Frequency and Outcome of Meconium Aspiration Syndrome in Babies Born with Meconium-Stained Liquor at Secondary Care Hospital in Pakistan: A Case Series Study

Background: Meconium aspiration syndrome (MAS) in the newborn is characterized by hypoxia, hypercapnia, and acidosis. MAS is a leading cause of morbidity and mortality in neonates. The primary objective of this study was to estimate the frequency of meconium aspiration syndrome (MAP) in babies born with meconium-stained liquor. The secondary outcome was to estimate the meconium aspiration syndrome; in terms of hospital stay, complications, and mortality. Methods: The study was done at Aga Khan Maternal and Child Care Centre, Hyderabad, Pakistan. Study design was case series and the duration of the study was of 6 months. All patients who fulfilled the inclusion criteria were included in the study after taking informed written consent. A brief history was taken, clinical examination was done and laboratory investigations were sent to the institutional laboratory. Study outcomes were measured from this data i.e. MAS, its complications, mortality, and a number of days in the hospital. Results: A total of 87 babies born with meconiumstained liquor at secondary care hospital were included. A total of 45 patients (52%) were males and 42 patients (48%) were females with a mean gestational age of babies 38.896 ± 1.210 weeks. The mean Apgar score at 5 minutes was 8.896 ± 0.404. MAS was present in 13 patients (14.9%). Complications were seen only one patient (1.1%) and there was no neonatal death reported. Discussion: MAS was present in 14.9% of babies; the complication of subacute bacterial infection was low seen in just 1.1% cases with no neonatal mortality.


Introduction
Meconium aspiration syndrome (MAS) is defined as respiratory distress in newborn born through meconium-stained amniotic fluid whose symptoms cannot be otherwise explained [1]. Meconium is the dark green, sterile fecal material that is produced in the intestine before birth. Normally, meconium is expelled only after birth when newborns started to feed. However, in response to stress, such as an inadequate level of oxygen in the blood, the fetus may pass meconium into the amniotic fluid [2]. Either in utero or with the first breath, thick, particulate meconium is aspirated into the lungs. The resulting small airway obstruction may produce respiratory distress within first hours, with tachypnea, retractions, grunting, and cyanosis [3].
MAS in the newborn is characterized by hypoxia, hypercapnia, and acidosis.
Although the pathophysiology of this syndrome is not completely understood, recent advances in management and respiratory care have decreased the mortality rate substantially. Perinatal hypoxia, airway obstruction shortly after birth, and significant pulmonary vasoconstriction and hypertension are the three major causes of mortality and morbidity [4].
Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants [5]. Meconium-stained amniotic fluid is found in 10% -15% of births and usually occurs in term and post-term infants [3]. International data found the incidence of meconium aspiration syndrome (MAS) to be 4.3%. Pneumothorax remains an important complication of MAS, occurring in 9.6% of MAS and the median number of days stayed in the hospital was 13 days in an international study [6]. Death directly related to meconium aspiration syndrome was reported to be 2.5% [6].
According to a local study, in the urban Pakistani population, the frequency of meconium aspiration syndrome in meconium stained liquor was observed to be 17.4% [7], which is significantly higher than the developed countries. The neonatal mortality from MAS is also very high, reported in Pakistan study as 14% [7]. One study recorded it as high as 32% [8].
As risk factors of meconium aspiration vary in different settings, so this study will help us in finding out the frequency of MAS in our local population of Hyderabad which is the fifth largest city of Pakistan as per population and the data in secondary care facilities is lacking. Furthermore, this study will also enable us to find out the outcome of meconium aspiration syndrome, in terms of hospital stay, complications, and mortality. Results of the outcome will enable us to anticipate the need for referral of meconium aspiration syndrome patients to tertiary care hospital.

Case Series
Setting:

Duration of Study
The duration of the study was 6 months starting from 22 nd April 2018 to 22 nd Oct. 2018.

Sample Size
The sample size was 87 and was calculated using the WHO calculator taking the margin of error as 8%, confidence interval as 95%, and taking frequency of meconium aspiration syndrome as 17.4% [7].

Sampling Technique
Non-probability consecutive sampling.

Inclusion Criteria
All term and post-term neonates (i.e. gestational age equal to or greater than 37 weeks) born with meconium-stained liquor.

Exclusion Criteria
• Preterm having less than 37 weeks gestation; as per estimation from last normal menstrual period. • Multi-fetal gestations as per ultrasound finding.
• Fetuses with major anomalies (e.g. neural tube defects & cardiac anomalies) detected on ultrasound were excluded from our study.

Data Collection Procedure
Data collection was started after approval of synopsis from The College of Physicians and Surgeons, Pakistan. The Ethical Review Committee of Aga Khan University Hospital, Karachi approved this study. All neonates born to mother with meconium-stained liquor at the secondary center of Aga Khan University Hospital in Hyderabad were enrolled in the study as per inclusion and exclusion criteria; and after taking informed consent. All the data was recorded on a structured proforma filled through history, examination, Chest X-ray for diagnosis of meconium aspiration syndrome, and its complications i.e. pneumothorax. For confidentiality, all study participants were allotted a unique ID (other than hospital registration number) for study enrolment. Principle investigator himself designed the proforma (See Annex A) and collected the data.

Data Analysis
All the collected data were entered and analyzed in SPSS software version 22.0.
Frequency and percentages were computed for categorical variables like gender, mode of delivery, booking status, meconium-stained liquor grading, complica-Open Journal of Pediatrics tions, and mortality. The mean standard deviation was calculated for gestational age, the weight of the child, Apgar score, and hospital stay. Data was stratified for confounding and effect modifiers' gender, gestational age, the weight of the child, mode of delivery, booking status, need for resuscitation at birth, and Apgar score on the outcome. The post-stratification chi-square test was applied by taking a p-value < 0.05 as significant.

Results
A total of 87 babies born with meconium-stained liquor at secondary care hospital were selected for this study. The mean gestational age of babies was 38.896  Table 1. A total of  The distribution of the number of days in the hospital is presented in Figure   2.
A total of 67 (77%) children were booked i.e. visit clinics through a prior appointment and 65 (75%) children had meconium-stained liquor grading classified as thin. Apgar score was more than 6 in 86(99%) of children (Table 2).

Discussion
Meconium aspiration syndrome continues to be a challenge for the neonatologists despite the fact that MAS has decreased in incidence, particularly in developed countries. The mortality attributed to MAS has decreased from 28 per 100,000 live births to 0.96 per 100,000 live births [6] [9]. It equates to 2.5% of the MAS cohort. This decline in developed countries has come about through an improvement in antenatal care i.e. avoidance of post-maturity [10] and aggressive management of fetal distress coupled with the use of advanced modalities such as surfactant [11], high-frequency ventilation [6] [9], inhaled nitric oxide [12], and extracorporeal membrane oxygenation [13] [14].
The presence of meconium liquor is a serious sign of fetal compromise, which is associated with an increase in perinatal morbidity [15], clear amniotic fluid, on the other hand, is considered reassuring. In earlier days, early amniotomy with active management of labor was done to detect meconium passed during labor. Amniotomy in labor is also commonly performed to detect meconium where fetal heart rate is unsatisfactory [16]. If meconium-stained amniotic fluid (MSAF) is found, then continuous fetal heart rate monitoring is required for fetal wellbeing. The exact etiology of MSAF remains unclear [17] [18]. Aspiration of meconium during intrauterine life may result in or contribute to meconium aspiration syndrome (MAS), representing a leading cause of perinatal death [19].
Prolonged labor is also a risk factor for the passage of meconium as proved by Saunder et al. [20] who showed that prolonged labor is associated with the worst outcome in the MSAF group. As meconium should always be considered a marker for fetal distress therefore there was a significant effect on the APGAR score of neonates [7].
In our study, the mean APGAR score of neonates was 8.896 ± 0.404 as compared to Rasheed et al. [7] study which showed the mean APGAR score of 6.7 ± 2.3 in neonates, this is also comparable with the study of Shaikh et al. [21], where they reported APGAR score as 6.0 ± 0.9.
In Rasheed et al. study [7], 57 (38.3%) of neonates were admitted to NICU. However, Scott et al. [22], reported a higher incidence as compared to Rasheed et al study of neonatal admissions to NICU [7].
In this study, the MAS was present in 13 patients (14.9%), as compared to Rasheed et al. [7] study which showed Meconium aspiration syndrome in 26 neonates (17.4%). Sood et al. [23] also showed a higher incidence of MAS as in 13% in our study. Patil et al. [24] had reported 12.8% of MAS. It might be due to the fact that MAS was primarily associated with acute hypoxia events late in labor or often a chronic prenatal disease related to acute events that occur late in labor or after birth and also depends on increasing consistency of meconium.
In our study, there was no mortality seen in babies with MAS in contrast to Gupta et al. [25] that found 4.9% mortality in meconium-stained amniotic fluid group compared to 2.8% in control. Khatun [26] found 2.9% mortality in neonates. Rasheed et al. [7] study showed 14.1% mortality which is very high as compared to other studies.
In our study, the no pneumothorax was seen as compared to Anwar et al. [8] study, the prevalence of pneumothorax has been documented as 25% in 2001 and 9.6% in 2009 [8]; In the same study, pneumothorax contributed to 43% of MAS related mortality while pneumothorax resulted in death in 54.5% of these cases [8]. It is not surprising considering the fact that 84% of the babies were manually bagged for variable periods of time and only half of these (41%) could be started on mechanical ventilation.
In our study, the complications of sub-acute bacterial infection were seen in one patient (1.1%) as compared to Anwar et al. [8] study. The infection was another important complication especially associated with a longer stay in the unit. Sepsis was strongly suspected or proven in 48% of the expired babies who had stayed beyond 3 days in the hospital despite the fact that antibiotics had started in all admitted babies. High contribution to mortality by sepsis is well documented in developing countries owing to multiple contributing factors such as cross-infection, overcrowding, and staff related negligence [6] [27].
In our study, the mean number of days in the hospital were 2.862 ± 1.122 days as compared to Anwar et al. [8] study where the mean duration of stay in the hospital reported in the literature has been quite varied and has changed over time, although it has been reported to be getting longer (mean of 13 days). The majority (around 70%) of the babies stayed for a week in the hospital and the stay of less than a day was associated with the highest mortality. The likely reason being that in a developed country setup, babies could have survived but due The limitation of this study is that it was a hospital-based study, so we cannot extrapolate these findings to the general population. More studies, both hospital, and population-based are needed to determine the impact of meconium aspiration on neonatal morbidity and mortality.

Conclusion
Meconium Aspiration Syndrome was present in 14.9% babies, the complication of subacute bacterial infection was low seen in just 1.15% case and no neonatal mortality was reported.

Ethics Approval and Consent to Participate
Aga Khan University Hospital ethical review committee approved the study in 2018 with ERC number 5249-Ped-ERC-18.

Funding
The study was self-funded by Dr. Abdul Moeed.

Authors' Contributions
AM, SA, and HL contributed to drafting the article. AM and SU collected the data from the hospital. AM and HL managed and analyzed data. KH and KA designed and supervised the study. All authors approved the final version of the article for submission. Open Journal of Pediatrics