Duration of third stage labour and postpartum blood loss: a secondary analysis of the WHO CHAMPION trial data

Background: Obstetric haemorrhage continues to be a leading cause of maternal mortality, contributing to more than a quarter of the 2,443,000 maternal deaths reported between 2003 and 2009. During this period, about 70% of the haemorrhagic deaths occurred postpartum. In addition to other identifiable risk factors for greater postpartum blood loss, the duration of the third stage of labour (TSL) seems to be important, as literature shows that a longer TSL can be associated with more blood loss. To better describe the association between the duration of TSL and postpartum blood loss in women receiving active management of third stage of labour (AMTSL), this secondary analysis of the WHO CHAMPION trial data has been conducted. Methods: This was a secondary analysis of the WHO CHAMPION trial conducted in twenty-three sites in ten countries. We studied the association between the TSL duration and blood loss in the sub cohort of women from the CHAMPION trial (all of whom received AMTSL), with TSL upto 60 min and no interventions for postpartum haemorrhage. We used a general linear model to fit blood loss as a function of TSL duration on the log scale, arm and center, using a normal distribution and the log link function. We showed this association separately for oxytocin and for Heat stable (HS) carbetocin. Results: For the 10,040 women analysed, blood loss rose steeply with third stage duration in the first 10 min, but more slowly after 10 min. This trend was observed for both Oxytocin and HS carbetocin and the difference in the trends for both drugs was not statistically significant (p-value = 0.2070). Conclusions: There was a positive association between postpartum blood loss and TSL duration with either uterotonic. Blood loss rose steeply with TSL duration until 10 min, and more slowly after 10 min.Fil: Chikkamath, Sumangala B.. S. Nijalingappa Medical College; IndiaFil: Katageri, Geetanjali M.. S. Nijalingappa Medical College; IndiaFil: Mallapur, Ashalata A.. S. Nijalingappa Medical College; IndiaFil: Vernekar, Sunil S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Somannavar, Manjunath S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Piaggio, Gilda. No especifíca;Fil: Carroli, Guillermo. Centro Rosarino de Estudios Perinatales; ArgentinaFil: de Carvalho, José Ferreira. No especifíca;Fil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Hofmeyr, G. Justus. University of Botswana; Estados Unidos. University of the Witwatersrand; SudáfricaFil: Widmer, Mariana. Organizacion Mundial de la Salud; ArgentinaFil: Gulmezoglu, Ahmet Metin. No especifíca;Fil: Goudar, Shivaprasad S.. Jawaharlal Nehru Medical College Belgaum; Indi

Causes and circumstances of maternal death:a secondary analysis of the Community-Level Interventions for (CLIP) trials cohort

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)

Community Engagement for Birth Preparedness and Complication Readiness in the Community Level Interventions for Pre-eclampsia (CLIP) Trial in India: A Mixed-Method Evaluation

Objective: To describe the process of community engagement (CE) in northern Karnataka, India and its impact on pre-eclampsia knowledge, birth preparedness and complication readiness, pregnancy-related care seeking and maternal morbidity. Design: This study was a secondary analysis of a cluster randomised trial of Community Level Interventions for Pre-eclampsia (CLIP). A total of 12 clusters based on primary health centre catchment areas were randomised to intervention or control. CE was conducted in intervention clusters. CE attendance was summarised according to participant group using both quantitative and qualitative assessment. Pre-eclampsia knowledge, birth preparedness, health services engagement and perinatal outcomes was evaluated within trial surveillance. Outcomes were compared between trial arms using a mixed effects logistic regression model on RStudio (RStudio, Boston, USA). Community feedback notes were thematically analysed on NVivo V.12 (QSR International, Melbourne, Australia). Setting: Belagavi and Bagalkote districts in rural Karnataka, India. Participants: Pregnant women and women of reproductive age, mothers and mothers-in-law, community stakeholders and male household decision-makers and health workers. Results: A total of 1379 CE meetings were conducted with 39 362 participants between November 2014 and October 2016. CE activities may have had an effect on modifying community attitudes towards hypertension in pregnancy and its complications. However, rates of pre-eclampsia knowledge, birth preparedness, health services engagement and maternal morbidities among individual pregnant women were not significantly impacted by CE activities in their area. Conclusion: Evaluation of our CE programme in India demonstrates the feasibility of reaching pregnant women alongside household decision-makers, community stakeholders and health workers. More research is needed to explore the pathways of impact between broad community mobilisation to strengthen support for maternal care seeking and clinical outcomes of individual pregnant women. Trial registration number: NCT01911494

Antenatal dexamethasone for early preterm birth in low-resource countries

BACKGROUND: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain. METHODS: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale. RESULTS: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P=0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P=0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection.Fil: Oladapo, Olufemi T.. Organizacion Mundial de la Salud; ArgentinaFil: Vogel, Joshua P.. Organizacion Mundial de la Salud; ArgentinaFil: Piaggio, Gilda. Organizacion Mundial de la Salud; ArgentinaFil: Nguyen, My-Huong. Organizacion Mundial de la Salud; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Metin Gülmezoglu, A.. Organizacion Mundial de la Salud; ArgentinaFil: Bahl, Rajiv. Organizacion Mundial de la Salud; ArgentinaFil: Rao, Suman P.N.. Organizacion Mundial de la Salud; ArgentinaFil: de Costa, Ayesha. Organizacion Mundial de la Salud; ArgentinaFil: Gupta, Shuchita. Organizacion Mundial de la Salud; ArgentinaFil: Shahidullah, Mohammod. No especifíca;Fil: Chowdhury, Saleha B.. No especifíca;Fil: Ara, Gulshan. No especifíca;Fil: Akter, Shaheen. No especifíca;Fil: Akhter, Nasreen. No especifíca;Fil: Dey, Probhat R.. No especifíca;Fil: Abdus Sabur, M.. No especifíca;Fil: Azad, Mohammad T.. No especifíca;Fil: Choudhury, Shahana F.. No especifíca;Fil: Matin, M.A.. No especifíca;Fil: Goudar, Shivaprasad S.. No especifíca;Fil: Dhaded, Sangappa M.. No especifíca;Fil: Metgud, Mrityunjay C.. No especifíca;Fil: Pujar, Yeshita V.. No especifíca;Fil: Somannavar, Manjunath S.. No especifíca;Fil: Vernekar, Sunil S.. No especifíca;Fil: Herekar, Veena R.. No especifíca;Fil: Bidri, Shailaja R.. No especifíca;Fil: Mathapati, Sangamesh S.. No especifíca;Fil: Patil, Preeti G.. No especifíca;Fil: Patil, Mallanagouda M.. No especifíca;Fil: Gudadinni, Muttappa R.. No especifíca;Fil: Bijapure, Hidaytullah R.. No especifíca;Fil: Mallapur, Ashalata A.. No especifíca;Fil: Katageri, Geetanjali M.. No especifíca;Fil: Chikkamath, Sumangala B.. No especifíca;Fil: Yelamali, Bhuvaneshwari C.. No especifíca;Fil: Pol, Ramesh R.. No especifíca;Fil: Misra, Sujata S.. No especifíca;Fil: Das, Leena. No especifíca

Community level interventions for pre-eclampsia (CLIP) in India: A cluster randomised controlled trial

Objectives: Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment.Study design: The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (\u3c4 \u3eh) or non-urgently (\u3c24 \u3eh), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts.Main outcome measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity.Results: All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p = 0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p \u3c 0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p = 0.072).Conclusions: As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka

A Comparison of Colorimetric Assessment of Vaginal pH with Nugent Score for the Detection of Bacterial Vaginosis

Background. A Nugent score > 7 has been defined as the gold standard for the diagnosis for bacterial vaginosis (BV), though it is resource intensive and impractical as point of care testing. We sought to determine if colorimetric assessment of vaginal pH can accurately predict the occurrence of BV. Methods. We performed a planned subanalysis of 1,216 pregnant women between 13 0/7 and 19 6/7 weeks who underwent vaginal examination as part of a randomized controlled trial. Using a standardized technique, specimens were obtained for colorimetric assessment and two separate slides for Gram staining. These slides were subsequently evaluated by two independent blinded microbiologists for Nugent scoring. Results. Interrater reliability of the interpretation of the Nugent score was excellent (intraclass correlation-individual 0.93 (95 CI 0.92 to 0.94) and average 0.96 (95% CI 0.95 to 0.97)). The sensitivity of an elevated pH > 5 for a Nugent score > 7 was 21.9% while the specificity was 84.5%. The positive predictive value in our population was 33.7% with a negative predictive value of 75.0%. Conclusion. Though the Nugent score is internally accurate, the prediction of BV using vaginal pH alone has poor sensitivity and specificity

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

Background Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. Methods In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. Findings The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47 394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50 743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48 219 women in the intervention group and 867 (2%) of 51 523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). Interpretation Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development.Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: McClure, Elizabeth M.. Rti International;Fil: Hemingway Foday, Jennifer. Rti International;Fil: Berrueta, Amanda Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ciganda, Alvaro. Unicem; Uruguay. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Goudar, Shivaprasad S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Kodkany, Bhalachandra S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Mahantshetti, Niranjana S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Dhaded, Sangappa M.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Katageri, Geetanjali M.. S. Nijalingappa Medical College; IndiaFil: Metgud, Mrityunjay C.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Joshi, Anjali M.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Bellad, Mrutyunjaya B.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Honnungar, Narayan V.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Derman, Richard J.. Christiana Health Care Services; Estados UnidosFil: Saleem, Sarah. The Aga Khan University; PakistánFil: Pasha, Omrana. The Aga Khan University; PakistánFil: Ali, Sumera. The Aga Khan University; PakistánFil: Hasnain, Farid. The Aga Khan University; PakistánFil: Goldenberg, Robert L. Columbia University; Estados UnidosFil: Esamai, Fabian. Moi University; KeniaFil: Nyongesa, Paul. Moi University; KeniaFil: Ayunga, Silas. University of Alabama at Birmingahm; Estados UnidosFil: Liechty, Edward A. Indiana University; Estados UnidosFil: Garces, Ana L. Francisco Marroquin University; Guatemala. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Figueroa, Lester. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Hambidge, K Michael. State University of Colorado - Fort Collins; Estados UnidosFil: Krebs, Nancy F. State University of Colorado - Fort Collins; Estados UnidosFil: Patel, Archana. Government Medical College Nagpur; India. Lata Medical Research Foundation; IndiaFil: Bhandarkar, Anjali. Lata Medical Research Foundation; IndiaFil: Waikar, Manjushri. Lata Medical Research Foundation; IndiaFil: Hibberd, Patricia L. Massachusetts General Hospital; Estados UnidosFil: Chomba, Elwyn. University Teaching Hospital Lusaka; ZambiaFil: Carlo, Waldemar A. University of Alabama at Birmingahm; Estados UnidosFil: Mwiche, Angel. University Teaching Hospital Lusaka; ZambiaFil: Chiwila, Melody. Centre For Infectious Disease Research; ZambiaFil: Manasyan, Albert. University of Alabama at Birmingahm; Estados UnidosFil: Pineda, Sayury. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Meleth, Sreelatha. Rti International; Estados UnidosFil: Thorsten, Vanessa. Rti International; Estados UnidosFil: Stolka, Kristen. Rti International; Estados UnidosFil: Wallace, Dennis D. Rti International; Estados UnidosFil: Koso-Thomas, Marion. National Instituto Of Child Health & Human Developm.; Estados UnidosFil: Jobe, Alan H. Cincinnati Children's Hospital Medical Center; Estados UnidosFil: Buekens, Pierre M. Tulane University School Of Public Health And Tropical Medicine; Estados Unido