lower than 1:400 did not cause intestinal damage. Histopathologic examination of the intestines of the 1:200 and 1:400 meconium groups showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic features of the intestines of the 1:600 and 1:800 meconium groups did not differ from the intestines of the control group. CONCLUSION: Intraamniotic meconium, which is responsible for intestinal damage in gastroschisis, must reach a threshold level to induce intestinal damage. J Pediatr Surg 36:1811-1815.

Amniotic Fluid↗

Meconium-stained amniotic fluid across gestation and neonatal acid-base status.

OBJECTIVE: To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation. METHODS: We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium-stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance. RESULTS: The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks. CONCLUSION: The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.

Adult↗

Effect of meconium on the surface properties of perflubron.

OBJECTIVE: Meconium passage with pulmonary aspiration in utero is associated with surfactant inactivation and is a major cause of neonatal morbidity and mortality. Ventilation with low surface tension perfluorocarbon in animal models of meconium aspiration has been shown to improve both oxygenation and lung compliance. Exogenously administered surfactant is inactivated by meconium. We wished to determine whether meconium would alter the surface properties of perfluorooctyl bromide (perflubron). DESIGN: Biophysical analysis using novel methods. SETTING: University research laboratory. SUBJECTS: Healthy newborns. INTERVENTIONS: First pass meconium was obtained from healthy newborns. MEASUREMENTS AND MAIN RESULTS: We evaluated the surface-active properties of perflubron after exposure to meconium-saline dilutions using the de Noüy ring distraction technique to measure interfacial tension and the sessile contact angle of meconium-saline suspensions. Both were assessed in the absence and presence of perflubron. Meconium-saline suspensions inhibited surfactant activity. In contrast, the surface properties of perflubron were unaffected by the presence of meconium-saline suspensions. CONCLUSIONS: These data are consistent with reported observations of increased lung compliance in perfluorocarbon-treated animals with meconium aspiration. In addition to these clinical implications, the novel interfacial tension technique described here could prove useful for assessing the interfacial properties of other poorly miscible biological fluids.

Biological Products↗

Bile acid patterns in meconium are influenced by cholestasis of pregnancy and not altered by ursodeoxycholic acid treatment.

BACKGROUND: Data on meconium bile acid composition in newborn babies of patients with intrahepatic cholestasis of pregnancy (ICP) are relatively scant, and changes that occur on ursodeoxycholic acid (UDCA) administration have not been evaluated. AIMS: To investigate bile acid profiles in meconium of neonates from untreated and UDCA treated patients with ICP. Maternal serum bile acid composition was also analysed both at diagnosis and delivery to determine whether this influences the concentration and proportion of bile acids in the meconium. PATIENTS/METHODS: The population included eight healthy pregnant women and 16 patients with ICP, nine of which received UDCA (12.5-15.0 mg/kg body weight/day) for 15+/-4 days until parturition. Bile acids were assessed in the meconium by gas chromatography-mass spectrometry and in maternal serum by high performance liquid chromatography. RESULTS: Total bile acid and cholic acid concentrations in the meconium were increased (p<0.01) in newborns from patients with ICP (13.5 (5.1) and 8.4 (4.1) micromol/g respectively; mean (SEM)) as compared with controls (2.0 (0.5) and 0.8 (0.3) micromol/g respectively), reflecting the total bile acid and cholic acid levels in the maternal serum (r = 0.85 and r = 0.84, p<0.01). After UDCA administration, total bile acid concentrations decreased in the mother ( approximately 3-fold, p<0. 05) but not in the meconium. UDCA concentration in the meconium showed only a 2-fold increase after treatment, despite the much greater increase in the maternal serum (p<0.01). Lithocholic acid concentration in the meconium was not increased by UDCA treatment. CONCLUSIONS: UDCA administration does not influence the concentration and proportion of bile acids in the meconium, which in turn are altered by ICP. Moreover, this beneficial treatment for the mother does not increase meconium levels of potentially toxic metabolites of UDCA such as lithocholic acid.

Bile Acids and Salts↗

Reversal of meconium inhibition of pulmonary surfactant by ferric chloride, copper chloride, and acetic acid.

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/- 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.

Acetic Acid↗

Human meconium has high phospholipase A2 activity and induces cellular injury and apoptosis in piglet lungs.

Aspiration of meconium produces an inflammatory reaction resulting in necrotic changes in lung tissue. To further investigate the mechanisms of the meconium-induced early pulmonary injury, twenty 10-12-d-old piglets were studied for lung tissue ultrastructural and apoptotic changes and phospholipase A2 activity. Twelve piglets received an intratracheal bolus (3 mL/kg) of a 20-mg/mL (thin, n = 6) or 65-mg/mL (thick, n = 6) mixture of human meconium, and control piglets (n = 5) received the same amount of intratracheal saline. Three ventilated piglets with no aspiration were also studied. Pulmonary hemodynamics and systemic oxygenation were followed for 6 h after meconium or saline insufflation. In the control groups, the pulmonary tissue showed open alveolar spaces and intact vascular walls, whereas meconium administration resulted in severe pneumonitis, with alveolar spaces filled with inflammatory exudate. Meconium instillation additionally resulted in edematous changes in the vascular walls and alveolar epithelium, whereas type II pneumocytes were intact. The amount of apoptotic cells was increased, especially in the respiratory epithelium, and the catalytic activity of phospholipase A2 in lung tissue samples was significantly elevated after thick meconium instillation. This activity rise proved to be mainly because of human group I phospholipase A2, introduced by meconium. Our data thus show that aspiration of meconium leads to severe lung tissue inflammation with early ultrastructural changes in the pulmonary alveolar walls and is associated with apoptotic cell death in the epithelium, already during the first hours after the insult. These results further suggest that high phospholipase A2 activity, mainly introduced into the lungs within the meconium, may have an important role in the initiation of these alterations in neonatal lungs.

Animals↗

Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration.

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.

Acute Disease↗