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Blood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.We did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15-49 years (12-49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP]120 mm Hg and diastolic blood pressure [dBP]80 mm Hg), elevated blood pressure (sBP 120-129 mm Hg and dBP80 mm Hg), stage 1 hypertension (sBP 130-139 mm Hg or dBP 80-89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140-159 mm Hg or dBP 90-109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.Between Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29-5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65-11·07]) and perinatal death (5·07 [3·64-7·07]), particularly stillbirth (8·53 [5·63-12·92]).In low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.University of British Columbia, the BillMelinda Gates Foundation.

Supplemental Digital Content is available in the text., In pregnancy in well-resourced settings, limited data suggest that higher blood pressure (BP) visit-to-visit variability may be associated with adverse pregnancy outcomes. Included were pregnant women in 22 intervention clusters of the CLIP (Community-Level Interventions for Preeclampsia) cluster randomized trials, who had received at least 2 prenatal contacts from a community health worker, including standardized BP measurement. Mixed-effects adjusted logistic regression assessed relationships between pregnancy outcomes and both BP level (median [interquartile range]) and visit-to-visit variability (SD and average real variability [ARV], adjusted for BP level), among all women and those who became hypertensive. The primary outcome was the CLIP composite of maternal and perinatal mortality and morbidity. Among 17 770 pregnancies, higher systolic and diastolic BP levels were associated with increased odds of the composite outcome per 5 mm Hg increase in BP (odds ratio [OR], 1.05 [95% CI, 1.03–1.07] and OR, 1.08 [1.06–1.11], respectively). Higher BP visit-to-visit variability was associated with increased odds, per a SD increase in BP variability measure, of (1) hypertension (systolic: OR, 2.09 [1.98–2.21] for SD and 1.52 [1.45–1.60] for ARV; diastolic: OR, 2.70 [2.54–2.87] for SD and 1.86 [1.76–1.96] for ARV); and (2) the composite outcome (systolic: OR, 1.10 [1.06–1.14] for SD and 1.06 [1.02–1.10] for ARV; diastolic: OR, 1.07 [1.03–1.11] for SD and 1.06 [1.02–1.09] for ARV). In 3 less-developed countries, higher BP level and visit-to-visit variability predicted adverse pregnancy outcomes, providing an opportunity for high-definition medicine.

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).