Where is the “E” in MCH? The need for an evidence-based approach in safe motherhood

Where Is the “E” in MCH? The Need for an Evidence-Based Approach in Safe Motherhood Suellen Miller, CNM, PhD, Nancy L. Sloan, DrPH, Beverly Winikoff, MD, MPH, Ana Langer, MD, and Fariyal F. Fikree, MD Measuring the impact of obstetric interventions on maternal mortality and/or morbidity is especially difficult in developing countries, where most maternal deaths occur. Therefore, program planning has been based on theory rather than proved effectiveness. After reviewing both the strategies that have been promoted to reduce maternal mortality and the adequacy of existing evidence used to justify their selection, the investigators highlight reasons why rigorous criteria for the selection and evaluation of interventions should be adopted. Adequate evaluation of intervention effectiveness under real-life conditions in developing countries is an efficient way to identify interventions for large-scale program replication and could speed progress in reducing maternal deaths. J Midwifery Womens Health 2003;48:10 –18 © 2003 by the American College of Nurse-Midwives. keywords: evidence-based approach, safe motherhood, maternal mortality

INTRODUCTION Midwives and other non-physicians deliver the majority of the world’s babies, particularly in the developing world, where more than 98% of deaths associated with pregnancy and childbirth occur.1 It has been estimated that nearly 600,000 women, pregnant, birthing, or newly delivered, die each year. Fifteen years ago, Rosenfield and Maine brought attention to the global problem of maternal mortality by asking: “Where is the M in MCH?”2 In l987, the Safe Motherhood Initiative was introduced at a conference in Nairobi. One goal of the initiative, an alliance of cosponsoring agencies, including the World Health Organization (WHO), United Nations Population Fund, the United Nations Children’s Fund, the International Confederation of Midwives, the International Federation of Gynecology and Obstetrics, the International Planned Parenthood Federation, the Population Council, the World Bank, the Regional Prevention of Maternal Mortality Network (Africa), the Safe Motherhood Network of Nepal, with Family Care International as the secretariat, was to halve maternal deaths by the year 2000. These global organizations act as the Safe Motherhood Inter-Agency Group, whose role is to raise international awareness about safe motherhood, set goals and programmatic priorities for the global Safe Motherhood Initiative, support national Safe Motherhood programs, stimulate research, mobilize resources, provide technical assistance, and share information to make childbirth and pregnancy safer.3– 6 The question of “Where is the M in MCH,” along with the start-up of the Safe Motherhood Initiative and other

Address correspondence to Suellen Miller, Women’s Global Health Initiative, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, 74 New Montgomery Street, Suite 600, UCSF Box 0886,San Francisco CA 94105-344. Support for this study was provided by the Population Council; when this article was written, all the authors were on the staff of the Population Council.

10 © 2003 by the American College of Nurse-Midwives Issued by Elsevier

international actions, rallied interest and commitment from donors, program planners, researchers, and practitioners to reduce maternal mortality in all countries. It has been noted that the maternal mortality ratio is the vital indicator with the greatest disparity between developed countries (maternal mortality ratio ⫽ 4/100,000 live births) and developing countries (maternal mortality ratio ⫽ 582/100,000 live births) countries.7 Because some developing countries, such as Thailand and Tunisia (with substantial socioeconomic progress and important social changes), have succeeded in reducing maternal mortality, advocates hoped that those experiences could be replicated in other countries. In the desire to save women’s lives quickly, research to determine the most effective, affordable public health interventions appeared to be an unnecessary, wasteful detour. In fact, the challenging nature of measuring maternal mortality and morbidity3,8 –13 discouraged impact evaluation. Rigorous research was deemed impractical and expensive, and waiting to determine intervention effectiveness might delay action far too long with too many lives lost. Therefore, the most common approach to reduce maternal mortality has been the identification of hypothetically useful, “good ideas” program interventions, with advocacy for their large-scale implementation.10 –14 In the belief that the “good ideas” programs are known to save women’s lives, extensive efforts have been made to promote and implement theoretically promising interventions. “GOOD IDEAS” INTERVENTIONS: TRADITIONAL BIRTH ATTENDANTS AND ANTENATAL RISK SCREENING Since 1987, international agencies and governments working together have dedicated time and funds without producing documented reductions in maternal mortality or clear evidence of how to reduce maternal mortality quickly.4,6,15 Two “good ideas” interventions that were promoted for large-scale implementation, training of traditional birth Volume 48, No. 1, January/February 2003 1526-9523/03/$30.00 • doi:10.1016/S1526-9523(02)00369-0

attendants and promotion of antenatal care risk screening, have not been demonstrated to affect maternal mortality.4,6,15 This disappointment has led many to believe that such efforts are misguided4 or too broad.6 Using the same “good ideas” approach, emergency obstetric care and skilled care at delivery are now proposed solutions.4 Although these might turn out to be useful interventions, for the poorest countries where maternal mortality is greatest, the evidence to support them is either theoretical,16 based on data used out of context17–19 or causal inference made erroneously.20 For example, causal associations demonstrated in environments capable of providing high-quality obstetric care will not necessarily hold true in the very different conditions of developing countries. As we will demonstrate, there are many practical and theoretical reasons why the “good ideas” approach has led to false paths and the loss of time, money, and credibility. EVIDENCED-BASED EVALUATION: THE NECESSARY NEXT STEP The time has come to question the “good ideas” approach and ask, “Where is the E (for Evidence) in MCH?” The question is an appeal to evaluate theoretically promising safe motherhood interventions for their effectiveness under real-life conditions before they are implemented as largescale programs.21–25 Using an evidence-based approach, at minimum, provides sufficient (or adequate) information to go forward while generating new knowledge on which to base effective policy and programming. Progress in choosing program priorities has been hindered by the fact that there is insufficient information on program effectiveness. In fact, well-designed and wellimplemented research may be the most cost-efficient, albeit difficult, mechanism to identify effective safe motherhood interventions for large-scale program implementation. Reflecting the recent emphasis within the Journal of Midwifery and Women’s Health,26 we propose that the principles of evidence-based practice be applied to assessment of promising safe motherhood interventions.

Suellen Miller, CNM, PhD, is currently Deputy Director of the Women’s Global Health Imperative and Adjunct Assistant Professor, School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco. She teaches international MCH at the University of California, Berkeley. At the time this article was written, she was Senior Program Associate, International Programs Division, Population Council, New York. Nancy Sloan, DrPH, is a perinatal and nutritional epidemiologist. She is a Senior Program Associate in Reproductive Health, International Programs Division of the Population Council. Beverly Winikoff, MD, MPH, is Program Director for Reproductive Health in the Population Council’s International Programs Division and a Senior Medical Associate. Ana Langer, MD, is the Population Council’s Regional Director for Latin America and the Caribbean. Fariyal Fikree, MD, is a Program Associate in the Population Council’s International Programs Division. She directs research and activities on postpartum health care, breastfeeding, refugee reproductive health, and other related topics.

Journal of Midwifery & Women’s Health • www.jmwh.org

EVIDENCE-BASED APPROACH: PRINICIPLES, CAUSAL METHODOLOGY, AND CRITERIA Causal evidence is the foundation of the evidence-based approach; however, the term “evidence-based approach” can be easily misconstrued.21 Causal evidence about the value of interventions is generated from data collected in properly controlled experiments and must demonstrate a temporal adequately strong preventive association in multiple evaluations conducted in different locations.27 The requirements for causal evidence for interventions to reduce maternal mortality are as follows: An experimental or quasi-experimental evaluation design The most rigorous design is an experimental evaluation, which allocates small sampling units (women, clinics, geographic clusters) to either an intervention group or a comparison group by a formal randomization procedure. Less rigorous, a quasi-experimental evaluation allocates sampling units to the intervention and comparison groups by time (pre- versus postprogram implementation) or by large clusters (of health facilities or geographic units). As demonstrated below, however, the lack of a concurrent comparison group may render the quasi-experimental findings misleading. Sometimes, however, the only evidence possible to obtain is quasi-experimental (due to funding limitations, ethical imperatives, or other real-life conditions or research restrictions). An adequate comparison group The non-intervention group must be statistically similar to the intervention group in all relevant aspects. Similarity is best achieved through randomization of an adequate number of sampling units to the intervention and comparison groups at the same time. Quasi-experimental designs are less likely to achieve adequate similarity between comparison groups. Any uncontrolled dissimilarity will confound research results. Statistical adjustment is often used to control analytically for between-group differences, but this “control” is imperfect and cannot achieve group comparability to the same extent as a randomized design. Sometimes, multiple studies can compensate for dissimilarities between intervention and comparison groups in an individual study. A concurrent comparison group It is not possible to ascribe cause without an adequately similar concurrent control group. For example, if a febrile epidemic occurs between the beginning and end of a project, and, as a consequence, maternal mortality rises, we cannot know, without a concurrent control group for comparison, whether this negative outcome is due to an intervening event (e.g., epidemic, economic change, etc.) or due to the intervention. Likewise, we cannot know from a simple before-and11

Table 1. Maternal Mortality Rates After a Febrile Epidemic Pre- and Postintervention

Intervention Comparison*

Pre (%)

Post (%)

Apparent Change (%)

10 10

20 30

10 20

*Note without a comparison group the increase in maternal mortality rate in the intervention group appears to be on the magnitude of 10%; however, using the comparison group, one can see that without the intervention, the maternal mortality rate would have increased by 20%; the intervention has actually prevented an additional 10% increase in maternal mortality rate.

after comparison whether a reduction in maternal mortality is due to our intervention or to other unknown factors, such as an improvement in the economy, a new road that improved access to care, a successful nutrition program implemented by others, and so forth. Table 1 demonstrates that without a concurrent control group, a 10% increase in maternal mortality might be attributed to an intervention that actually prevented an additional 10% increase in maternal mortality during a febrile epidemic. Consistency of effect Important evidence of causality is provided if the association is generally consistent across multiple evaluations conducted in different locations or under different circumstances. Although a single well-designed experimental trial may provide strong evidence, and is a necessary start, it alone is insufficient to demonstrate causality. Single studies demonstrating preventive impact merit replication. Inconsistent results merit review of each study’s methodology for its individual adequacy. A temporal association The intervention (i.e., the causal factor) must occur before the outcome of interest. An adequately strong association The magnitude of the effect of the intervention is important (e.g., percent reduction in maternal mortality), not simply whether a comparative trend in the desired direction is detectable. Statistical significance is not the same as strength of the association. Statistical significance depends on sample size, so even a small, weak association can be statistically significant if the sample size is large enough. An intervention could be considered worthwhile at different magnitudes of effect, depending on the context. For example, a 10% reduction in maternal mortality ratio where maternal mortality is high may be considered adequately strong, whereas a 10% reduction in maternal mortality might be considered too weak to be a worthwhile program end point in geographic locations where maternal mortality is already low. 12

A preventive effect This is the potential for the intervention to prevent negative (or increase positive) outcomes. Although this criterion is not always necessary to determine a causal association, it is necessary to demonstrate the effectiveness of an intervention. The preventive effect of the association may depend on the magnitude of the problem where the study is conducted. For example, if vitamin A supplementation could reduce maternal mortality rate, it would theoretically have a smaller preventive effect on maternal mortality in Thailand than in Nepal, because Thailand has fewer women with vitamin A deficiency than has Nepal.

A contextual effect Each maternal death occurs in a specific social, cultural, and political context. The context, both macro and micro, greatly affects individual and community health, even within developed countries. For example, the maternal mortality ratio in the United States, where women are well nourished, transportation and roads are available, and emergency obstetric services are high quality, is approximately 12/100,000 live births.28 Yet in 1995, African American women had a maternal mortality ratio nearly four times greater than white women.29,30 A review of maternal mortality in New York City, the same macro environment, found the maternal mortality ratio of whites, blacks, and Hispanics to be substantially different, 7.1, 39.5, and 14.4 per 100,000 live births, respectively.31 Even more extreme contextual factors can prevail: for example, in 1982 to 1995, the maternal mortality rate of Faith Assembly members, a religious sect living in the state of Kansas in the United States was 872/100,000 live births, approximately 100 times that of women living in the surrounding community.17,18 Although these American women lived in the same macro-environment, their community’s cultural and religious beliefs created a micro-environment that prohibited them from using the available obstetric care nearby.17,18 Nor did improvements in the Western health care systems, to which some attribute historical reductions in maternal mortality,19 occur in isolation from other improvements in living conditions.32 Because the associations observed under one set of circumstances may not happen in another set of circumstances, the effectiveness of each intervention must be demonstrated within the general macro- and micro-context in which it is to be implemented. Thus, for an association to be considered causal, multiple, adequately controlled evaluations of plausible interventions using comparable intervention and comparison groups must consistently demonstrate a temporal, adequately strong preventive and context-specific association. Volume 48, No. 1, January/February 2003

WHERE IS THE EVIDENCE IN SAFE MOTHERHOOD PROGRAMS? Sources of Evidence in Safe Motherhood Much of the knowledge currently driving safe motherhood programs comes from descriptive (i.e., non-experimental) data. These data include historical trends, ecologic analyses, retrospective hospital record reviews, and data from small non-representative special studies and qualitative research.32 They also include information from poorly controlled quasi-experimental studies, most often studies looking at specific outcome measures before and after an intervention is introduced within a geographic locale. All of these methodologies have their place in increasing our understanding of factors contributing to maternal mortality. All are important first steps in the identification of associated events, and they are often simpler and more affordable to undertake than studies producing causal data. However, statistically significant associations alone do not constitute causal evidence. Likewise, these methodologies are inadequate tools to assess intervention effectiveness.21–23,27 Because many descriptive studies demonstrate that the majority of maternal deaths occur outside a health care institution,17,32,33 such deaths are most often attributed to the lack of adequate delivery care. On reflection, death outside the hospital could also be due to many other factors besides the adequacy of health care services including cultural or religious prohibitions on institutional care for delivery, lack of money or transportation to get trained assistance, lack of confidence in the health care system, fears of the insensitivity of health care providers, lack of recognition about when institutional care needs to be sought, poor or untimely response by health care providers and health care facilities, or low status of women, which then decreases their access to available services, adequate or not.4,14,15,34 Women who are poorer, less educated, and with less access to health care, die more often than those who are not impoverished.4,33,35,36 Because so many of the factors associated with high maternal mortality rate have social, political, and medical etiologies, Dr. France Donnay speaking as UNICEF’s Women’s Health Advisor, noted that women continue to die in childbirth due to a lack of political will and the absence of a “high level commitment to protecting women’s health.”1 Traditional Birth Attendant Training Because it is difficult, if not impossible, for the public health community to alter these multiple contextual factors and, perhaps also, from a recognition that multifaceted problems often require incremental solutions, initial steps to reduce maternal mortality often focus on a single preventive measure. Two such preventive interventions that received attention in the earlier days of safe motherhood were traditional birth attendant training4,37,38 and antenatal care risk screening.4,40,41 Because traditional birth attendants frequently provide Journal of Midwifery & Women’s Health • www.jmwh.org

birthing assistance to women who do not have the money for, access to, or confidence in doctors and trained midwives, this was one theoretical method of ameliorating problems caused by social and political inequities. In the l990s, the benefits of training traditional birth attendants came under question after years of financial and human resource investments. For example, Smith et al. compared various maternal and infant outcomes of those receiving care from trained with untrained traditional birth attendants in Ghana and found that training accounted for almost no effect.42 Even a subsequent metanalysis43 provides no statistically significant or clinical rationale for the effects of traditional birth attendant training on maternal mortality. Antenatal Risk Screening Programs Antenatal risk screening has also been questioned for effectiveness in reducing maternal mortality.39,41,42 Women not identified as “high-risk” not only develop obstetric complications, but the majority of obstetric complications occur among women with no risk factors. For example, at a health center in Kasongo, Zaire, a prenatal care program was implemented to screen women at risk for developing obstetric complications. Women with a previous history of difficult delivery or of having needed interventions in previous delivery were identified as “high-risk” for developing obstructed labor. Only 29% of women who actually did develop obstructed labor were from the high-risk group, whereas more than two thirds of the women who had obstructed labor were not predicted by the screening program.41 According to the WHO, United Nations Population Fund, and United Nations Children’s Fund, although 15% of all pregnant women develop serious complications that require lifesaving quality services; the majority of those who develop these serious complications cannot be predicted by antenatal care risk screening.46,47 Recently, the WHO conducted a randomized, multicenter trial in five countries to assess the effectiveness of an experimental antenatal care program. This program included 1) only those components of antenatal care proven efficacious for normal antenatal care and 2) special care deemed appropriate for each individual woman dependent on her history and condition during the pregnancy. This experimental program was compared with the standard antenatal care package provided in the study sites. Although findings revealed differences in both the number of antenatal care visits and the time women spent with providers and although more women in the experimental than standard model were referred to higher levels of care, there were no differences found in rates of hospital admission, diagnosis, length of stay, or adverse maternal or perinatal outcomes between the standard and experimental groups.48 Preventive approaches undertaken as “good ideas” have been accepted on the basis of a priori advocacy and, subsequently, became entrenched as public health practices. 13

When they ultimately appear ineffective, they have to be discouraged, representing not only a costly delay of progress but also reducing the future credibility of program advocates and implementers. This effect is seen today in resistance to efforts to investigate the value of spending time and resources to train skilled attendants in emergency care instead of training traditional birth attendants or on antenatal risk screening. EVIDENCE FOR THE IMPORTANCE OF EMERGENCY OBSTETRIC CARE AND SKILLED ATTENDANCE AT DELIVERY In the late l980s and l990s, safe motherhood program priorities shifted to the management of obstetric problems, with particular emphasis on emergency obstetric care and skilled attendance at delivery. To date, these concepts are also based in theory and have been supported only by non-causal data.16,19,20,32,48,49 The potential for medical management of life-threatening conditions to save women’s lives has been noted over the past decade.16 Using information from a variety of sources including historical patterns and descriptive data from industrialized countries,19,20 Loudon concluded that the overall standard of health care in Northern Europe and the United States is the main determinant of the sharp decline in maternal mortality noted to have occurred between 1937 and 1950. Loudon attributed the reduction in maternal mortality rate particularly to the introduction of sulfonamides, and other factors, including blood transfusion, ergometrine, penicillin, anesthesia, better training, organization of obstetric services, less unnecessary interference, and a decline in the virulence of streptococcal infection,49 contending that reduction in poverty and maternal malnutrition played little role in the decline in maternal mortality during this period.49 In fact, positive changes over the same time period were also apparent in these living condition factors.32 However, we have no way of knowing (beyond hypothesis) whether medical care improvements, living condition improvements, or declines in infectious disease virulence contributed the most to the documented reduction in mortality, nor what contribution the synergy (interactions) of these elements had on the reduction of deaths in childbirth. Existing data used to justify promotion of skilled attendance at delivery document associations but do not meet rigorous standards of causality either. Loudon suggests that the lower rates of maternal mortality in Sweden, the Netherlands, Norway, and Denmark compared with England, Wales, and the United States between 1890 and 1900 were attributable to well-trained midwives’ use of rigorous aseptic techniques for home and institutional births in the former countries.19,49 An ecologic analysis of United Nations Children’s Fund and WHO data from 84 countries20 demonstrated that a greater proportion of deliveries with a trained attendant and a higher contraceptive prevalence rate were both independently associated with lower national 14

maternal mortality ratios and that lower maternal mortality ratios were highly correlated with other societal factors, which then influence the proportion of deliveries with a trained attendant and the contraceptive prevalence rate. So we cannot know a priori whether changing the proportion of deliveries (or the contraceptive prevalence rates) in the absence of those other societal factors would produce the same association with maternal mortality reduction. These historical and ecologic analyses also cannot explain which other contextual factors associated with skilled delivery attendance might result in the documented relationship. Who were the skilled people? What was the content of their training? What was the order of their training in relationship to other education and training? Could the association between use of trained providers and lower maternal mortality be related to a social and economic environment that values women’s lives and allows women access to good services? Many other factors may have influenced outcomes for women using trained attendants compared with women using less-trained attendants, such as the influence of professional associations, the percentage of the population living in substandard conditions, the percentage of immigrants outside of the mainstream health care system, the rise of the middle classes, women’s education, the effects of the woman’s suffrage movement, and so forth. Three quasi-experimental studies have shed additional light on both the effectiveness and the limitations of emergency obstetric care and skilled attendance at delivery as solutions to the problem of high maternal mortality. In Matlab, Bangladesh, community-based birth attendants were trained to identify and refer women with specific symptoms to upgraded local facilities, which also provided transportation services. This intervention resulted in an increase of women seeking obstetric services from the local clinic and district hospital and a 34% reduction in maternal mortality rate (P ⬍ .02).50 In a reanalysis, Maine et al.51 attributed much of the reduction in maternal mortality in the intervention group to the availability and use of the district hospital for obstetric services as opposed to an improved referral pattern by community-based birth attendants specifically. This interpretation is consistent with the results of two quasi-experimental studies in Vietnam,52 which showed improvement in the quality of emergency obstetric services at clinics and district hospitals improved management (including referral) of life-threatening obstetric conditions only in district hospitals. Such findings neither prove nor disprove the importance of referral systems, early identification of complications, and available transportation. What these studies do reveal is the effectiveness of care received at the district hospital level compared with that received at the community level. Improving emergency obstetric care may not significantly reduce maternal mortality where women’s access to or use of adequate institutional care at delivery is poor, as our prior example of the Faith Assembly demonstrates. Volume 48, No. 1, January/February 2003

There are many known obstacles for poor, rural, and other vulnerable women to receive adequate institutional care at delivery. On the other hand, if good care is not available, then women’s lives will not be saved, even if they reach facilities in emergency situations. Nonetheless, we do not know the extent to which improving institutional services alone can reduce maternal mortality in a country like Bangladesh, where only 5% of women deliver in health care facilities. At present, fewer than 50% of women in developing countries give birth in health facilities;53 an even smaller proportion do so on the Indian subcontinent and in sub-Saharan Africa where maternal mortality is highest.53 The impact of increasing the coverage of deliveries by skilled attendants alone, without referral systems, solid relationships among various levels within the health system, and transportation to reach institutional support for delivery, also is unknown. Trained attendants, if they lack adequate institutional support cannot provide the required obstetric services without other major concomitant changes. Additional unanswered questions about skilled attendance relate to the adequacy of training opportunities, the type and length of training, and the frequency of skills updates and supervisory visits.54 RECOMMENDATION: RIGOROUS STUDIES IN CONTEXT ARE FEASIBLE The impact of promising interventions requires rigorous investigation. However, such studies are neither easy nor cheap. Measuring the magnitude of impact of interventions on maternal mortality requires special studies with large samples. To accurately measure a reduction of 25% in maternal mortality ratio from a baseline of 850/100,000 live births with a 95% confidence interval and statistical power of 80% and a one-sided test (to identify that the intervention reduces maternal mortality or not), an adequately controlled trial would have to measure 20,120 postpartum women or their survivors in each of the intervention and comparison groups.55 As Table 2 shows, it is much more difficult to measure changes in maternal mortality when maternal mortality is low or effect size is small. At minimum, this level of research requires resolve, considerable funding, adequate and appropriate samples, sound study design, and diligent implementation. Conducting such assessments appears logistically and economically daunting. However, similar concerns arose in the area of child survival, where investments in adequate and appropriate investigations have proved to be both extremely beneficial and an efficient way to identify effective interventions. The challenges of adequate assessment should not deter us because, unlike trial and error, the fruitfulness of causal investigation (knowledge) is certain.56,57 Rigorous research is not only necessary, it is feasible. It is likely to be as or more cost- and time-efficient than implementation of unproved interventions. It is possible to achieve high-quality evaluation for maternal mortality decreasing interventions, as evidenced Journal of Midwifery & Women’s Health • www.jmwh.org

Table 2. Numbers of Women Needed in Intervention and Control Groups to Measure Three Different Effect Sizes of Interventions at Three Different Levels of Maternal Mortality Rate (MMR)* No. of Participants Needed

Estimated Reduction in MMR Anticipated with Intervention (%)

Baseline MMR 850/100,000 Births (N)

Baseline MMR 500/100,000 Births

Baseline MMR 150/100,000 Births

40 25 10

7,115 20,120 137,050

12,125 34,310 233,755

40,530 114,715 781,775

*Numbers based on ␣ ⫽ 0.05, 1 ⫺ ␤ ⫽ 80%, one-sided test.

by the clinic-based studies of calcium supplementation to reduce preeclampsia,22,58 active management of the third stage of labor to reduce postpartum hemorrhage,59 and the community-based randomized controlled trial of vitamin A supplementation and maternal mortality in Nepal.60 To date, only one randomized controlled trial in a developing country has evaluated the impact of an intervention on maternal mortality. The study by West et al. in Nepal in l999 demonstrated a 44% reduction in maternal morality associated with ante- and postpartum vitamin A or beta-carotene supplementation (P ⬍ .02).60 However, because single studies are insufficient to demonstrate causality, recommended replication studies are currently being conducted. STRATEGIC CONSIDERATIONS: PRIORITIES AND COSTS Research priorities and costs must be strategically considered to reduce expenditures and delays. Affordable and replicable interventions for the intra- and postpartum conditions that most contribute to maternal mortality (hemorrhage, dysfunctional labor, eclampsia, infection) should be given first priority. Reducing the detail of the investigation can greatly reduce the complexity and cost. Cluster randomization and concurrently controlled quasi-experimental studies can help to reduce the financial burdens and logistical difficulties of randomized controlled trials while still providing valid research. Another methodological approach is to use as end points more easily measured mediating events that precipitate maternal mortality. Reasonable mediating variables include percentage of women referred and received for institutional care, percent of deliveries by skilled providers with adequate institutional support, percent of anemia or vitamin A deficiency, and so forth as summarized in Table 3. However, the effect of such mediating variables on maternal mortality must be demonstrated rather than assumed. Reproductive Age Mortality Studies, a direct method of studying maternal mortality, which involves the identification of the causes of deaths of women in reproductive age, with a limited retrospective period (e.g., 5 years) could be used as a supplement or alternative to longitudinal house15

Table 3. Key Interventions that Require Evaluation, Recommended Evaluation Design, Sample and Outcome Measures Interventions Requiring Further Investigation

Recommended Evaluation Design

Sample (per group)

Emergency obstetric first aid

RCT cluster*

ⱖ30 clusters

Trained attendant at delivery

RCT cluster

ⱖ30 clusters

Emergency obstetric care

RCT facility area cluster‡

ⱖ30 clusters

Iron supplementation

RCT1 cluster2

ⱖ30 clusters

Prenatal and postpartum vitamin A supplementation Misoprostol for postpartum hemorrhage (community-based administration) Sulfadoxine-pyrimethamine for parasitemia/anemia/infection Improving transportation

RCT1 cluster2

ⱖ30 clusters

RCT1 cluster2

ⱖ30 clusters

RCT1 cluster2

ⱖ 30 clusters

RCT1 cluster2

ⱖ 30 clusters

Outcome Measures Mediating: % referred and received institutional care Outcome: MMR† Mediating: % trained attendant at delivery (mediating) Outcome: MMR Mediating: % receiving institutional care at emergency obstetric care facility Outcome: MMR Mediating: % anemia§ Outcome: MMR Mediating: % vitamin A deficient Outcome: MMR Mediating: % PPH Outcome: MMR Mediating: % parasitemia Outcome: MMR Mediating: % transported Outcome: % institutional deliveries

MMR indicates maternal mortality ratio; PPH, postpartum hemorrhage; RCT, randomized controlled trial. *A cluster is a single or groups of communities can constitute a cluster. Determination of cluster composition should be the smallest unit possible that avoid a reasonable (likely, realistic) risk of contamination (exposure of comparison clusters to the intervention). † MMR and mediating variables may be measured by carefully conducted and complete quarterly household surveillance systems or before and after the interventions implementation. If the latter pre-post method is used, the referent period for MMR and mediating variables should be identical (and cannot exceed) the duration of the interventions implementation. The required number of pregnant women per group to measure reductions in MMR for example baseline levels are provided in Table 2 (type I error ⫽ .05; type II error ⫽ 20); these estimates require adjustment for cluster design effect (specific to each location). ‡ Facility area cluster means the composition of the cluster should be the geographic coverage area of the facility receiving the emergency obstetric care intervention (i.e., upgrading). § Anemia requires measurement of both hemoglobin and serum ferritin to determine if anemia is iron deficiency anemia; anemia requires reporting as a dichotomous variable.

hold surveillance systems to assess change in maternal mortality ratio over time.61,62 Finally, limiting research to a reasonable amount of replication is cost-efficient. Evaluation of interventions is not feasible or warranted in each specific environment. Nor can all combinations of individual interventions (like those that make up obstetric services) be tested. Replication studies can be conducted in a limited, yet adequately diverse, number of settings to demonstrate causality and the direction of impact that should be expected under similar conditions. Research should never become endless or an end in itself. The purpose of research is to support or challenge a hypothesis; once this is done, in applied disciplines such as nursing, medicine, and public health, the research findings then compel action. KEY INTERVENTIONS TO REDUCE MATERNAL MORALITY Table 3 summarizes key interventions designed to save mothers’ lives that require rigorous evaluation. In this table, we also make suggestions for evaluation design, sample size, and the measure of effect and outcomes, including the possibility of using easier to measure mediating variables. 16

CONCLUSIONS Over the past 15 years, awareness has been raised, attention has been drawn, projects have been proposed and funded, money and human resources expended, and much has been written and published on safe motherhood. Still, we do not really know the impact of proposed interventions on maternal mortality. Some believe there has been only limited success in reducing maternal mortality;4,6,15 however, improved measurement techniques may have masked any progress.7,61,62 Whatever the statistical situation, women’s access to adequate care at delivery remains poor,33,35 and there is no clear evidence on the best way to ensure appropriate care of women in developing countries who require lifesaving interventions in the delivery and postpartum periods. Ultimately, use of evidence-based approaches may be the most cost- and time-efficient way to select programs for large-scale implementation to save women’s lives. If we want to make effective decisions to reduce maternal mortality, we need further evaluations using the best research designs possible. The safe motherhood advocacy community urgently needs to enlist greater support for maternal mortality impact assessment before further implementation Volume 48, No. 1, January/February 2003

of “good ideas” interventions is enacted. Midwives, who work not only as the primary care providers for women globally, but as advocates, researchers, and disseminators of evidence-based practice, should become leaders in producing and supporting rigorous research to provide solid evidence for safe motherhood.44,45 We thank all those involved in the safe motherhood initiative in whose work this article is founded. Dr. John Townsend provided the title for this article for which we are grateful. We give our special thanks to Ms. Sandra Bjegovic for her work on this manuscript.

world: the major challenges. Br J Obstet Gynaecol Sept 1999;106: 877–80. 16. Winikoff B, Carignan C, Bernardik E, Semeraro P. Medical services to save mother’s lives: feasible approaches to reducing maternal mortality. New York: Population Council Working Paper No. 4, 1991:58. 17. Spence C, Danielson TS, Kaunita AM. The faith assembly: a study of perinatal and maternal mortality. Indiana Med 1984;77:180 –3. 18. Kaunitz AM, Spence C, Danielson TA, Rochat RW, Grimes DA. Perinatal and maternal mortality in a religious group avoiding obstetric care. Am J Obstet Gynecol 1984;150:826 –31.

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