TM7SF3 controls TEAD1 splicing to prevent MASH-induced liver fibrosis.

The mechanisms of hepatic stellate cell (HSC) activation and the development of liver fibrosis are not fully understood. Here, we show that deletion of a nuclear seven transmembrane protein, TM7SF3, accelerates HSC activation in liver organoids, primary human HSCs, and in vivo in metabolic-dysfunction-associated steatohepatitis (MASH) mice, leading to activation of the fibrogenic program and HSC proliferation. Thus, TM7SF3 knockdown promotes alternative splicing of the Hippo pathway transcription factor, TEAD1, by inhibiting the splicing factor heterogeneous nuclear ribonucleoprotein U (hnRNPU). This results in the exclusion of the inhibitory exon 5, generating a more active form of TEAD1 and triggering HSC activation. Furthermore, inhibiting TEAD1 alternative splicing with a specific antisense oligomer (ASO) deactivates HSCs in vitro and reduces MASH diet-induced liver fibrosis. In conclusion, by inhibiting TEAD1 alternative splicing, TM7SF3 plays a pivotal role in mitigating HSC activation and the progression of MASH-related fibrosis.

Cellular Microenvironment Stiffness Regulates Eicosanoid Production and Signaling Pathways.

Pathological changes in the biomechanical environment are implicated in the progression of idiopathic pulmonary fibrosis (IPF). Stiffened matrix augments fibroblast proliferation and differentiation and activates TGF-ß1 (transforming growth factor-ß1). Stiffened matrix impairs the synthesis of the antifibrogenic lipid mediator prostaglandin E2 (PGE2) and reduces the expression of the rate-limiting prostanoid biosynthetic enzyme cyclooxygenase-2 (COX-2). We now show that prostaglandin E synthase (PTGES), the final enzyme in the PGE2 biosynthetic pathway, is expressed at lower levels in the lungs of patients with IPF. We also show substantial induction of COX-2, PTGES, prostaglandin E receptor 4 (EP4), and cytosolic phospholipase A2 (cPLA2) expression in human lung fibroblasts cultured in soft collagen hydrogels or in spheroids compared with conventional culture on stiff plastic culture plates. Induction of COX-2, cPLA2, and PTGES expression in spheroid cultures was moderately inhibited by the p38 mitogen-activated protein kinase inhibitor SB203580. The induction of prostanoid biosynthetic enzyme expression was accompanied by an increase in PGE2 levels only in non-IPF-derived fibroblast spheroids. Our study reveals an extensive dysregulation of prostanoid biosynthesis and signaling pathways in IPF-derived fibroblasts, which are only partially abrogated by culture in soft microenvironments.

Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-ß in Pulmonary Fibrosis.

Transforming growth factor-beta (TGF-ß) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition of TGF-ß is limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover a little-known connection between TGF-ß signaling and casein kinase (CK) activity. We have examined the abundance of CK1 delta and epsilon (CK1δ/ε) in lung tissue from IPF patients and non-diseased controls, and investigated whether inhibition of CK1δ/ε with PF670462 inhibits pulmonary fibrosis. CK1δ/ε levels in lung tissue from IPF patients and non-diseased controls were assessed by immunohistochemistry. Anti-fibrotic effects of the CK1δ/ε inhibitor PF670462 were assessed in pre-clinical models, including acute and chronic bleomycin mouse models and in vitro experiments on spheroids made from primary human lung fibroblast cells from IPF and control donors, and human A549 alveolar-like adenocarcinoma-derived epithelial cells. Increased expression of CK1δ and ε in IPF lungs compared to non-diseased controls was accompanied by increased levels of the product, phospho-period 2. In vitro, PF670462 prevented TGF-ß-induced epithelial-mesenchymal transition. The stiffness of IPF-derived spheroids was reduced by PF670462 and TGF-ß-induced fibrogenic gene expression was inhibited. The CK1δ/ε inhibitor PF670462 administered systemically or locally by inhalation prevented both acute and chronic bleomycin-induced pulmonary fibrosis in mice. PF670462 administered in a 'therapeutic' regimen (day 7 onward) prevented bleomycin-induced lung collagen accumulation. Elevated expression and activity of CK1 δ and ε in IPF and anti-fibrogenic effects of the dual CK1δ/ε inhibitor, PF670462, support CK1δ/ε as novel therapeutic targets for IPF.

Magnitude of Antiretroviral Drug Toxicity in Adult HIV Patients in Ethiopia: A cohort study at seven teaching hospitals.

BACKGROUND: The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia. METHODS: This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART. Adverse drug reactions (ADR) due to ART were identified based on clinical assessment and/or laboratory parameters. Multivariable random effects Poisson regression analysis was used to identify factors independently associated with toxicity. RESULT: ADR due to ART drugs was reported in 867 (22.1 %) of the participants; 374 (9.5%) had severe forms. About 87% of reported toxicities were limited to three organ systems - the skin, nervous system and blood. The overall incidence of ADR was 9 per 100 person years. About a third of toxicities occurred during the first six months after ART initiation with the incidence rate of 22.4 per 100 person years. Concomitant anti-tuberculosis treatment was the strongest independent predictor of toxicity. CONCLUSION: ADR was found to be highly prevalent in HIV patients on ART at tertiary hospitals in Ethiopia. Most of these conditions occurred early after ART initiation and in those with concomitant anti-tuberculosis treatment. Thus, routine monitoring of patients on ART should be strengthened with particular emphasis in the first 6 months. Strategies should also be devised to replace older and more toxic agents with newer and safer drugs available.

Annexin A2 contributes to lung injury and fibrosis by augmenting factor Xa fibrogenic activity.

In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into factor Xa (FXa), a coagulant protease with fibrogenic actions. Extracellular annexin A2 binds to FXa, augmenting activation of the protease-activated receptor-1 (PAR-1). In this study, the contribution of annexin A2 in lung injury and fibrosis was investigated. Annexin A2 immunoreactivity was observed in regions of fibrosis, including those associated with fibroblasts in lung tissue of IPF patients. Furthermore, annexin A2 was detected in the conditioned media and an EGTA membrane wash of human lung fibroblast (LF) cultures. Incubation with human plasma (5% vol/vol) or purified FXa (15-50 nM) evoked fibrogenic responses in LF cultures, with FXa increasing interleukin-6 (IL-6) production and cell number by 270 and 46%, respectively (P < 0.05, n = 5-8). The fibrogenic actions of plasma or FXa were attenuated by the selective FXa inhibitor apixaban (10 µM, or antibodies raised against annexin A2 or PAR-1 (2 µg/ml). FXa-stimulated LFs from IPF patients (n = 6) produced twice as much IL-6 as controls (n = 10) (P < 0.05), corresponding with increased levels of extracellular annexin A2. Annexin A2 gene deletion in mice reduced bleomycin-induced increases in bronchoalveolar lavage fluid (BALF) IL-6 levels and cell number (*P < 0.05; n = 4-12). Lung fibrogenic gene expression and dry weight were reduced by annexin A2 gene deletion, but lung levels of collagen were not. Our data suggest that annexin A2 contributes to lung injury and fibrotic disease by mediating the fibrogenic actions of FXa. Extracellular annexin A2 is a potential target for the treatment of IPF.

The Coagulant Factor Xa Induces Protease-Activated Receptor-1 and Annexin A2-Dependent Airway Smooth Muscle Cytokine Production and Cell Proliferation.

During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved in thrombin activation and an agonist of protease-activated receptor-1 (PAR-1). Extracellular annexin A2 and integrins are also implicated in PAR-1 signaling. In this study, the potential role of PAR-1 in mediating the effects of FXa on human airway smooth muscle (ASM) cell cytokine production and proliferation was investigated. FXa (5-50 nM), but not FX, stimulated increases in ASM IL-6 production and cell number after 24- and 48-hour incubation, respectively (P < 0.05; n = 5). FXa (15 nM) also stimulated increases in the levels of mRNA for cytokines (IL-6), cell cycle-related protein (cyclin D1), and proremodeling proteins (FGF-2, PDGF-B, CTGF, SM22, and PAI-1) after 3-hour incubation (P < 0.05; n = 4). The actions of FXa were insensitive to inhibition by hirudin (1 U/ml), a selective thrombin inhibitor, but were attenuated by SCH79797 (100 nM), a PAR-1 antagonist, or Cpd 22 (1 µM), an inhibitor of integrin-linked kinase. The selective targeting of PAR-1, annexin A2, or ß1-integrin by small interfering RNA and/or by functional blocking antibodies also attenuated FXa-evoked responses. In contrast, the targeting of annexin A2 did not inhibit thrombin-stimulated ASM function. In airway biopsies of patients with asthma, FXa and annexin A2 were detected in the ASM bundle by immunohistochemistry. These findings establish FXa as a potentially important asthma mediator, stimulating ASM function through actions requiring PAR-1 and annexin A2 and involving integrin coactivation.

Should magnesium sulfate be administered to women with mild pre-eclampsia? A systematic review of published reports on eclampsia.

AIM: Magnesium sulfate is an evidence-based anticonvulsant drug used to prevent and control eclampsia. Controversy persists on routine administration of magnesium sulfate in cases of pre-eclampsia without severe features. Our objective was to assess the pattern of blood pressure and maternal symptoms preceding eclamptic seizure based on the current published work. MATERIAL AND METHODS: A comprehensive computer-based publication search was conducted in the African Journals Online, Google scholar, HINARI, PubMed, and MEDLINE databases and the Cochrane library to identify descriptive study reports for blood pressure, severity symptoms or stage of pregnancy during convulsion in women with eclampsia. RESULTS: A total of 59 publications were eligible for this review. Overall, 21,149 eclamptic women from 26 countries were included for the interest of one or more of the selected variables. Out of 18,488 eclamptic women, the proportion of antepartum, intrapartum and post-partum eclampsia was 59%, 20% and 21%, respectively. Out of 3443 eclamptic women, 25% were normotensive; 20% had mild-to-moderate hypertension; 32% had severe hypertension; and 21% were hypertensive but unclassified. Out of 2163 eclamptic women, 66% and 27% had a headache and visual disturbance, respectively, preceding the occurrence of convulsion. Out of 2053 eclamptic women, 25% had epigastric area pain, and out of 1092 women with eclampsia, 25% were asymptomatic. CONCLUSION: Although eclampsia is known to result from severe pre-eclampsia with or without organ function derangement, this review has revealed that a significant number of eclamptic women had either normal blood pressure or mild-to-moderate hypertension immediately before seizure. The findings are apparently in support of initiating magnesium sulfate prophylaxis to all women with mild pre-eclampsia.

A Meta-Analysis of Risky Sexual Behaviour among Male Youth in Developing Countries.

The purpose of this meta-analysis was to assess the association between risky sexual behaviour and level of education and economic status in male youth. Previous tests of the association of risky sexual behaviour with levels of education and economic status have yielded inconsistent results. Using data from 26 countries, from both within and outside Africa, we performed a meta-analysis with a specific focus on male youths' risky sexual behaviour. We applied a random effects analytic model and calculated a pooled odds ratio. Out of 19,148 males aged 15-24 years who reported having sexual intercourse in the 12 months preceding the survey, 75% engaged in higher-risk sex. The proportion of higher-risk sex among male youth aged 15-19 years was nearly 90% in 21 of the 26 countries. The pooled odds ratio showed a statistically significant association of higher-risk sex with male youth younger than 20 years, living in urban centers, well educated, and of a high economic status. The overall proportion of condom use during youths' most recent higher-risk sexual encounter was 40% and 51% among 15-19-year-olds and 20-24-year-olds, respectively. Our findings suggest that male youth's socioeconomic status is directly related to the likelihood that they practice higher-risk sex. The relationship between income and sexual behaviour should be explored further.

Is higher risk sex common among male or female youths?

There are several studies that showed the high prevalence of high-risk sexual behaviors among youths, but little is known how significant the proportion of higher risk sex is when the male and female youths are compared. A meta-analysis was done using 26 countries' Demographic and Health Survey data from and outside Africa to make comparisons of higher risk sex among the most vulnerable group of male and female youths. Random effects analytic model was applied and the pooled odds ratios were determined using Mantel-Haenszel statistical method. In this meta-analysis, 19,148 male and 65,094 female youths who reported to have sexual intercourse in a 12-month period were included. The overall OR demonstrated that higher risk sex was ten times more prevalent in male youths than in female youths. The practice of higher risk sex by male youths aged 15-19 years was more than 27-fold higher than that of their female counterparts. Similarly, male youths in urban areas, belonged to a family with middle to highest wealth index, and educated to secondary and above were more than ninefold, eightfold and sixfold at risk of practicing higher risk sex than their female counterparts, respectively. In conclusion, this meta-analysis demonstrated that the practice of risky sexual intercourse by male youths was incomparably higher than female youths. Future risky sex protective interventions should be tailored to secondary and above educated male youths in urban areas.

Review of maternal mortality in Ethiopia: a story of the past 30 years.

BACKGROUND: Ethiopia is one of the six countries which have contributed to more than 50% of all maternal deaths across the world. This country has adopted the millennium development goals (MDGs) including reducing the maternal mortality by three-quarter, and put improvement in maternal health as one of the health sector development program (HSDP) performance indicators. The purpose of this study was to review the maternal mortality ratio (MMR) in Ethiopia in the past 30 years using available literature. METHODS: A computer based literature search in the databases of MEDLINE, PubMed, HINARI, EBASE, MEASURE DHS, The Cochrane Library, Google Search and Google Scholar was carried out. Manual search for local articles that are not available electronically in full document were also conducted. Eighteen data sources (3 nationally representative surveys, 2 secondary data analyses, 5 small scale community based studies, and 8 hospital based studies) were included in the review. The results of this review are presented in the form of line and stock graphs. RESULTS: The national maternal mortality trend estimated by the central statistics agency of Ethiopia, The Institute for Health Metrics and Evaluation, WHO and other UN agencies showed inconsistent results. Similarly, although there were marked variations in the 95% confidence intervals among individual studies, the small scale community based and hospital based studies have shown that there has been no significant change in maternal mortality over the last three decades. A 22-year cohort analysis from Atat Hospital is the only evidence that demonstrated a very significant drop in maternal mortality among mothers who were kept in the maternity waiting area before the onset of labor. CONCLUSION: Although the MDG and HSDP envisaged significant improvement in maternal health by this time, this review has shown that the performances are still far from the target. The multisectoral huge investment by the Ethiopian Government is a big hope to reduce the maternal mortality by three-quarters in the near future beyond 2015.

Causes of maternal mortality in Ethiopia: a significant decline in abortion related death.

BACKGROUND: Although the common direct obstetric causes of maternal mortality are known from the literature, the contribution of each cause and the change in trend over decades is unknown in Ethiopia. The objective of this review was to assess the trend of proportion of maternal mortality due to the common direct causes. METHODS: This systematic review was done on eighteen health facility based maternal mortality studies conducted between 1980 and 2012 in Ethiopia. Emphasis was given to the proportion of maternal mortality due to direct causes and their case fatality rates. RESULTS: The summary of the findings has shown that the top four causes of maternal mortality in the year 1980-1999 were abortion related complications (31%), obstructed labor/uterine rupture (29%), sepsis/infection (21%) and hemorrhage (12%). In the last decade, however, the top four causes of maternal mortality were obstructed labor/uterine rupture (36%), hemorrhage (22%), hypertensive disorders of pregnancy (19%) and sepsis/infection (13%). CONCLUSION: Abortion and infection related maternal deaths have declined significantly in the last decade. Obstructed labor continues to be the major cause of maternal deaths; maternal deaths due to hypertensive disorders and hemorrhage showed an increasing trend. The findings in this review were somehow comparable with the WHO analysis for Africa in the same period with the exception of obstructed labor.

A meta-analysis of socio-demographic factors for perinatal mortality in developing countries: a subgroup analysis of the national surveys and small scale studies.

BACKGROUND: Although the perinatal mortality in low income countries is about five-folds higher than in the high income countries, little is known about the association of socio-demographic factors with perinatal mortality. National and small scale studies so far reported have shown very contradictory results. The objective of this meta-analysis was to assess the association of perinatal mortality with selected sociodemographic factors. METHODS: A computer based literature search was conducted mainly in the databases of African Journals Online, MEASURE Demographic and Health Survey (DHS), Google Scholar, HINARI, PUBMED, MEDLINE and the Cochrane Library. The inclusion criteria were: 1) studies that assessed the perinatal mortality in developing countries in relation to socio-demographic predictors and 2) studies published in English and conducted after the year 1990. Subgroup meta-analyses of perinatal mortality were performed for mothers' age, residence, educational level and wealth status. Sensitivity analysis and heterogeneity testing were done. RESULTS: In this meta-analysis, several inconsistent associations of perinatal mortality with the selected socio-demographic variables were observed in the primary studies level, both DHS and small scale studies. However, the overall odds ratio (OR) demonstrated statistically significant association of perinatal mortality with low maternal age (OR=1.2) and short birth interval (OR=1.4) but was not influenced by the mothers' residence, low educational level and household wealth index. Very consistently, the highest perinatal mortality rates reported when the birth intervals were either too short (<15 months) or too long (>39 months). CONCLUSION: Because of the disagreement among previous studies, the present study demonstrated a small effect size on the increased risk of perinatal mortality among women who were pregnant during teenage ages and gave birth too frequently or after a long interval. Therefore, to confirm the strong predictors of perinatal mortality, further studies on sociodemographic factors are needed.

Perinatal mortality trends in Ethiopia.

BACKGROUND: Although the magnitude of perinatal mortality in Ethiopia was among the highest in Sub Saharan Africa, there was no systematic review done to assess the trend and causes of perinatal death. The objective of this review was to assess the trend of perinatal mortality rate (PMR) and the causes attributed to perinatal deaths. METHODS: Studies included in this systematic review were sixteen hospital and community based perinatal mortality studies, which were conducted between 1974 and 2013 using data concerning Ethiopia accessed either electronically or from local journals. The trend of PMR, stillbirth rate (SBR) and early neonatal mortality rate (ENMR) were given emphasis. RESULTS: The PMRs reported from ten hospital based studies were in the range of 66 to 124 per 1000 births. The reports of the large scale community based PMRs were in the range of 37 to 52 per 1000 births. The proportion of stillbirths and early neonatal deaths reported from the hospital based and community based studies was very high (60-110 and 20-34/1000 births); the regression lines demonstrated that SBRs in the hospitals were mirror reflections of ENMRs in the community. The neonatal mortality rate (NMR), however, declined by more than 40% between 1990 and 2011. CONCLUSION: The PMR of Ethiopia was among the highest in Sub Saharan Africa. Over the decades, both hospital based and community based studies did not show a reduction in perinatal mortality. The trend of perinatal mortality rate has been stable between 90 and 40 per 1000 total births in the hospital and community setting, respectively. The significant reduction in NMR was due to significant decline in late neonatal mortality.

A meta-analysis of selected maternal and fetal factors for perinatal mortality.

BACKGROUND: In several developing countries, achieving Millennium Development Goal 4 is still off track. Multiple maternal and fetal risk factors were inconsistently attributed to the high perinatal mortality in developing countries. However, there was no meta-analysis that assessed the pooled effect of these factors on perinatal mortality. The purpose of this meta-analysis was to identify maternal and fetal factors predicting perinatal mortality. METHODS: In this meta-analysis, we included 23 studies that assessed perinatal mortality in relation to antenatal care, parity, mode of delivery, gestational age, birth weight and sex of the fetus. A computer based search of articles was conducted mainly in the databases of PUBMED, MEDLINE, HINARI, AJOL, Google Scholar and Cochrane Library. The overall odds ratios (OR) were determined by the random-effect model. Heterogeneity testing and sensitivity analysis were also conducted. RESULTS: The pooled analysis showed a strong association of perinatal mortality with lack of antenatal care (OR=3.2), prematurity (OR=7.9), low birth weight (OR=9.6), and marginal association with primigravidity (OR=1.5) and male sex (OR=1.2). The regression analysis also showed down-going trend lines of stillbirth and neonatal mortality rates in relation to the proportion of antenatal care. The metaanalysis showed that there was no association between mode of delivery and perinatal mortality. CONCLUSION: The present meta-analysis indicated a significant reduction in perinatal mortality among women who attended antenatal care, gave birth to term and normal birth weight baby. However, the association of perinatal mortality with parity, mode of delivery and fetal sex needs further investigation.

Skilled health personnel attended delivery as a proxy indicator for maternal and perinatal mortality: a systematic review.

BACKGROUND: Several demographic and health surveys in Africa have shown the high prevalence of home delivery, but little is known how strongly skilled person unattended deliveries are associated with maternal and perinatal mortality. The aim of this review was to assess the gross correlation of maternal mortality ratios (MMR) and perinatal mortality rates (PMR) with the proportion of skilled health personnel attended deliveries. METHODS: In this study, a systematic review was conducted after a computer based literature search was run in the electronic databases from 1990 through September 2013. Bivariate linear regression analyses were done for the proportion of skilled person attended deliveries in relation with MMR, stillbirth and neonatal mortality rates using national survey data of 41 African countries. RESULTS: African countries with relatively small population sizes and with middle to high income were found to have above 90% skilled person attended deliveries. Several African countries with a high proportion of skilled person attended deliveries (60%-100%) were able to reduce the MMR to the range of 56-370/100,000 live births. Several Sub Saharan African (SSA) countries were far from their northern counterparts. The regression analyses demonstrated a negative correlation of the proportion of skilled health personnel attended deliveries with the MMR, stillbirth rate and neonatal mortality rate. CONCLUSION: According to the national data of the included African countries, skilled delivery attendance was associated with significant reduction of maternal, fetal and neonatal mortality. SSA countries need to benchmark the experience of the North African countries to reduce the high maternal and perinatal deaths.

A meta-analysis of socio-demographic factors predicting birth in health facility.

BACKGROUND: The low proportion of health facility delivery in developing countries is one of the main challenges in achieving the Millennium Development Goal of a global reduction of maternal deaths by 75% by 2015. There are several primary studies which identified socio-demographic and other predictors of birth in health facility. However, there are no efforts to synthesis the findings of these studies. The objective of this meta-analysis was to determine the strength of the association of birth in the health facility with selected sociodemographic factors. METHODS: A meta-analysis of Mantel-Haenszel odds ratios was conducted by including 24 articles which were reported between 2000 and 2013 from developing countries. A computer-based search was done from MEDLINE, African Journals Online, Google Scholar and HINARI databases. Included studies did compare the women's' health facility delivery in relation to their selected socio-demographic characteristics. RESULTS: The pooled analysis demonstrated association of health facility delivery with living in urban areas (OR = 9.8), secondary and above educational level of the parents (OR = 5.0), middle to high wealth status (OR = 2.3) and first time pregnancy (OR = 2.8). The risk of delivering outside the health facility was not significantly associated with maternal age (teenage vs 20 years and above) and marital status. The distance of pregnant women's residence from the health facility was found to have an inverse relation to the proportion of health facility delivery. CONCLUSION: Although the present meta-analysis identified several variables which were associated with an increase in health facility delivery, the most important predictor of birth in the health facility amenable to intervention is educational status of the parents to be. Therefore, formal and informal education to women and family members on the importance of health facility delivery needs to be strengthened. Improving the wealth status of the population across the world may not be achieved soon, but should be in the long-term strategy to increase the birth rate in the health facility.

Antenatal care as a means of increasing birth in the health facility and reducing maternal mortality: a systematic review.

BACKGROUND: Although there is a general agreement on the importance of antenatal care to improve the maternal and perinatal health, little is known about its importance to improve health facility delivery in developing countries. The objective of this study was to assess the association of antenatal care with birth in health facility. METHODS: A systematic review with meta-analysis of Mantel-Haenszel odds ratios was conducted by including seventeen small scale studies that compared antenatal care and health facility delivery between 2003 and 2013. Additionally, national survey data of African countries which included antenatal care, health facility delivery and maternal mortality in their report were included. Data were accessed via a computer based search from MEDLINE, African Journals Online, HINARI and Google Scholar databases. RESULTS: The regression analysis of antenatal care with health facility delivery revealed a positive correlation. The pooled analysis also demonstrated that woman attending antenatal care had more than 7 times increased chance of delivering in a health facility. The comparative descriptive analysis, however, demonstrated a big gap between the proportion of antenatal care and health facility delivery by the same individuals (27%-95% vs 4%-45%). Antenatal care and health facility delivery had negative correlation with maternal mortality. CONCLUSION: The present regression and meta-analysis has identified the relative advantage of having antenatal care to give birth in health facilities. However, the majority of women who had antenatal care did not show up to a health facility for delivery. Therefore, future research needs to give emphasis to identifying barriers to health facility delivery despite having antenatal care follow up.

Reasons for persistently high maternal and perinatal mortalities in Ethiopia: Part II-Socio-economic and cultural factors.

BACKGROUND: The major causes of maternal and perinatal deaths are mostly pregnancy related. However, there are several predisposing factors for the increased risk of pregnancy related complications and deaths in developing countries. The objective of this review was to grossly estimate the effect of selected socioeconomic and cultural factors on maternal mortality, stillbirths and neonatal mortality in Ethiopia. METHODS: A comprehensive literature review was conducted focusing on the effect of total fertility rate (TFR), modern contraceptive use, harmful traditional practice, adult literacy rate and level of income on maternal and perinatal mortalities. For the majority of the data, regression analysis and Pearson correlation coefficient were used as a proxy indicator for the association of variables with maternal, fetal and neonatal mortality. RESULTS: Although there were variations in the methods for estimation, the TFR of women in Ethiopia declined from 5.9 to 4.8 in the last fifteen years, which was in the middle as compared with that of other African countries. The preference of injectable contraceptive method has increased by 7-fold, but the unmet contraceptive need was among the highest in Africa. About 50% reduction in female genital cutting (FGC) was reported although some women's attitude was positive towards the practice of FGC. The regression analysis demonstrated increased risk of stillbirths, neonatal and maternal mortality with increased TFR. The increased adult literacy rate was associated with increased antenatal care and skilled person attended delivery. Low adult literacy was also found to have a negative association with stillbirths and neonatal and maternal mortality. A similar trend was also observed with income. CONCLUSION: Maternal mortality ratio, stillbirth rate and neonatal mortality rate had inverse relations with income and adult education. In Ethiopia, the high total fertility rate, low utilization of contraceptive methods, low adult literacy rate, low income and prevalent harmful traditional practices have probably contributed to the high maternal mortality ratio, stillbirth and neonatal mortality rates.