Transitional Hemodynamics in Neonates Born Through Meconium-Stained Amniotic Fluid: A Prospective Observational Study.

Neonates born through meconium-stained amniotic fluid (MSAF) are at increased risk of altered cardiopulmonary transition at birth. There is a paucity of literature evaluating the transitional hemodynamics in these neonates. We aimed to evaluate transitional hemodynamics via echocardiography in neonates born through MSAF, compared to healthy neonates. The primary objective was to assess pulmonary vascular resistance using left pulmonary artery-velocity time integral (LPA-VTI). The secondary objectives were to assess other pulmonary vascular parameters and myocardial function. We enrolled 35 MSAF-born and 35 healthy neonates. Echocardiography was performed at 24 and 48 h of life by a pediatric cardiologist. Echocardiographic parameters were compared between MSAF-born and healthy neonates, and between MSAF-born neonates who developed meconium aspiration syndrome (MAS) and who did not (non-MAS). Among 35 MSAF-born neonates, 14 (40%) were non-vigorous, 18 (51%) required admission to neonatal intensive care unit, 8 (23%) developed MAS, 3 (9%) pulmonary hypertension and 1 (3%) air leak. On echocardiography, LPA-VTI (cm; mean ± SD) was significantly decreased at 24 and 48 h in MSAF-born neonates (14.38 ± 2.48; 15.55 ± 2.48), compared to healthy neonates (16.60 ± 2.14; 17.66 ± 2.71), respectively. Further, LPA-VTI was significantly reduced at 24 and 48 h among MAS (11.81 ± 3.0; 12.43 ± 2.5), compared to non-MAS neonates (15.15 ± 1.72; 16.48 ± 1.55), respectively. Other pulmonary vascular and myocardial function parameters were comparable between the two groups. Pulmonary adaptation was significantly delayed in neonates with MSAF, which was more pronounced in MAS neonates. Further studies should explore the utility of these parameters for early prediction of cardiorespiratory morbidities in this population.

Intrapartum amnioinfusion reduces meconium aspiration syndrome and improves neonatal outcomes in patients with meconium-stained fluid: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and other adverse neonatal and maternal outcomes. DATA SOURCES: From inception to November 2021, a systematic search of the literature was performed in PubMed, Embase, Web of Science, and Scopus databases and gray literature sources. STUDY ELIGIBILITY CRITERIA: We identified randomized controlled trials of patients with intrapartum moderate to thick meconium-stained amniotic fluid that evaluated the effect of amnioinfusion on adverse neonatal and maternal outcomes. METHODS: Of note, 2 reviewers independently abstracted data and gauged study quality by assigning a modified Jadad score. Meconium aspiration syndrome constituted the primary outcome. The secondary outcomes were meconium below the cords, Apgar scores of <7 at 5 minutes, neonatal acidosis, cesarean delivery, cesarean delivery for fetal heart rate abnormalities, neonatal intensive care unit admission, and postpartum endometritis. This study calculated the odds ratios with 95% confidence intervals for categorical outcomes and weighted mean differences with 95% confidence intervals for continuous outcomes. RESULTS: A total of 24 randomized studies with 5994 participants met the inclusion criteria. The overall odds of meconium aspiration syndrome was reduced by 67% in the amnioinfusion group (pooled odds ratio, 0.33; 95% confidence interval, 0.21-0.51). Except for postpartum endometritis, amnioinfusion was associated with a significant reduction in all secondary outcomes. CONCLUSION: Our study found that the use of intrapartum amnioinfusion in the setting of meconium-stained amniotic fluid significantly reduces the odds of meconium aspiration syndrome and other adverse neonatal outcomes.

Meconium-stained amniotic fluid.

Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.

[Clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for severe MAS in neonates with meconium-stained amniotic fluid]. / èƒŽç²ªæ±¡æŸ“ç¾Šæ°´æ–°ç”Ÿå„¿å‘ç”Ÿé‡åº¦èƒŽç²ªå¸å ¥ç»¼åˆå¾çš„ä¸´åºŠç‰¹å¾åŠé¢„è­¦å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF). METHODS: A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group (n=199), a mild/moderate MAS group (n=77), and a severe MAS group (n=19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF. RESULTS: Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score (P<0.05) and a significantly higher blood lactate level in the umbilical artery (P<0.05). Compared with the non-MAS group, the severe MAS group had a significantly higher level of interleukin-6 (IL-6) in peripheral blood at 1 hour after birth (P<0.017). In the severe MAS group, 79% (15/19) of the neonates were born inactive, among whom 13 underwent meconium suctioning, and 100% of the neonates started to receive mechanical ventilation within 24 hours. Peripheral blood IL-6 >39.02 pg/mL and white blood cell count (WBC) >30.345×109/L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF (P<0.05). CONCLUSIONS: Meconium suctioning cannot completely prevent the onset of severe MAS in neonates with MSAF. The neonates with severe MAS may develop severe respiratory distress and require mechanical ventilation early after birth. Close monitoring of blood lactate in the umbilical artery and peripheral blood IL-6 and WBC at 1 hour after birth may help with early prediction of the development and severity of MAS.

Time needed to intubate and suction a manikin prior to instituting positive pressure ventilation: a simulation trial.

Tracheal suctioning in non-vigorous newborn delivered through meconium-stained amniotic fluid (MSAF) is supposed to delay initiation of positive pressure ventilation (PPV), but the magnitude of such delay is unknown. To compare the time of PPV initiation when performing immediate laryngoscopy with intubation and suctioning vs. performing immediate PPV without intubation in a manikin model. Randomized controlled crossover (AB/BA) trial comparing PPV initiation with or without endotracheal suctioning in a manikin model of non-vigorous neonates born through MSAF. Participants were 20 neonatologists and 20 pediatric residents trained in advanced airway management. Timing of PPV initiation was longer with vs. without endotracheal suctioning in both pediatric residents (mean difference 13 s, 95% confidence interval 8 to 18 s; p < 0.0001) and neonatologists (mean difference 12 s, 95% confidence interval 8 to 16 s; p < 0.0001). The difference in timing of PPV initiation was similar between pediatric residents and neonatologists (mean difference - 1 s, 95% confidence interval - 7 to 6 s; p = 0.85).Conclusions: Performing immediate laryngoscopy with intubation and suctioning was associated with longer-but not clinically relevant-time of initiation of PPV compared with immediate PPV without intubation in a manikin model. While suggesting negligible delay in starting PPV, further studies in a clinical setting are warranted.Registration: clinicaltrial.gov NCT04076189. What is Known: • Management of the non-vigorous newborn delivered through meconium-stained amniotic fluid remains still controversial. • Tracheal suctioning in non-vigorous newborn delivered through meconium-stained amniotic fluid is supposed to delay initiation of positive pressure ventilation, but the magnitude of such delay is unknown. What is New: • Performing immediate ventilation without intubation was associated with shorter-but not clinically relevant-time of initiation of ventilation compared to immediate laryngoscopy with intubation and suctioning in a manikin model. • Further studies in a clinical setting are warranted.

The clinical effects of high-frequency oscillatory ventilation in the treatment of neonatal severe meconium aspiration syndrome complicated with severe acute respiratory distress syndrome.

OBJECTIVE: To explore the efficacy and safety of high-frequency oscillatory ventilation (HFOV) in the treatment of severe meconium aspiration syndrome (MAS) complicated with severe acute respiratory distress syndrome (ARDS). METHODS: A total of 65 infants with severe MAS complicated with severe ARDS were included in the study. The clinical efficacy of treatment for the HFOV group (n = 31) and the conventional mechanical ventilation (CMV) group (n = 34) was retrospectively analysed. The partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), PaO2/fraction of inspired oxygen (FiO2), and oxygen index values before and at 6, 12, 24, 48, and 72 h after mechanical ventilation, the mechanical ventilation time, oxygen inhalation time, incidence of complications, and outcomes of the two groups were compared. RESULTS: At 6, 12, 24, and 48 h after mechanical ventilation, the PaO2 in the HFOV group was significantly higher than in the CMV group, while the PaCO2 in the HFOV group was significantly lower than in the CMV group (P < 0.05). At 6, 12, 24, 48, and 72 h after mechanical ventilation, PaO2/FiO2 in the HFOV group was significantly higher than in the CMV group, and the OI in the HFOV group was significantly lower than in the CMV group (P < 0.05). Mechanical ventilation time, oxygen inhalation time, and the incidence of air leakage were significantly lower in the HFOV than in the CMV group (P < 0.05). CONCLUSIONS: Overall, HFOV can effectively improve lung ventilation and oxygenation function, shorten ventilator treatment time, and reduce the incidence rate of air leakage for neonatal MAS, making it a safe and effective treatment option.

Ultrasound-guided lung lavage for life-threatening bronchial obstruction due to meconium plug.

We present a case of life-threatening airway obstruction caused by meconium aspiration, a condition with significant neonatal mortality and morbidity. Lung ultrasound detected the obstruction and helped in the clinical management allowing to perform a quick and selective bronchoalveolar lavage with diluted surfactant.

The Effects of Different Types of Steroids on Clinical Outcomes in Neonates with Meconium Aspiration Syndrome: A Systematic Review, Meta-Analysis and GRADE Assessment.

Background and Objectives: Meconium aspiration syndrome (MAS) is a condition caused by the aspiration of meconium-stainted amniotic fluid into the lungs, resulting in pulmonary inflammation, neonatal morbidity, and mortality. It is important that these MAS infants receive appropriate care to avoid further complications. Steroids have an anti-inflammatory effect and may be effective in the management of MAS. The objective of the this study was to evaluate the effect of different steroids on clinical outcomes in infants with MAS. Materials and Methods: We systematically searched of PubMed/Medline, Scopus, Embase, Clinical Trials.gov, and Cochrane Library databases from inception to 24 January 2021 without language restriction. Only randomized controlled trials (RCTs) evaluating the effects of steroids in neonates with MAS were included. We calculated relative risks and weighted mean differences (MDs) with 95% confidence intervals (CIs) using a random-effects model to determine the associations between MAS and steroids and GRADE approach was employed for quality of evidence. The main outcomes measures were duration of respiratory distress, oxygen requirement, hospitalization, need for mechanical ventilation, death, and adverse drug reactions. Results: Seven RCTs involving 397 patients were analyzed. Nebulized budesonide and intravenous (IV) methylprednisolone shortened the duration of respiratory distress (MD, -2.46 days; 95% CI, -3.09 to -1.83 and MD, -3.30 days; 95% CI, -4.07 to -2.52, respectively) (moderate certainty). There was a reduction in duration of oxygen requirement in nebulized budesonide use (MD, -2.40 days; 95% CI, -3.40 to -1.40) (low certainty) and IV methylprednisolone use (MD, -3.30 days; 95% CI, -4.07 to -2.52) (moderate certainty). Nebulized budesonide shortened hospitalization stay (MD, -4.47 days; 95% CI, -8.64 to -0.30 days) (low certainty) as IV methylprednisolone use (MD, -7.23 days; 95% CI, -8.19 to -6.07 days) (moderate certainty). None of steroids benefits in death (low certainty). Conclusions: Certain types of steroids may benefit the respiratory aspect, but there was no decrease in mortality in MAS infants.

Postnatal causes and severity of persistent pulmonary Hypertension of Newborn.

BACKGROUND & OBJECTIVE: Persistent pulmonary hypertension of the newborn (PPHN) is described as severe respiratory failure along with hypoxaemia. PPHN is known to be linked with high morbidity and mortality around the world. This study was planned to determine the postnatal causes and assess the severity of persistent pulmonary hypertension of newborn in babies presenting to the Children's Hospital, Multan. METHODS: This observational study was conducted at the Department of Paediatric Cardiology, The Children Hospital &Institute of Child Health, Multan, Pakistan from July to December 2019. A total of 122 confirmed cases of PPHN admitted having gestational age above 34 weeks were enrolled. Demographic data of the newborns was recorded along with maternal medical history, pregnancy status and postnatal causes of PPHN. Severity of PPHN was also recorded. RESULTS: Out of a total of 122 cases of PPHN, 81 (66.3%) were male. Majority, 78 (64.0%) had gestational age above 37 weeks. Mode of delivery as cesarean section was noted in 70 (57.4%). Meconium aspiration syndrome 52 (42.6%), birth asphyxia 48 (39.3%), respiratory distress syndrome 23 (18.8%) and sepsis 33 (27.0%) were found to be the commonest causes of PPHN. Severe PPHN was found to be the most frequent, noted among 63 (51.6%) while Moderate PPHN was observed in 40 (32.8%) and Mild PPHN in 19 (15.6%). Morality was noted among 26 (21.3%) of cases. CONCLUSION: Meconium aspiration syndrome, birth asphyxia and respiratory distress syndrome were the commonest postnatal causes of PPHN. Severe PPHN was found to be the most frequent form of PPHN.

Clinical features and prognosis of severe meconium aspiration syndrome with acute respiratory distress syndrome. / é‡åº¦èƒŽç²ªå¸å ¥ç»¼åˆå¾å¹¶å‘æ€¥æ€§å‘¼å¸çª˜è¿«ç»¼åˆå¾ä¸´åºŠç‰¹å¾åŠè½¬å½’åˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of neonates with severe meconium aspiration syndrome (MAS) and acute respiratory distress syndrome (ARDS). METHODS: A retrospective analysis was performed on the medical data of 60 neonates with severe MAS who were admitted from January 2017 to December 2019. According to the presence or absence of ARDS, they were divided into two groups: ARDS (n=45) and non-ARDS (n=15). Clinical features and prognosis were compared between the two groups. RESULTS: Among the 60 neonates with severe MAS, 45 (75%) developed ARDS. Arterial blood gas analysis showed that the ARDS group had a significantly higher median oxygenation index within 1 hour after birth than the non-ARDS group (4.7 vs 2.1, P<0.05), while there was no significant difference between the two groups in white blood cell count, C-reactive protein (CRP), and interleukin-6 (IL-6) on admission and the peak values of procalcitonin, CRP, and IL-6 during hospitalization (P>0.05). The ARDS group had a significantly higher incidence rate of shock than the non-ARDS group (84% vs 47%, P<0.05). There was no significant difference between the two groups in the incidence rates of persistent pulmonary hypertension, pneumothorax, pulmonary hemorrhage, hypoxic-ischemic encephalopathy, intracranial hemorrhage, and disseminated intravascular coagulation (P>0.05). The ARDS group required a longer median duration of mechanical ventilation than the non-ARDS group (53 hours vs 3 hours, P<0.05). In the ARDS group, 43 neonates (96%) were cured and 2 neonates (4%) died. In the non-ARDS group, all 15 neonates (100%) were cured. CONCLUSIONS: Neonates with severe MAS and ARDS tend to develop respiratory distress earlier, require a longer duration of mechanical ventilation, and have a higher incidence rate of shock. During the management of children with severe MAS, it is recommended to closely monitor oxygenation index, give timely diagnosis and treatment of ARDS, evaluate tissue perfusion, and actively prevent and treat shock. Citation.

Surfactant Injury in the Early Phase of Severe Meconium Aspiration Syndrome.

No in vivo data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS (n = 14) or no lung disease (n = 18). Surfactant lipids were analyzed by liquid chromatography-high-resolution mass spectrometry. Secretory phospholipase A2 subtypes IB, V, and X and SP-A (surfactant protein A) were assayed by ELISA. SP-B and SP-C were analyzed by Western blotting under both nonreducing and reducing conditions. Surfactant function was assessed by adsorption test and captive bubble surfactometry, and lung aeration was evaluated by semiquantitative lung ultrasound. Surfactant nanostructure was studied using cryo-EM and atomic force microscopy. Several changes in phospholipid subclasses were detected during MAS. Lysophosphatidylcholine species released by phospholipase A2 hydrolysis were increased. SP-B and SP-C were significantly increased together with some shorter immature forms of SP-B. Surfactant function was impaired and correlated with poor lung aeration. Surfactant nanostructure was significantly damaged in terms of vesicle size, tridimensional complexity, and compactness. Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration and were due to hydrolysis and inflammation and a defensive response. This impairs both surfactant structure and function, finally resulting in reduced lung aeration. These findings support the development of new surfactant protection and antiinflammatory strategies for severe MAS.

Meconium aspiration syndrome: incidence, associated risk factors and outcome-evidence from a multicentric study in low-resource settings in Nepal.

AIM: The aim of this study was to identify the incidence, risk factors and outcome associated with meconium aspiration syndrome (MAS). METHODS: An observational study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. All babies born within the study period were included in the study. Babies who were diagnosed as MAS were designated as outcome. Data were analysed with bivariate analysis followed by multiple regression analysis. RESULTS: The overall incidence of MAS was 2.0 per 1000 livebirths. Babies born at post-term gestation (adjusted odds ratio (AOR) = 2.41; 95% confidence interval (CI): 1.05-5.55), nulliparity (AOR = 2.26; 95% CI: 1.20-4.28), instrumental delivery (AOR = 4.79; 95% CI: 2.52-9.10) and caesarean delivery (AOR = 3.67; 95% CI: 2.29-5.89) were significantly associated with MAS. Babies with MAS had a 10-fold risk for pre-discharge mortality (odds ratio = 9.87; 95% CI: 5.81-16.76). CONCLUSIONS: The findings in this study are consistent with that reported in other studies. MAS has a high risk of neonatal mortality. Thus, monitoring during pregnancy and labour is necessary for early identification of high-risk conditions associated with MAS. Strengthening of newborn care services is essential to curtail mortality.

Endotracheal suctioning for prevention of meconium aspiration syndrome: a randomized controlled trial.

The current version of Neonatal Resuscitation Program no longer favors routine endotracheal suctioning (ETS) in non-vigorous newborns with meconium-stained amniotic fluid (MSAF) due to possibility of procedure-related harms and questionable benefits. However, it calls for additional research on this procedure to provide a definitive answer. The present study was conducted to evaluate the role of ETS in non-vigorous neonates of ≥ 34 weeks' gestation born through MSAF on the incidence of meconium aspiration syndrome (MAS). In this open-label randomized controlled trial, 132 non-vigorous neonates with MSAF were randomized to receive ETS (n = 66) or no-ETS (n = 66) during delivery room resuscitation (DRR). Primary outcome variable was incidence of MAS. Secondary outcome variables were requirement of DRR, need of respiratory support, development of complications, duration of hospitalization, and mortality. Both the groups were comparable with respect to maternal and neonatal characteristics. Incidence of MAS was 21 (31.8%) and 15 (22.7%) cases in ETS and no-ETS groups, respectively (relative risk (RR), 1.400, 95% confidence interval (CI), 0.793-2.470). The two groups did not differ with regard to DRR, need for respiratory support, and development of complications. Nine (13.6%) neonates in ETS group, and 5 (7.5%) in no-ETS group died (p > 0.05). Median (interquartile range) duration of hospital stay was 54 (31-141) h and 44 (26-102) h in ETS and no-ETS groups, respectively (p > 0.05).Conclusions: Routine ETS at birth is not useful in preventing MAS in non-vigorous neonates of ≥ 34 weeks' gestation born through MSAF.Trial registration: Clinical Trials Registry of India (CTRI/2015/04/008819).What is Known:• Routine endotracheal suctioning is of questionable benefit in non-vigorous newborns with meconium stained amniotic fluid and may have a possibility of procedure-related harms.What is New:• Routine endotracheal suctioning at birth is not useful in preventing meconium aspiration syndrome in non-vigorous newborns of ≥ 34 weeks' gestation born through meconium stained amniotic fluid.

HandS ECMO: Preliminary Experience With "Hub and Spoke" Model in Neonates With Meconium Aspiration Syndrome.

We aim to evaluate clinical outcomes of emergent extracorporeal membrane oxygenation (ECMO) implantation in newborns with life-threatening meconium aspiration syndrome (MAS) in peripheral hospitals with Hub and Spoke (HandS) setting. We retrospectively reviewed all neonates presenting with MAS, with no other comorbidities, treated with HandS ECMO, in peripheral hospitals. Team activation time (TAT) was described as the time from first alerting call to ECMO support initiation. From May 2014 to December 2016, 4 patients met our inclusion criteria. In addition, 2 cases occurred on the same day, requiring a second simultaneous HandS ECMO team activation. All patients were younger than 8 days of life (1, 1, 4, and 7), with a mean BSA 0.21 ± 0.03m2 , and TAT of 203, 265, 320, and 340 min. One patient presented ventricular fibrillation after priming administration. Veno-arterial ECMO was established in all patients after uneventful surgical neck vessels cannulation (right carotid artery and jugular vein). Mean time from skin incision to ECMO initiation was 19 ± 1.4 min. Mean length of ECMO support was 2.75 ± 1.3 days. All patients were weaned off support without complications. At a mean follow up of 20.5 ± 7.8 months, all patients are alive, with no medications, normal somatic growth, and neuropsychological development. MAS is a life-threatening condition that can be successfully managed with ECMO support. A highly trained multidisciplinary HandS ECMO team is crucial for the successful management of these severely ill newborns in peripheral hospitals.

Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome.

BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. METHODS: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. RESULTS: Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). CONCLUSION: These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.

Surfactant Lung Lavage vs. Standard Care in the Treatment of Meconium Aspiration Syndrome-A Randomized Trial.

OBJECTIVE: The objective of this study was to evaluate the effect of surfactant lung lavage (SLL) on duration of respiratory support in neonates with meconium aspiration syndrome (MAS). PATIENTS AND METHODS: Sixty term infants with MAS who had moderate to severe respiratory distress (Downes score >4) were randomized toSLL (n = 31) or no lung lavage-NLL (n = 29). Neonates in intervention group underwent lung lavage with dilute surfactant and those in control group were managed as per unit protocol. RESULTS: The median duration of respiratory support was 34 h in SLL group and 44 h in NLL group (p value = 0.994). The duration of oxygen therapy post-respiratory support decreased by 78% in SLL as compared with NLL group (4 vs. 18 h) (p value = 0.005). Lavage procedure was well tolerated with fall in mean heart rate by just 20/min and in mean saturation drop by just 6% during the procedure. CONCLUSION: Lung lavage is well tolerated by neonates, but it does not alter overall duration of respiratory support.

Meconium aspiration syndrome requiring ECMO in newborns with gastroschisis: incidence and surgical outcomes.

AIM OF THE STUDY: To evaluate the incidence of respiratory failure requiring ECMO in newborns with gastroschisis (GC), compare it to the incidence in the general population, review the surgical outcomes of newborns with GC requiring ECMO and compare them to newborns with GC not requiring ECMO. METHODS: This is a retrospective review of all neonatal admissions for GC from December 2010 to September 2015. MAIN RESULTS: 110 newborns with GC were admitted to our NICU between 12/2010 and 9/2015; 36 were term. Four cases, all term, all prenatally diagnosed, all outborn, developed respiratory failure requiring ECMO secondary to meconium aspiration syndrome (MAS). This 11% (4/36 term GC) represents a 300-fold increase in the incidence of MAS-associated respiratory failure requiring ECMO compared to the general population of term newborns (0.037%). Median time on ECMO was 12 (9-20) days. The time to achieve full enteral feedings in the GC/ECMO group was twice the time of the 106 newborns in the GC/non-ECMO group [median: 70 (48-77) vs. 35 (16-270) days, respectively]. Time to hospital discharge was three times longer in the GC/ECMO group compared to the GC/non-ECMO group (median: 42 [20-282] versus 125 [69-223] days, respectively). All patients survived. CONCLUSION: The incidence of respiratory failure requiring ECMO is remarkably higher in patients with GC than in the general population and much higher in the subgroup of term GC. While infrequent, the possibility of this event supports the concept that fetuses with GC benefit from being delivered at tertiary centers with immediate pediatric surgery and ECMO capabilities.

Recombinant Human Superoxide Dismutase and N-Acetylcysteine Addition to Exogenous Surfactant in the Treatment of Meconium Aspiration Syndrome.

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits were instilled with meconium suspension (Mec) and treated by surfactant alone (Surf) or surfactant in combination with i.v. NAC (Surf + NAC) or i.t. rhSOD (Surf + SOD), and oxygen-ventilated for 5 h. Dynamic lung-thorax compliance, mean airway pressure, PaO2/FiO2 and ventilation efficiency index were evaluated every hour; post mortem, inflammatory and oxidative markers (advanced oxidation protein products, total antioxidant capacity, hydroxynonenal (HNE), p38 mitogen activated protein kinase, caspase 3, thromboxane, endothelin-1 and secretory phospholipase A2) were assessed in pulmonary tissue homogenates. rhSOD addition to surfactant improved significantly, but transiently, gas exchange and reduced levels of inflammatory and oxidative molecules with higher impact; Surf + NAC had stronger effect only on HNE formation, and duration of treatment efficacy in respiratory parameters. In both antioxidants, it seems that targeting reactive oxygen species may be strong supporting factor in surfactant treatment of MAS due to redox sensitivity of many intracellular pathways triggered by meconium.

Is Extracorporeal Membrane Oxygenation for a Neonate Ever Ethically Obligatory?

Certain interventions in the neonatal intensive care unit are considered ethically obligatory, and should be provided over parental objections. After reviewing a case, comparative outcome data, and relevant ethical principles, we propose that extracorporeal membrane oxygenation for meconium aspiration syndrome may, in some cases, be an ethically obligatory treatment.

Anti-IL-8 antibody potentiates the effect of exogenous surfactant in respiratory failure caused by meconium aspiration.

AIM: Meconium aspiration syndrome (MAS) is life-threatening respiratory failure of newborns which can be treated by exogenous surfactant. In response to meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil infiltration of the lungs. Local accumulation and activation of neutrophils, on-going inflammation, lung edema, and oxidative damage contribute to inactivation of endogenous and therapeutically given surfactants. Therefore, we have hypothesized that addition of monoclonal anti-IL-8 antibody into exogenous surfactant can mitigate the neutrophil-induced local injury and the secondary surfactant inactivation and may finally result in improvement of respiratory functions. METHODS: New Zealand rabbits with intratracheal meconium-induced respiratory failure (meconium 25 mg/ml, 4 ml/kg) were divided into three groups: untreated (M), surfactant-treated (M + S), and treated with combination of surfactant and anti-IL-8 antibody (M + S + anti-IL-8). Surfactant therapy consisted of two lung lavages with diluted porcine surfactant Curosurf (10 ml/kg, 5 mg phospholipids (PL)/ml) followed by undiluted Curosurf (100 mg PL/kg) delivered by means of asymmetric high-frequency jet ventilation (f. 300/min, Ti 20%). In M + S + anti-IL-8 group, anti-IL-8 antibody (100 µg/kg) was added directly to Curosurf dose. Animals were oxygen-ventilated for additional 5 h, respiratory parameters were measured regularly. Subsequently, cell counts in bronchoalveolar lavage fluid (BAL), lung edema formation, oxidative damage, levels of interleukins (IL)-1ß and IL-6 in the lung homogenate were evaluated. RESULTS: Surfactant instillation significantly improved lung function. Addition of anti-IL-8 to surfactant further improved gas exchange and ventilation efficiency and had longer-lasting effect than surfactant-only therapy. Combined treatment showed the trend to reduce neutrophil count in BAL fluid, local oxidative damage, and levels of IL-1ß and IL-6 more effectively than surfactant-alone, however, these differences were not significant. CONCLUSION: Addition of anti-IL-8 antibody to surfactant could potentiate the efficacy of Curosurf on the gas exchange in experimental model of MAS.