The most important consequence for a neonate born through meconium stained liquor (MSL) is Meconium aspiration syndrome (MAS), that occurs in 1-3% of live births [1,2]. It is an important cause of neonatal morbidity and mortality in otherwise healthy term and post-term infants, with a case fatality rate approaching 40% [3]. Only a few studies from developing countries have looked at the clinical profile of MAS, associated morbidities and predictors of mortality [4-6]. In this study, we aimed to evaluate the morbidity profile of neonates with MAS, and identify the risk factors that predict mortality during hospital stay in such neonates.

Babies born through MSL were managed as per NRP guidelines as modified from time to time [7]. Pediatric residents/neonatology trainees attended all deliveries with MSL and performed endotracheal suction if indicated. Babies who had significant respiratory distress were started on non-invasive ventilation, Continuous Positive Airway Pressue (CPAP) or Non-invasive Mechanical Ventilation (NIMV), and mechanically ventilated whenever indicated. Inhaled nitric oxide was available only in the later part of the study period. Case records of the patients were retrieved. Ante-partum and intra-partum risk factors were recorded. Chorio-amnionitis was defined as intra-partum maternal fever of ≥37.80C with at least two of the four: fetal tachycardia (>180/min), uterine tenderness, maternal leucocyte count >15,000/mm3 and foul smelling vaginal discharge. Risk factors were compared among survivors and those who died.

For the purpose of the study, Persistent pulmonary hypertension of newborn (PPHN) was defined on the basis of labile oxygen saturation, a pre-and post-ductal oxygen saturation difference of >10% or pre-and postductal partial pressure of arterial oxygen (PaO₂) difference of >20 mmHg with or without the presence of echocardiographic evidence of PPHN. Diagnosis of PPHN on echocardiogram was based on the peak velocity of a tricuspid regurgitant jet with a peak pulmonary pressure gradient of >20 mmHg [8,9]. Hypotensive shock was defined as presence of low pulse volume, tachycardia, skin mottling and a capillary refill time >3 seconds along with a systolic blood pressure (BP) and/or a diastolic BP <5th centile [10]. A diagnosis of hypoxic ischemic encephalopathy (HIE) was made based on Sarnat and Sarnat staging in babies ≥36 weeks of gestation and Levene’s staging in babies <36 weeks [11,12]. Myocardial dysfunction was diagnosed on the basis of edema, third space fluid collection, hepatomegaly, S3 gallop or cardiogenic shock, manifesting with capillary filling time (CFT) >3 seconds or low BP along with elevated Creatinine Phosphokinase – Muscle Brain (CPK-MB >75 IU/L). Renal dysfunction was defined as an elevated blood urea (>60 mg/dL) or serum creatinine (>1 mg/dL) in the presence of normal maternal renal function.

TABLE I Comparison of Risk Factors Between Neonates Who Died vs. Survivors

Risk factors of mortality are presented in Table I. Of the 18 putative risk factors that emerged significant in univariate analysis, 5 factors namely birth weight (in grams unit), Apgar score at 5 minute (in a scale of 1 to 10), initial oxygen requirement (FiO2 in % unit), and need for mechanical ventilation, and myocardial dysfunction were entered into the regression model. Myocardial dysfunction was chosen over presence of shock as both these variables had a high degree of correlation between them on a correlation matrix and based on a biological assumption that myocardial dysfunction would have preceded shock. The prediction model identified that presence of myocardial dysfunction and a higher initial oxygen requirement increased the odds of death whereas a higher birth weight reduced the odds of death in these neonates with every 1% increase in initial O2 requirement increasing the odds of death by 4.4% in comparison to baseline. We also observed that for every 100 grams increase in birth weight, the odds of death decreased by 20% from the baseline risk (Table II). This model as a whole had a sensitivity of 78%, specificity of 94%, positive predictive value of 83%, negative predictive value of 93%, a positive likelihood ratio of 13 and a negative likelihood ratio of 0.2. The concordance statistic (c-statistic) of the model was 0.95 (95% CI 91.6-98.9; P<0.001).

TABLE II Multivariate Logistic Regression Model for Predicting Death in Neonates With Meconium Aspiration Syndrome

In this study on 170 neonates who developed MAS, one-fourth died. About half of the neonates had HIE whereas a significant number of neonates developed complications. Presence of myocardial dysfunction and a higher initial oxygen requirement independently increased the odds of mortality.

Previous studies have shown a wide range (5-40%) in the mortality among infants with MAS with recent studies showing lower (<15%) mortality rate [13-15]. A higher mortality rate observed in the current study could be related to higher proportion of small for gestational age (SGA) neonates. An association between intra-uterine growth retardation (IUGR) and MAS has been described earlier [5]. The emergence of myocardial dysfunction as an independent risk factor for death indicates the major role of cardiovascular instability in modifying the outcome in such neonates. This also emphasizes the need for aggressive and close cardiovascular monitoring and early vascular support in such neonates. Previous studies have observed PPHN, pneumothorax, birth asphyxia, need for respiratory support in the first 48 hours of life and the need for vasopressor support as independent predictors of mortality [5,15,16].

Our study has few limitations. First, PPHN and myocardial dysfunction were diagnosed primarily on the basis of clinical presentation, and were not always confirmed by echocardiography. Second, MAS associated mortality (cause-specific) could not be separated out of all-cause mortality due to the presence of various co-morbidities, especially HIE.

To conclude, MAS is associated with significant mortality during the hospital stay. Myocardial dysfunction and a higher initial oxygen requirement increased the odds of death whereas a higher birth weight decreases the odds of death.