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Meconium stained amniotic fluid: antenatal, intrapartum and neonatal attributes.

OBJECTIVES: To find out the incidence, outcome as well as antenatal, intrapartum and neonatal attributes of meconium stained amniotic fluid (MSAF). DESIGN: Prospective study. SETTING: Neonatal Unit of Hospital. SUBJECTS: 1426 live births occurring in 1500 consecutive deliveries, over one year period. INTERVENTIONS: In all babies born through MSAF, thorough oropharyngeal suction as soon as the head was delivered followed by immediate intratracheal intubation and suctioning in infants depressed at birth. RESULTS: 204 (14.3%) deliveries had MSAF of which thick meconium was present in 141. Hepatitis in mother, fetal distress during labor and intrauterine growth retardation were significant factors associated with MSAF. One fifth of babies born through MSAF suffered severe birth anoxia compared to 5.6% in non-MSAF group. The consistency of meconium had direct bearing on the neonatal outcome. Severe birth asphyxia (SBA) occurred in 27.0 and 6.3% of babies with thick and thin meconium staining, respectively. Meconium aspiration syndrome was observed in 9 babies of thick meconium group and 8 of these were depressed at birth. All deaths occurred in thick meconium group and were associated with SBA. CONCLUSIONS: Selective approach can be adopted for babies with MSAF reserving intratracheal suctioning at birth for depressed neonate or evidence of fetal distress in utero. Rest of the neonates only need careful observation after thorough oronasopharyngeal suctioning.

Amniotic Fluid↗

Influence of the legal imperative and medical guidelines on the incidence and management of the meconium-stained newborn.

Following a legal action that resulted from the death of a newborn with the meconium aspiration syndrome, I investigated the incidence and management at a community hospital of the meconium-stained newborn during March in each of the years 1973 through 1985. During March in 1973 through 1981, 4.3% of all live births (1368) were meconium stained. After the newborn's death, which initiated a period of legal negotiations, the incidence of meconium staining increased to 14.4% among 582 live births during March of 1982 through 1985. Laryngoscopy increased to include 64.3% of meconium-stained newborns, and endotracheal suctioning was associated with laryngoscopy in 72.2% of the patients. Also, oxygen administration to newborns with and without meconium staining increased from 10.5% in March of 1973 through 1981 to 45.7% in March of 1982 through 1985. There was no improvement in outcome from the increased recognition and more aggressive management. While the issuance of medical guidelines alone had little effect on the incidence and care of the meconium-stained newborn, the combination of the legal imperative with medical guidelines had a profound and corruptive effect.

Humans↗

Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs.

To investigate whether aspiration of meconium induces a hemodynamic and histologic pulmonary response similar to that frequently seen in experimental acute respiratory distress syndrome, twelve 10-week-old pigs with postnatally adapted lungs were studied. Six 10-week-old pigs received 3 ml/kg 20% human meconium via the endotracheal tube. Six control pigs of the same age were given sterile saline. Ventilator settings were adjusted to keep PaO2 above 8 kPa and PaCO2 below 5 kPa. The pulmonary hemodynamic response to aspiration consisted of two separate hypertensive components. An initial peak in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) was followed by a progressive increase in PAP and PVR in the meconium group, whereas in the saline group these parameters returned to baseline levels. The distribution of PVR, determined by pulmonary artery occlusion, was characterized by an increase in the postarterial resistance immediately after meconium aspiration and a progressive increase in both arterial and postarterial resistance during the later phase. On histological examination, marked neutrophil sequestration was seen in the meconium lungs. In addition, lung edema formation was significantly enhanced in the meconium group, as shown by an increased lung wet/dry weight ratio. Thus, meconium aspiration resulted in a biphasic pulmonary pressor response and severe pulmonary inflammation. This response resembled that of models of experimental acute respiratory distress syndrome following diverse types of precipitating insults; this suggests that similar pathophysiologic mechanisms are elicited and cause similar pulmonary dysfunction following different forms of lung injury.

Animals↗

Effects of exogenous surfactant on gas exchange and compliance in rabbits after meconium aspiration.

Success in using adjunctive surfactant therapy for meconium aspiration has been inconsistent. We tested the hypothesis that the ability of exogenous surfactant to improve gas exchange and pulmonary compliance after meconium aspiration is related to the method of surfactant administration. In anesthetized rabbits (2.4 +/- 0.16 kg body weight), an endotracheal tube (ETT) was placed in the lower trachea, and the lungs were ventilated mechanically. After a control period, filtered meconium (3-5 mL/kg) was instilled through the ETT. Group 1 (n = 5) was not given surfactant. Thirty minutes after meconium instillation, group 2 (n = 5) was given a bolus of bovine surfactant (Beractant, 4 mL/kg) through the ETT, and group 3 (n = 5) was given an infusion of Beractant (4 mL/kg for 1 hr) through the side-port of the ETT. Thirty minutes after meconium instillation, tracheal pressure increased by 8 +/- 1 cm H(2)O (mean +/- SEM), dynamic compliance decreased by 0.36 +/- 0.07 mL/cm H(2)O/kg, arterial PO(2) (PaO(2)) decreased by 49 +/- 6.0 mmHg, arterial PCO(2) (PaCO(2)) increased by 12 +/- 2.4 mmHg, and arterial pH (pHa) decreased by 0.09 +/- 0.02. After 3 hr of exposure to meconium, tracheal pressure was significantly (P < 0.001) lower in group 3 compared to groups 1 or 2. PaO(2) remained below baseline in all groups. Group 3 had a significantly (P = 0.001) higher dynamic compliance than groups 1 or 2. Likewise, static compliance was higher for group 3 compared to groups 1 or 2, with the greatest difference at low lung volume. Mean arterial blood pressure, pulse rate, PaCO(2), and pHa were not significantly different between groups. These results suggest that continuous infusion of exogenous surfactant is more effective than bolus administration in improving pulmonary function after meconium aspiration.

Animals↗

Perfluorocarbon broncho-alveolar lavage and liquid ventilation versus saline broncho-alveolar lavage in adult guinea pig experimental model of meconium inhalation.

OBJECTIVE: This study compares perfluorocarbon broncho-alveolar lavage (PFC-BAL) with isotonic saline broncho-alveolar lavage (saline-BAL) in an experimental model of meconium aspiration in adult guinea pigs. DESIGN: Prospective controlled experimental study. PATIENTS AND METHODS: Ten male guinea pigs were given 1 ml of human meconium, diluted to 10% in isotonic saline, via tracheostomy and then artificially ventilated. After stabilization, five animals (control group) underwent BAL with 10 ml/ kg isotonic saline solution. After bronchial suctioning, a further BAL with 2 ml/kg saline was performed. The other five animals (study group) underwent BAL with 100 ml/kg of PFC (RIMAR 101). Bronchosuction was effected at 5 min and then a BAL with PFC 2 ml/kg was performed. Both groups received conventional mechanical ventilation during the lavage procedures. Within 20 min all the saline-BAL treated animals died, whereas the PFC-BAL treated animals survived and were then treated with total liquid ventilation (TLV) by gravity. MEASUREMENTS AND RESULTS: After meconium inhalation in both groups, a large alveolar-arterial oxygen difference, hypercarbia, severe acidosis and tachycardia were noticed. In PFC treated animals, an improvement in blood gases was noted and acid-base balance remained stable compared to saline-BAL treated animals. No haemodynamic change was observed during or after PFC-BAL, while during saline-BAL there was evidence of bradycardia, hypotension and respiratory failure, which led to the death of the animals. The histological lung sections in the PFC-BAL group showed evidence of normal alveolar expansion with a minimal presence of meconium debris in the small bronchioles. In saline-BAL treated animals, the lung structure appeared severely compromised with the presence of meconium in bronchioles and alveoli, intra-alveolar oedema and haemorrhagic areas. CONCLUSIONS: This study confirms the detrimental effects of meconium aspiration and the impairment of lung function following saline-BAL. By contrast, PFC-BAL and TLV by gravity seemed to prevent absorption of meconium, facilitate its removal, improve gas exchange and reduce lung barotrauma.

Acute Disease↗

Is gastric lavage needed in neonates with meconium-stained amniotic fluid?

UNLABELLED: We compared the incidence of complications from meconium-containing gastric fluid in a group of neonates born with meconium-stained amniotic fluid (MSAF) who did not routinely have gastric lavage prior to feeds, versus a group who had elective gastric lavage before the first feed. In the first group, 275 neonates born with MSAF were fed without prior gastric lavage. While 13 developed feeding problems, the other 262 infants (95%) who did not undergo routine gastric lavage remained free of later feeding difficulties or secondary meconium aspiration. In the second group, all 227 neonates with MSAF had elective gastric lavage performed after birth. All remained free of later feeding difficulties or secondary meconium aspiration. CONCLUSION: Our data suggest that gastric lavage is not necessary in most neonates born with meconium-stained amniotic fluid, regardless of the thickness of the meconium-stained fluid, as no complications from meconium-containing gastric fluid were observed.

Amniotic Fluid↗

Significance of meconium during labor.

Continuous fetal heart rate (FHR) monitoring and routine fetal scalp blood sampling was utilized in the evaluations of 366 fetuses during labor. One hundred and six patients had meconium in the amniotic fluid at some time during labor. A total of 26,110 uterine contractions were monitored during these 366 labors. The incidence of FHR patterns as a percentage of uterine contractions was calculated for the meconium and nonmeconium groups. Although there was a 3 1/2-fold increase in the incidence of low five-minute Apgar scores (less than 7) in the meconium group, signs of fetal distress were, with rare esception, not significantly different from those in the nonmeconium group. The presence of meconium in the amniotic fluid without signs of fetal asphyxia (late decelerations and acidosis) is not a sign of fetal distress and need not be an indication for active intervention. The combination of fetal asphyxia and meconium staining of the amniotic fluid, however, does enhance the potential for meconium aspiration and a poor neonatal outcome. Universal fetal heart rate monitoring and appropriate fetal acid-base evaluation is recommended for following patients with meconium in the amniotic fluid during labor.

Acid-Base Equilibrium↗

Screening for cystic fibrosis by analysis of meconium for albumin and protease inhibitors.

A qualitative method of detecting elevated meconium protein concentration was compared with a method of determining meconium albumin concentration by electroimmunoassay since elevated meconium protein levels can indicate pancreatic insufficiency caused by cystic fibrosis. Between 5 and 10 per 1000 healthy infants passed meconium specimens that gave a false positive reaction with the Boehringer Mannheim test strip and contained a greater than expected concentration of albumin. It was possible to exclude pancreatic insufficiency in all of these children by determining the ratio, albumin : alpha1-antitrypsin in meconium and subsequent faecal specimens, since it was found that values of this ratio in excess of 2.0 suggested pancreatic insufficiency of the type associated with cystic fibrosis. Three of 14 neonates with subsequently proven cystic fibrosis yielded meconium specimens giving negative test strip results and low albumin concentrations. In two of these patients, the ratio, albumin : alpha1-antitrypsin in the meconium was within normal limits but, within two months of birth, the albumin : alpha1-antitrypsin ratio in the faeces of both children was greater than 3.0 suggesting that pancreatic insufficiency had developed.

Albumins↗

Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets.

BACKGROUND: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. AIMS: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. STUDY DESIGN: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. RESULTS: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. CONCLUSIONS: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

8-Hydroxy-2'-Deoxyguanosine↗

Apoptosis of airway epithelial cells in response to meconium.

Meconium aspiration syndrome (MAS) is common among newborn children but its mechanism is unclear. The syndrome is known to produce a strong inflammatory reaction in the lungs resulting in massive cell death. In this work we studied lung cell death by apoptosis after meconium aspiration in forty two-week-old rabbit pups. Analyzing lung samples by ISEL-DNA end labeling demonstrated the specific spread of apoptotic bodies throughout the lungs. These bodies were shrunken and smaller in size compared to normal cells and many of them were lacking cell membranes. About 70% of all apoptotic bodies were found among the airway epithelium cell eight hours after meconium instillation. In comparison, among lung alveolar cells, only about 20% cells were apoptotic in the same animals. In meconium-treated lungs and A549 cells, a significant increase of angiotensinogen mRNA and Caspase-3 expression were observed. The pretreatment of cells with Caspase-3 inhibitor ZVAD-fmk significantly inhibited meconium-induced lung cell death by apoptosis. These findings demonstrate the apoptotic process in meconium-instilled lungs or A549 cells in culture. Our results show lung airway epithelial and A549 cell apoptosis after meconium instillation. We suggest that studies of lung airway epithelial cell death are essential to understanding the pathophysiology of MAS and may present a key point in future therapeutic applications.

Amino Acid Chloromethyl Ketones↗

Meconium enhances platelet-activating factor and tumor necrosis factor production by rat alveolar macrophages.

Meconium aspiration syndrome (MAS) frequently results in inactivation of surfactant, persistent pulmonary hypertension (PPHN) and respiratory failure among newborn infants. Inflammation and inflammatory mediators play an important role in MAS. Since alveolar macrophages are thought to be very important cells in the pathogenesis of various inflammatory diseases, we evaluated whether meconium could stimulate rat alveolar macrophages to generate platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha in vitro. We also examined the response to A23187 (calcium ionophore), 1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (synthetic PAF) and dexamethasone on meconium-induced release of PAF and TNF-alpha. PAF and TNF-alpha concentrations from supernatant fluid were measured after high-performance liquid chromatography purification by specific radioimmunoassay, and TNF-alpha concentrations were determined by using an enzyme-linked immunosorbent assay. Our results showed that alveolar macrophages exposed to meconium could enhance PAF and TNF-alpha production in a dose (0.1, 1, 5 and 10%, P<0.01)-dependent way. In the presence of A23187, the capability of meconium to stimulate PAF production was further enhanced in the supernatant fluids. Furthermore, treatment with synthetic PAF significantly increased the generation of TNF-alpha in response to meconium. On the other hand, dexamethasone effectively inhibited both PAF and TNF-alpha production stimulated by 5% meconium (P<0.01, P<0.01; respectively). We suggest that alveolar macrophages and PAF, TNF-alpha play an important role in the pathogenesis of lung injury and severe complications in MAS. Furthermore, the protective effect of glucocorticoids in MAS could be due, at least in part, to a suppression of PAF and TNF-alpha generation.

Animals↗

The effects of intraamniotic human neonatal urine and meconium on the intestines of the chick embryo with gastroschisis.

BACKGROUND/PURPOSE: Urinary waste products in the amniotic fluid has been implicated as a cause of intestinal damage (ID) in gastroschisis based on the fact that fetus urinates physiologically into the amniotic cavity. However, experimental and clinical data suggest that intrauterine defecation is a physiological event, thus gastrointestinal waste products also may be responsible for ID in gastroschisis. An experimental study was performed to investigate the effects of intraamniotic human neonatal urine and diluted meconium on the intestines of chick embryo with gastroschisis. METHODS: Five-day-old fertilized chick eggs (Gallus domesticus) were used. Gastroschisis was created through amniotic cavity without opening the allantoic cavity. Sterile urine and meconium were obtained from newborn humans, and 1% meconium suspension was prepared. The eggs were divided in to 3 groups. In the first group, gastroschisis was created, and amniotic fluid was reinstilled without changing its composition (control group). Equal amounts of amniotic fluid and urine mixture was instilled into the amniotic cavity in second group (urine group) and 1% meconium suspension was instilled in similar fashion in the third group after creation of gastroschisis (meconium group). RESULTS: Histopathologic features of the intestines of the urine group did not differ from the intestines of the control group. The meconium group's bowel showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic changes of intestines induced by intraamniotic diluted meconium are consistent with the ones described for human gastroschisis specimens. CONCLUSION: Gastrointestinal waste products seem responsible for the ID in gastroschisis rather than urinary waste products.

Amniotic Fluid↗

Meconium stimulates cyclooxygenase-2 expression in rat lungs.

Since meconium aspiration often induces an inflammatory respiratory disorder, we investigated the effects of intrapulmonary meconium on the expression of cyclooxygenase-1 and 2 in rat lungs. Suspension of human meconium was instilled intratracheally into ventilated lungs of anesthetized rats, while control rats received an equal volume of saline. The meconium lungs were ventilated either with air or 100% oxygen, and control lungs were ventilated with air. After 3 h, the lungs were removed and the amount of cyclooxygenase-1 and 2 mRNA was measured by Northern blot analysis. Cyclooxygenase-1 mRNA was clearly expressed in control rat lungs, while cyclooxygenase-2 expression was minimal. Meconium administration markedly upregulated the expression of cyclooxygenase-2 mRNA, while cyclooxygenase-1 expression remained unchanged. Increased expression of cyclooxygenase-2 was detected in rat lungs ventilated with either air or oxygen. Our data thus indicate that meconium aspiration induces pulmonary expression of cyclooxygenase-2, suggesting an important role for prostaglandins in the meconium aspiration-induced inflammation in neonatal lungs.

Animals↗

Delivery room risk factors for meconium aspiration syndrome.

The objective of this study is to identify risk factors for meconium aspiration syndrome (MAS) in newborns born through meconium-stained amniotic fluid (MSAF). From May 27, 1994 to June 9, 1997 maternal and neonatal data were prospectively collected on all infants born through MSAF. Development of MAS was the primary outcome. Using bivariate and logistic regression analysis we identified risk factors for MAS. There were 8,967 births during this period: 7.9% (708 of 8,967) were delivered through MSAF. Respiratory symptoms developed in 6.8% (48 of 708) of births. Of these, 50% (24 of 48) were excluded due to the diagnosis of transient tachypnea of the newborn (17), respiratory distress syndrome (4), group B streptococcus pneumonia (1), congenital cytomegalic inclusion disease (1), and supraventricular tachycardia (1). Of the 24 infants with respiratory symptoms consistent with MAS, 45.8% (11 of 24) required ventilatory support, one required extracorporeal-membrane oxygenation. Bivariate analysis identified six risk factors ( p <0.05): Apgar <7 at 1 minute, Apgar <7 at 5 minutes, thick meconium, fetal distress, suction of infant's stomach by delivery room team at <5 minutes of age, and need for resuscitation. Tracheal meconium was very prevalent in our population at 74% of all intubated infants, and was not significantly associated with MAS. Logistic regression analysis identified four independent risk factors. Looking at multiple prediction models, an infant with fetal distress, Apgar <7 at 1 and 5 minutes and thick meconium has a 79.8% probability of developing respiratory symptoms. If these risk factors are not present, there is a 0.8% risk. In our cohort, this group had 16.7% positive predictive value (4 of 24) and 99.6% negative predictive value (657 of 660). In meconium deliveries, infants with thick meconium, fetal distress, and Apgar scores <7 at 1 and 5 minutes are at high risk for development of respiratory symptoms. Infants delivered in the absence of all of these risk factors are at low risk for development of MAS.

Apgar Score↗

The need for delivery room intubation of thin meconium in the low-risk newborn: a clinical trial.

The delivery room management of meconium-stained amniotic fluid remains controversial. We attempted to determine if intubation of the low-risk newborn with thin meconium affects the incidence of respiratory symptoms. Exclusion criterion included moderate or thick meconium, fetal distress, neonatal depression, or prematurity. Eligible infants were randomized to either an intubation (group I) or to a nonintubation group (group II). The outcome was the presence of respiratory symptoms. Patients were studied from May 1994 to June 1997. There were 8967 births during this period: 7.9% (708/8967) were delivered through meconium. Thin meconium was noted in 50.3% (356/708) of all births. 24/356 infants with thin meconium were excluded for medical criterion. One hundred sixty-three infants were medically eligible but could not be randomized due to lack of consent, late arrival of the team, or obstetrician request. These were placed into intubation (group I B) and nonintubation (group II B) groups. Seventy-seven infants were randomized into group I and 92 infants into group II. From the intubation groups I and I B, one required supplemental oxygen and was weaned to room air in 7 hr. From the nonintubation groups II and II B, two infants required oxygen, weaning to room air in 11 and 46 hr. Comparing birth weight, gestational age, sex, mode of delivery and 5-min Apgar, there were no significant differences. However, the intubation groups had significantly lower 1-min Apgar scores. There was no airway morbidity reported in the intubation groups. In the infant with thin meconium and an otherwise low-risk pregnancy, we were unable to demonstrate a difference in respiratory symptoms with intubation and intratracheal suctioning.

Airway Obstruction↗

Amnioinfusion for the prevention of the meconium aspiration syndrome.

BACKGROUND: It is uncertain whether amnioinfusion (infusion of saline into the amniotic cavity) in women who have thick meconium staining of the amniotic fluid reduces the risk of perinatal death, moderate or severe meconium aspiration syndrome, or both. METHODS: We performed a multicenter trial in which 1998 pregnant women in labor at 36 or more weeks of gestation who had thick meconium staining of the amniotic fluid were stratified according to the presence or absence of variable decelerations in fetal heart rate and then randomly assigned to amnioinfusion or to standard care. The composite primary outcome measure was perinatal death, moderate or severe meconium aspiration syndrome, or both. RESULTS: Perinatal death, moderate or severe meconium aspiration syndrome, or both occurred in 44 infants (4.5 percent) of women in the amnioinfusion group and 35 infants (3.5 percent) of women in the control group (relative risk, 1.26; 95 percent confidence interval, 0.82 to 1.95). Five perinatal deaths occurred in the amnioinfusion group and five in the control group. The rate of cesarean delivery was 31.8 percent in the amnioinfusion group and 29.0 percent in the control group (relative risk, 1.10; 95 percent confidence interval, 0.96 to 1.25). CONCLUSIONS: For women in labor who have thick meconium staining of the amniotic fluid, amnioinfusion did not reduce the risk of moderate or severe meconium aspiration syndrome, perinatal death, or other major maternal or neonatal disorders.

Amniotic Fluid↗

Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis.

OBJECTIVE: To compare the sensitivity and specificity of maternal interview, maternal hair analysis, and meconium analysis in detecting perinatal exposure to cocaine, opiate, and cannabinoid. DESIGN/METHODS: The use of cocaine, opiate, and cannabinoid during pregnancy was determined prospectively in 58 women by 3 methods: structured maternal interview, maternal hair analysis, and meconium analyses. The results of the 3 methods were compared with one another. RESULTS: The maternal interview showed the lowest sensitivity in detecting cocaine and opiate exposures (65% and 67%, respectively), but it had the highest sensitivity in detecting cannabinoid exposure (58%). Both hair and meconium analyses had high sensitivity for detecting cocaine or opiate exposures. Hair analysis had a sensitivity of 100% for cocaine and 80% for opiate detection. However, it had a false-positive rate of 13% for cocaine and 20% for opiate, probably as a result of passive exposure. Meconium analysis had a sensitivity of 87% for cocaine and 77% for opiate detection, but unlike hair analysis, it had no false-positive test results for cocaine. Both hair and meconium analyses had low sensitivity in detecting cannabinoid exposure (21%-22.7%), most probably because of the sporadic use of cannabinoid. CONCLUSION: Meconium and hair analyses had the highest sensitivities for detecting perinatal use of cocaine and opiate, but not for cannabinoid. The principal drawback of hair analysis is its potential for false-positive test results associated with passive exposure to drugs. Maternal interview is a time-consuming test of low sensitivity. The high sensitivity of meconium analysis and the ease of collection make this test ideal for perinatal drug screening.

Adult↗

Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration.

To investigate the possible protective effects of nitric oxide (NO) inhalation in newborns with meconium aspiration, 18 10-12-d-old piglets were studied for 6h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium. Twelve of the piglets were treated with continuous NO inhalation at a dose of 1 ppm (n = 6) or 10 ppm (n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence of ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm NO, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulmonary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemically, treatment with 1 or 10 ppm NO inhalation did not protect the lungs against meconium-induced inflammatory injury. Further, ultrastructural lung tissue analysis revealed a significant amount of alveolar exudate and oedematous alveolar epithelium and endothelium after meconium instillation, also in the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These results thus show that early continuous NO inhalation controls the rise in pulmonary artery pressure and improves the efficiency of arterial oxygenation, and further prevents the increase in epithelial apoptosis, but does not protect against early inflammatory damage caused by meconium aspiration.

Administration, Inhalation↗