Causes and circumstances of maternal death: a secondary analysis of the Community-Level Interventions for Pre-eclampsia (CLIP) trials cohort
Authors: Annet M Aukes, Kristina Arion, Jeffrey N Bone, Jing Li, Marianne Vidler, Mrutyunjaya B Bellad, Umesh Charantimath, Shivaprasad S Goudar, Zahra Hoodbhoy, Geetanjali Katageri, Salésio Macuacua, Ashalata A Mallapur, Khátia Munguambe, Rahat N Qureshi, Charfudin Sacoor, Esperança Sevene, Sana Sheikh, Anifa Valá, Gwyneth Lewis, Zulfiqar A Bhutta, Peter von Dadelszen, Laura A Magee, Mai-Lei Woo Kinshella, Hubert Wong, Peter von Dadelszen, Faustino Vilanculo, Marianne Vidler, Anifa Valá, Ugochi V Ukah, Domena K Tu, Lehana Thabane, Corsino Tchavana, Jim Thornton, John O Sotunsa, Joel Singer, Sana Sheikh, Sumedha Sharma, Esperança Sevene, Nadine Schuurman, Diane Sawchuck, Charfudin Sacoor, Amit P Revankar, Farrukh Raza, Umesh Y Ramdurg, Rahat N Qureshi, Rosa Pires, Beth A Payne, Vivalde Nobela, Cláudio Nkumbula, Ariel Nhancolo, Zefanias Nhamirre, Khátia Munguambe, Geetanjali I Mungarwadi, Dulce Mulungo, Sibone Mocumbi, Craig Mitton, Mario Merialdi, Javed Memon, Analisa Matavele, Sphoorthi S Mastiholi, Ernesto Mandlate, Ashalata A Mallapur, Laura A Magee, Sónia Maculuve, Salésio Macuacua, Eusébio Macete, Marta Macamo, Mansun Lui, Jing Li, Gwyneth Lewis, Simon Lewin, Tang Lee, Ana Langer, Uday S Kudachi, Bhalachandra S Kodkany, Marian Knight, Gudadayya S Kengapur, Avinash J Kavi, Geetanjali Katageri, Chirag Kariya, Chandrappa C Karadiguddi, Namdev A Kamble, Anjali M Joshi, Eileen Hutton, Amjad Hussain, Narayan V Honnungar, Zahra Hoodbhoy, William Grobman, Shivaprasad S Goudar, Emília Gonçálves, Tabassum Firoz, Veronique Fillipi, Paulo Filimone, Susheela M Engelbrecht, Dustin T Dunsmuir, Guy Dumont, Sharla K Drebit, France Donnay, Shafik Dharamsi, Vaibhav B Dhamanekar, Richard Derman, Brian Darlow, Silvestre Cutana, Keval S Chougala, Rogério Chiaú, Umesh Charantimath, Romano Nkumbwa Byaruhanga, Jeffrey N Bone, Helena Boene, Ana Ilda Biz, Cassimo Bique, Zulfiqar A Bhutta, Ana Pilar Betrán, Mrutyunjaya B Bellad, Shashidhar G Bannale, Annet M Aukes, Orvalho Augusto, Kristina Arion, J Mark Ansermino, Felizarda Amose, Imran Ahmed, Olalekan O Adetoro
Journal: The Lancet Global Health (2021)

BackgroundIncomplete vital registration systems mean that causes of death during pregnancy and childbirth are poorly understood in low-income and middle-income countries. To inform global efforts to reduce maternal mortality, we compared physician review and computerised analysis of verbal autopsies (interpreting verbal autopsies [InterVA] software), to understand their agreement on maternal cause of death and circumstances of mortality categories (COMCATs) in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials.MethodsThe CLIP trials took place in India, Pakistan, and Mozambique, enrolling pregnant women aged 12–49 years between Nov 1, 2014, and Feb 28, 2017. 69 330 pregnant women were enrolled in 44 clusters (36 008 in the 22 intervention clusters and 33 322 in the 22 control clusters). In this secondary analysis of maternal deaths in CLIP, we included women who died in any of the 22 intervention clusters or 22 control clusters. Trained staff administered the WHO 2012 verbal autopsy after maternal deaths. Two physicians (and a third for consensus, if needed) reviewed trial surveillance data and verbal autopsies, and, in intervention clusters, community health worker-led visit data. They determined cause of death according to the WHO International Classification of Diseases-Maternal Mortality (ICD-MM). Verbal autopsies were also analysed by InterVA computer models (versions 4 and 5) to generate cause of death. COMCAT analysis was provided by InterVA-5 and, in India, by physician review of Maternal Newborn Health Registry data. Causes of death and COMCATs assigned by physician review, Inter-VA-4, and InterVA-5 were compared, with agreement assessed with Cohen's κ coefficient.FindingsOf 61 988 pregnancies with successful follow-up in the CLIP trials, 143 maternal deaths were reported (16 deaths in India, 105 in Pakistan, and 22 in Mozambique). The maternal death rate was 231 (95% CI 193–268) per 100 000 identified pregnancies. Most deaths were attributed to direct maternal causes (rather than indirect or undetermined causes as per ICD-MM classification), with fair to good agreement between physician review and InterVA-4 (κ=0·56 [95% CI 0·43–0·66]) or InterVA-5 (κ=0·44 [0·30–0·57]), and InterVA-4 and InterVA-5 (κ=0·72 [0·60–0·84]). The top three causes of death were the same by physician review, InterVA-4, and InterVA-5 (ICD-MM categories obstetric haemorrhage, non-obstetric complications, and hypertensive disorders); however, attribution of individual patient deaths to obstetric haemorrhage varied more between methods (physician review, 38 [27%] deaths; InterVA-4, 69 [48%] deaths; and InterVA-5, 82 [57%] deaths), than did attribution to non-obstetric causes (physician review, 39 [27%] deaths; InterVA-4, 37 [26%] deaths; and InterVA-5, 28 [20%] deaths) or hypertensive disorders (physician review, 23 [16%] deaths; InterVA-4, 25 [17%] deaths; and InterVA-5, 24 [17%] deaths). Agreement for all nine ICD-MM categories was fair for physician review versus InterVA-4 (κ=0·48 [0·38–0·58]), poor for physician review versus InterVA-5 (κ=0·36 [0·27–0·46]), and good for InterVA-4 versus InterVA-5 (κ=0·69 [0·59–0·79]). The most commonly assigned COMCATs by InterVA-5 were emergencies (68 [48%] of 143 deaths) and health systems (62 [43%] deaths), and by physician review (India only) were health systems (seven [44%] of 16 deaths) and inevitability (five [31%] deaths); agreement between InterVA-5 and physician review (India data only) was poor (κ=0·04 [0·00–0·15]).InterpretationOur findings indicate that InterVA-5 is less accurate than InterVA-4 at ascertaining causes and circumstances of maternal death, when compared with physician review. Our results suggest a need to improve the next iteration of InterVA, and for researchers and clinicians to preferentially use InterVA-4 when recording maternal deaths.FundingUniversity of British Columbia (grantee of the Bill & Melinda Gates Foundation).