Internal Medicine: Open Access

Internal Medicine: Open Access
Open Access

ISSN: 2165-8048

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Research Article - (2018) Volume 8, Issue 1

Pregnancy Outcomes Associated with Chronic Indoor Air PollutionRelated Maternal Respiratory III Health in Ndola and Masaiti, Zambia

Mulenga D*, Nyirenda HT, Chileshe-Chibangula M, Mwila P and Siziya S
Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia
*Corresponding Author: Mulenga D, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia, Tel: +260973104128 Email:

Abstract

Introduction: Adverse pregnancy outcomes have been associated with impaired lung function and increased respiratory symptoms among women using biomass for cooking/heating houses. We investigated the association between maternal respiratory health and pregnancy outcomes among pregnant women predominantly using biomass for cooking/heating in Masaiti and Ndola, Zambia.
Methods: A cross-sectional study involved collection of information from 1,170 consenting pregnant women using a standard questionnaire and Spirometry conducted simultaneously. Data was analyzed using Stata Version 13 and association between maternal respiratory health and birth outcomes determined after adjusting for potential confounders using multivariate logistic regression analysis.
Results: The mean differences of lung function were statistically significant between mothers of LBW and those of normal weight; FEV1/FVC (p value 0.023) and FVC (p value 0.0176). The mean differences were statistically significant between mothers of SGA babies and those of normal; FEV1/FVC (p value < 0.0001) and FEV1 (p value 0.0134). There was a statistically significant association between FEV1/FVC and preterm in the urban (p value<0.0001) and small for gestational age (p value<0.0001) in the rural area for all the three trimesters. In the urban area, LBW was statistically associated with recurrent nasal symptoms OR [1.69 (95% C.I; 1.0-2.8)] and prolonged secretion of phlegm OR [0.58 (95% C.I; 0.3-1.0)]. In the multivariate analysis, there was a significant association between FVC and LBW in the rural area OR [0.09 (99% C.I; 0.0-0.4)]. Preterm delivery was statistically significantly associated with FVC OR [0.39 (99% C.I; 0.2-0.8)] in the entire study population.
Conclusion: Our results demonstrated substantial increased risk of several adverse pregnancy outcomes for pregnant women with poor respiratory health. These findings suggest the need for cleaner fuels for cooking and better ventilated cooking environment for the poor women who are the main victims in this health hazard. The respiratory health of pregnant women needs to be constantly monitored using Spirometry.

Keywords: Biomass; Spirometry; Respiratory symptoms; Low birth weight; Preterm; Small for gestational age

Introduction

Chronic exposure to emissions from solid fuels such as wood, charcoal, crop residues and cow dung is a significant cause of ill health conditions such as chronic obstructive lung diseases (chronic bronchitis and asthma), lung cancer, acute respiratory infections (ARI) in children and pregnancy-related outcomes [1]. In sub-Saharan Africa and many other low income countries where the main energy source for cooking/heating houses is biomass, women are chronically exposed to emissions which contain a lot of pollutants harmful to their health. Many other studies in developing countries have demonstrated a number of health effects linked to household biomass combustion and these include chronic obstructive pulmonary disease (COPD), asthma, respiratory infection, heart diseases, pulmonary diseases, cataract and adverse pregnancy outcomes [2,3]. In all these health burdens, women and children carry the heaviest burden compared to men; they are more susceptible to these health problems from household air pollutants because they spend longer times in the home environment [4,5]. A large body of evidence exists of biomass fuel being a significant contributor to increased respiratory symptoms and impaired lung functions [4,5].

Many studies have explored the relationship between pregnancy outcomes and exposure to air pollution due to indoor biomass combustion [6], second hand smoking [7] or smoking in pregnancy [8] but very few have tried to relate maternal respiratory symptoms and lung function to pregnancy outcomes. It is clear now that combustion products of unprocessed biomass fuels used by the poor urban and rural people for cooking and heating the house are the most important causes of indoor air pollution in developing countries. Indoor biomass fuel smoke has been shown to adversely affect the host defense against the respiratory infections and causes inflammation of airways and alveoli and it is thus plausible that it increases the incidence of respiratory ill health among the exposed [9,10]. Since air pollution has been associated to a number of adverse pregnancy-related outcomes, and then maternal respiratory health, influenced by indoor air pollution should have an influence on pregnancy-related outcomes. However, there has been a paucity of epidemiologic evidence regarding the relationship between maternal respiratory health and pregnancyrelated outcomes. Although there is a lack of evidence investigating how maternal respiratory health is associated with adverse pregnancy outcomes, it appears that respiratory health of the woman is linked to the pregnancy outcome through the impact of chronic indoor air pollution exposure, a situation that is common in many developing.

Other available associations of maternal respiratory health and lung functions are those that demonstrate that adverse environment in utero may affect fetal growth and have lasting effects on lung function in adulthood and old age [11]. For instance, previous studies indicate that low birth weight predicts lower lung function later in adult life after adjusting for maternal and adult factors [12]. However, this is not the focus for our study; the focus for our study is to relate maternal respiratory health with selected birth outcomes such as low birth weight, preterm birth and small for gestational age and available research has shown that poor maternal respiratory health is associated with intrauterine factors that affect fetal growth [13]. Studies elsewhere have also shown that suboptimal lung function in pregnancy is associated with adverse birth outcome [14]. The study of the relationship between asthma during pregnancy and selected infant and maternal outcomes, after significant confounding variables are adjusted for, gives important information regarding the association between respiratory ill health during pregnancy and several adverse infant outcomes, including preterm birth, small for gestational age and maternal outcomes like idiopathic preterm labor [15]. In addition this, several other studies previously have evaluated the association between birth weight and lung function with some, [11,16] though not all obtaining positive association. Therefore, this study aims at investigating the relationship between maternal respiratory ill health and pregnancy-related outcomes.

Materials and Methods

Questionnaire

A structured questionnaire was used to obtain information on background characteristics and symptoms of respiratory conditions.

Spirometry

Lung function was determined using a spirometer, MIR Spirobank-G (Italy) with an attached printout of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC% ratio.

For each assessment a research nurse demonstrated the technique to the participant. The participants then performed some practice efforts. They were then required to perform a minimum of three reproducible FVC measures (within 5% of maximum FVC produced). The output that produced the highest sum of FVC and FEV1 were used in the analyses. Women who could not perform three reproducible measures or who were unable to attempt the lung function assessment were excluded. All assessments were carried out by one of nine research nurses who were trained to carry out the assessment in a similar manner.

Pregnancy outcomes

Pregnancy outcomes were recorded by the research nurse and the main outcomes of interest in the study were low birth weight (LBW), preterm birth (PTB) and small for gestational age (SGA). Neonatal length, weight and gestation age on delivery was recorded by the study nurse immediately after birth. General maternal health status, sex of the neonate and birth order was recorded together with any other birth outcomes such as stillbirth and congenital abnormalities.

Data processing and analysis

Lung function parameters of interest were categorized as follows: FEV1/FVC%: > 70 is Normal, FEV1% and FVC%: >80 is Normal. In the logistic regression, categories mild to severe were classified as impaired lung function. Preliminary analysis involving bivariate analysis was conducted in Epi Info. The independent predictors of outcome were obtained using the stepwise logistic regression in SPSS. Magnitudes of association were estimated using odds ratios and their 95% confidence intervals. Statistical significance was set at 5%. Ethical Consideration: The project was approved by the tropical Diseases Research Centre (TDRC) Ethics Committee. Further approval was obtained from the Zambia Health Research Authority of the Ministry of Zambia.

Results

Background characteristics

Out of a total of 1,210 pregnant women recruited from the nine antenatal clinics (ANC), forty (3.3%) households were excluded from the analysis due to incompleteness of data and failure to perform three reproducible Spirometry measures or who were unable to attempt the lung function assessment, leaving a total of 1,170 participants for analysis. Majority (80%) of the participants enrolled in the study were 35 years and below. Close to three thirds (91.2%) of the participants were married and over half (54.6%) had attained secondary and a third (30.0%) primary education.

Above two thirds of the participants (69.6%) were unemployed housewives. Over a quarter participants (87.8%) were taking nutritional supplements (ferrous sulphate and folic acid) and about the same proportion (84.6%) were under malaria chemo prophylaxis-Fansida. Close to one fifth (19.7%) of participants took alcohol and only 3.1% cigarette smoking in pregnancy. Hypertension was reported in 3.7% and diabetes in 1.8%.

Respiratory symptoms of the pregnant women in the study population

The summary of the maternal respiratory symptoms in the study population has been shown in Table 1. Majority (71.5%)of the pregnant women reported prolonged cough, while not having flu, during the last 12 months and close to half (45.9%) of them had recurrent secretion of phlegm from lungs during the last 12 months. Close to one third (30.4%) of the pregnant women reported wheezing during the last 12 months (wheezing caused by bronchi, not nose) while 16.3% of the pregnant women presented with uncomfortable feeling of breathlessness (tight chest and complicated breathing), during the last 12 months.

  Rural % 95% CI Urban % 95% CI Total % 95% CI Population
Estimates
Cough 20.6 [17.3-24.3] 31.1 [27.8-34.6] 28.5 [25.9-31.3] 6,850
Sputum 48 [43.8-52.3] 45.3 [41.7-49.0] 45.9 [43.0-48.9] 11,037
Wheezing 33.7 [29.8-37.8] 29.3 [26.1-32.8] 30.4 [27.7-33.2] 7,296
Breathlessness 17.3 [14.3-20.8] 16 [13.5-18.8] 16.3 [14.2-18.6] 3,910
Nasal Symptoms 40.7 [36.6-45.0] 47.2 [43.5-50.8] 45.6 [42.7-48.6] 10,956
Throat Symptoms 36.9 [32.8-41.1] 31.6 [28.3-35.1] 32.9 [30.2-35.7] 7,901

Table 1: Showing proportions of maternal respiratory symptoms according to region.

Prolonged nasal symptoms when not having flu during the last 12 months were reported by 45.6% of the pregnant women and about one third (32.9%) presented throat symptoms when not having a flu during the last 12 months.

Lung function test results of the pregnant women in the study population

Almost all the pregnant women (99.3%) had an FEV1/FVC higher than 70% and close to two thirds (60.5%) of pregnant women had a normal FEV1 while more than one third (38.4%) recorded mild obstruction. Normal FVC was obtained in 35.6% of pregnant women while mild reduction and moderate reduction was recorded in 37.4% and 26.9% of pregnant women respectively. Only a very small proportion (0.4%) of the population presented with COPD (Table 2).

  Rural % 95% CI Urban % 95% CI Total % 95% CI Population
Estimates
FEV1/FVC  
<70 0.4 [0.1-1.6] 0.7 [0.3-1.7] 0.7 [0.3-1.4] 156
70 0.2 [0.0-1.4] 0   0.1 [0.0-0.3] 12
>70 99.4 [98.2-99.8] 99.3 [98.3-99.7] 99.3 [98.6-99.7] 23,852
FEV1  
Moderate Obstruction 0   1.5 [0.8-2.6] 1.1 [0.6-2.0] 264
Mild Obstruction 34.1 [30.2-38.3] 39.8 [36.2-43.4] 38.4 [35.5-41.3] 9,221
Normal 65.9 [61.7-69.8] 58.8 [55.1-62.3] 60.5 [57.6-63.4] 14,535
FVC  
Moderate Reduction 28.1 [24.4-32.1] 26.6 [23.4-29.9] 26.9 [24.4-29.6] 6,468
Mild Reduction 34.7 [30.8-38.9] 38.3 [34.8-41.9] 37.4 [34.6-40.4] 8,994
Normal 37.2 [33.2-41.4] 35.1 [31.7-38.7] 35.6 [32.8-38.5] 8,559

Table 2: Showing proportions of lung function of participants according to region.

Pregnancy outcomes in the study population according to region (Table 3)

Birth outcomes Rural (%) 95% CI Urban (%) 95% CI Total (%) 95% CI
Low birth weight 43.5 [39.3-47.7] 18.9 [16.2-21.9] 24.8 [22.5-27.3]
Preterm 7.9 [5.9-10.6] 5.2 [3.8-7.1] 5.9 [4.7-7.4]
Small for Gestational Age 55.1 [50.8-59.3] 21.3 [18.5-24.5] 29.5 [27.1-32.1]

Table 3: Showing proportions of adverse birth outcomes with their respective confidence intervals for rural and urban areas.

Mean differences of selected birth outcomes between rural and urban (Table 4)

Factor Group Obs Mean Std. Err. Std. Dev. 95% Conf. Interval P-value
Gestational Age Rural 481 38.1684 0.0700015 1.535252 38.03085 38.30595 <0.001
Urban 689 38.94194 0.0610658 1.602903 38.82205 39.06184
combined 1170 38.62393 0.0473658 1.62016 38.531 38.71686
diff   -0.773546 0.0936087   -0.9572057 -0.5898857
Neonatal length Rural 481 47.31601 0.2109482 4.626456 46.90151 47.7305 0.0926
Urban 689 46.94775 0.1794335 4.709916 46.59545 47.30005
combined 1170 47.09915 0.1367425 4.677312 46.83086 47.36743
diff   0.368258 0.2778219   -0.1768279 0.9133438
Neonatal weight Rural 481 2.604366 0.0234998 0.5153899 2.558191 2.650541 <0.001
Urban 689 3.00479 0.0211744 0.5558021 2.963215 3.046364
combined 1170 2.840171 0.0167875 0.5742194 2.807234 2.873108
diff   -0.400424 0.0320591   -0.4633235 -0.3375238

Table 4: Showing mean differences of selected birth outcomes between rural and urban.

There was a statistically significant difference in gestational age and neonatal weight between rural and urban areas.

Mean differences of selected lung function parameters between rural and urban area

The mean FEV1/FVC were 96.69% (SD 0.64) and 104.2% (SD 0.43) respectively observed in rural and urban area. The two means varied significantly with a p-value of <0.0001. The mean FVC between rural and urban did not vary significantly while the mean FEV1 in the rural (84.75% SD 0.44) and urban (83.07% SD 0.39) varied significantly with the p-value 0.003. Table 5 below presents the mean differences of the lung functions together with the standard error, standard deviations, and p-values at 95% confidence interval between rural and urban area.

Factor Group Obs Mean Std. Err. Std. Dev. 95% Conf. Interval P-value
FEV1/FVC Rural 481 96.69 0.64 14.08 95.42 97.95 <0.0001
Urban 687 104.2 0.43 11.22 103.4 105.1
Combined 1168 101.1 0.38 13.01 100.4 101.9
Diff   -7.53 0.74   -8.98 -6.07
FVC Rural 481 75.89 0.36 7.857 75.18 76.59 0.374
Urban 689 75.74 0.3 7.767 75.16 76.32
Combined 1170 75.8 0.23 7.801 75.35 76.25
Diff   0.149 0.46   -0.76 1.059
FEV1 Rural 481 84.75 0.44 9.706 83.88 85.62 0.003
Urban 689 83.07 0.39 10.32 82.3 83.84
combined 1170 83.76 0.3 10.1 83.18 84.34
diff   1.684 0.6   0.51 2.859

Table 5: Showing mean differences of Spirometry together with the standard error, standard deviations, and p-values at 95% confidence interval between rural and urban area.

There were statistically significant mean differences in FEV1/FVC (p value<0.0001) and FEV1 (p value=0.003) between rural and urban areas.

Mean differences of lung functions between mothers of LBW and of normal weight babies

There was a significant variation with a p-value of 0.023 at 95% C.I of 100.37%-101.86% between the mean FEV1/FVC (101.60%, SD 12.31) of mothers to normal weight babies and mothers to babies who had a low birth weight (99.92%, SD 14.55). The mean difference was 1.68% with a standard error of 0.84. The mean FVC for mothers to normal weight babies (75.49%, SD 7.80) and that of low birth weight babies (76.55%, SD 7.78) also varied significantly at a p-value of 0.0176 at 95% C.I of 75.72%-77.38% with a mean difference of -1.06% and a standard error of 0.50. The mean FEV1 of 83.53% (SD 10.30) and 84.32% (SD 9.62) respectively observed in mothers to normal birth weight and low birth weight, did not vary significantly. However, the mean difference was -0.79% with a standard error of 0.651. Table 6 below shows the summary of the mean differences of the lung functions together with the standard error, standard deviations, and p-values at 95% confidence interval between normal birth weight mothers and low birth weight mothers. The mean differences were statistically significant between.

Factor Group Obs Mean Std. Err. Std. Dev. 95% Conf. Interval P-value
FEV1/FVC Normal Birth weight 830 101.5976 0.427273 12.30962 100.7589 102.4363 0.023
LBW 338 99.92308 0.791262 14.54717 98.36664 101.4795
combined 1168 101.113 0.380752 13.01259 100.366 101.86
diff   1.674513 0.838557   0.029265 3.319762
FVC Normal Birth weight 831 75.49338 0.270441 7.796023 74.96255 76.02421 0.0176
LBW 339 76.55162 0.422296 7.775292 75.72096 77.38228
combined 1170 75.8 0.228079 7.801494 75.35251 76.24749
diff   -1.05824 0.502032   -2.04323 -0.07326
FEV1 Normal Birth weight 831 83.53189 0.356849 10.2869 82.83146 84.23232 0.1127
LBW 339 84.32153 0.523087 9.631057 83.29262 85.35045
combined 1170 83.76068 0.295379 10.10353 83.18115 84.34022
diff   -0.78964 0.650996   -2.0669 0.487607

Table 6: Showing mean differences of Spirometry between mothers of low birth weight babies and normal weight.

The mean differences were statistically significant between LBW and normal weight for FEV1/FVC (p value 0.023) and FVC (p value=0.0176).

Mean differences of lung functions between mothers of SGA and of normal for gestational age babies

The mean FEV1/FVC of mothers to normal for gestational age babies (102.50%, SD 12.10) and mothers to SGA babies (98.60%, SD 14.27) varied significantly with a p-value of < 0.0001 at 95% C.I of 100.37% - 101.86%. The mean difference was 3.88% with a standard error of 0.79. The mean FVC for mothers of normal for gestational age babies (75.64%, SD 7.83) and that of SGA babies (76.10%, SD 7.75) did not vary significantly. However, there was a mean difference of -0.46% at a standard error of 0.48. The mean FEV1 of 83.28% (SD 10.22) and 84.65% (SD 9.84) respectively observed in mothers of normal for gestational age babies and SGA babies, varied significantly with a p-value of 0.0134 at 95% CI of 83.18% - 84.37. The mean difference was -1.37% at a standard error of 0.62. Table 7 below shows the summary of the mean differences of the lung functions together with the standard error, standard deviations, and p-values at 95% confidence interval between mothers for normal gestational age babies and SGA babies.

Factor Group Obs Mean Std. Err. Std. Dev. 95% Conf. Interval P-value
FEV1/FVC Normal for gestation age 757 102.4782 0.438582 12.06699 101.6172 103.3392 <0.0001
SGA 411 98.59854 0.703985 14.27199 97.21467 99.98241
combined 1168 101.113 0.380752 13.01259 100.366 101.86
Diff   3.879663 0.789498   2.330668 5.428659
FVC Normal for gestation age 758 75.6372 0.284314 7.827671 75.07907 76.19534 0.1666
SGA 412 76.09951 0.381995 7.753646 75.34861 76.85042
combined 1170 75.8 0.228079 7.801494 75.35251 76.24749
Diff   -0.46231 0.477528   -1.39922 0.474598
FEV1 Normal for gestation age 758 83.27836 0.371111 10.21734 82.54984 84.00689 0.0134
SGA 412 84.64806 0.484847 9.841316 83.69497 85.60115
combined 1170 83.76068 0.295379 10.10353 83.18115 84.34022
Diff   -1.36969 0.617384   -2.581 -0.15839

Table 7: Showing mean differences of Spirometry between mothers to SGA and mothers to normal babies.

The mean differences were statistically significant between SGA and normal for gestational age for FEV1/FVC (p value<0.0001) and FEV1 (p value=0.0134).

Mean differences of lung functions between mothers of preterm and mothers of full term babies

The mean FEV1/FVC of 101.01% (SD 12.85) and 102.72% (SD 15.2) respectively observed in mothers of full term babies and mothers of preterm babies did not vary significant (p-value 0.1368). However, there was a mean difference of -1.712% at a standard error of 1.56. The FVC had a mean of 75.75% (SD 7.77) among mothers of full term babies and 76.60% (SD 0.960) among mothers of preterm babies. The two means did not vary significantly (p-value 0.183). However, there was a mean difference of -0.85% at a standard error of 0.94. The mean FEV1 of 83.80% (SD 10.13) and 83.14% (SD 9.70) respectively observed in mothers of full term babies and mothers of preterm babies did not vary significant (p-value 0.295) at 95% CI of 83.18% - 84.37%. There was however, a mean difference of 0.653% at a standard error of 1.21. Table 8 below shows the summary of the mean differences of the lung functions together with the standard error, standard deviations, and p-values at 95% confidence interval between mothers of full term babies and mothers of preterm babies.

Factor Group Obs Mean Std. Err. Std. Dev. 95% Conf. Interval P-value
FEV1/FVC Full term baby 1094 101.0046 0.38863 12.8542 100.242 101.7671 0.1368
PTB 74 102.7162 1.763772 15.17254 99.20102 106.2314
combined 1168 101.113 0.380752 13.01259 100.366 101.86
Diff   -1.71165 1.562872   -4.778 1.35471
FVC Full term baby 1096 75.74635 0.234682 7.769363 75.28587 76.20683 0.1828
PTB 74 76.59459 0.962249 8.27758 74.67683 78.51235
combined 1170 75.8 0.228079 7.801494 75.35251 76.24749
Diff   -0.84824 0.937094   -2.68682 0.990331
FEV1 Full term baby 1096 83.80201 0.306092 10.13345 83.20141 84.4026 0.2953
PTB 74 83.14865 1.127011 9.694911 80.90252 85.39478
combined 1170 83.76068 0.295379 10.10353 83.18115 84.34022
Diff   0.653359 1.213883   -1.72828 3.034993

Table 8: Showing mean difference of Spirometry between mothers to preterm and mothers to full term babies.

No statistically significant difference in lung functions between mothers with preterm delivery and term delivery.

Bivariate analysis

Association between maternal respiratory symptoms and low birth weight (Tables 9-11)

  Rural
  Normal birth weight Low birth weight Total P-value
% 95% CI % 95% CI % 95% CI
Cough 81.3 [76.4-85.3] 77 [71.1-82.1] 79.4 [75.7-82.7] 0.238
Sputum 48.2 [42.5-53.9] 47.8 [41.4-54.4] 48 [43.8-52.3] 0.943
Wheezing 32 [26.9-37.5] 35.9 [29.9-42.3] 33.7 [29.7-37.9] 0.35
Breathlessness 17 [13.1-21.7] 17.7 [13.3-23.2] 17.3 [14.3-20.8] 0.827
Nasal 41.2 [35.7-46.9] 40.2 [34.0-46.7] 40.7 [36.6-45.0] 0.82
Throat 36.2 [30.9-41.8] 37.8 [31.7-44.3] 36.9 [32.8-41.1] 0.701
  Urban
Cough 69.6 [65.7-73.2] 66.2 [57.8-73.6] 68.9 [65.4-72.2] 0.438
Sputum 46.7 [42.7-50.8] 39.2 [31.3-47.7] 45.3 [41.7-49.0] 0.117
Wheezing 28.8 [25.3-32.6] 31.5 [24.3-39.9] 29.3 [26.1-32.8] 0.53
Breathlessness 16.6 [13.8-19.9] 13.1 [8.4-19.9] 16 [13.5-18.8] 0.21
Nasal 46 [41.9-50.1] 52.3 [43.9-60.6] 47.2 [43.5-50.8] 0.185
Throat 30.4 [26.8-34.3] 36.9 [29.2-45.4] 31.6 [28.3-35.1] 0.143

Table 9: Association between low birth weight and maternal respiratory symptoms in rural and urban areas.

  Rural
FEV1/FVC  
<70 0.4 [0.1-2.4] 0.5 [0.1-3.1] 0.4 [0.1-1.6] 0.646
70 0.4 [0.1-2.4] 0   0.2 [0.0-1.4]
>70 99.3 [97.3-99.8] 99.5 [96.9-99.9] 99.4 [98.2-99.8]
FEV1
Mild Obstruction 35.3 [30.0-40.9] 32.5 [26.7-38.9] 34.1 [30.1-38.3] 0.51
Normal 64.7 [59.1-70.0] 67.5 [61.1-73.3] 65.9 [61.7-69.9]
FVC
Moderate Reduction 29.8 [24.8-35.3] 25.8 [20.6-31.9] 28.1 [24.4-32.1] 0.337
Mild Reduction 35.7 [30.4-41.3] 33.5 [27.6-39.9] 34.7 [30.7-38.9]
Normal 34.6 [29.3-40.2] 40.7 [34.5-47.2] 37.2 [33.2-41.5]
Urban
FEV1/FVC  
<70 0.9 [0.4-2.1] 0   0.7 [0.3-1.7] 0.269
70 0   0   0  
>70 99.1 [97.9-99.6] 100   99.3 [98.3-99.7]
FEV1
Moderate obstruction 1.4 [0.7-2.8] 1.5 [0.4-5.8] 1.5 [0.8-2.6] 0.513
Mild Obstruction 40.8 [36.9-44.8] 35.4 [27.8-43.8] 39.8 [36.2-43.4]
Normal 57.8 [53.7-61.7] 63.1 [54.6-70.8] 58.8 [55.1-62.3]
FVC
Moderate Reduction 27.5 [24.1-31.3] 22.3 [16.1-30.1] 26.6 [23.4-29.9] 0.321
Mild Reduction 38.5 [34.6-42.5] 37.7 [29.9-46.2] 38.3 [34.8-41.9]
Normal 34 [30.2-37.9] 40 [32.1-48.5] 35.1 [31.7-38.7]

Table 10: Association between maternal lung function and low birth weight.

Lung function Rural
Preterm birth
%
Term birth
95% CI
Total
%
P-value
95% CI
FEV1/FVC  
<70 0.5 [0.1-3.0] 0.4 [0.1-2.4] 0.4 [0.1-1.6] 0.506
70 0.5 [0.1-3.0] 0 - 0.2 [0.0-1.4]
>70 99.1 [96.6-99.8] 99.6 [97.6-99.9] 99.4 [98.2-99.8]
FEV1  
Mild Obstruction 35.2 [29.3-41.5] 33.2 [28.0-38.9] 34.1 [30.1-38.3] 0.635
Normal 64.8 [58.5-70.7] 66.8 [61.1-72.0] 65.9 [61.7-69.9]
FVC  
Moderate Reduction 28.2 [22.8-34.3] 27.9 [23.0-33.4] 28.1 [24.4-32.1] 0.98
Mild Reduction 34.3 [28.5-40.6] 35.1 [29.8-40.8] 34.7 [30.7-38.9]
Normal 37.5 [31.5-43.9] 37 [31.6-42.7] 37.2 [33.2-41.5]
Urban
FEV1/FVC  
<70 0.8 [0.3-1.8] 0 - 0.7 [0.3-1.7] 0.233
70 0   0 - - - -
>70 99.2 [98.2-99.7] 100 - 99.3 [98.3-99.7] -
FEV1  
Moderate Obstruction 1.5 [0.7-2.9] 1.4 [0.3-5.2] 1.5 [0.8-2.6] -
Mild Obstruction 41 [37.0-45.1] 35.4 [28.2-43.3] 39.8 [36.2-43.4] 0.446
Normal 57.6 [53.4-61.6] 63.3 [55.3-70.5] 58.8 [55.1-62.3] -
FVC  
Moderate Reduction 27.7 [24.1-31.5] 22.4 [16.5-29.8] 26.6 [23.4-29.9] -
Mild Reduction 37.5 [33.5-41.5] 41.5 [33.9-49.5] 38.3 [34.8-41.9] 0.408
Normal 34.9 [31.0-38.9] 36.1 [28.8-44.0] 35.1 [31.7-38.7] -

Table 11: Showing association between preterm birth and maternal lung functions.

There was no significant association between maternal respiratory health and preterm delivery. (Tables 12 and 13).

  Rural
Normal SGA Total P-value
% 95% CI % 95% CI % 95% CI
Cough 81 [75.5-85.5] 78.1 [73.0-82.5] 79.4 [75.7-82.7] 0.414
Sputum 49.5 [43.2-55.9] 46.8 [41.1-52.6] 48 [43.8-52.3] 0.533
Wheezing 31.5 [25.9-37.7] 35.5 [30.1-41.2] 33.7 [29.7-37.9] 0.964
Breathlessness 17.2 [12.9-22.6] 17.4 [13.4-22.2] 17.3 [14.3-20.8] 0.7
Nasal 41.7 [35.5-48.1] 40 [34.5-45.8] 40.7 [36.6-45.0] 0.59
Throat 38.1 [32.1-44.5] 35.8 [30.5-41.6] 36.9 [32.8-41.1] 0.912
Urban
Cough 69.4 [65.4-73.1] 67.3 [59.5-74.3] 68.9 [65.4-72.2] 0.632
Sputum 45.6 [41.5-49.7] 44.2 [36.5-52.2] 45.3 [41.7-49.0] 0.766
Wheezing 28.2 [24.7-32.1] 33.3 [26.3-41.2] 29.3 [26.1-32.8] 0.22
Breathlessness 17 [14.1-20.3] 12.2 [7.9-18.5] 16 [13.5-18.8] 0.158
Nasal 46.5 [42.4-50.6] 49.7 [41.8-57.5] 47.2 [43.5-50.8] 0.488
Throat 31 [27.3-34.9] 34 [26.9-41.9] 31.6 [28.3-35.1] 0.477

Table 12: Showing association between Small for Gestational Age and maternal respiratory health.

  Rural
Lung functions Norma SGA Total P-value
  % 95% CI % 95% CI % 95% CI
FEV1/FVC
<70 0.5 [0.1-3.0] 0.4 [0.1-2.4] 0.4 [0.1-1.6] 0.646
70 0.5 [0.1-3.0] 0   0.2 [0.0-1.4]
>70 99.1 [96.6-99.8] 99.6 [97.6-99.9] 99.4 [98.2-99.8]
FEV1
Mild Obstruction 35.2 [29.3-41.5] 33.2 [28.0-38.9] 34.1 [30.1-38.3] 0.446
Normal 64.8 [58.5-70.7] 66.8 [61.1-72.0] 65.9 [61.7-69.9]
FVC
Moderate Reduction 28.2 [22.8-34.3] 27.9 [23.0-33.4] 28.1 [24.4-32.1] 0.337
Mild Reduction 34.3 [28.5-40.6] 35.1 [29.8-40.8] 34.7 [30.7-38.9]
Normal 37.5 [31.5-43.9] 37 [31.6-42.7] 37.2 [33.2-41.5]
Urban
FEV1/FVC
<70 0.9 [0.4-2.1] 0   0.7 [0.3-1.7] 0.233
70 0   0   0  
>70 99.1 [97.9-99.6] 100   99.3 [98.3-99.7]
FEV1
Moderate obstruction 1.5 [0.7-2.9] 1.4 [0.3-5.2] 1.5 [0.8-2.6] 0.446
Mild Obstruction 41 [37.0-45.1] 35.4 [28.2-43.3] 39.8 [36.2-43.4]
Normal 57.6 [53.4-61.6] 63.3 [55.3-70.5] 58.8 [55.1-62.3]
FVC
Moderate Reduction 27.7 [24.1-31.5] 22.4 [16.5-29.8] 26.6 [23.4-29.9] 0.313
Mild Reduction 37.5 [33.5-41.5] 41.5 [33.9-49.5] 38.3 [34.8-41.9]
Normal 34.9 [31.0-38.9] 36.1 [28.8-44.0] 35.1 [31.7-38.7]

Table 13: Showing association between small for gestational age and maternal lung functions.

There was no significant association between maternal respiratory health and small for gestational age.

Assessment of influence of gestational age on the relationship between lungs functions and birth outcomes (Table 14)

Low Birth weight
Rural-Masaiti Urban - Ndola
  OR SE SD [95% C.I] P-value OR SE SD [95% C.I] P-value
FEV1  
1st trimester 1.019 0 .012 1.69 0.997 1.042 0.091 1.016 0.013 1.31 0.992 0.992 0.19
_cons 0.161 0.149 1.97 0.026 0.995 0.049 0.061 0.063 2.73 0.008 0.457 0.006
2nd trimester 1.019 0.012 1.69 0.997 1.042 0.091 1.017 0.013 1.37 0.993 1.042 0.172
_cons 0.174 0.153 1.98 0.031 0.984 0.048 0.062 0.06 2.86 0.009 0.42 0.004
3rd trimester 1.019 0.011 1.69 0.997 1.042 0.091 1.017 0.013 1.37 0.993 1.042 0.173
_cons 0.21 0.162 2.02 0.046 0.955 0.044 0.074 0.063 3.07 0.014 0.391 0.002
FVC  
1st trimester 1 0.009 0.03 0.983 1.018 0.979 1.006 0.009 0.7 0.989 1.024 0.486
_cons 0.752 0.62 0.35 0.148 3.806 0.73 0.133 0.108 2.49 0.027 0.652 0.013
2nd trimester 1 0.009 0.03 0.983 1.018 0.979 1.006 0.009 0.7 0.989 1.024 0.486
_cons 0.752 0.594 0.36 0.159 3.55 0.719 0.136 0.106 2.57 0.03 0.623 0.01
3rd trimester 1 0.009 0.03 0.983 1.018 0.979 1.006 0.009 0.7 0.989 1.024 0.486
_cons 0.754 0.528 -0.4 0.191 2.983 0.687 0.145 0.099 2.82 0.038 0.557 0.005
FEV1/FVC  
1st trimester 0.989 0.006 1.74 0.977 1.001 0.083 1.022 0.012 1.85 0.999 1.045 0.064
_cons 2.416 1.605 1.33 0.655 8.91 0.185 0.022 0.028 2.95 0.002 0.277 0.003
2nd trimester 0.989 0.006 1.74 0.977 1.001 0.083 1.022 0.012 1.85 0.999 1.045 0.064
_cons 2.31 1.476 1.31 0.659 8.104 0.19 0.023 0.029 2.99 0.002 0.276 0.003
3rd trimester 0.989 0.006 1.74 0.977 1.001 0.083 1.022 0.012 1.85 0.999 1.045 0.064
_cons 2.311 1.476 1.31 0.659 8.104 0.19 0.029 0.033 3.11 0.003 0.272 0.002
Preterm birth
  OR SE SD [95% C.I] P-value OR SE SD [95% C.I] P-value
FEV1  
1st trimester 1.017 0.022 0.76 0.974 1.061 0.45 1.011 0.023 0.48 0.967 1.057 0.631
_cons 0.022 0.04 2.11 0.001 0.769 0.035 0.022 0.042 2.01 5.00E-04 0.924 0.045
2nd trimester 1.017 0.022 0.76 0.974 1.061 0.45 1.011 0.023 0.48 0.967 1.057 0.633
_cons 0.238 0.048 2.18 0.001 0.693 0.03 0.023 0.042 2.08 7.00E-04 0.804 0.037
3rd trimester 1.017 0.022 0.76 0.974 1.06 0.45 1.011 0.023 0.47 0.966 1.057 0.641
_cons 0.028 0.042 2.38 0.002 0.534 0.018 0.027 0.042 2.31 0.001 0.582 0.021
FVC  
1st trimester 0.989 0.015 0.76 0.961 1.018 0.45 0.994 0.017 0.35 0.962 1.027 0.727
_cons 0.235 0.315 1.08 0.017 3.263 0.28 0.093 0.14 1.58 0.005 1.78 0.115
2nd trimester 0.989 0.015 0.76 0.961 1.018 0.45 0.994 0.017 0.35 0.962 1.028 0.727
_cons 0.225 0.288 1.17 0.018 2.781 0.244 0.091 0.13 1.67 0.005 1.524 0.095
3rd trimester 0.989 0.015 0.76 0.961 1.018 0.45 0.994 0.017 0.35 0.962 1.027 0.727
_cons 0.201 0.228 1.41 0.022 1.865 0.158 0.086 0.109 1.94 0.007 1.034 0.053
FEV1/FVC  
1st trimester 0.984 0.011 1.41 0.962 1.01 0.16 1.068 0.018 3.94 1.034 1.103 <0.0001
_cons 0.441 0.513 -0.7 0.045 4.32 0.481 3.00E-05 6.00E-05 5.27 7.00E-07 0.002 <0.0001
2nd trimester 0.984 0.011 1.41 0.962 1.01 0.16 1.068 0.018 3.94 1.033 1.103 <0.0001
_cons 0.414 0.462 0.79 0.046 3.704 0.429 4.00E-05 8.00E-05 5.32 1.00E-06 0.002 <0.0001
3rd trimester 0.984 0.011 1.41 0.962 1.006 0.16 1.068 0.018 3.94 1.033 1.103 <0.0001
_cons 0.352 0.353 1.04 0.049 2.523 0.298 8.00E-05 1.00E-04 5.45 3.00E-06 0.002 <0.0001
Small for Gestational Age
  OR SE SD [95% C.I] P-Value OR SE SD [95% C.I] P-value
FEV1  
1st trimester 1.005 0.011 0.45 0.983 1.027 0.655 1.01 0.012 0.85 0.987 1.033 0.395
_cons 0.814 0.751 0.22 0.132 4.99 0.823 0.12 0.116 -2.2 0.018 0.797 0.028
2nd trimester 1.005 0.011 0.45 0.983 1.027 0.655 1.01 0.012 0.91 0.988 1.034 0.365
_cons 0.83 0.729 0.21 0.148 4.664 0.832 0.119 0.109 2.32 0.02 0.02 0.021
3rd trimester 1.005 0.011 0.45 0.983 1.027 0.655 1.01 0.012 0.9 0.988 1.034 0.368
_cons 0.873 0.669 0.18 0.194 3.938 0.859 0.133 0.106 2.52 0.027 0.64 0.012
FVC  
1st trimester 1.002 0.009 0.24 0.985 1.02 0.809 1.015 0.009 1.68 0.998 1.032 0.093
_cons 1.005 0.831 0.01 0.198 5.104 0.995 0.072 0.058 -3.3 0.015 0.345 0.001
2nd trimester 1.002 0.009 0.24 0.985 1.02 0.809 1.015 0.009 1.68 0.998 1.033 0.093
_cons 1.014 0.802 0.02 0.214 4.797 0.986 0.077 0.058 3.37 0.017 0.342 0.001
3rd trimester 1.002 0.009 0.24 0.985 1.02 0.809 1.015 0.009 1.68 0.998 1.032 0.093
_cons 1.037 0.726 0.05 0.262 4.109 0.959 0.089 0.06 3.59 0.024 0.334 <0.001
FEV1/FVC  
1st trimester 0.974 0.006 3.98 0.962 0.987 <0.0001 1.014 0.01 1.37 0.994 1.034 0.17
_cons 17.79 12.03 4.26 4.713 67.17 <0.0001 0.059 0.066 2.52 0.006 0.535 0.012
2nd trimester 0.974 0.006 3.98 0.962 0.987 <0.0001 1.014 0.01 1.37 0.994 1.034 0.17
_cons 16.03 10.43 4.27 4.469 57.53 <0.0001 0.062 0.067 2.56 0.007 0.523 0.011
3rd trimester 0.974 0.006 3.98 0.962 0.987 <0.0001 1.014 0.01 1.37 0.994 1.034 0.17
_cons 12.36 7.238 4.29 3.912 39.07 <0.0001 0.071 0.07 2.68 0.01 0.493 0.007

Table 14: Showing association between maternal lung functions in different trimesters and birth outcomes for rural and urban areas.

There was a statistically significant association between FEV1/FVC and preterm in the urban (p value<0.0001) and small for gestational age (p value<0.0001) in the rural area for all the three trimesters.

Multivariate logistic regression

Impact of maternal respiratory health on birth outcomes (Table 15)

  Rural Urban Study population
Factor LBW PTD SGA LBW PTD SGA LBW PTD SGA
Mild Reduction (FVC 70-79) 0.09*** - - - - - - 0.39*** -
  (0.0 - 0.4)             (0.2 - 0.8)  
Had recurrent nasal Symptoms last 12 months       1.69**          
- - - (1.0 - 2.8) - - - - -
Had prolonged(>month) secretion of phlegm       0.58**          
- - - (0.3 - 1.0) - - - - -
ciEform in parenthese* p<0.1 *** p<0.01 ** p<0.05

Table 15: Showing association between maternal respiratory health and birth outcomes in the multivariate analysis.

In the urban area, LBW was statistically associated with recurrent nasal symptoms OR [1.69 (95% C.I; 1.0-2.8)] and prolonged secretion of phlegm OR [0.58 (95% C.I; 0.3-1.0)]. Pregnant women presenting with recurrent nasal symptoms were 1.69 times more likely to have a LBW child compared to the pregnant women with no recurrent nasal symptoms. While pregnant women with prolonged secretion of phlegm were 0.58 times less likely to have a low birth weight.

There was a significant association between FVC and LBW in the rural area OR [0.09 (99% C.I; 0.0-0.4)], pregnant women with mild reduction were 0.09 times less likely to have LBW compared to those with severe reduction of FVC. Preterm delivery was statistically significantly associated with FVC OR [0.39 (99% C.I; 0.2-0.8)] in the entire study population, pregnant women with mild reduction in the FVC were 0.39 times less likely to have a preterm delivery compared to pregnant women with a severe reduction in FVC.

Results and Discussion

This is the first research in Zambia exploring the association between pregnancy- related outcomes and maternal respiratory symptoms and lung functions among both rural and urban pregnant women. The current study found that impaired lung function is linked to biomass fuel smoke and this is supported by results of a study in Ethiopia that found that exposure to indoor air pollution has been linked with a reduction of forced vital capacity and an increased risk of acute respiratory problems [14]. In the urban area, LBW was statistically associated with recurrent nasal symptoms and prolonged secretion of phlegm. Pregnant women presenting with recurrent nasal symptoms were 1.69 times more likely to have a LBW child compared to the pregnant women with no recurrent nasal symptoms. While pregnant women with prolonged secretion of phlegm were 0.58 times less likely to have a low birth weight. Respiratory ill health has been cited in another study as being associated with adverse pregnancy outcomes. This study observed that the prevalence of adverse birth outcome is high among women with poor respiratory health. This finding is in line with the results of other researchers who also found that mothers with acute respiratory infectious diseases (ARID) during pregnancy had a longer gestational age at delivery than mothers without ARID [17]. Other studies elsewhere also observed that women who presented with asthma like symptoms of wheezing and breathlessness had a high prevalence of adverse birth outcomes for instance a study among Australian population showed that asthma in pregnancy is associated with increased poor outcomes for the mother and neonate and these poor outcomes include preterm birth, small for gestational age and preterm labor [18]. Similarly, Kallen and colleagues [19] also observed that the pregnancies of women with asthma are more likely to be complicated by preterm birth, lower birth weight and pre-eclampsia than pregnancies in non-asthmatic women [20].

This study found that there was a statistically significant association between FVC and LBW in the rural area. Pregnant women with mild reduction in FVC were 0.09 times less likely to have LBW compared to those with severe reduction of FVC. This is in accord with the findings in another study where low rates of fetal growth were observed in reduced lung function in adults [21] and a positive linear trend has been recorded between adult lung function and birth weight after adjusting for maternal factors [12]. Other findings elsewhere however, reported association of FEV1 and LBW and observed that a direct relationship between maternal FEV1 during pregnancy and infant birth weight [22]. Low FEV1 has also been reported to be associated with preterm delivery by Odegaard and colleagues [23]. However, in our current study preterm delivery was significantly associated with FVC and pregnant women with mild reduction in the FVC were 0.39 times less likely to have a preterm delivery compared to pregnant women with a severe reduction in FVC. Our findings in this study showed that the gestational age of the pregnant women did not alter lung functions of the pregnant women. This agrees with findings in previous studies of impact of pregnancy on pulmonary function, results obtained by forced Spirometry, showed largely that forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) remain unchanged during pregnancy [14].

Conclusion

Maternal respiratory health had an influence on the adverse birth outcomes of pregnant women. Therefore, pregnant women with respiratory disease need frequent monitoring of respiratory symptoms and simultaneously conducting spirometry to help optimize their respiratory health throughout pregnancy.

References

  1. Bruce N, Perez-Padilla R, Albalak R (2002) The health effects of indoor air pollution exposure in developing countries World Health Organization.
  2. Misra P, Srivastava R, Krishnan A, Sreenivaas V, Pandac CS (2012) Indoor air pollution-related acute lower respiratory infections and low birth weight: A systematic review. J Trop Pediat 58: 457-466.
  3. Fullerton DG, Bruce N, Gordon SB (2008) Indoor air pollution from biomass fuel smoke is a major health concern in the developing world. Trans R Soc Trop Med Hyg 102: 843-851
  4. Kumar R, Nagar JK, Gaur SN (2005) Indoor air pollutants and respiratory morbidity: a review. Indian J Allergy Asthma Immunol 19: l-9.
  5. Pope CA, Dockery DW (2012) Health effects of fine particulate air pollution: lines that connect. J Air Waste ManagAssoc 56: 709-742.
  6. Amegah AK, Quansah R, Jouni JK, Jaakkola JJK (2014) Household Air Pollution from Solid Fuel Use and Risk of Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis of the Empirical Evidence. PLoS ONE 9: 113920.
  7. Khader YS, Al-Akour N, AlZubi IM, Lataifeh I (2011) The association between second hand smoke and low birth weight and preterm delivery. Matern Child Health J 15: 453-459.
  8. Cnattingius S (2004) The epidemiology of smoking during pregnancy: Smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine and Tob Res 6: S125-S140.
  9. Shah PS, Balkhair T (2011) Air pollution and birthout comes: a systematic review. Environ Int 37: 498-516.
  10. Vadillo-Ortega F, Osornio-Vargas A, Buxton MA, Sanchez BN, Rojas-BrachoL, et al. (2014) Air pollution, inflammation and preterm birth: a potential mechanistic link. Med.Hypotheses 82: 219-224.
  11. Barker DJ, Godfrey KM, Fall C, Osmond C, Winter PD, et al. (1991) Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. BMJ 303: 671-675.
  12. Edwards CA, Osman LM, Godden DJ, Campbell DM, Douglas JG (2003) Relationship between birth weight and adult lung function: controlling for maternal factors. Thorax 58:1061-1065.
  13. Warner JO, Jones CA (2001) Fetal origins of lung disease. In: Barker DJP, eds. Fetal origins of cardiovascular and lung disease. New York: Marcel Dekker 297-321.
  14. Grindheim G, Toska K, Estensen M, Rosseland L (2012) Changes in pulmonary function during pregnancy: a longitudinal cohort study. BJOG 119: 94-101.
  15. Lui S, Wen Sw, Demissie K, Marcoux S, Kramer MS (2001) Maternal asthma and pregnancy outcomes: A retrospective cohort study. Am J Obstet Gynecol 184: 90-96.
  16. Boezen HM, Vonk JM, van Aalderen WM, Brand PL, Gerritsen J, et al. (2002) Perinatal predictors of respiratory symptoms and lung function at a young adult age. EurRespir J 20: 383-390.
  17. Banhidy F, Acsnandor, Puho EH, Czeizel AE (2008) Use of specified critical periods of different congenital abnormalities instead of the first trimester concept. Birth Defects Res. Part A, Clini and Mol Teratology 82: 139-146.
  18. Hodyl NA, Stark MJ, Scheil W, Grzeskowiak LE, Clifton VL (2014) Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy. Eur respir J 43: 704-716.
  19. Kallen B, Rydhstroem H, Aberg A (2000) Asthma during pregnancy-a population based study. Eur J Epidemiol 16: 167-171.
  20. Laerum BN, Svanes C, Gulsvik A, Iversen M, Thorarinsdottir HR, et al. (2004) Is birth weight related to lung function and asthma symptoms in Nordic-Baltic adults? Respir Med 98: 611-618.
  21. Stein CE, Kumaran K, Fall CH, Shaheen SO, Osmond C, et al. (1997) Relation of fetal growth to adult lung function in south India. Thorax 52: 895-899.
  22. Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, et al. (2006) Spirometry is related to perinatal outcomes in pregnant women with asthma. Am J Obstet Gynecol 194: 120-126.
  23. Odegaard I, Stray-Pedersen B, Hallberg K, Haanaes OC, Storrosten OT, et al. (2002) Maternal and fetal morbidity in pregnancies of Norwegian and Swedish women with cystic fibrosis. ActaObstetGynecolScand 81: 698-705.
Citation: Mulenga D, Nyirenda HT, Chileshe-Chibangula M, Mwila P, Siziya S (2018) Pregnancy Outcomes Associated with Chronic Indoor Air Pollution-Related Maternal Respiratory III Health in Ndola and Masaiti, Zambia. Intern Med 8:  269.

Copyright: © 2018 Mulenga D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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