Background

Incomplete 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.

Methods

The 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.

Findings

Of 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]).

Interpretation

Our 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.

Funding

University of British Columbia (grantee of the Bill & Melinda Gates Foundation).

中文翻译：

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孕产妇死亡的原因和情况：对先兆子痫社区干预 (CLIP) 试验队列的二次分析

背景

不完整的生命登记系统意味着低收入和中等收入国家对怀孕和分娩期间的死亡原因知之甚少。为了为降低孕产妇死亡率的全球努力提供信息，我们比较了医生审查和口头尸检的计算机分析（解释口头尸检 [InterVA] 软件），以了解他们对社区中孕产妇死亡原因和死亡情况类别 (COMCAT) 的一致意见-先兆子痫 (CLIP) 集群随机试验的水平干预。

方法

CLIP 试验在印度、巴基斯坦和莫桑比克进行，招募了 2014 年 11 月 1 日至 2017 年 2 月 28 日期间 12-49 岁的孕妇。69 330 名孕妇被纳入 44 个集群（22 个干预集群中的 36 008 名）和 22 个控制集群中的 33 322 个）。在 CLIP 中孕产妇死亡的二次分析中，我们包括了在 22 个干预组或 22​​ 个控制组中的任何一个中死亡的妇女。受过培训的工作人员在孕产妇死亡后进行了世卫组织 2012 年的口头尸检。两名医生（如果需要，第三名医生达成共识）审查了试验监测数据和口头尸检，并在干预集群中审查了社区卫生工作者主导的访问数据。他们根据世界卫生组织国际疾病分类——孕产妇死亡率（ICD-MM）确定死因。InterVA 计算机模型（第 4 版和第 5 版）还对口头尸检进行了分析，以得出死因。COMCAT 分析由 InterVA-5 提供，在印度，由医生审查孕产妇新生儿健康登记数据提供。比较死亡原因和由医师审查、Inter-VA-4 和 InterVA-5 分配的 COMCAT，并与 Cohen κ 系数评估一致。

发现

在 CLIP 试验中成功随访的 61 988 例妊娠中，报告了 143 例孕产妇死亡（印度 16 例，巴基斯坦 105 例，莫桑比克 22 例）。孕产妇死亡率为 231 (95% CI 193–268) 每 100 000 次确定的妊娠。大多数死亡归因于直接的产妇原因（而不是根据 ICD-MM 分类的间接或未确定原因），医生审查和 InterVA-4 之间具有相当到良好的一致性（κ=0·56 [95% CI 0·43–0 ·66]）或InterVA-5（κ=0·44 [0·30-0·57]），以及InterVA-4和InterVA-5（κ=0·72 [0·60-0·84]）。医生审查、InterVA-4 和 InterVA-5（ICD-MM 类别产科出血、非产科并发症和高血压疾病）的前三大死因相同；然而，不同方法之间个体患者死亡归因于产科出血的差异更大（医师审查，38 [27%] 例死亡；InterVA-4，69 [48%] 例死亡；InterVA-5，82 [57%] 例死亡），而不是归因非产科原因（医师审查，39 [27%] 例死亡；InterVA-4，37 [26%] 例死亡；InterVA-5，28 [20%] 例死亡）或高血压疾病（医师审查，23 [16%] 例死亡） ] 死亡；InterVA-4，25 [17%] 死亡；和 InterVA-5，24 [17%] 死亡）。所有九个 ICD-MM 类别的一致性对于医师审查与 InterVA-4 (κ=0·48 [0·38–0·58]) 是公平的，对于医师审查与 InterVA-5 (κ=0·36 [0 ·27-0·46]），对InterVA-4 和InterVA-5 有利（κ=0·69 [0·59-0·79]）。InterVA-5 最常分配的 COMCAT 是紧急情况（143 人死亡中的 68 人 [48%]）和卫生系统（62 人 [43%] 死亡），医生审查（仅限印度）是卫生系统（16 例死亡中的 7 例 [44%]）和不可避免性（5 例 [31%] 死亡）；InterVA-5 和医师审查（仅印度数据）之间的一致性很差（κ=0·04 [0·00–0·15]）。

解释

我们的研究结果表明，与医生审查相比，InterVA-5 在确定孕产妇死亡原因和情况方面不如 InterVA-4 准确。我们的结果表明需要改进 InterVA 的下一次迭代，并且研究人员和临床医生在记录孕产妇死亡时优先使用 InterVA-4。

资金

不列颠哥伦比亚大学（比尔和梅琳达盖茨基金会的资助者）。