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Journal ArticleDOI

191 Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the pithagore6 cluster-randomised controlled trial

01 Apr 2010-Quality & Safety in Health Care (BMJ Publishing Group Ltd)-Vol. 19

TL;DR: This educational intervention did not affect the rate of severe PPH, although it improved some practices, and further research is needed on the role of organisational factors as well as individual components of the care recommended for PPH on the risk ofsevere PPH.

AbstractContext, objective Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality and the main component of severe maternal morbidity in developed countries. Decreasing the prevalence of severe PPH is a major obstetrical challenge. In most cases, these are considered to be associated with substandard care. A number of PPH-related clinical guidelines have therefore been developed, both nationally and internationally. The harder job, however, is ensuring the actual translation of these guidelines into clinical practice. Guidelines do not by themselves change professionals’ practices, and the effectiveness of active intervention strategies must be assessed. We tested the hypothesis that a multifaceted educational intervention, aimed at improving practices for PPH management, would reduce the incidence of severe PPH. Methods In a cluster-randomised trial spanning 6 regions in France, 106 maternity units (accounting for 17% of French maternity units, and 20% of deliveries nationwide) were randomly assigned to receive a multi-faceted intervention -combining outreach visits, reminders, and peer reviews of severe cases- to implement a protocol for early management of PPH, or to have the protocol passively disseminated. The primary outcome was the incidence of severe PPH, defined as a composite of one or more of the following: transfusion, embolisation, surgery, transfer to intensive care, peripartum haemoglobin delta of 4 g/dl or more, or death. The main secondary outcomes were the rates of the principal procedures for PPH management recommended in the protocol. During the 1 year data collection period (November 2005–October 2006), all deliveries with PPH were prospectively identified in each unit. Information on the patient9s characteristics, those of the pregnancy and delivery, and outcome data was collected from the chart of every delivery with PPH. Differences in outcomes between the intervention group and the control group were tested with a two-level logistic regression with a random intercept, to take into account the hierarchical structure of the data with women clustered in maternity units. Primary and secondary outcomes were estimated for each of the four trimesters of the 1-year-inclusion period. The effect of time was tested in the intervention and control groups separately, and the intervention effect on this temporal evolution was quantified. Results The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in the control units; the difference was not significant. The intervention was associated with a higher rate of some recommended PPH management procedures: calling for help from senior staff (p=0.005), administration of sulprostone in severe PPH due to uterine atony (p=0.06), blood test within 60 min of diagnosis in severe PPH (p=0.09). The mean rate of severe PPH decreased between the first and third trimesters (1.79% (SD 1.21) and 1.52% (SD 0.87) respectively; p=0.07) in the intervention units, and was significantly lower in both the third and fourth trimesters than in the first trimester (1.60% (SD 1.05), 1.45% (SD 1.05) and 1.91% (SD1.44) respectively; p=0.01 and 0.03) in the control units. The trend of decrease with trimester of the rate of severe PPH was not significantly different between the two groups. Conclusion This educational intervention did not affect the rate of severe PPH, although it improved some practices. A parallel effect in the intervention units (through contamination by the intervention or external factors) may have contributed to the absence of a major difference between the two arms. Further research is needed on the role of organisational factors as well as individual components of the care recommended for PPH on the risk of severe PPH, for many of these are not evidence-based. Such evidence will help to focus future educational interventions on the most important aspects of care. Contexte, objectif L9hemorragie du postpartum (HPP) est l9une des causes majeures de mortalite maternelle et la cause principale de morbidite maternelle severe dans les pays developpes. Diminuer la prevalence de l9HPP severe constitue une priorite en obstetrique. La plupart de ces cas severes semblent associes a une prise en charge suboptimale. En reponse, des recommandations de pratique clinique relatives a l9HPP ont ete edictees, au niveau national et international. Cependant, l9existence de telles recommandations ne suffit pas pour obtenir leur traduction effective dans la pratique clinique, et il necessaire d9evaluer l9efficacite de strategies d9intervention specifiques dans ce but. Notre objectif etait d9evaluer l9efficacite d9un programme d9intervention multifacettes destine a favoriser l9integration dans la pratique clinique de recommandations de prise en charge de l9HPP, afin de diminuer l9incidence de l9HPP severe. Methodes Dans un essai randomise en cluster conduit dans 6 regions francaises, 106 maternites (representant 17% des maternites francaises et realisant 20% des accouchements du pays) ont ete assignees par tirage au sort au bras intervention -programme multifacette combinant une discussion des recommandations dans chaque maternite, l9utilisation de “reminders” et un audit clinique-, ou au bras reference -diffusion passive des recommandations. Le critere de jugement principal etait l9incidence de l9HPP severe, definie par la presence d9un au moins des criteres suivants: transfusion, embolisation, chirurgie, trasfert en reanimation, delta peripartum d9hemoglobine de 4g/dl ou plus, deces. Les criteres de jugements secondaires portaient sur la conformite des pratiques reelles de prise en charge de l9HPP aux principales etapes des recommandations. Tous les accouchements avec HPP ont ete identifies prospectivement pendant une annee (Novembre 2005–Octobre 2006) dans chaque maternite. Pour chacun de ces cas, l9information sur les caracteristiques de la femme, de sa grossesse, de son accouchement, et le deroulement del9HPP, etait collectee a partir du dossier obstetrical. Les differences entre les 2 bras pour les criteres de jugement ont ete testees en utilisant un modele de regression logistique a 2 niveaux prenant en compte la structure hierarchique des donnees et la correlation intra-maternite. Les criteres de jugement ont ete calcules pour chacun des quatre trimestres de l9annee d9inclusion. L9effet du temps a ete teste separement dans le bras intervention et dans le bras reference, et l9effet de l9intervention sur cette evolution temporelle a ete quantifie. Resultats L9incidence moyenne de l9HPP severe etait de 1.64% (SD 0.80) dans le bras intervention et 1.65% (SD 0.96) dans le bras reference; cette difference n9etait pas significative. Certaines pratiques etaient plus souvent conformes aux recommandations dans le bras intervention: appel d9un medecin senior(p=0.005); administration de sulprostone en cas d9HPP severe par atonie uterine (p=0.06), bilan biologique dans les 60 min en cas d9HPP severe(p=0.09). L9incidence moyenne de l9HPP severe est passee de 1.79% (SD1.21) au premier trimestre a 1.52% (SD 0.87) au troisieme trimestre dans les le bras intervention (p=0.07), et etait significativement plus basse aux 3eme et 4eme trimestres qu9au 1er trimestre (1.60% (SD 1.05), 1.45% (SD 1.05) et 1.91% (SD1.44) respectivement; p=0.01 et 0.03) dans le bras reference. La diminution de l9incidence de l9HPP severe au cours du temps n9etait pas differente entre les 2 groupes. Conclusion L9intervention n9a pas modifie l9incidence de l9HPP severe, bien qu9elle ait ameliore la conformite de certaines pratiques cliniques relatives a l9HPP. Un effet parallele dans les maternites du bras reference a pu contribuer a l9absence de difference majeure entre les bras. Des travaux ulterieurs sont necessaires pour preciser le role des facteurs organisationnels et des composantes specifiques de la prise en charge recommandee de l9HPP vis-a-vis du risque d9HPP severe, car la plupart ne reposent pas sur des preuves scientifiques solides. Ceci permettrait de cibler les interventions d’education sur les aspects les plus determinants des soins.

Topics: Intensive care (52%)

Summary (4 min read)

Introduction

  • Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality (1, 2) and the main component of severe maternal morbidity (3) (4) (5) .
  • Decreasing the prevalence of severe PPH is a major obstetrical challenge, in both developed and developing countries.
  • These findings suggest that increasing the appropriateness of care should improve PPH-related health indicators.
  • The harder job, however, is ensuring the actual translation of these guidelines into clinical practice.
  • The relevance of their results in other and more diverse settings is however questionable.

Design

  • The study was a cluster-randomised controlled trial, with the maternity unit as the randomisation unit.
  • One group of maternity units was assigned to receive a multifaceted intervention to implement guidelines for PPH management.
  • The control group of maternity units received no intervention.

Setting

  • The trial was conducted in six perinatal networks in France.
  • The six perinatal networks were the Perinat Centre network around Tours (23 units), the Port-Royal St Vincent de Paul network in Paris (25 units), and the 4 networks of the Rhône-Alpes region: the Aurore network around Lyon (33 units), the Savoie network around Chambery (14 units), the Grenoble network (5 units), and the St-Etienne network (9 units).

Participants

  • Maternity units were eligible if they belong to one of the six networks.
  • No other eligibility criterion was applied, in accord with their population-based approach.
  • Two units were excluded because they were involved in a concomitant clinical study not compatible with their trial.
  • The authors sample therefore included 106 maternity units of the 109 in the six regional networks .
  • They accounted for about 17% of all French maternity units, and 20% of deliveries nationwide.

Randomisation

  • The random allocation was produced centrally by the Biostatistics department of the Hospices Civils de Lyon, France.
  • A design stratified according to perinatal network and size was used to ensure that the two arms of the trial were as similar as possible at baseline.
  • Perinatal network was divided into five classes, with the Grenoble and St-Etienne networks regrouped in one class because of their geographic proximity and small number of units.
  • For each stratum, a random allocation was made using a random number generator available in SAS software, with a different seed value for each stratum.

Intervention group

  • The multifaceted intervention consisted of a combination of three components  an outreach visit with academic detailing, reminders, and peer review of deliveries with severe PPH-to facilitate the translation into practice of the protocol for the early management of PPH.
  • For each network, an obstetrician and a midwife identified as opinion leaders in their professional community were teamed to implement the intervention's components in each maternity unit.
  • These six teams met together during two one-day meetings for training in the different facets of the intervention.
  • This academic detailing is thought to facilitate changes in behaviours when it provides a clear message that meets the needs of the target audience (28) (29) (30) .
  • This box was intended to provide a single place where all drugs and materials needed for PPH management were available, as well as a list of useful phone numbers, forms for transfusion order and lab exams, and a chronometer to keep exact track of the time.

Reference group

  • In the maternity units of the reference group, the protocol for early management of PPH was presented at a staff meeting and passively disseminated.
  • This occurred during the same time frame as the first phase of the intervention.

Definitions and Outcomes

  • PPH was clinically assessed by the care givers, or biologically defined by a peripartum haemoglobin delta greater than 2 g/dl (considered equivalent to the loss of more than 500 ml of blood).
  • Prepartum haemoglobin was collected as part of routine prenatal care during the last weeks of pregnancy; postpartum haemoglobin was the lowest haemoglobin level found in the three days after delivery.
  • The primary outcome for the trial was the rate of severe PPH, expressed as the number of deliveries with severe PPH divided by the total number of deliveries during the trial period.
  • Severe PPH was defined as a PPH associated with one or more of the following events related to blood loss: blood transfusion, arterial embolisation, arterial ligation, other conservative uterine surgery, hysterectomy, transfer to intensive care unit, peripartum haemoglobin delta of 4 g/dl or more (considered equivalent to the loss of 1000 ml or more of blood), or maternal death.
  • The authors chose the rate of severe PPH as the primary outcome because their primary goal was to assess the effect of the intervention on health and not only its impact on practices.

Data collection

  • Data collection began after the first phase of the intervention, and lasted for one year in both groups.
  • In addition, a research assistant reviewed the delivery suite logbook of each unit monthly, as well as computerised patient charts when available.
  • A research assistant collected from the medical charts of every delivery with confirmed PPH the patient's characteristics, those of the pregnancy, labour and delivery, and outcome data.
  • The component procedures of PPH management were considered to have been performed only if they were specifically mentioned in the patient's chart.
  • The times of the different procedures/exams were extracted from the medical charts where they were written down by the care givers as events occurred.

Sample size

  • The sample size estimation took into account the cluster-randomised design.
  • This estimation was derived from the rates of severe PPH provided by the 65 maternity units of five French regions for the year 2003 (Euphrates survey (16) , secondary data analysis).
  • The average cluster size was determined according to the number of deliveries observed in maternity units of the six networks in 2002.

Analysis

  • Analyses were performed according to the intention-to-treat principle, and all data from all maternity units assigned to the intervention or the control group were included in the analysis.
  • The difference between the mean rate of severe PPH between the intervention group and the control group was tested and quantified with a two-level logistic regression with a random intercept (34) , which allowed us to take into account the natural hierarchical structure of the data with women clustered in maternity units.
  • The intra-cluster correlation (ICC) coefficient, , was calculated (35).
  • These subgroup analyses were pre-specified in the protocol.
  • A two-level logistic regression with random intercept was used to test and quantify the intervention effect on secondary outcomes.

Characteristics of maternity units

  • Intervention to decrease severe postpartum haemorrhage 10 Fifty-four units were allocated to the intervention group, and 52 to the control group.
  • Once entered, all 106 units completed the trial .
  • The characteristics of the units in each group were similar (Table 1 ), in particular with regard to factors that affect the PPH risk (multiple pregnancy and caesarean delivery rates) and resources likely to influence the content of care provided for PPH (onsite embolisation, intensive care unit, presence of anaesthetist).

Outcome measures

  • The trial period covered 76 074 deliveries in the intervention group and 70 707 in the control group.
  • Analyses tested the effect of the intervention on the main components of the primary outcome (Table 2 ).
  • In the intervention arm, the rates of transfusion, of surgery and Intervention to decrease severe postpartum haemorrhage 12 of embolisation did not decrease over time.

Discussion

  • This trial, involving 106 maternity units and 146 781 parturient women, tested the impact of an educational intervention to improve the translation into clinical practice of guidelines for PPH management.
  • Another report from a hospital in New York described how a systemic approach to improving the safety of patients with PPH was adopted in late 2001 and reported that it was associated with fewer maternal deaths due to PPH in 2002-2005 than in 2000-2001, despite a significant increase in major obstetric haemorrhage cases (24) .
  • Whether their approach can be replicated in other units is especially uncertain given the importance of local context in the process of improving practices (29, 30) .
  • In the present randomized trial, , the rates of PPH and severe PPH tended to be lower in both groups in subsequent time periods than in the first three month-period of assessment.
  • This suggests that the intervention may have had a concomitant effect in the control group, and that this parallel effect contributed to the absence of a major difference between the two arms of the trial.

Conclusion

  • Changes in outcomes occurred in both groups.
  • The educational intervention was not associated with a significant additional impact on the rate of severe PPH as compared to control units.
  • These results illustrate the challenge of designing and evaluating behavioural interventions to improve clinical practices.
  • Yet, as more evidence on the efficacy of components of care becomes available, such programs are increasingly needed.

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Intervention to decrease severe postpartum haemorrhage
1
Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the 1
PITHAGORE6 cluster-randomised controlled trial 2
3
C Deneux-Tharaux
1
*, C Dupont
2
, C Colin
3
, M Rabilloud
4
, S Touzet
3
, J Lansac
5
, T Harvey
6
, V 4
Tessier
6
, C Chauleur
7
, G Pennehouat
8
,
X Morin
9
, MH Bouvier-Colle
1
, R Rudigoz
2
5
6
1
INSERM, UMR S953, UPMC, Epidemiological research unit on perinatal health and women’s and 7
children’s health, Paris, France 8
2
Aurore Perinatal network, Hospices civils de Lyon; EA 4129, Lyon 1 University, Lyon, France. 9
3
Department of medical information and health care evaluation, Hospices Civils de Lyon; EA4129, 10
Lyon 1 University, Lyon, France. 11
4
Hospices Civils de Lyon, Service de Biostatistique, Lyon, F-69003, France ; Université de Lyon, F-12
69000, Lyon ; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe 13
Biostatistique Santé, Pierre-Bénite, F-69310, France. 14
5
PerinatCentre Perinatal network, Tours University Hospital, France 15
6
Port Royal St Vincent de Paul Perinatal network, Paris, France 16
7
Loire Nord Ardeche Perinatal network, Saint Etienne University Hospital, France 17
8
2 Savoie Perinatal network, Chambery Hospital, France 18
9
Alpes Isere Perinatal network, Grenoble University Hospital, France 19
20
* Corresponding author: INSERM U953, Batiment de recherche, Hopital Tenon, 4 rue de la Chine, 21
75020 Paris, France. Email: catherine.deneux-tharaux@inserm.fr; Tel: + 33 (0)1 56 01 83 67 22
23

Intervention to decrease severe postpartum haemorrhage
2
Abstract 24
Objective-Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical 25
challenge. These are often considered to be associated with substandard initial care. Strategies to 26
increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis 27
that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early 28
management of PPH, would reduce the incidence of severe PPH. 29
Design- Cluster-randomised trial 30
Population- 106 maternity units in 6 French regions 31
Methods- Maternity units were randomly assigned to receive the intervention, or to have the protocol 32
passively disseminated. The intervention combined outreach visits to discuss the protocol in each local 33
context, reminders, and peer reviews of severe cases, and was implemented in each maternity hospital 34
by a team pairing an obstetrician and a midwife. 35
Main outcome measures- The primary outcome was the incidence of severe PPH, defined as a 36
composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, 37
peripartum haemoglobin delta of 4 g/dl or more, death. The main secondary outcomes were PPH 38
management practices. 39
Results- The mean rate of severe PPH was 1.64% (SD0.80) in the intervention units and 1.65% 40
(SD0.96) in control units; difference not significant. Some elements of PPH management were applied 41
more frequently in intervention units help from senior staff (p=0.005)-, or tended to second line 42
pharmacological treatment (p=0.06), timely blood test (p=0.09). 43
Conclusion-This educational intervention did not affect the rate of severe PPH as compared to control 44
units, although it improved some practices. 45
Trial registration: ClinicalTrials.gov NCT 00344929 46
47
Keywords- Maternal health, postpartum haemorrhage, clinical practices, educational intervention, 48
cluster-randomised trial49

Intervention to decrease severe postpartum haemorrhage
3
Introduction 50
Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality(1, 2) and the main 51
component of severe maternal morbidity (3-5). Decreasing the prevalence of severe PPH is a major 52
obstetrical challenge, in both developed and developing countries. Because individual risk factors do 53
not predict PPH well(6, 7), interest has increasingly focused on factors related to the care provided, 54
which are potentially more amenable to change. 55
In the area of prevention of PPH, a high level of evidence supports the efficacy of the routine 56
administration of oxytocics during the third stage of labour (8) and the effective translation of these 57
results into clinical practice through behavioural interventions has been recently described (9, 10). 58
Conversely, improving obstetric care for the management of PPH remains difficult, although greatly 59
needed. Reports from confidential enquiries into maternal deaths show that most deaths due to PPH 60
involve delayed and substandard care in the diagnosis and management of haemorrhage (11-13). A 61
population-based study of severe non-lethal PPH reached a similar conclusion (14). A recent study 62
demonstrated a wide heterogeneity in maternity unit policies for the immediate management of PPH 63
within individual European countries as well as between them (15, 16). These findings suggest that 64
increasing the appropriateness of care should improve PPH-related health indicators. A number of 65
PPH-related clinical guidelines have therefore been developed, both nationally and internationally (17-66
21). 67
The harder job, however, is ensuring the actual translation of these guidelines into clinical practice. 68
Guidelines do not by themselves change professionals’ practices (22), and the effectiveness of active 69
intervention strategies must be assessed. Results from educational interventions strictly focused on 70
PPH prevention cannot be generalized to PPH management, because of the differential nature of care 71
involved routine versus emergency care. A few previous reports have described the effectiveness of 72
local strategies in individual institutions aimed at improving the management of PPH (23, 24). The 73
relevance of their results in other and more diverse settings is however questionable. 74
We present the results of a cluster-randomised controlled trial to test the hypothesis that a multifaceted 75
educational intervention, aimed at improving practices for early PPH management, would reduce the 76
rate of severe PPH in diverse obstetric care settings. 77

Intervention to decrease severe postpartum haemorrhage
4
78
Methods 79
Design 80
The study was a cluster-randomised controlled trial, with the maternity unit as the randomisation unit. 81
One group of maternity units was assigned to receive a multifaceted intervention to implement 82
guidelines for PPH management. The control group of maternity units received no intervention. 83
Setting 84
The trial was conducted in six perinatal networks in France. A 1998 French statute aimed at 85
optimising the organisation of obstetric care made it mandatory for all maternity units to belong to a 86
perinatal network (25), organised around one or more level 3 units (reference centres with an onsite 87
neonatal intensive care unit) and including units rated as level 1 (no facilities for non-routine neonatal 88
care) and 2 (with a neonatal care unit), both public and private. The six perinatal networks were the 89
Perinat Centre network around Tours (23 units), the Port-Royal St Vincent de Paul network in Paris 90
(25 units), and the 4 networks of the Rhône-Alpes region: the Aurore network around Lyon (33 units), 91
the Savoie network around Chambery (14 units), the Grenoble network (5 units), and the St-Etienne 92
network (9 units). 93
Participants 94
Maternity units were eligible if they belong to one of the six networks. No other eligibility criterion 95
was applied, in accord with our population-based approach. Two units were excluded because they 96
were involved in a concomitant clinical study not compatible with our trial. One unit decided not to 97
participate. Our sample therefore included 106 maternity units of the 109 in the six regional networks 98
(listed in the Appendix). They accounted for about 17% of all French maternity units, and 20% of 99
deliveries nationwide. 100
The trial took place between September 2004 and November 2005 in the Aurore network, and between 101
September 2005 and November 2006 in the other five. 102
Randomisation 103
The random allocation was produced centrally by the Biostatistics department of the Hospices Civils 104
de Lyon, France. A design stratified according to perinatal network and size was used to ensure that 105

Intervention to decrease severe postpartum haemorrhage
5
the two arms of the trial were as similar as possible at baseline. Perinatal network was divided into 106
five classes, with the Grenoble and St-Etienne networks regrouped in one class because of their 107
geographic proximity and small number of units. Size was classified in two categories: an annual 108
number of deliveries equal to or greater than the 50
th
percentile for the network, or less than the 50
th
109
percentile. In each stratum, a balanced number of maternity units was assigned at random to one of the 110
two arms (intervention or control). For each stratum, a random allocation was made using a random 111
number generator available in SAS software, with a different seed value for each stratum. 112
113
Intervention 114
Protocol for early management of PPH 115
The protocol for stepwise management of PPH was consistent with the national clinical 116
guidelines.(26) Overall, the main recommended steps were the following: examination of the uterine 117
cavity and/or manual removal of placenta within 15 minutes of PPH diagnosis; call for additional staff 118
obstetrician or anaesthetist within 15 minutes of PPH diagnosis; instrumental examination of the 119
vagina and cervix; immediate intravenous administration of therapeutic oxytocin; and if PPH 120
persisted, intravenous administration of sulprostone (second line oxytocic) within 30 minutes of the 121
initial diagnosis, and a blood test within 60 minutes of it. 122
Intervention group 123
The multifaceted intervention consisted of a combination of three components an outreach visit 124
with academic detailing, reminders, and peer review of deliveries with severe PPH- to facilitate the 125
translation into practice of the protocol for the early management of PPH. 126
For each network, an obstetrician and a midwife identified as opinion leaders in their professional 127
community were teamed to implement the intervention’s components in each maternity unit. The 128
demonstrated role of opinion leaders in facilitating the adoption of guidelines derives from their 129
influence and power, as people of social importance.(27) These six teams met together during two 130
one-day meetings for training in the different facets of the intervention. 131
The components of the intervention were implemented in two phases. The first phase lasted three 132
months and consisted of outreach visits to each maternity unit (two visits per unit). During these visits, 133

References
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Journal ArticleDOI
TL;DR: Haemorrhage and hypertensive disorders are major contributors to maternal deaths in developing countries and these data should inform evidence-based reproductive health-care policies and programmes at regional and national levels.
Abstract: Methods We selected datasets using prespecifi ed criteria, and recorded dataset characteristics, methodological features, and causes of maternal deaths. All analyses were restricted to datasets representative of populations. We analysed joint causes of maternal deaths from datasets reporting at least four major causes (haemorrhage, hypertensive disorders, sepsis, abortion, obstructed labour, ectopic pregnancy, embolism). We examined datasets reporting individual causes of death to investigate the heterogeneity due to methodological features and geographical region and the contribution of haemorrhage, hypertensive disorders, abortion, and sepsis as causes of maternal death at the country level. Findings 34 datasets (35 197 maternal deaths) were included in the primary analysis. We recorded wide regional variation in the causes of maternal deaths. Haemorrhage was the leading cause of death in Africa (point estimate 33·9%, range 13·3-43·6; eight datasets, 4508 deaths) and in Asia (30·8%, 5·9-48·5; 11, 16 089). In Latin America and the Caribbean, hypertensive disorders were responsible for the most deaths (25·7%, 7·9-52·4; ten, 11 777). Abortion deaths were the highest in Latin America and the Caribbean (12%), which can be as high as 30% of all deaths in some countries in this region. Deaths due to sepsis were higher in Africa (odds ratio 2·71), Asia (1·91), and Latin America and the Caribbean (2·06) than in developed countries. Interpretation Haemorrhage and hypertensive disorders are major contributors to maternal deaths in developing countries. These data should inform evidence-based reproductive health-care policies and programmes at regional and national levels. Capacity-strengthening eff orts to improve the quality of burden-of-disease studies will further validate future estimates.

3,300 citations