For the CLIP cRCT, maternal mortality is defined as the number of deaths during pregnancy or within 42 days of pregnancy (in women aged 10-49) per 100,000 identified pregnancies. Although the World Health Organization (WHO) definition of reproductive age women is 15-29 years, CLIP is suggesting 10 years as the lower limit since a proportion of girls may be married by 10 years old in some study sites.
The classic WHO definition of the maternal mortality ratio (MMR) is events per 100,000 live births. A different denominator has been chosen for the reporting of maternal mortality and morbidity for the CLIP cRCT, than that classically used by the WHO. The reason for this is that it is hoped that the CLIP intervention will reduce the burden of stillbirth in women with pre-eclampsia. Therefore, even in the absence of any absolute change in maternal adverse event rates (per pregnancy), the MMR per 100,000 live births could fall artificially as the proportion of live born infants increases. For the CLIP cRCT, the term “maternal death rate (MDR)” will be used. Classically defined MMR will be reported.
When a maternal death is identified, a verbal autopsy will be initiated to identify the cause of death. When possible, data obtained from the verbal autopsy will be triangulated with data obtained from health care records. The 2012 WHO Verbal Autopsy questionnaire will be used, using the inter VA application.
Social autopsies will be undertaken to identify and understand the social, behavioural, and health systems contributors to maternal deaths and major morbidities (see below). The themes relating to delays in identification, arranging transport and seeking treatment were drawn from the MAPEDIR (Maternal and Perinatal Death Inquiry Response) tool.
The main challenge has been around selecting appropriate indicators for maternal morbidity and their definitions, particularly, at the community level. The literature has shown that self-reported maternal morbidity is often inaccurate and inconsistent. Therefore, indicators were selected that would be both clinically meaningful and significant to the woman in order to reduce recall bias. In developing definitions for the indicators, the challenge was to remain simple, objective, context specific and cognisant of resource implications. This process also highlighted the need for an assessment tool that would be more reliable than self-reporting of maternal morbidity.
PRE-EMPT members Peter von Dadelszen, Tabassum Firoz and Laura Magee continue to participate in the WHO Maternal Morbidity Working Group (MMWG). Now in its final year of the project, the MMWG has made tremendous progress towards meeting its five objectives. The group achieved consensus from relevant stakeholders at a meeting held in Istanbul, Turkey (2014) for the following definition:
Any health condition attributed to and/or complicating pregnancy and childbirth that has a negative impact on the woman’s wellbeing and/or functioning.
To achieve the second objective of estimating the magnitude of maternal morbidity based upon existing evidence, the MMWG is in the process of publishing a number of systematic reviews on the prevalence of chronic hypertension, myocardial infarction, sepsis, and peripartum psychosis. The third and fourth objectives focus on developing identification criteria and an assessment tool for maternal morbidity.
A framework, the maternal morbidity matrix, has been developed. Using the definition, a list of potential maternal conditions has been identified and categorised in a fashion similar to the ICD-10 Application to Maternal Mortality. As this framework is focussed on community and primary healthcare level assessment, the objective is to identify morbidity within the broad categories. Each category has accompanying symptoms, signs, investigations and management strategies. Wherever possible, evidence has been used to inform the identification criteria. To understand the impact of morbidity (and to capture morbidity when the identification criteria cannot), several dimensions of functional disability will be used. A maternal history section will accompany these two components and will contain information about risk factors, obstetric and medical history. We plan to use and validate the tool developed by the MMWG to capture maternal morbidity in the community setting. Alas, we plan to build on this tool by developing a probabilistic model to diagnose maternal morbidity.
The definitions for maternal morbidity have been derived from the WHO Near Miss Approach for Maternal Health, as well as from relevant literature reviews and current practices at CLIP study sites. The aim was to select indicators that reflect pre-eclampsia related morbidity in addition to the other leading causes of maternal mortality (sepsis, postpartum haemorrhage and obstructed labour).
Severe maternal morbidity is defined as the number of women with one/more life-threatening complications of pregnancy during pregnancy or within 42 days of pregnancy (or last contact day if contact not maintained to 42 days) per 100,000 identified pregnancies.
The current indicators of severe maternal morbidity in the CLIP Trial are:
- Serious end-organ complications of pre-eclampsia:
- Eclampsia: occurrence of generalised convulsions during pregnancy, labour or within 42 days of
- delivery in the absence of epilepsy or another condition predisposing to convulsions
- Stroke: hemiparesis and/or blindness developed during pregnancy or in the 42 days postpartum lasting greater than 48 hours
- Coma: prolonged unconsciousness ≥12 hours
- Antepartum haemorrhage: vaginal bleeding ≥ 15 mL with or without pain before the onset of labour
- Disseminated intravascular coagulation (DIC): abnormal bleeding from mucosa (mouth and/or ears)
- Other major causes of maternal mortality:
- Obstetric sepsis: In the community, defined as fever and one of: abdominal/uterine tenderness, foul smelling vaginal discharge/lochia, productive cough and shortness of breath, dysuria or flank pain, headache and neck stiffness. In the facility, defined as presence of fever (>38°C), a confirmed or suspected infection (e.g., chorioamnionitis, septic abortion, endometritis, pneumonia) and at least one of the following: heart rate >90/min, respiratory rate >20/min, leukopoenia (total leukocyte count [TLC] <4 x 109/L) or leukocytosis (TLC >12 × 109/L)
- Vesicovaginal or rectovaginal fistula: continuous loss of urine and/or faeces after delivery
- Cardiopulmonary resuscitation: a set of emergency procedures including chest compressions and lung ventilation applied in cardiac arrest victims
- Dialysis: haemodialysis and/or peritoneal dialysis
- Mechanical ventilation (other than for Caesarean section): intubation and ventilation not related to anaesthesia
- Blood transfusion: ≥1 unit
- Interventions for major postpartum haemorrhage: brace sutures, external and internal uterine compression, anti-shock garment use, internal iliac artery ligation and/or hysterectomy with or without transfusion
To understand the impact of morbidity on the woman’s wellbeing, functional disability has been included as an “other” outcome. Functional disability defined as physical inability to perform usual daily duties at specific points in time during the postpartum period that would be acceptable and expected culturally.
Perinatal Mortality and Severe Morbidity
Perinatal and neonatal mortality
The primary outcome for CLIP will include perinatal and late neonatal death. Perinatal death is defined as stillbirth [≥20+0 and/or ≥500g] and/ or early neonatal mortality [days 0-7 of postnatal life]. Late neonatal mortality is defined as death from days 8-28 of postnatal life. The denominator will be per 100,000 identified pregnancies in keeping with our rationale previously described.
As with maternal mortality, verbal and social autopsies for perinatal and neonatal deaths will be conducted. The WHO 2012 Verbal Autopsy questionnaire (death of a child under 4 weeks) and the MAPEDIR questions described above will be used as the tools to audit perinatal mortality.
There are indicators of neonatal morbidity occurring between days 0-28 of postnatal life and determined at both the community and facility levels. The denominator for neonatal morbidity is will also be per 1000 identified pregnancies. These indictors are The indicators and their corresponding questions were drawn from the Child Health Epidemiology Reference Group (CHERG) verbal autopsy and cross-referenced with the WHO Verbal Autopsy questionnaire.
The following are the primary perinatal/neonatal morbidities:
- Feeding difficulty
- Breathing difficulty
- Umbilical cord infection
- Skin infection
- Say L, Barreix M, Chou D, Tunçalp Ö, Cottler S, McCaw-Binns A, Gichuhi GN, Taulo F, Hindin M. Maternal morbidity measurement tool pilot: study protocol. Reproductive Health. 2016 Jun 9;13(1):1.
- Chou D, Tunçalp Ö, Firoz T, Barreix M, Filippi V, von Dadelszen P, van den Broek N, Cecatti JG, Say L. Constructing maternal morbidity–towards a standard tool to measure and monitor maternal health beyond mortality. BMC Pregnancy and Childbirth. 2016 Mar 2;16(1):1.
- Andreucci CB, Bussadori JC, Pacagnella RC, Chou D, Filippi V, Say L, Cecatti JG. Sexual life and dysfunction after maternal morbidity: a systematic review. BMC Pregnancy and Childbirth. 2015 Nov 23;15(1):1.