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1.  Maternal near miss and mortality in a rural referral hospital in northern Tanzania: a cross-sectional study 
Background
Maternal morbidity and mortality in sub-Saharan Africa remains high despite global efforts to reduce it. In order to lower maternal morbidity and mortality in the immediate term, reduction of delay in the provision of quality obstetric care is of prime importance. The aim of this study is to assess the occurrence of severe maternal morbidity and mortality in a rural referral hospital in Tanzania as proposed by the WHO near miss approach and to assess implementation levels of key evidence-based interventions in women experiencing severe maternal morbidity and mortality.
Methods
A prospective cross-sectional study was performed from November 2009 until November 2011 in a rural referral hospital in Tanzania. All maternal near misses and maternal deaths were included. As not all WHO near miss criteria were applicable, a modification was used to identify cases. Data were collected from medical records using a structured data abstraction form. Descriptive frequencies were calculated for demographic and clinical variables, outcome indicators, underlying causes, and process indicators.
Results
In the two-year period there were 216 maternal near misses and 32 maternal deaths. The hospital-based maternal mortality ratio was 350 maternal deaths per 100,000 live births (95% CI 243–488). The maternal near miss incidence ratio was 23.6 per 1,000 live births, with an overall case fatality rate of 12.9%. Oxytocin for prevention of postpartum haemorrhage was used in 96 of 201 women and oxytocin for treatment of postpartum haemorrhage was used in 38 of 66 women. Furthermore, eclampsia was treated with magnesium sulphate in 87% of all cases. Seventy-four women underwent caesarean section, of which 25 women did not receive prophylactic antibiotics. Twenty-eight of 30 women who were admitted with sepsis received parenteral antibiotics. The majority of the cases with uterine rupture (62%) occurred in the hospital.
Conclusion
Maternal morbidity and mortality remain challenging problems in a rural referral hospital in Tanzania. Key evidence-based interventions are not implemented in women with severe maternal morbidity and mortality. Progress can be made through up scaling the use of evidence-based interventions, such as the use of oxytocin for prevention and treatment of postpartum haemorrhage.
doi:10.1186/1471-2393-13-141
PMCID: PMC3716905  PMID: 23826935
Maternal near miss; Severe acute maternal morbidity; Maternal mortality; Quality of obstetric care; WHO near miss approach; WHO near miss criteria
2.  Maternal near miss and death among women with severe hypertensive disorders: a Brazilian multicenter surveillance study 
Reproductive Health  2014;11:4.
Background
Hypertensive disorders represent the major cause of maternal morbidity in middle income countries. The main objective of this study was to identify the prevalence and factors associated with severe maternal outcomes in women with severe hypertensive disorders.
Methods
This was a cross-sectional, multicenter study, including 6706 women with severe hypertensive disorder from 27 maternity hospitals in Brazil. A prospective surveillance of severe maternal morbidity with data collected from medical charts and entered into OpenClinica®, an online system, over a one-year period (2009 to 2010). Women with severe preeclampsia, severe hypertension, eclampsia and HELLP syndrome were included in the study. They were grouped according to outcome in near miss, maternal death and potentially life-threatening condition. Prevalence ratios and 95% confidence intervals adjusted for cluster effect for maternal and perinatal variables and delays in receiving obstetric care were calculated as risk estimates of maternal complications having a severe maternal outcome (near miss or death). Poisson multiple regression analysis was also performed.
Results
Severe hypertensive disorders were the main cause of severe maternal morbidity (6706/9555); the prevalence of near miss was 4.2 cases per 1000 live births, there were 8.3 cases of Near Miss to 1 Maternal Death and the mortality index was 10.7% (case fatality). Early onset of the disease and postpartum hemorrhage were independent variables associated with severe maternal outcomes, in addition to acute pulmonary edema, previous heart disease and delays in receiving secondary and tertiary care.
Conclusions
In women with severe hypertensive disorders, the current study identified situations independently associated with a severe maternal outcome, which could be modified by interventions in obstetric care and in the healthcare system. Furthermore, the study showed the feasibility of a hospital system for surveillance of severe maternal morbidity.
doi:10.1186/1742-4755-11-4
PMCID: PMC3896751  PMID: 24428879
Organ dysfunction; Organ failure; Severe preeclampsia; Eclampsia; Maternal mortality; Maternal morbidity
3.  An Autopsy Study of Maternal Mortality in Mozambique: The Contribution of Infectious Diseases 
PLoS Medicine  2008;5(2):e44.
Background
Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios.
Methods and Findings
We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths.
Conclusions
In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.
Clara Menendez and colleagues analyze 139 complete autopsies following maternal deaths in Maputo, Mozambique and find a predominance of infectious and preventable causes.
Editors' Summary
Background.
Every year, half a million women—many of them living in developing countries—die during pregnancy or childbirth or within a few weeks of delivery. (The term “maternal deaths” is used to designate such deaths.) For women living in sub-Saharan Africa, the situation is particularly grim. Half of all maternal deaths occur in this region. The maternal mortality ratio (MMR)—the number of maternal deaths per 100,000 live births—in sub-Saharan Africa is nearly 1,000; in industrialized countries it is 8. The lifetime risk of maternal death in sub-Saharan Africa is 1 in 22; in industrialized countries it is 1 in 8,000. Faced with the magnitude of the global maternal death toll, in September 2000 the United Nations pledged, as its fifth Millennium Development Goal, that the global MMR would be reduced to a quarter of its 1990 level by 2015. Currently, it seems unlikely that this target will be met. Between 1990 and 2005 global maternal deaths decreased by only 1% per annum. In sub-Saharan Africa the annual reduction was even less—0.1% per annum.
Why Was This Study Done?
One reason for this slow progress is that public-health professionals in developing countries rarely have accurate data about the causes of maternal death, information that they need to guide their efforts to reduce these deaths. A detailed examination of the body after death (a medical autopsy) is the only sure way to ascertain the causes of maternal death, but in most developing countries, clinical records and verbal autopsies (asking relatives about the circumstances of the mother's death) are the main sources of these data and neither source is optimally accurate. The currently available information indicates that birth (obstetric) complications are the most frequent causes of maternal death in developing countries, in particular, hemorrhage (uncontrollable bleeding) after the baby is born. However, little is known about the impact of the HIV/AIDS epidemic (which is worst in Sub-Saharan Africa), malaria, or other infectious diseases on maternal deaths. In this study, the researchers use complete autopsies to determine the causes of maternal death in the Maputo Central Hospital, Mozambique, a tertiary-level hospital to which women with high-risk pregnancies are referred for specialized care.
What Did the Researchers Do and Find?
Between October 2002 and December 2004, there were 179 maternal deaths in the Maputo Central Hospital and 31,135 live births, corresponding to a ratio of 874 maternal deaths per 100,000 live births. (Because the hospital was a referral center, this ratio would not be expected to reflect the actual MMR for the general population of the Maputo area.) Complete autopsies were done on 139 of the women, HIV infection was measured using standard tests, and malaria was diagnosed by looking for parasites and malaria-associated changes in postmortem samples. Of these 139 women, just over one-third died because of obstetric complications; hemorrhage was the most common cause of death (one in six maternal deaths). The commonest nonobstetric causes of maternal death were HIV/AIDS- related conditions, including infections and cancers (about 1 in 8 maternal deaths; about half the women in the study were HIV positive). Other common causes were pyogenic (pus-forming) bacterial infections of the lungs and brain, and malaria. Together, these infectious diseases accounted for nearly half of the maternal deaths.
What Do These Findings Mean?
These findings indicate that infectious diseases account for a large proportion of maternal deaths at Maputo Central Hospital and identify which obstetric complications are responsible for most maternal deaths in this setting. They may not, however, accurately reflect the causes of maternal death elsewhere in Mozambique. For example, maternal deaths from some obstetric complications may be over-represented in this study because women at risk of these complications would have been referred to this hospital. Conversely, the proportion of women dying from hemorrhage may be higher in the community because this complication usually happens shortly after birth, leaving little time for women to reach a hospital for treatment. Nevertheless, these findings suggest that the implementation of effective measures to prevent and treat HIV/AIDS, malaria, and infections with pyogenic bacteria, together with improvements in health services for obstetric complications, should greatly reduce the maternal death toll in Mozambique and perhaps in other countries in sub-Saharan Africa.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050044.
UNICEF (the United Nations Children's Fund) provides information on maternal mortality including the WHO/UNICEF/UNFPA/The World Bank) estimates of maternal mortality for 2005 by country, and an article on maternal mortality in the Cabo Delgado province of Mozambique
More information on the WHO/UNICEF/UNFPA/The World Bank estimates of maternal mortality in 2005
The UK Department for International Development provides information about Millenium Development Goal 5: the improvement of maternal health
The US Centers for Disease Control and Prevention has a page on pregnancy-related deaths (in English and Spanish)
The Partnership for Maternal, Newborn and Child Health provides information on maternal deaths (in English, Spanish, French, Russian, Arabic, and Chinese)
The United Nations Development Fund for Women (UNIFEM) focuses on improving conditions for women worldwide, especially those in poverty
doi:10.1371/journal.pmed.0050044
PMCID: PMC2245982  PMID: 18288887
4.  Maternal near miss and maternal deaths in Mozambique: a cross-sectional, region-wide study of 635 consecutive cases assisted in health facilities of Maputo province 
Background
Life-threatening events during pregnancy are currently used as a measure to assess quality of obstetric care. The aim of this study is to assess prevalence of near miss cases and maternal deaths, to elucidate the causes and to analyze avoidable factors based upon the three-delays approach in southern Mozambique.
Methods
Near miss cases comprised five categories: eclampsia, severe hemorrhage, severe sepsis, uterine rupture and severe malaria. Pregnant women surviving the event were interviewed during a 5-month period within five health facilities offering comprehensive emergency obstetric care in Maputo City and Province. Family members gave additional information and were interviewed in case of the patient’s death.
Results
Out of 27,916 live births, 564 near miss cases and 71 maternal deaths were identified, giving a total maternal near miss ratio of 20/1,000 live births and maternal mortality ratio of 254/100,000 live births, respectively. Near miss fatality rate was 11.2%. Among near miss cases hemorrhage accounted for the most common event (58.0%), followed by eclampsia (35.5%); HIV seroprevalence was 22.3%. Inappropriate attendance in antenatal care services (21.1%), late or wrong diagnosis (12.6%), inadequate management immediately after delivery (9.6%), no monitoring of blood pressure and other vital signs (9.2%) were the most prevalent factors contributing to the severe morbidity under study. Third delay was identified in 69.7% of the interviews. In more than one fourth of near miss cases treatment was not started immediately. Lack of blood derivates and unavailable operating room were reported in 42.0% and 35.0%, respectively.
Conclusions
Near miss cases were frequent and related to delays in reaching and receiving adequate care. First and third type of delay contributed significantly to the number of maternal near miss cases and deaths. Maternal health policies need to be concerned not only with averting the loss of life, but also with ameliorating care of severe maternal complications at all levels including primary care. Sexual and reproductive health services for adolescents should be prioritized to prevent adverse outcomes.
doi:10.1186/s12884-014-0401-3
PMCID: PMC4269100  PMID: 25491393
Near miss; Severe acute maternal morbidity; Maternal mortality; Substandard care
5.  Clinico-Pathological Discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis 
PLoS Medicine  2009;6(2):e1000036.
Background
Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death.
Methods and Findings
A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n = 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%).
Conclusions
Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.
Jaume Ordi and colleagues examine the discrepancies between clinical diagnoses of causes of maternal deaths and pathological findings by necropsy in Mozambique.
Editors' Summary
Background.
Every year, about half a million women die during pregnancy or childbirth or soon after delivery—so-called “maternal deaths.” Although nearly all these maternal deaths occur in developing countries, the situation is particularly bad in sub-Saharan Africa where more than a quarter of a million maternal deaths occur annually. The number of maternal deaths per 100,000 live births in this region is nearly 1,000, whereas in developed regions it is only nine deaths. A 15-year-old girl living in sub-Saharan Africa has a lifetime risk of dying during pregnancy or childbirth of 1 in 22, but a girl living in the developed regions of the world has a lifetime risk of only 1 in 7,300. Maternal deaths can be caused by obstetric (childbirth-related) complications such as puerperal septicemia (an infection of the blood contracted during delivery) and eclampsia (seizures associated with high blood pressure during pregnancy), and by nonobstetric conditions such as HIV/AIDS-related infections and other infections.
Why Was This Study Done?
In 2000, the United Nations made reduction of the global burden of maternal mortality one of its Millennium Development Goals (a set of targets designed to eradicate poverty by 2015), but little progress has been made toward achieving this goal. One possible explanation for this failure might be that limited access to diagnostic tests in developing countries results in more clinical diagnostic errors than in developed countries and that, consequently, mothers in developing countries don't always get the right treatment when they become ill. Unfortunately, it is difficult to test this hypothesis, because there is very little accurate information on the causes of maternal death in many developing countries. What information there is comes mainly from clinical records and verbal autopsies (asking relatives about the mother's death) rather than from examination of the body after death (a medical autopsy), the only sure way to ascertain the cause of death. In this study, the researchers retrospectively analyze discrepancies between the clinical diagnoses and autopsy diagnoses of 139 mothers who died at the Maputo Central Hospital, Mozambique, a large hospital providing specialized care for women with high-risk pregnancies.
What Did the Researchers Do and Find?
All the organs from the mothers were visually examined by a pathologist and samples of any abnormal tissues and of the internal organs were examined microscopically. Two pathologists independently established the cause of each death by considering both the clinical diagnosis and the autopsy results (the “autopsy diagnosis”). The discrepancies between the clinical and autopsy (“gold standard”) diagnoses were then analyzed. Major diagnostic errors (errors involving the cause of death) occurred in nearly half of the maternal deaths; the clinical and autopsy diagnoses completely agreed in only a third of cases. 80% of the major diagnostic errors were “class I errors.” That is, errors where a correct diagnosis would have changed patient management and prolonged survival or provided a cure. For example, 12 women were given an incorrect diagnosis of eclampsia when they had other conditions that could have been successfully treated if correctly diagnosed. Furthermore, many infections detected in the autopsies were missed in the clinical diagnoses (false-negative diagnoses), some of which could have been treated.
What Do These Findings Mean?
These findings show that clinical and autopsy diagnoses of the causes of maternal death frequently disagree in this hospital. Further studies are needed to see whether similar levels of disagreement exist in other hospitals in sub-Saharan Africa. The discrepancy reported here might, for example, be an overestimate of the general situation, because the high-risk pregnancies referred to this hospital might involve more hard-to-diagnose problems than the routine pregnancies referred to other hospitals. Nevertheless, these findings suggest that misdiagnosed conditions may affect maternal mortality rates in sub-Saharan Africa and that an increased use of autopsy in the region could reduce maternal mortality by providing more accurate information about why mothers die. In particular, these findings suggest that a more thorough evaluation of cases thought to be eclampsia and a better awareness of the involvement of infectious diseases in maternal deaths might reduce diagnostic errors and consequently reduce the incidence of maternal deaths.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000036.
UNICEF (the United Nations Children's Fund) provides information on maternal mortality and the WHO/UNICEF/UNFPA/The World Bank estimates of maternal mortality for 2005 by country
The WHO/UNICEF/UNFPA/The World Bank estimates of maternal mortality in 2005 also provides full information about global maternal mortality
The UK Department for International Development provides information about Millenium Development Goal 5: the improvement of maternal health
The Partnership for Maternal, Newborn and Child Health provides information on maternal deaths (in several languages), including information on the situation in Mozambique
doi:10.1371/journal.pmed.1000036
PMCID: PMC2646780  PMID: 19243215
6.  Obstetric near-miss and maternal mortality in maternity university hospital, Damascus, Syria: a retrospective study 
Background
Investigating severe maternal morbidity (near-miss) is a newly recognised tool that identifies women at highest risk of maternal death and helps allocate resources especially in low income countries. This study aims to i. document the frequency and nature of maternal near-miss at hospital level in Damascus, Capital of Syria, ii. evaluate the level of care at maternal life-saving emergency services by comparatively analysing near-misses and maternal mortalities.
Methods
Retrospective facility-based review of cases of near-miss and maternal mortality that took place in the years 2006-2007 at Damascus Maternity University Hospital, Syria. Near-miss cases were defined based on disease-specific criteria (Filippi 2005) including: haemorrhage, hypertensive disorders in pregnancy, dystocia, infection and anaemia. Main outcomes included maternal mortality ratio (MMR), maternal near miss ratio (MNMR), mortality indices and proportion of near-miss cases and mortality cases to hospital admissions.
Results
There were 28 025 deliveries, 15 maternal deaths and 901 near-miss cases. The study showed a MNMR of 32.9/1000 live births, a MMR of 54.8/100 000 live births and a relatively low mortality index of 1.7%. Hypertensive disorders (52%) and haemorrhage (34%) were the top causes of near-misses. Late pregnancy haemorrhage was the leading cause of maternal mortality (60%) while sepsis had the highest mortality index (7.4%). Most cases (93%) were referred in critical conditions from other facilities; namely traditional birth attendants homes (67%), primary (5%) and secondary (10%) healthcare unites and private practices (11%). 26% of near-miss cases were admitted to Intensive Care Unit (ICU).
Conclusion
Near-miss analyses provide valuable information on obstetric care. The study highlights the need to improve antenatal care which would help early identification of high risk pregnancies. It also emphasises the importance of both: developing protocols to prevent/manage post-partum haemorrhage and training health care professionals to manage infrequent but fatal conditions like sepsis. An urgent review of the referral system and the emergency obstetric care in Syria is highly recommended.
doi:10.1186/1471-2393-10-65
PMCID: PMC2973846  PMID: 20959012
7.  "Near-miss" obstetric events and maternal deaths in Sagamu, Nigeria: a retrospective study 
Aim
To determine the frequency of near-miss (severe acute maternal morbidity) and the nature of near-miss events, and comparatively analysed near-miss morbidities and maternal deaths among pregnant women managed over a 3-year period in a Nigerian tertiary centre.
Methods
Retrospective facility-based review of cases of near-miss and maternal death which occurred between 1 January 2002 and 31 December 2004. Near-miss case definition was based on validated disease-specific criteria, comprising of five diagnostic categories: haemorrhage, hypertensive disorders in pregnancy, dystocia, infection and anaemia. The near-miss morbidities were compared with maternal deaths with respect to demographic features and disease profiles. Mortality indices were determined for various disease processes to appreciate the standard of care provided for life-threatening obstetric conditions. The maternal death to near-miss ratios for the three years were compared to assess the trend in the quality of obstetric care.
Results
There were 1501 deliveries, 211 near-miss cases and 44 maternal deaths. The total near-miss events were 242 with a decreasing trend from 2002 to 2004. Demographic features of cases of near-miss and maternal death were comparable. Besides infectious morbidity, the categories of complications responsible for near-misses and maternal deaths followed the same order of decreasing frequency. Hypertensive disorders in pregnancy and haemorrhage were responsible for 61.1% of near-miss cases and 50.0% of maternal deaths. More women died after developing severe morbidity due to uterine rupture and infection, with mortality indices of 37.5% and 28.6%, respectively. Early pregnancy complications and antepartum haemorrhage had the lowest mortality indices. Majority of the cases of near-miss (82.5%) and maternal death (88.6%) were unbooked for antenatal care and delivery in this hospital. Maternal mortality ratio for the period was 2931.4 per 100,000 deliveries. The overall maternal death to near-miss ratio was 1: 4.8 and this remained relatively constant over the 3-year period.
Conclusion
The quality of care received by critically ill obstetric patients in this centre is suboptimal with no evident changes between 2002 and 2004. Reduction of the present maternal mortality ratio may best be achieved by developing evidence-based protocols and improving the resources for managing severe morbidities due to hypertension and haemorrhage especially in critically ill unbooked patients. Tertiary care hospitals in Nigeria could also benefit from evaluation of their standard of obstetric care by including near-miss investigations in their maternal death enquiries.
doi:10.1186/1742-4755-2-9
PMCID: PMC1291401  PMID: 16262901
8.  Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study 
PLoS Medicine  2014;11(7):e1001672.
Marion Knight and colleagues conducted a national prospective case-control study in the UK from June 2011 through May 2012 to estimate the incidence, describe the causative organisms and sources of infection, and identify the risk factors for severe maternal sepsis.
Please see later in the article for the Editors' Summary
Background
In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.
Methods and Findings
A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%).
Conclusions
For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly 300,000 women worldwide die during pregnancy or labour, or shortly after. According to a recent World Health Organization estimate, sepsis (blood poisoning) is responsible for 10.7% of these maternal deaths. Sepsis is caused by an inappropriate immune response to an infection. Normally, when bacteria or other microbes enter the human body, the immune system efficiently destroys the invaders. In sepsis, the immune system goes into overdrive, and the chemicals it releases into the blood to combat infection trigger widespread inflammation. This inflammation leads to the formation of small blood clots and leaky blood vessels that block the flow of blood to the vital organs. In the most severe cases (septic shock), blood pressure falls to dangerously low levels, multiple organs fail, and the patient can die. Symptoms of sepsis include fever, rapid breathing, and a fast heart rate. Sepsis, which often progresses rapidly, can be treated in its early stages with antibiotics alone. People with severe sepsis need to be admitted to an intensive care unit, where their vital organs can be supported while the infection is treated.
Why Was This Study Done?
Deaths from maternal sepsis mainly occur in low- and middle-income countries, but the rate of such deaths is increasing in countries with advanced healthcare systems. In the UK, for example, the incidence (the number of cases) of fatal maternal sepsis has increased markedly over the past two decades, and although the absolute risk of maternal death from sepsis is low, increasing numbers of women are experiencing severe maternal sepsis. To avoid preventable maternal illness and death in the UK, it is essential that clinical management and infection control strategies for maternal sepsis are improved. Here, to learn more about the incidence of maternal sepsis, the causative organisms and sources of infection, and the risk factors for maternal sepsis in the UK, the researchers undertake a national case-control study of severe maternal sepsis. A case-control study compares the characteristics of individuals with and without a given disease.
What Did the Researchers Do and Find?
For this study, clinicians in all the UK obstetrician-led maternity units (obstetricians care for women throughout pregnancy, labour, and the post-labour period) sent information about every woman who developed severe sepsis between June 2011 and May 2012 (365 cases) and about two unaffected (control) women per case to the United Kingdom Obstetric Surveillance System (UKOSS). Using this information and data on the number of maternities in the UK during this 12-month period, the researchers calculated that the incidence of severe sepsis was 4.7 per 10,000 maternities. Seventy-one women with severe sepsis (19.5% of cases) developed septic shock, and five women (1.4% of cases) died. The most common source of sepsis (implicated in about a third of cases) was a genital tract infection. Statistical analyses identified several risk factors for severe maternal sepsis, including having a fever or taking antibiotics in the two weeks preceding sepsis and all types of operative delivery (including cesarean delivery). Importantly, although Escherichia coli was the most common causative organism in severe maternal sepsis (present in a fifth of cases), infection with group A streptococcus was strongly associated with progression to septic shock. Moreover, in half the women with a group A streptococcal infection, severe sepsis was diagnosed within two hours of the first signs of a systemic inflammatory response.
What Do These Findings Mean?
These findings show that for every death from maternal sepsis in the UK, about 50 women develop life-threatening severe sepsis, that the onset of severe sepsis is very rapid, and that women who have recently had an infection are at particularly high risk of developing maternal sepsis. Although some pregnant women who developed severe sepsis during the study period may not have been included in the study, these findings have important clinical implications for the management of maternal sepsis in the UK and elsewhere. The findings suggest that pregnant or recently pregnant women with an infection need closer attention than women who are not pregnant, and adequate follow-up to ensure eradication of the infection. The findings also highlight the importance of giving high-dose intravenous antibiotics to anyone with suspected sepsis within an hour of admission to hospital as recommended by the international Surviving Sepsis Campaign, an initiative that was developed to improve the management, diagnosis, and treatment of sepsis. Finally, these findings suggest that signs of severe sepsis, particularly in women with a confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001672.
The UK National Health Service Choices website has information about sepsis
The international Surviving Sepsis Campaign guidelines for the treatment of sepsis are available through the campaign's website
The Sepsis Alliance, a US not-for-profit organization, also provides information about sepsis for patients and their families (in English and Spanish), including information about maternal sepsis and several personal stories about maternal sepsis (see the stories of Alanna Basinger, Alisa Proctor, Sandy C, and Natalie Banathy)
The not-for profit UK Sepsis Trust is another useful source of information about sepsis that includes patient stories
MedlinePlus provides links to additional resources about sepsis (in English and Spanish)
UKOSS provides more information about its national case-control study on severe maternal sepsis in the UK
doi:10.1371/journal.pmed.1001672
PMCID: PMC4086731  PMID: 25003759
9.  “Near Miss” Obstetric Events and Maternal Deaths in a Tertiary Care Hospital: An Audit 
Journal of Pregnancy  2013;2013:393758.
Objectives. (1) To determine the frequency of maternal near miss, maternal near miss incidence ratio (MNMR), maternal near miss to mortality ratio and mortality index. (2) To compare the nature of near miss events with that of maternal mortality. (3) To see the trend of near miss events. Design. Audit. Setting. Kasturba Hospital, Manipal University, Manipal, India. Population. Near miss cases & maternal deaths. Methods. Cases were defined based on WHO criteria 2009. Main Outcome Measures. Severe acute maternal morbidity and maternal deaths. Results. There were 7390 deliveries and 131 “near miss” cases during the study period. The Maternal near miss incidence ratio was 17.8/1000 live births, maternal near miss to mortality ratio was 5.6 : 1, and mortality index was 14.9%. A total of 126 cases were referred, while 5 cases were booked at our hospital. Hemorrhage was the leading cause (44.2%), followed by hypertensive disorders (23.6%) and sepsis (16.3%). Maternal mortality ratio (MMR) was 313/100000 live births. Conclusion. Hemorrhage and hypertensive disorders are the leading causes of near miss events. New-onset viral infections have emerged as the leading cause of maternal mortality. As near miss analysis indicates the quality of health care, it is worth presenting in national indices.
doi:10.1155/2013/393758
PMCID: PMC3710620  PMID: 23878737
10.  The Effectiveness of Emergency Obstetric Referral Interventions in Developing Country Settings: A Systematic Review 
PLoS Medicine  2012;9(7):e1001264.
In a systematic review of the literature, Julia Hussein and colleagues seek to determine the effect of referral interventions that enable emergency access to health facilities for pregnant women living in developing countries.
Background
Pregnancy complications can be unpredictable and many women in developing countries cannot access health facilities where life-saving care is available. This study assesses the effects of referral interventions that enable pregnant women to reach health facilities during an emergency, after the decision to seek care is made.
Methods and findings
Selected bibliographic databases were searched with no date or language restrictions. Randomised controlled trials and quasi experimental study designs with a comparison group were included. Outcomes of interest included maternal and neonatal mortality and other intermediate measures such as service utilisation. Two reviewers independently selected, appraised, and extracted articles using predefined fields. Forest plots, tables, and qualitative summaries of study quality, size, and direction of effect were used for analysis.
Nineteen studies were included. In South Asian settings, four studies of organisational interventions in communities that generated funds for transport reduced neonatal deaths, with the largest effect seen in India (odds ratio 0·48 95% CI 0·34–0·68). Three quasi experimental studies from sub-Saharan Africa reported reductions in stillbirths with maternity waiting home interventions, with one statistically significant result (OR 0.56 95% CI 0.32–0.96). Effects of interventions on maternal mortality were unclear. Referral interventions usually improved utilisation of health services but the opposite effect was also documented. The effects of multiple interventions in the studies could not be disentangled. Explanatory mechanisms through which the interventions worked could not be ascertained.
Conclusions
Community mobilisation interventions may reduce neonatal mortality but the contribution of referral components cannot be ascertained. The reduction in stillbirth rates resulting from maternity waiting homes needs further study. Referral interventions can have unexpected adverse effects. To inform the implementation of effective referral interventions, improved monitoring and evaluation practices are necessary, along with studies that develop better understanding of how interventions work.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 350,000 women die from pregnancy- or childbirth-related complications. Almost all of these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (MMR, the number of maternal deaths per 100,000 live births) is 500 and a woman's life-time risk of dying from complications of pregnancy or childbirth is 1 in 39. By contrast, the MMR in industrialized countries is 12 and women have a life-time risk of maternal death of 1 in 4,700. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy, all of which are preventable or treatable conditions. Unfortunately, it is hard to predict which women will develop pregnancy complications, many complications rapidly become life-threatening and, in developing countries, women often deliver at home, far from emergency obstetric services; obstetrics deals with the care of women and their children during pregnancy, childbirth, and the postnatal period.
Why Was This Study Done?
It should be possible to reduce maternal deaths (and the deaths of babies during pregnancy, childbirth, and early life) in developing countries by ensuring that pregnant women are referred to emergency obstetric services quickly when the need arises. Unfortunately, in such countries referral to emergency obstetric care is beset with problems such as difficult geographical terrain, transport costs, lack of vehicles, and suboptimal location and distribution of health care facilities. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers assess the effectiveness of interventions designed to reduce the “phase II delay” in referral to emergency obstetric care in developing countries—the time it takes a woman to reach an appropriate health care facility once a problem has been recognized and the decision has been taken to seek care. Delays in diagnosis and the decision to seek care are phase I delays in referral, whereas delays in receiving care once a women reaches a health care facility are phase III delays.
What Did the Researchers Do and Find?
The researchers identified 19 published studies that described 14 interventions designed to overcome phase II delays in emergency obstetric referral and that met their criteria for inclusion in their systematic review. About half of the interventions were organizational. That is, they were designed to overcome barriers to referral such as costs. Most of the remaining interventions were structural. That is, they involved the provision of, for example, ambulances and maternity waiting homes—placed close to a health care facility where women can stay during late pregnancy. Although seven studies provided data on maternal mortality, none showed a sustained, statistically significant reduction (a reduction unlikely to have occurred by chance) in maternal deaths. Four studies in South Asia in which communities generated funds for transport reduced neonatal deaths (deaths of babies soon after birth), but the only statistically significant effect of this community mobilization intervention was seen in India where neonatal deaths were halved. Three studies from sub-Saharan Africa reported that the introduction of maternity waiting homes reduced stillbirths but this reduction was only significant in one study. Finally, although referral interventions generally improved the utilization of health services, in one study the provision of bicycle ambulances to take women to the hospital reduced the proportion of women delivering in health facilities, probably because women felt that bicycle ambulances drew unwanted attention to them during labor and so preferred to stay at home.
What Do These Findings Mean?
These findings suggest that community mobilization interventions may reduce neonatal mortality and that maternity waiting rooms may reduce stillbirths. Importantly, they also highlight how referral interventions can have unexpected adverse effects. However, because the studies included in this systematic review included multiple interventions designed to reduce delays at several stages of the referral process, it is not possible to disentangle the contribution of each component of the intervention. Moreover, it is impossible at present to determine why (or even if) any of the interventions reduced maternal mortality. Thus, the researchers conclude, improved monitoring of interventions and better evaluation of outcomes is essential to inform the implementation of effective referral interventions, and more studies are needed to improve understanding of how referral interventions work.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001264.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF./UNFPA/World Bank 2008 country estimates of maternal mortality
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Veil of Tears contains personal stories from Afghanistan about loss in childbirth; the non-governmental health development organization AMREF provides personal stories about maternal health in Africa
Maternal Death: The Avoidable Crisis is a briefing paper published by Médecins Sans Frontières (MSF) in March 2012
doi:10.1371/journal.pmed.1001264
PMCID: PMC3393680  PMID: 22807658
11.  Maternal near-miss and mortality in Sayaboury Province, Lao PDR 
BMC Public Health  2014;14(1):945.
Background
Maternal near-miss (MNM) incidence is the indicator reflecting maternal healthcare services. This study aimed to determine the burden of maternal near-miss and maternal deaths in Sayaboury Province, Lao PDR.
Methods
A descriptive study was done in a cohort of 1215 pregnant women, who had their last normal menstrual period (LMP) between 1 August and 31 December, 2010. WHO criteria for MNM were used to identify near-miss cases and maternal deaths during February – November 2011. Data of maternal characteristics, MNM, and maternal deaths were prospectively collected by primary health care workers in the villages under supervision of health staff in local health centers and by the head nurses of the gynecology - obstetric wards in the studied hospitals. Frequencies with 95% confidence intervals (CIs) were used to describe maternal near-misses and maternal deaths.
Results
Overall, 92.5% of the 1215 pregnancies were delivered, 7.5% were aborted. Eleven women were identified as near-miss cases, giving a maternal near miss (MNM) ratio of 9.8 (95% CI: 4.9 -17.5)/1,000 live births. With two maternal deaths, the maternal mortality ratio (MMR) was 178 (95% CI: 50–650)/100,000 live births. Together, these constituted 13 cases of severe maternal outcome (SMO) and given the SMO ratio of 11.6 (95% CI: 6.2 - 19.8)/1,000 live births.
Conclusion
The study shows a surprisingly low MNM ratio and MMR in Sayaboury Province, Lao PDR. Generalization of the results is limited by problems in applying standard criteria for the identification of near-misses in the communities and local hospitals. However, the findings are considered to have important implications for the improvement of maternal health services in low resource settings, e.g. to obtain valid and reliable maternal near miss and maternal deaths for the whole country.
doi:10.1186/1471-2458-14-945
PMCID: PMC4177158  PMID: 25213771
Maternal near- miss; Maternal mortality; Severe maternal outcome; Maternal complication
12.  Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis 
PLoS Medicine  2010;7(4):e1000264.
A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years.
Background
Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India.
Methods and Findings
Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold (∼23%–35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness.
Conclusions
Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women's needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than half a million women—most of them living in developing countries—die from pregnancy- or childbirth-related complications. About a quarter of these “maternal” deaths occur in India. In 2005, a woman's lifetime risk of maternal death in India was 1 in 70; in the UK, it was only one in 8,200. Similarly, the maternal mortality ratio (MMR; number of maternal deaths per 100,000 live births) in India was 450, whereas in the UK it was eight. Faced with the enormous maternal death toll in India and other developing countries, in September 2000, the United Nations pledged, as its fifth Millennium Development Goal (MDG 5), that the global MMR would be reduced to a quarter of its 1990 level by 2015. Currently, it seems unlikely that this target will be met. Between 1990 and 2005, global maternal deaths decreased by only 1% per annum instead of the 5% needed to reach MDG 5; in India, the decrease in maternal deaths between 1990 and 2005 was about 1.8% per annum.
Why Was This Study Done?
Most maternal deaths in developing countries are caused by severe bleeding after childbirth, infections soon after delivery, blood pressure disorders during pregnancy, and obstructed (difficult) labors. Consequently, experts agree that universal access to high-quality routine care during labor (“obstetric” care) and to emergency obstetrical care is needed to reduce maternal deaths. However, there is less agreement about how to adapt these “ideal recommendations” to specific situations. In developing countries with weak health systems and predominantly rural populations, it is unlikely that all women will have access to emergency obstetric care in the near future—so would beginning with improved access to family planning and to safe abortions (unsafe abortion is another major cause of maternal death) be a more achievable, more cost-effective way of reducing maternal deaths? How would family planning and safe abortion be coupled efficiently and cost-effectively with improved access to intrapartum care? In this study, the researchers investigate these questions by estimating the health and economic outcomes of various strategies to reduce maternal mortality in India.
What Did the Researchers Do and Find?
The researchers used a computer-based model that simulates women through pregnancy and childbirth to estimate the effect of different strategies (for example, increased family planning or increased access to obstetric care) on clinical outcomes (pregnancies, live births, or deaths), costs, and cost-effectiveness (the cost of saving one year of life) in India. Increased family planning was the most effective single intervention for the reduction of pregnancy-related mortality. If the current unmet need for family planning in India could be fulfilled over the next 5 years, more than 150,000 maternal deaths would be prevented, more than US$1 billion saved, and at least half of abortion-related deaths averted. However, increased family planning alone would reduce maternal deaths by 35% at most, so the researchers also used their model to test the effect of combinations of strategies on maternal death. They found that an integrated and stepwise approach (increased family planning and safe abortion combined with consecutively increased skilled birth attendants, improved care before and after birth, reduced home births, and improved emergency obstetric care) could eventually prevent nearly 80% of maternal deaths. All the steps in this strategy either saved money or involved an additional cost per year of life saved of less than US$500; given one suggested threshold for cost-effectiveness in India of the per capita GDP (US$1,068) per year of life saved, these strategies would be considered very cost-effective.
What Do These Findings Mean?
The accuracy of these findings depends on the assumptions used to build the model and the quality of the data fed into it. Nevertheless, these findings suggest that early intensive efforts to improve family planning and to provide safe abortion accompanied by a systematic, stepwise effort to improve integrated maternal health services could reduce maternal deaths in India by more than 75% in less than a decade. Furthermore, such a strategy would be cost-effective. Indeed, note the researchers, the cost savings from an initial focus on family planning and safe abortion provision would partly offset the resources needed to assure that every woman had access to high quality routine and emergency obstetric care. Thus, overall, these findings suggest that MDG 5 may be within reach in India, a conclusion that should help to mobilize political support for this worthy goal.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000264.
UNICEF (the United Nations Children's Fund) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/The World Bank 2005 country estimates of maternal mortality
The World Health Organization also provides information on maternal health and about MDG 5 (in several languages)
The United Nations Millennium Development Goals Web site provides detailed information about the Millennium Declaration, the MDGs, their targets and their indicators, and about MDG 5.
The Millennium Development Goals Report 2009 and its progress chart provide an up-to-date assessment of progress toward all the MDGs
Computer simulation modeling as applied to health is further discussed at the Center for Health Decision Science at Harvard University
doi:10.1371/journal.pmed.1000264
PMCID: PMC2857650  PMID: 20421922
13.  Maternal near miss and quality of maternal health care in Baghdad, Iraq 
Background
The maternal near-miss concept has been developed as an instrument for assisting health systems to evaluate and improve their quality of care. Our study aimed at studying the characteristics and quality of care provided to women with severe complications in Baghdad through the use of the World Health Organization (WHO) near-miss approach for maternal health.
Methods
This is a facility-based, cross-sectional study conducted in 6 public hospitals in Baghdad between March 1, 2010 and the June 30, 2010. WHO near-miss approach was utilized to analyze the data in terms of indicators of maternal near miss and access to and quality of maternal care.
Results
The maternal near-miss rate was low at 5.06 per 1,000 live births, while the overall maternal near miss: mortality ratio was 9:1. One third of the near-miss cases were referred from other facilities and the mortality index was the same for referred women and for in-hospital women (11%). The intensive care unit (ICU) admission rate was 37% for women with severe maternal outcomes (SMO), while the overall admission rate was 0.28%. Anemia (55%) and previous cesarean section (45%) were the most common associated conditions with severe maternal morbidity. The use of magnesium sulfate for treatment of eclampsia, oxytocin for prevention and treatment of postpartum hemorrhage, prophylactic antibiotics during caesarean section, and corticosteroids for inducing fetal lung maturation in preterm birth is suboptimum.
Conclusions
The WHO near-miss approach allowed systematic identification of the roadblocks to improve quality of care and then monitoring the progress. Critical evidence-based practices, relevant to the management of women experiencing life-threatening conditions, are underused. In addition, possible limitations in the referral system result in a very high proportion of women presenting at the hospital already in a severe health condition (i.e. with organ dysfunction). A shortage of ICU beds leading to women taken care of without admission to ICU may also contribute to a high proportion of maternal deaths and organ dysfunction.
doi:10.1186/1471-2393-13-11
PMCID: PMC3558361  PMID: 23324222
Maternal morbidity; Obstetric complications; WHO near-miss approach; Quality improvement; Developing countries; Baghdad
14.  Maternal near-miss in a rural hospital in Sudan 
Background
Investigation of maternal near-miss is a useful complement to the investigation of maternal mortality with the aim of meeting the United Nations' fifth Millennium Development Goal. The present study was conducted to investigate the frequency of near-miss events, to calculate the mortality index for each event and to compare the socio-demographic and obstetrical data (age, parity, gestational age, education and antenatal care) of the near-miss cases with maternal deaths.
Methods
Near-miss cases and events (hemorrhage, infection, hypertensive disorders, anemia and dystocia), maternal deaths and their causes were retrospectively reviewed and the mortality index for each event was calculated in Kassala Hospital, eastern Sudan over a 2-year period, from January 2008 to December 2010. Disease-specific criteria were applied for these events.
Results
There were 9578 deliveries, 205 near-miss cases, 228 near-miss events and 40 maternal deaths. Maternal near-miss and maternal mortality ratio were 22.1/1000 live births and 432/100 000 live births, respectively. Hemorrhage accounted for the most common event (40.8%), followed by infection (21.5%), hypertensive disorders (18.0%), anemia (11.8%) and dystocia (7.9%). The mortality index were 22.2%, 10.0%, 10.0%, 8.8% and 2.4% for infection, dystocia, anemia, hemorrhage and hypertensive disorders, respectively.
Conclusion
There is a high frequency of maternal morbidity and mortality at the level of this facility. Therefore maternal health policy needs to be concerned not only with averting the loss of life, but also with preventing or ameliorating maternal-near miss events (hemorrhage, infections, hypertension and anemia) at all care levels including primary level.
doi:10.1186/1471-2393-11-48
PMCID: PMC3141596  PMID: 21714881
15.  Applying the new concept of maternal near-miss in an intensive care unit 
Clinics  2012;67(3):225-230.
OBJECTIVES:
The World Health Organization has recommended investigating near-misses as a benchmark practice for monitoring maternal healthcare and has standardized the criteria for diagnosis. We aimed to study maternal morbidity and mortality among women admitted to a general intensive care unit during pregnancy or in the postpartum period, using the new World Health Organization criteria.
METHODS:
In a cross-sectional study, 158 cases of severe maternal morbidity were classified according to their outcomes: death, maternal near-miss, and potentially life-threatening conditions. The health indicators for obstetrical care were calculated. A bivariate analysis was performed using the Chi-square test with Yate's correction or Fisher's exact test. A multiple regression analysis was used to calculate the crude and adjusted odds ratios, together with their respective 95% confidence intervals.
RESULTS:
Among the 158 admissions, 5 deaths, 43 cases of maternal near-miss, and 110 cases of potentially life-threatening conditions occurred. The near-miss rate was 4.4 cases per 1,000 live births. The near-miss/death ratio was 8.6 near-misses for each maternal death, and the overall mortality index was 10.4%. Hypertensive syndromes were the main cause of admission (67.7% of the cases, 107/158); however, hemorrhage, mainly due to uterine atony and ectopic pregnancy complications, was the main cause of maternal near-misses and deaths (17/43 cases of near-miss and 2/5 deaths).
CONCLUSIONS:
Hypertension was the main cause of admission and of potentially life-threatening conditions; however, hemorrhage was the main cause of maternal near-misses and deaths at this institution, suggesting that delays may occur in implementing appropriate obstetrical care.
doi:10.6061/clinics/2012(03)04
PMCID: PMC3297030  PMID: 22473402
Maternal mortality; Maternal near-miss; Organ dysfunction or failure; Obstetrical hemorrhage; Severe pre-eclampsia/eclampsia
16.  Risk factors for reported obstetric complications and near misses in rural northwest Bangladesh: analysis from a prospective cohort study 
Background
In rural Bangladesh, more than 75% of all births occur at home in the absence of skilled birth attendants. Population-based data are lacking on the burden and risk factors for obstetric complications in settings with low rates of institutional delivery. We sought to describe the prevalence of reported complications and to analyze risk factors for obstetric complications and near misses, using data from a representative, rural setting of Bangladesh.
Methods
This study utilized existing data on 42,214 pregnant women enrolled in a micronutrient supplementation cohort trial between 2007 and 2011 in rural northwest Bangladesh. Based on self-report of complications, women were categorized as having obstetric complications, near misses, or non-complicated pregnancies using definitions modified from the World Health Organization. Multivariable multinomial regression was used to analyze the association of biological, socioeconomic, and psychosocial variables with obstetric complications or near misses.
Results
Of enrolled women, 25% (n = 10,380) were classified as having at least one obstetric complication, 2% (n = 1,004) with reported near misses, and 73% (n = 30,830) with non-complicated pregnancies. Twelve percent (n = 5,232) reported hemorrhage and 8% (n = 3,259) reported sepsis. Of the 27,241 women with live births or stillbirths, 11% (n = 2,950) reported obstructed labor and 1% (n = 328) reported eclampsia. Biological risk factors including women’s age less than 18 years (Relative Risk Ratio [RRR] 1.26 95%CI:1.14-1.39) and greater than 35 years (RRR 1.23 95%CI:1.09-1.38), history of stillbirth or miscarriage (RRR 1.15 95%CI:1.07-1.22), and nulliparity (RRR 1.16 95%CI:1.02-1.29) significantly increased the risk of obstetric complications. Neither partner wanting the pregnancy increased the risk of obstetric complications (RRR 1.33 95%CI:1.20-1.46). Mid-upper arm circumference <21.5 cm increased the risk of hemorrhage and sepsis.
Conclusions
These analyses indicate a high burden of obstetric morbidity. Maternal age, nulliparity, a history of miscarriage or stillbirth, and lack of pregnancy wantedness were associated with increased risk of obstetric complications. Policies to address early marriage, unmet need for contraception, and maternal undernutrition may help mitigate this morbidity burden in rural Bangladesh.
doi:10.1186/1471-2393-14-347
PMCID: PMC4287506  PMID: 25282340
17.  Applicability of the WHO Maternal Near Miss Criteria in a Low-Resource Setting 
PLoS ONE  2013;8(4):e61248.
Background
Maternal near misses are increasingly used to study quality of obstetric care. Inclusion criteria for the identification of near misses are diverse and studies not comparable. WHO developed universal near miss inclusion criteria in 2009 and these criteria have been validated in Brazil and Canada.
Objectives
To validate and refine the WHO near miss criteria in a low-resource setting.
Methods
A prospective cross-sectional study was performed in a rural referral hospital in Tanzania. From November 2009 until November 2011, all cases of maternal death (MD) and maternal near miss (MNM) were included. For identification of MNM, a local modification of the WHO near miss criteria was used, because most laboratory-based and some management-based criteria could not be applied in this setting. Disease-based criteria were added as they reflect severe maternal morbidity. In the absence of a gold standard for identification of MNM, the clinical WHO criteria were validated for identification of MD.
Results
32 MD and 216 MNM were identified using the locally adapted near miss criteria; case fatality rate (CFR) was 12.9%. WHO near miss criteria identified only 60 MNM (CFR 35.6%). All clinical criteria, 25% of the laboratory-based criteria and 50% of the management-based criteria could be applied. The threshold of five units of blood for identification of MNM led to underreporting of MNM. Clinical criteria showed specificity of 99.5% (95%CI: 99.4%–99.7%) and sensitivity of 100% (95%CI: 91.1%–100%). Some inclusion criteria did not contribute to the identification of cases and therefore may be eligible for removal.
Conclusion
The applicability of the WHO near miss criteria depends on the local context, e.g. level of health care. The clinical criteria showed good validity. Lowering the threshold for blood transfusion from five to two units in settings without blood bank and addition of disease-based criteria in low-resource settings is recommended.
doi:10.1371/journal.pone.0061248
PMCID: PMC3629023  PMID: 23613821
18.  Obstetric near miss and deaths in public and private hospitals in Indonesia 
Background
Falling numbers of maternal deaths have stimulated an interest in investigating cases of life threatening obstetric morbidity or near miss. The purpose of this study was to document the frequency and causes of near miss and maternal deaths in four hospitals in West Java, Indonesia.
Methods
Cross sectional study in four hospitals in two districts in Banten province, Indonesia. We reviewed registers and case notes to identify the numbers and causes of near miss and death between November 2003 and October 2004. Near miss cases were defined based on organ dysfunction, clinical and management criteria. Near miss were categorized by whether or not the woman was at a critical state at admission by reviewing the final signs at admission.
Results
The prevalence of near miss was much greater in public than in private hospitals (17.3% versus 4.2%, p = 0.000). Hemorrhage and hypertensive diseases were the most common diagnoses associated with near miss, and vascular dysfunction was the most common criterion of organ dysfunction. The occurrence of maternal deaths was 1.6%, with non-obstetric complications as the leading cause. The majority (70.7%) of near miss in public hospitals were in a critical state at admission but this proportion was much lower in private hospitals (31.9%).
Conclusion
This is the first study to document near miss in public and private hospitals in Indonesia. Close to a fifth of admissions in public hospitals were associated with near miss; and the critical state in which the women arrived suggest important delays in reaching the hospitals. Even though the private sector takes an increasingly larger share of facility-based births in Indonesia, managing obstetric emergencies remains the domain of the public sector.
doi:10.1186/1471-2393-8-10
PMCID: PMC2311270  PMID: 18366625
19.  Awareness about a Life-Threatening Condition: Ectopic Pregnancy in a Network for Surveillance of Severe Maternal Morbidity in Brazil 
BioMed Research International  2014;2014:965724.
Objective. To assess occurrence of severe maternal complications associated with ectopic pregnancy (EP). Method. A multicenter cross-sectional study was conducted, with prospective surveillance of potentially life-threatening conditions (PLTC), maternal near miss (MNM), and maternal death (MD). EP complications, patient sociodemographic/obstetric characteristics, and conditions of severity management were assessed, estimating prevalence ratios with respective 95% CI. Factors independently associated with greater severity were identified using multiple regression analysis. Results. Of the 9.555 severe maternal morbidity patients, 312 women (3.3%) had complications after EP: 286 (91.7%) PLTC, 25 (8.0%) MNM, and 1 (0.3%) MD. Severe maternal outcome ratio (SMOR) was 0.3/1000 LB among EP cases and 10.8/1000 LB among other causes. Complicated EP patients faced a higher risk of blood transfusion, laparotomy, and lower risk of ICU admission and prolonged hospitalization than women developing complications resulting from other causes. Substandard care was the most common in more severe maternal morbidity and EP cases (22.7% MNM and MD versus 15% PLTC), although not significant. Conclusion. Increased maternal morbidity due to EP raised awareness about the condition and its impact on female reproductive life. No important risk factors for greater severity were identified. Care providers should develop specific guidelines and interventions to prevent severe maternal morbidity.
doi:10.1155/2014/965724
PMCID: PMC3977561  PMID: 24772441
20.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Background
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Conclusions
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001295.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project http://www.healthpolicyproject.com has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
doi:10.1371/journal.pmed.1001295
PMCID: PMC3424253  PMID: 22927800
21.  Maternal morbidity and near miss associated with maternal age: the innovative approach of the 2006 Brazilian demographic health survey 
Clinics  2013;68(7):922-927.
OBJECTIVE:
To study the prevalence of potentially life-threatening maternal conditions and near miss in Brazil according to maternal age.
METHODS:
A secondary analysis of the 2006 Brazilian demographic health survey database using a validated questionnaire to evaluate maternal morbidity with a focus on age extremes. The study included 5,025 women with at least 1 live birth in the 5-year reference period preceding their interviews. Three age range periods were used: 15-19 years (younger age), 20-34 years (control), and 35-49 years (advanced maternal age). According to a pragmatic definition, any woman reporting eclampsia, hysterectomy, blood transfusion, or admission to the intensive care unit during her pregnancy/childbirth was considered a near-miss case. The associations between age and severe maternal morbidity were further assessed.
RESULTS:
For the 6,833 reported pregnancies, 73.7% of the women were 20-34 years old, 17.9% were of advanced maternal age, and only 8.4% were of younger age. More than 22% of the women had at least one of the complications appraised, and blood transfusion, which was more prevalent among the controls, was the only variable with a significant difference among the age groups. The overall rate of maternal near miss was 21.1 per 1000 live births. There was a trend of higher maternal near miss with increasing age. The only significant risk factor identified for maternal near miss was a lower literacy level among older women.
CONCLUSIONS:
There is a trend towards worse results with increasing age. The investigation of the determinants of maternal near miss at the community level using an innovative approach through a demographic health survey is an example suggested for under-resourced settings.
doi:10.6061/clinics/2013(07)06
PMCID: PMC3715023  PMID: 23917654
Morbidity; Obstetric Complication; Pregnancy in Adolescence; Maternal Age
22.  The WHO Maternal Near-Miss Approach and the Maternal Severity Index Model (MSI): Tools for Assessing the Management of Severe Maternal Morbidity 
PLoS ONE  2012;7(8):e44129.
Objectives
To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments.
Methods
In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity.
Results
Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56–114.6)). The maternal severity index (MSI) model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909–0.993)).
Conclusion
The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.
doi:10.1371/journal.pone.0044129
PMCID: PMC3430678  PMID: 22952897
23.  The Influence of Distance and Level of Care on Delivery Place in Rural Zambia: A Study of Linked National Data in a Geographic Information System 
PLoS Medicine  2011;8(1):e1000394.
Using linked national data in a geographic information system system, Sabine Gabrysch and colleagues investigate the effects of distance to care and level of care on women's use of health facilities for delivery in rural Zambia.
Background
Maternal and perinatal mortality could be reduced if all women delivered in settings where skilled attendants could provide emergency obstetric care (EmOC) if complications arise. Research on determinants of skilled attendance at delivery has focussed on household and individual factors, neglecting the influence of the health service environment, in part due to a lack of suitable data. The aim of this study was to quantify the effects of distance to care and level of care on women's use of health facilities for delivery in rural Zambia, and to compare their population impact to that of other important determinants.
Methods and Findings
Using a geographic information system (GIS), we linked national household data from the Zambian Demographic and Health Survey 2007 with national facility data from the Zambian Health Facility Census 2005 and calculated straight-line distances. Health facilities were classified by whether they provided comprehensive EmOC (CEmOC), basic EmOC (BEmOC), or limited or substandard services. Multivariable multilevel logistic regression analyses were performed to investigate the influence of distance to care and level of care on place of delivery (facility or home) for 3,682 rural births, controlling for a wide range of confounders. Only a third of rural Zambian births occurred at a health facility, and half of all births were to mothers living more than 25 km from a facility of BEmOC standard or better. As distance to the closest health facility doubled, the odds of facility delivery decreased by 29% (95% CI, 14%–40%). Independently, each step increase in level of care led to 26% higher odds of facility delivery (95% CI, 7%–48%). The population impact of poor geographic access to EmOC was at least of similar magnitude as that of low maternal education, household poverty, or lack of female autonomy.
Conclusions
Lack of geographic access to emergency obstetric care is a key factor explaining why most rural deliveries in Zambia still occur at home without skilled care. Addressing geographic and quality barriers is crucial to increase service use and to lower maternal and perinatal mortality. Linking datasets using GIS has great potential for future research and can help overcome the neglect of health system factors in research and policy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Approximately 360,000 women die each year in pregnancy and childbirth, of which more than 200,000 in sub-Saharan Africa, where a woman's lifetime risk of dying during or following pregnancy remains as high as 1 in 31 (compared to 1 in 4,300 in the developed world). The target of Millennium Development Goal 5 is to reduce the maternal mortality ratio by three quarters by 2015. Most maternal and neonatal deaths in low-income countries could be prevented if all women delivered their babies in settings where skilled birth attendants (such as midwives) were available and could provide emergency obstetric care to both mothers and babies in case of complications. Yet every year roughly 50 million women give birth at home without skilled care.
Why was this study done?
The likelihood of a woman giving birth in a health facility under the care of a skilled birth attendant depends on many factors. These include characteristics of the mother and her family, such as education level and household wealth, and aspects of the health service environment—distance to the nearest health facility and the quality of care provided at that facility, for example. However, research to date has typically focused on household and individual factors, neglecting the influence of the health service environment on choice of delivery place, largely because suitable data was not available. In this study in rural Zambia, the researchers aimed to quantify the effects of the health service environment, namely distance to health care and the level of care provided, on pregnant women's use of health facilities for giving birth. To put these factors in context, the researchers compared the impact of distance to quality care on place of delivery to that of other important factors, such as poverty and education.
What did the researchers do and find?
Using a geographic information system (GIS), the researchers linked national household data (from the 2007 Zambia Demographic and Health Survey) with national facility data (from the 2005 Zambian Health Facility Census) and calculated straight-line distances between women's villages and health facilities. Health facilities were classified as providing comprehensive emergency obstetric care, basic emergency obstetric care, or limited or substandard services by using reported capability to perform a certain number of the eight emergency obstetric care signal functions: injectable antibiotics, injectable oxytocics, injectable anticonvulsants, manual removal of placenta, manual removal of retained products, assisted vaginal delivery, cesarean section, and blood transfusion, as well as criteria on staffing, opening hours and referral capacity. The researchers used data from 3,682 rural births and multivariable multilevel logistic regression analyses to investigate whether distance to, and level of care at the closest delivery facility influence place of delivery (health facility or home), keeping other influential factors constant.
The researchers found that only a third of births in rural Zambia occurred at a health facility, and half of all mothers who gave birth lived more than 25 km from a health facility that provided basic emergency obstetric services. As distance to the closest health facility doubled, the odds of a women giving birth in a health facility decreased by 29%. Independently, each step increase in the level of emergency obstetric care provided at the closest delivery facility led to an increased likelihood (26% higher odds) of a woman delivering her baby at a facility. The researchers estimated that the impact of poor geographic access to emergency obstetric services was of similar magnitude as that of low maternal education, household poverty, or lack of female autonomy.
What do these findings mean?
The results of this study suggest that poor geographic access to emergency obstetric care is a key factor in explaining why most women in rural Zambia still deliver their babies at home without skilled care. Therefore, in order to increase the number of women delivering in health facilities and thus reduce maternal and neonatal mortality, it is crucial to address the geographic and quality barriers to delivery service use. Furthermore, the methodology used in this study—linking datasets using GIS— has great potential for future research as it can help explore the influence of health system factors also for other health problems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000394.
Information about emergency obstetric care is provided by the United Nations Population Fund (UNFPA)
Various topics on maternal health are presented by WHO, WHO Regional Office Africa, by UNPFA, and UNICEF
WHO offers detailed information about MDG5
Family Care International offers more information about maternal and neonatal health
The Averting Maternal Death and Disability program (AMDD) provides information on needs assessments of emergency obstetric and newborn care
Countdown to 2015 tracks progress in maternal, newborn, and child survival
WHO provides free online viewing of BBC Fight for Life videos describing delivery experiences in different countries
doi:10.1371/journal.pmed.1000394
PMCID: PMC3026699  PMID: 21283606
24.  Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial 
PLoS Medicine  2014;11(9):e1001735.
Clara Menéndez and colleagues conducted a randomized controlled trial among HIV-positive pregnant women in Kenya, Mozambique, and Tanzania to investigate the safety and efficacy of mefloquine as intermittent preventative therapy for malaria in women receiving cotrimoxazole prophylaxis and long-lasting insecticide treated nets.
Please see later in the article for the Editors' Summary
Background
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).
Methods and Findings
A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.
Conclusions
An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.
Trial registration
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria, a mosquito-borne parasitic disease, kills about 600,000 people every year. Most of these deaths occur among young children living in sub-Saharan Africa but pregnant women living in Africa are also very vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birthweight babies, and is responsible for the deaths of many African women and their babies. To reduce the loss of life from malaria in pregnancy, the World Health Organization (WHO) recommends that pregnant women living in Africa receive the antimalarial drug sulfadoxine-pyrimethamine (SP) at each scheduled antenatal care visit given at least a month apart (intermittent preventive treatment in pregnancy [IPTp]). In addition, WHO advises pregnant women to sleep under insecticide-treated bed nets to protect themselves from the bites of infected mosquitoes and recommends effective case management of pregnant women with malarial illness.
Why Was This Study Done?
Pregnant women living in Africa are often infected with HIV, the virus that causes AIDS. HIV infection increases both the risk and severity of malaria infection during pregnancy, and at least one million pregnancies are complicated by co-infection with malaria and HIV in sub-Saharan Africa every year. WHO recommends that HIV-positive pregnant women take cotrimoxazole (CTX) daily to prevent opportunistic infections (CTX prophylaxis [CTXp]). Unfortunately, both CTX and SP are antifolate drugs and taking two drugs of this type increases a woman's risk of developing a severe skin reaction. Moreover, although CTXp protects children and HIV-infected adults against malaria, it is not known whether CTXp alone protects HIV-infected pregnant women adequately against malaria. Thus, evaluations of alternative drugs for use in IPTp in HIV-positive pregnant women are needed. In this randomized placebo-controlled trial, the researchers study the safety and efficacy of the antimalarial drug mefloquine (MQ) in HIV-infected women receiving CTXp. A randomized, placebo-controlled trial compares outcomes among people chosen through the play of chance to receive either the drug under investigation or a “dummy” (placebo) drug.
What Did the Researchers Do and Find?
The researchers allocated 1,071 HIV-infected pregnant women from Kenya, Mozambique, and Tanzania to receive three doses of MQ (IPTp-MQ), given at least one month apart, or three doses of placebo. All the women received CTXp and were given an insecticide-treated bed net. In an intention-to-treat analysis (an analysis that considers the outcomes of all trial participants irrespective of whether they receive their allocated treatment), the prevalence of parasitemia (parasites in the blood) at delivery among women given IPTp-MQ was 3.5% whereas the prevalence among women given the placebo was 6.9%. In other words, compared to placebo, IPTp-MQ was associated with a reduced risk of maternal parasitemia. IPTp-MQ was also associated with a reduced rate of placental malaria (parasites in the placenta) and a reduced incidence of hospital admissions for non-pregnancy related causes. There was no difference in adverse pregnancy outcomes such as stillbirth between the intervention groups but drug tolerability was poorer in the MQ group than in the placebo group. Finally, in an exploratory (unplanned) according-to-protocol analysis (an analysis that only considers outcomes in trial participants who receive their allocated intervention), women in the MQ group had a higher HIV viral load at delivery than women in the control group and were nearly twice as likely to transmit HIV to their child around the time of birth.
What Do These Findings Mean?
These findings suggest that the addition of IPTp-MQ to CTXp and the use of insecticide-treated bed nets can improve malaria prevention and maternal health in HIV-infected pregnant women in Africa. However, the poor tolerability of MQ and the association of MQ treatment with both an increased HIV viral load at delivery and a higher frequency of mother-to-child-transmission of HIV when compared to placebo raise concerns about the use of MQ in IPTp. Because these last two findings came from an exploratory analysis, which is more likely to throw up a chance finding than a pre-planned analysis further studies are needed to confirm these unexpected but potentially important findings. Nevertheless, overall, the findings of this study suggest that MQ should not be recommended for IPTp in HIV-infected pregnant women in Africa and highlight the need to find alternative drugs for malaria prevention in this group of women who are particularly vulnerable to malaria.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001735.
This study is further discussed in a PLOS Medicine Perspective by Richard Steketee.
A related PLOS Medicine Research Article by González et al. compares the efficacy of IPTp-MQ and IPTp-SP in HIV-negative women
Information is available from the World Health Organization on malaria (in several languages) and on malaria in pregnancy; information on IPTp and the current WHO policy recommendation on IPTp with SP are available; the 2013 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention also provides information on malaria; a personal story about malaria in pregnancy is available
Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy
The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy
MedlinePlus provides links to additional information on malaria (in English and Spanish)
More information about the trial protocol is available
doi:10.1371/journal.pmed.1001735
PMCID: PMC4172537  PMID: 25247995
25.  Incidence, determinants and perinatal outcomes of near miss maternal morbidity in Ile-Ife Nigeria: a prospective case control study 
Background
Maternal mortality ratio in Nigeria is one of the highest in the world. Near misses occur in larger numbers than maternal deaths hence they allow for a more comprehensive analysis of risk factors and determinants as well as outcomes of life-threatening complications in pregnancy. The study determined the incidence, characteristics, determinants and perinatal outcomes of near misses in a tertiary hospital in South-west Nigeria.
Methods
A prospective case control study was conducted at the maternity units of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife Nigeria between July 2006 and July 2007. Near miss cases were defined based on validated disease-specific criteria which included severe haemorrhage, hypertensive disorders in pregnancy, prolonged obstructed labour, infection and severe anemia. Four unmatched controls of pregnant women were selected for every near miss case. Three categories of risk factors (background, proximate, clinical) which derived from a conceptual framework were examined. The perinatal outcomes were also assessed. Bi-variate logistic regressions were used for multivariate analysis of determinants and perinatal outcomes of near miss.
Results
The incidence of near miss was 12%. Severe haemorrhage (41.3%), hypertensive disorders in pregnancy (37.3%), prolonged obstructed labour (23%), septicaemia (18.6%) and severe anaemia (14.6%) were the direct causes of near miss. The significant risk factors with their odds ratio and 95% confidence intervals were: chronic hypertension [OR=6.85; 95% CI: (1.96 – 23.93)] having experienced a phase one delay [OR=2.07; 95% CI (1.03 – 4.17)], Emergency caesarian section [OR=3.72; 95% CI: (0.93 – 14.9)], assisted vaginal delivery [OR=2.55; 95% CI: (1.34 – 4.83)]. The protective factors included antenatal care attendance at tertiary facility [OR=0.19; 95% CI: (0.09 – 0.37)], knowledge of pregnancy complications [OR=0.47; 95% CI (0.24 – 0.94)]. Stillbirth [OR=5.4; 95% CI (2.17 – 13.4)] was the most significant adverse perinatal outcomes associated with near miss event.
Conclusions
The analysis of near misses has evolved as a useful tool in the investigation of maternal health especially in life-threatening situations. The significant risk factors identified in this study are amenable to appropriate public health and medical interventions. Adverse perinatal outcomes are clearly attributable to near miss events. Therefore the findings should contribute to Nigeria’s effort to achieving MDG 4 and 5.
doi:10.1186/1471-2393-13-93
PMCID: PMC3651395  PMID: 23587107
Near miss maternal morbidity; Maternal health; Pregnancy complications; Perinatal outcomes; Nigeria

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