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The cardiovascular effects of partial liquid ventilation in newborn lambs after experimental meconium aspiration.

OBJECTIVE: To study the effects of partial liquid ventilation with perfluorocarbon on cardiovascular function, pulmonary gas exchange, and lung mechanics in term newborn lambs with pulmonary hypertension induced by tracheal instillation of human meconium. DESIGN: Prospective, randomized study. SETTING: Research Unit at a university-affiliated hospital. SUBJECTS: Twelve term newborn lambs (<6 days old). INTERVENTIONS: Lambs were studied in two groups (n = 6): meconium aspiration (3-5 ml/kg 20% meconium solution) managed on pressure-limited conventional mechanical ventilation with or without partial liquid ventilation with perfluorocarbon. MEASUREMENTS AND MAIN RESULTS: Heart rate, systemic and pulmonary arterial pressures, arterial pH and blood gases, cardiac output, and pulmonary mechanics were measured. Partial liquid ventilation in term newborn lambs with experimental meconium aspiration did not alter cardiovascular profile: heart rate, systemic arterial pressure, and cardiac output maintained initial values throughout the experiment. There was a significant improvement in gas exchange (oxygenation increased from values of <100 torr to 338 torr, and ventilation reached normal values in 15 mins). Dynamic compliance increased in 30 mins, reaching basal values (1.1 +/- 0.3 ml/cm H(2)O per kg). Despite the good response (blood gases and cardiovascular profile) to partial liquid ventilation in meconium aspiration syndrome, pulmonary hypertension did not decrease. CONCLUSIONS: Partial liquid ventilation with perfluorocarbon could be a good noninvasive alternative technique that improves gas exchange and pulmonary mechanics in meconium aspiration syndrome without impairing cardiovascular function.

Journal Article↗

Risk of meconium-stained amniotic fluid in different ethnic groups.

BACKGROUND: Recent studies indicate that the risk of meconium-stained amniotic fluid (MSAF) varies in different ethnic groups. This study prospectively examined the ethnic variation of MSAF and meconium aspiration syndrome, adjusting for gravidity, gestational age (GA), and birth weight. METHOD: The study population consisted of 6901 consecutive live births and included 31 different nationalities, seven main ethnic (race) groups, gravidity between 1 and 19, GA between 22 and 44 weeks, and birth weights between 350 and 6292 gm. RESULTS: The overall incidence of MSAF was 19% (13% thin, 6% thick). The prevalence of meconium aspiration syndrome was 5% in thick MSAF and none in thin MSAF. The incidence of MSAF differs significantly by ethnicity (14% to 30%), gravidity (17% to 23%), GA (6% to 46%), and birth weight (11% to 28%). Multivariate logistic regression analysis using the same variable showed that being black African, post-term, with a gravidity of > or = 7 and a birth weight of > or = 4000 gm significantly increased the chance for MSAF but not meconium aspiration syndrome. After controlling for these clinical variables, the black African infants had a higher percentage of MSAF at all GAs compared with the other ethnic groups. CONCLUSION: This study showed that the risk of MSAF varied by ethnicity and increased with higher gravidity, a GA of > 42 weeks, and a birth weight of > or = 4000 gm The higher incidence of MSAF without an increase in meconium aspiration syndrome in some ethnic groups may indicate advancing maturity of the gastrointestinal system in black ethnic groups compared with others of the same GA.

Amniotic Fluid↗

Amnioinfusion for meconium-stained liquor.

Amnioinfusion reduces the risk of meconium aspiration by the infants of women with thick meconium staining of the amniotic fluid. The benefits are clear in facilities with high baseline rates of meconium aspiration, and are therefore likely to outweigh the risk of uncommon but serious maternal side-effects. Larger randomized trials are needed to determine more precisely the relative risks and benefits in facilities with low baseline rates of meconium aspiration. The addition of antibiotics to the infusate has not been shown to reduce the risk of sepsis related to meconium.

Amniotic Fluid↗

The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 2. Zimbabwe.

OBJECTIVE: To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labour. DESIGN: Multicentre randomised controlled trial. SETTING: A large urban academic hospital. Electronic fetal heart rate monitoring was not used. PARTICIPANTS: Women in labour at term with moderate or thick meconium staining of the amniotic fluid. INTERVENTIONS: Transcervical amnioinfusion of 500 mL saline over 30 minutes, then 500 mL at 30 drops per minute. The control group received routine care. Blinding of the intervention was not possible. MAIN OUTCOME MEASURES: Caesarean section, meconium aspiration syndrome and perinatal mortality. RESULTS: There was no difference in risk for caesarean section in the two groups (amnioinfusion 9.5% vs control 12.3%; RR 0.84, 95% CI 0.53-1.32). Meconium aspiration syndrome was significantly less frequent in the amnioinfusion group (3.1% vs 12.8%; RR 0.24, 95% CI 0.12-0.48), and there was a trend towards fewer perinatal deaths (1.2% vs 3.6%; RR 0.34, 95% CI 0.11-1.06). CONCLUSIONS: Amnioinfusion is technically feasible in a developing country situation with limited intrapartum facilities. In this study amnioinfusion for meconium stained amniotic fluid was associated with striking improvements in perinatal outcome.

Abnormalities, Multiple↗

Possible causes linking asphyxia, thick meconium and respiratory distress.

The cause of fetal distress and neonatal respiratory distress (RD) in association with meconium-stained liquor is not always clear. To clarify this, a prospective study was undertaken in a tertiary referral maternity hospital for 1 year. In all infants born after meconium-stained liquor who developed RD, evidence was sought for 1) fetal distress (from the cardiotocograph (CTG), the cord blood pH, the Apgar score and the asphyxial complications in the neonate) 2) causes of fetal distress (including maternal risk factors, fetal infection and fetal malnutrition) 3) causes of respiratory distress (including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN) and infection). Of 4,026 livebirths, 717 (17.8%) had meconium-stained liquor and 44 term and 5 preterm infants developed RD. In the 44 term infants, there was frequent evidence of fetal distress possibly caused by previously unrecognized factors such as fetal malnutrition with reduced neonatal skinfold thickness in 35% triceps and 41% subscapular measurements, and histological chorioamnionitis (CA) in 74%. The cause for respiratory distress was identified in only 48% of infants, and included clinical evidence of PPHN (41%), MAS (16%) and infection (2%). However in preterm infants, 80% had definite or suspected infection. The findings indicate that fetal distress is common in infants who develop respiratory distress after meconium-stained liquor. A role for histological CA and reduced nutrition in the fetus, as factors contributing to the vulnerability of the term infant to intrapartum fetal distress, is suggested.

Apgar Score↗

Amnioinfusion for the prevention of meconium aspiration during labour.

The aim of this observational study is to review the outcome of prophylactic intrapartum amnioinfusion (AI) in pregnancies complicated by moderate to thick meconium-stained liquor (MSL). The labour and neonatal outcome of all 298 AIs performed over a 3-year period were compared to a matched-control group of patients whose labour was complicated by moderate or thick MSL but without AI. The incidence of moderate or thick meconium below the vocal cords of the neonate were significantly lower in the AI group (6.4% and 3.4%) compared with the control group (15.4% and 6.7%). The incidence of meconium aspiration syndrome in the AI group was half (1.7%) that of the control group (3.7%), although the difference did not reach statistical significance. There was a significant higher incidence of cardiotocographic abnormalities in the AI group (30.5% versus 14.7%), with higher incidences of Caesarean section and operative vaginal deliveries. The reduction in the incidence and thickness of meconium after AI was not accompanied by any statistically significant reduction in adverse fetal outcomes such as low Apgar scores, cord pH values, admissions to and duration of admission to the neonatal unit, or the incidence of meconium-aspiration syndrome.

Adult↗

Meconium induced IL-8 production and intratracheal albumin alleviated lung injury in newborn pigs.

We have recently shown that albumin added to meconium before intratracheal instillation in newborn pigs limits detrimental effect on the lungs and reduces increase of IL-8. The aim of this study was to test the effect of albumin instillation as rescue treatment in meconium aspiration syndrome (MAS). MAS was induced in hypoxic piglets by lung instillation of meconium (MAS I = 675 mg/kg, n=12; MAS II=540 mg/kg, n=14). Morbidity and mortality differed (MAS I, dead=7/12; MAS II, dead=5/14). MAS groups were randomized to postmeconium instillation of either bovine albumin (30%, 1.4 mL/kg; MAS I, n=6; MAS II, n=7) or isotonic saline (9 mg/mL, 1.4 mL/kg; MAS I, n=6; MAS II, n=7). The controls (n=4) were tested by sequential instillation of saline (9 mg/mL, 5 mL/kg) and albumin (30%, 1.4 mL/kg). Lung function and gas exchange deteriorated significantly after instillation of meconium [oxygenation index (OI): MAS I, +814%; MAS II, +386%; ventilation index (VI): MAS I, +256%; MAS II, +162%; compliance: MAS I, -53%; MAS II, -44%]. Increases of tracheal IL-8 correlated to deterioration of lung function were 10- (MAS I) and 5-fold (MAS II) (p <0.001). Lung compliance was higher in albumin instillation versus saline instillation (MAS I, p=0.008; MAS II, p=0.002). Albumin did not influence intergroup differences in IL-8, hemodynamics, OI, or VI. MAS-induced IL-8 increases correlated with deterioration of lung function (OI, VI, and compliance). Rescue treatment with albumin in meconium aspiration improved lung compliance in piglets and may represent a new therapeutic approach to MAS.

Albumins↗

Ultrastructural changes in the lungs of neonatal rats intratracheally inoculated with meconium.

Meconium aspiration syndrome has been for many years an important cause of neonatal respiratory distress in newborn babies and sporadically reported in animals. This investigation was designed to study the ultrastructural and morphometric changes in the lungs of neonatal rats following the intratracheal inoculation of meconium. Seven-day-old Fischer-344 rats (n = 24) were randomly allocated in two groups. One group was intratracheally inoculated with saline solution and the second group received homologous meconium. Neonates were euthanatized at 1, 3 and 7 postinoculation days (PID) and lungs were examined by light and electron microscopy. Saline solution did not induce any ultrastructural changes in the lung. In contrast, meconium induced deciliation, recruitment of neutrophils and pulmonary alveolar macrophages to the bronchoalveolar space, intravascular sequestration of neutrophils and aggregation of platelets at PID 1 and 3. Other ultrastructural changes at PID 1 and 3 included interstitial edema and escape of red cells and fibrin into the alveolar space and interstitium. Interstitial edema and sequestration of neutrophils were responsible for the significant increase in thickness of alveolar septa. At PID 7 there was hyperplasia and enlargement of type II pneumocytes as well as interstitial proliferation of mesenchymal cells with intra-alveolar fibrosis. It was concluded that intratracheal inoculation of meconium in neonatal rats induces acute ultrastructural changes followed by a reparative response.

Animals↗

THE MECONIUM-PLUG SYNDROME AND HIRSCHSPRUNG'S DISEASE.

A mass of inspissated meconium in the distal colon or rectum is a relatively common cause of neonatal intestinal obstruction. The meconium-plug syndrome is unrelated to cystic fibrosis and meconium ileus. The clinical picture is frequently indistinguishable, without contrast study of the colon, from other forms of mechanical intestinal obstruction requiring laparotomy. A barium enema examination is almost always diagnostic, and use of this procedure usually results in dislodgement and passage of the plug.No single cause for the excessive viscosity and tenaciousness of the obstructive meconium mass has been identified. Previous reports have generally emphasized the normal ganglion-cell content of the colon in affected patients.Two infants are described who fulfilled all criteria for this syndrome but who were not rendered asymptomatic, as normally anticipated, by removal of the plug. Subsequent studies revealed the presence of Hirschsprung's disease in both patients. This diagnosis should be considered when an infant with meconium-plug obstruction of the colon fails to follow the usual satisfactory clinical course after the plug has been passed.

Barium Sulfate↗

Intrapartum suctioning of meconium: comparative efficacy of bulb syringe and De Lee catheter.

Intrapartum suctioning of the newborn's pharynx with a De Lee catheter (DL) has reduced the incidence of meconium aspiration syndrome (MAS) in neonates born with meconium staining of the amniotic fluid. However, the bulb syringe (BLB) is used more often for this purpose because of greater technical convenience. In a prospective study, 60 offspring of such deliveries received intrapartum pharyngeal suctioning either by BLB (29 cases) or by DL (31 cases), according to random selection. The presence and amount of meconium in the trachea, incidence and severity of MAS, and mortality from the disease were similar between the two groups. This study suggests that the BLB is as effective as the DL for intrapartum removal of nasopharyngeal meconium in deliveries with meconium staining of the amniotic fluid. Since the BLB is easier to use, less expensive and probably safer, our results suggest that it may be the preferable method.

Amniotic Fluid↗

Studies in meconium. An approach to screening tests to detect cystic fibrosis.

Screening for cystic fibrosis (CF) in newborns is desirable, and efforts should continue in establishing a system of easily available, reliable, simple, and inexpensive tests. In addition to the Boehringer-Mannheim (BM) test for the detection of albumin, we propose the assay for lactase and beta-D-fucosidase in meconium. These latter two enzymes are present in the meconium of babies with CF and absent in meconium of most healthy babies. In a mass screening program for CF involving 20,182 specimens of meconium using only the BM strip, we found 46 positive results. Twenty-nine specimens came from infants with CF, six of whom had meconium ileus. Seventeen specimens yielded false-positive results by the BM test. Eleven of these would have been excluded by the addition of the lactase and beta-D-fucoside assay, thus reducing the false-positive test results by nearly 61%. In a comparative study of the three methods, the lactase and beta-D-fucosidase yielded 1.2% false-positives when examined independently. Performance of these two assays may allow greater specificity in diagnosis when used in addition to the BM test.

Albumins↗

Incidence of meconium abnormalities in newborn infants with cystic fibrosis.

Review of the newborn nursery notes of 87 infants who had cystic fibrosis without meconium ileus (MI) indicated that 12 of them had clinical features consistent with the meconium plug syndrome (MPS). This high incidence of meconium abnormalities suggests that MI and the MPS probably represent different gradations of the same underlying pathologic abnormality. The findings further suggest that a quantitative pilocarpine iontophoresis sweat test be performed in every newborn infant with any type of meconium abnormality, including the spontaneous passage of meconium plugs.

Child, Preschool↗

Histopathologic effects of meconium on human umbilical artery and vein: in vitro study.

OBJECTIVE: To determine the histopathologic effects of meconium on human umbilical artery and vein. METHODS: Umbilical cords from six patients with uncomplicated, singleton, term gestations were obtained immediately after delivery. One centimeter segments from each cord were flushed, isolated, placed in either modified Krebs solution alone or modified Krebs solution with various concentrations (1%, 10%, or 25%) of fresh meconium, and then incubated at pH 7.2, temperature 37 degrees C, PCO2 50-55 mmHg, PO2 40-45 mmHg for 1, 6, 12, or 24 h. The specimens were then fixed, stained, and examined under light microscopy. RESULTS: Umbilical arteries exhibited focal vacuolation of the endothelium after exposure of the cord to meconium. Umbilical veins revealed: 1) endothelial loss proportionate to the meconium concentration at all intervals (P < 0.05), 2) increased density or focal absence of the internal elastic lamina, and 3) focal loss of myocyte nuclei. Rare nonpigmented macrophages and increased mast cells were identified in the Wharton's jelly. CONCLUSIONS: Exposure to meconium in vitro results in histopathologic changes in the umbilical artery and vein.

Cell Nucleus↗

Effect of meconium on the hemoglobin-oxygen association curve.

OBJECTIVE: Our purpose was to determine the effect of meconium-stained amniotic fluid on the hemoglobin-oxygen association curve of maternal whole blood. METHODS: Whole blood was obtained from term gravidas in active labor. Hemoglobin-oxygen association curves were generated for blood incubated with meconium vs. controls. Oxygen association curves were determined at pH 7.4 and 37 degrees C utilizing an automated device consisting of a spectrophotometer cuvette fitted with a magnetic stirrer, gas exchange line, and a Clark oxygen electrode. The samples were deoxygenated with nitrogen and association curves recorded while reoxygenating. Data was analyzed with Sigma Plot and Sigma Stat software. Analysis included log transformation, linear regression, and paired t-test. RESULTS: Twenty-eight hemoglobin oxygen association curves were generated. In all 14 pairs, meconium shifted the hemoglobin-oxygen association curve to the right. Partial pressures of oxygen required for various degrees of hemoglobin saturation were higher in meconium-exposed samples; P50 (30.1+/-0.6 vs. 27.8+/-0.4 mmHg, P < 0.01); P75 (46.9+/-0.6 vs. 43.1+/-0.5 mmHg, P < .001); P90 (69.2+/-1 vs. 63.3+/-1 mmHg, P < 0.01). CONCLUSIONS: Meconium-stained amniotic fluid causes a statistically significant, but clinically small, right shift in the hemoglobin-oxygen association curve.

Female↗

Steroid therapy for meconium aspiration syndrome in newborn infants.

BACKGROUND: Meconium aspiration syndrome may cause severe respiratory distress in the newborn infant, with an associated high morbidity and mortality. A chemical pneumonitis is believed to occur secondary to bile, bile acids and pancreatic secretions contained in meconium. It has therefore been hypothesised that corticosteroids may be of benefit in the management of this condition through their anti-inflammatory properties. OBJECTIVES: The objective of this review was to determine whether steroid therapy for meconium aspiration syndrome decreases the morbidity and mortality associated with this condition without adverse effects. SEARCH STRATEGY: Searches were made of PREMEDLINE and MEDLINE from 1966 to April 2003, CINAHL back to 1982, Current Contents back to 1998, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2003) and Oxford Database of Perinatal Trials. The search included cross-referencing of previous reviews, and a review of abstracts, conference and symposia proceedings published in Pediatric Research from 1993 to 2003. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials comparing steroid treatment to no steroid treatment for neonates with meconium aspiration syndrome were considered for this review. DATA COLLECTION AND ANALYSIS: The methodological quality of each trial was assessed independently by each author. Data were extracted, analysed and results reviewed independently by each author. Meta-analysis was performed with RevMan 4.2, using the fixed effects model. Mean difference (MD) and weighted mean differences (WMD) with 95% confidence intervals in brackets for continuous variables and Relative Risk (RR) with 95% confidence intervals for categorical data were reported. MAIN RESULTS: Three randomised controlled trials were identified. Two trials, by Wu 1999 (50 participants) and Yeh 1977 (35 participants), were included in the review. The trial by Davey 1995, as yet unpublished, was excluded from this review as insufficient information about methodology and results were available. On meta-analysis, there was no significant reduction in mortality [typical RR 0.95 (0.20, 4.58)]. A small but significant increase in duration of oxygen therapy was seen with the use of steroids [WMD 30.0 hours (8.4, 51.6)]. There was no significant difference in duration of hospital stay in the study by Wu 1999 [MD 0.00 days (-3.09, 3.09)]. Duration of mechanical ventilation was reported by Wu 1999 with no significant difference seen [MD -1.10 days (-2.79, 0.59)]. Incidence of air leak was reported by Yeh 1977 with no significant difference detected [RR 0.64 (0.18, 2.26)]. Long-term outcome was not reported in either of the two studies. REVIEWER'S CONCLUSIONS: At present, there is insufficient evidence to assess the effects of steroid therapy in the management of meconium aspiration syndrome. A further large randomised controlled trial assessing potential benefits and harm would be required to determine its role.

Humans↗

Biochemical analysis of meconium in fetuses presumed to have cystic fibrosis.

A series of proteins (albumin, transferrin, alpha 1-antitrypsin, alpha-fetoprotein and pancreatic oncofetal antigen) and enzymes (gamma-glutamyltranspeptidase, aminopeptidase M, alkaline phosphatase, alpha-glucosidase and protease) was measured in fetal meconium extracts. There were 19 fetuses thought to have cystic fibrosis (CF), 13 with neural tube defects, three with chromosome abnormalities and 19 normal controls, all with gestational ages between 18 and 21 weeks. With the exception of alpha-fetoprotein, all the proteins and enzymes were significantly elevated in the CF meconium extracts. The most definitive indicator of a CF fetus was the albumin concentration, where the mean level was five times that found in the control groups. However, five of 19 fetuses assumed to have CF had albumin in the normal range. In these cases the meconium protease levels were grossly elevated. Furthermore, in the same five fetuses meconium concentration of pancreatic oncofetal antigen, a protein synthesized in the fetal pancreas, was also greatly raised. We suggest that post-mortem examination of a fetus thought to have CF should include measurement of meconium albumin, protease and pancreatic oncofetal antigen.

Abortion, Induced↗

Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model.

In order to evaluate further the physiological and inflammatory changes of meconium aspiration syndrome (MAS), 25 newborn piglets (1-2 days old, 1.5 +/- 0.4 kg) were studied. Piglets were briefly ventilated with 100% oxygen and then received an intratracheal bolus of 3 mL/kg of a 20% suspension of human meconium. They were then further ventilated, keeping PaCO2 at approximately 40 torr and PaCO2 at 70 torr during 4, 12, 24, and 48 h studies. Pulmonary function studies and tracheal aspirates were obtained at time zero and serially throughout the study. Bronchoalveolar lavage was performed at the end of the study to examine endogenous surfactant function. Control piglets received 3 mL/kg of intratracheal saline and were then ventilated for 48 h at an inspired oxygen concentration and mean airway pressure matched to the meconium treated group (to control for the effects of hyperoxia and barotrauma on the lung). MAS caused acute decreases in gas exchange and dynamic lung compliance, which returned toward baseline by 48 h (P < 0.001, ANOVA). Tracheal aspirate absolute neutrophil count, neutrophil chemotactic activity, albumin, and total protein concentrations also increased significantly over time (P < 0.001). Endogenous surfactant function appeared to be significantly inhibited by the meconium. All variables of lung injury were significantly higher in the meconium group compared to the saline control group over the 48 h study. Newborn piglets provide a clinically relevant model of MAS, demonstrating physiological and inflammatory changes with apparent alterations in endogenous surfactant function. Effective therapies for MAS may require interventions directed at all of these components of lung injury.

Animals↗

Fetal meconium peritonitis without sequelae.

Meconium peritonitis is a chemical peritonitis usually resulting from antenatal bowel rupture. Prenatal ultrasound findings include ascites, intraabdominal masses, bowel dilatation and the development of intraabdominal calcifications [1-5]. The most common bowel disorders which lead to meconium peritonitis in utero are those resulting in bowel obstruction and perforation, such as small bowel atresias, volvulus and meconium ileus [1-5]. Meconium ileus is associated with cystic fibrosis in most cases, although extraluminal abdominal calcifications are usually scarce in cases of cystic fibrosis [1, 6]. Postnatal outcome for infants with meconium peritonitis depends on the etiology for bowel rupture and underlying disease.

Ascites↗