Adverse pregnancy outcome disclosure and women's social networks: a qualitative multi-country study with implications for improved reporting in surveys.

BACKGROUND: Globally, approximately 6,700 newborn deaths and 5,400 stillbirths occur daily. The true figure is likely higher, with under reporting of adverse pregnancy outcomes (APOs) noted. Decision-making in health is influenced by various factors, including one's social networks. We sought to understand APOs disclosure within social networks in Uganda, Ghana, Guinea-Bissau and Bangladesh and how this could improve formal reporting of APOs in surveys.  METHODS: A qualitative, exploratory multi-country study was conducted within four health and demographic surveillance system sites. 16 focus group discussions were held with 147 women aged 15-49 years, who had participated in a recent household survey. Thematic analysis, with both deductive and inductive elements, using three pre-defined themes of Sender, Message and Receiver was done using NVivo software. RESULTS: Disclosure of APOs was a community concern, with news often shared with people around the bereaved for different reasons, including making sense of what happened and decision-making roles of receivers. Social networks responded with comfort, providing emotional, in-kind and financial support. Key decision makers included men, spiritual and traditional leaders. Non-disclosure was usually to avoid rumors in cases of induced abortions, or after a previous bad experience with health workers, who were frequently excluded from disclosure, except for instances where a woman sought advice on APOs. CONCLUSIONS: Communities must understand why they should report APOs and to whom. Efforts to improve APOs reporting could be guided by diffusion of innovation theory, for instance for community entry and sensitization before the survey, since it highlights how information can be disseminated through community role models. In this case, these gatekeepers we identified could promote reporting of APOs. The stage at which a person is in decision-making, what kind of adopter they are and their take on the benefits and other attributes of reporting are important. In moving beyond survey reporting to getting better routine data, the theory would be applicable too. Health workers should demonstrate a more comforting and supportive response to APOs as the social networks do, which could encourage more bereaved women to inform them and seek care.

Neonatal and child mortality data in retrospective population-based surveys compared with prospective demographic surveillance: EN-INDEPTH study.

BACKGROUND: Global mortality estimates remain heavily dependent on household surveys in low- and middle-income countries, where most under-five deaths occur. Few studies have assessed the accuracy of mortality data or determinants of capturing births in surveys. METHODS: The Every Newborn-INDEPTH study (EN-INDEPTH) included a large, multi-country survey of women aged 15-49 interviewed about livebirths and their survival status in five Health and Demographic Surveillance Systems (HDSSs). The HDSSs undertake regular household visits to register births and deaths for a given population. We analysed EN-INDEPTH survey data to assess background factors associated with not recalling a complete date-of-birth. We calculated Kaplan-Meier survival estimates for both survey and HDSS data and describe age-at-death distributions during the past 5 years for children born to the same women. We assessed the proportion of HDSS-births that could be matched on month-of-birth to survey-births and used regression models to identify factors associated with matching. RESULTS: 69,176 women interviewed in the survey reported 109,817 births and 3064 deaths in children under 5 years in the 5 years prior to the survey. In the HDSS data, the same women had 83,768 registered births and 2335 under-five deaths in the same period. A complete date-of-birth was not reported for 1-7% of survey-births. Birthdates were less likely to be complete for dead children and children born to women of higher parity or with little/no education. Distributions of reported age-at-death indicated heaping at full weeks (neonatal period) and at 12 months. Heaping was more pronounced in the survey data. Survey estimates of under-five mortality rates were similar to HDSS estimates of under-five mortality in two of five sites, higher in the survey in two sites (15%, 41%) and lower (24%) in one site. The proportion of HDSS-births matched to survey-births ranged from 51 to 89% across HDSSs and births of children who had died were less likely to be matched. CONCLUSIONS: Mortality estimates in the survey and HDSS were not markedly different for most sites. However, neither source is a "gold standard" and both sources miss some events. Research is required to improve capture and accuracy to better track newborn and child survival targets.

Stillbirth maternity care measurement and associated factors in population-based surveys: EN-INDEPTH study.

BACKGROUND: Household surveys remain important sources of maternal and child health data, but until now, standard surveys such as Demographic and Health Surveys (DHS) have not collected information on maternity care for women who have experienced a stillbirth. Thus, nationally representative data are lacking to inform programmes to address the millions of stillbirths which occur annually. METHODS: The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with additional questions on pregnancy losses (FBH+) or full pregnancy history (FPH). A sub-sample, including all women reporting a recent stillbirth or neonatal death, was asked additional maternity care questions. These were evaluated using descriptive measures. Associations between stillbirth and maternal socio-demographic characteristics, babies' characteristics and maternity care use were assessed using a weighted logistic regression model for women in the FBH+ group. RESULTS: A total of 15,591 women reporting a birth since 1 January 2012 answered maternity care questions. Completeness was very high (> 99%), with similar proportions of responses for both live and stillbirths. Amongst the 14,991 births in the FBH+ group, poorer wealth status, higher parity, large perceived baby size-at-birth, preterm or post-term birth, birth in a government hospital compared to other locations and vaginal birth were associated with increased risk of stillbirth after adjusting for potential confounding factors. Regarding association with reported postnatal care, women with a stillbirth were more likely to report hospital stays of > 1 day. However, women with a stillbirth were less likely to report having received a postnatal check compared to those with a live birth. CONCLUSIONS: Women who had experienced stillbirth were able to respond to questions about pregnancy and birth, and we found no reason to omit questions to these women in household surveys. Our analysis identified several potentially modifiable factors associated with stillbirth, adding to the evidence-base for policy and action in low- and middle-income contexts. Including these questions in DHS-8 would lead to increased availability of population-level data to inform action to end preventable stillbirths.

Stillbirth outcome capture and classification in population-based surveys: EN-INDEPTH study.

BACKGROUND: Household surveys remain important sources of stillbirth data, but omission and misclassification are common. Classifying adverse pregnancy outcomes as stillbirths requires accurate reporting of vital status at birth and gestational age or birthweight for every pregnancy. Further categorisation, e.g. by sex, or timing (intrapartum/antepartum) improves data to understand and prevent stillbirth. METHODS: We undertook a cross-sectional population-based survey of women of reproductive age in five health and demographic surveillance system sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with pregnancy loss questions (FBH+) or a full pregnancy history (FPH). A sub-sample across both groups were asked additional stillbirth questions. Questions were evaluated using descriptive measures. Using an interpretative paradigm and phenomenology methodology, focus group discussions with women exploring barriers to reporting birthweight for stillbirths were conducted. Thematic analysis was guided by an a priori codebook. RESULTS: Overall 69,176 women reported 98,483 livebirths (FBH+) and 102,873 pregnancies (FPH). Additional questions were asked for 1453 stillbirths, 1528 neonatal deaths and 12,620 surviving children born in the 5 years prior to the survey. Completeness was high (> 99%) for existing FBH+/FPH questions on signs of life at birth and gestational age (months). Discordant responses in signs of life at birth between different questions were common; nearly one-quarter classified as stillbirths on FBH+/FPH were reported born alive on additional questions. Availability of information on gestational age (weeks) (58.1%) and birthweight (13.2%) was low amongst stillbirths, and heaping was common. Most women (93.9%) were able to report the sex of their stillborn baby. Response completeness for stillbirth timing (18.3-95.1%) and estimated proportion intrapartum (15.6-90.0%) varied by question and site. Congenital malformations were reported in 3.1% stillbirths. Perceived value in weighing a stillborn baby varied and barriers to weighing at birth a nd knowing birthweight were common. CONCLUSIONS: Improving stillbirth data in surveys will require investment in improving the measurement of vital status, gestational age and birthweight by healthcare providers, communication of these with women, and overcoming reporting barriers. Given the large burden and effect on families, improved data must be made available to end preventable stillbirths.

Electronic data collection in a multi-site population-based survey: EN-INDEPTH study.

BACKGROUND: Electronic data collection is increasingly used for household surveys, but factors influencing design and implementation have not been widely studied. The Every Newborn-INDEPTH (EN-INDEPTH) study was a multi-site survey using electronic data collection in five INDEPTH health and demographic surveillance system sites. METHODS: We described experiences and learning involved in the design and implementation of the EN-INDEPTH survey, and undertook six focus group discussions with field and research team to explore their experiences. Thematic analyses were conducted in NVivo12 using an iterative process guided by a priori themes. RESULTS: Five steps of the process of selecting, adapting and implementing electronic data collection in the EN-INDEPTH study are described. Firstly, we reviewed possible electronic data collection platforms, and selected the World Bank's Survey Solutions® as the most suited for the EN-INDEPTH study. Secondly, the survey questionnaire was coded and translated into local languages, and further context-specific adaptations were made. Thirdly, data collectors were selected and trained using standardised manual. Training varied between 4.5 and 10 days. Fourthly, instruments were piloted in the field and the questionnaires finalised. During data collection, data collectors appreciated the built-in skip patterns and error messages. Internet connection unreliability was a challenge, especially for data synchronisation. For the fifth and final step, data management and analyses, it was considered that data quality was higher and less time was spent on data cleaning. The possibility to use paradata to analyse survey timing and corrections was valued. Synchronisation and data transfer should be given special consideration. CONCLUSION: We synthesised experiences using electronic data collection in a multi-site household survey, including perceived advantages and challenges. Our recommendations for others considering electronic data collection include ensuring adaptations of tools to local context, piloting/refining the questionnaire in one site first, buying power banks to mitigate against power interruption and paying attention to issues such as GPS tracking and synchronisation, particularly in settings with poor internet connectivity.

Barriers and enablers to reporting pregnancy and adverse pregnancy outcomes in population-based surveys: EN-INDEPTH study.

BACKGROUND: Risks of neonatal death, stillbirth and miscarriage are highest in low- and middle-income countries (LMICs), where data has most gaps and estimates rely on household surveys, dependent on women reporting these events. Underreporting of pregnancy and adverse pregnancy outcomes (APOs) is common, but few studies have investigated barriers to reporting these in LMICs. The EN-INDEPTH multi-country study applied qualitative approaches to explore barriers and enablers to reporting pregnancy and APOs in surveys, including individual, community, cultural and interview level factors. METHODS: The study was conducted in five Health and Demographic Surveillance System sites in Guinea-Bissau, Ethiopia, Uganda, Bangladesh and Ghana. Using an interpretative paradigm and phenomenology methodology, 28 focus group discussions were conducted with 82 EN-INDEPTH survey interviewers and supervisors and 172 women between February and August 2018. Thematic analysis was guided by an a priori codebook. RESULTS: Survey interview processes influenced reporting of pregnancy and APOs. Women found questions about APOs intrusive and of unclear relevance. Across all sites, sociocultural and spiritual beliefs were major barriers to women reporting pregnancy, due to fear that harm would come to their baby. We identified several factors affecting reporting of APOs including reluctance to speak about sad memories and variation in recognition of the baby's value, especially for APOs at earlier gestation. Overlaps in local understanding and terminology for APOs may also contribute to misreporting, for example between miscarriages and stillbirths. Interviewers' skills and training were the keys to enabling respondents to open up, as was privacy during interviews. CONCLUSION: Sociocultural beliefs and psycho-social impacts of APOs play a large part in underreporting these events. Interviewers' skills, careful tool development and translation are the keys to obtaining accurate information. Reporting could be improved with clearer explanations of survey purpose and benefits to respondents and enhanced interviewer training on probing, building rapport and empathy.

Gestational age data completeness, quality and validity in population-based surveys: EN-INDEPTH study.

BACKGROUND: Preterm birth (gestational age (GA) <37 weeks) is the leading cause of child mortality worldwide. However, GA is rarely assessed in population-based surveys, the major data source in low/middle-income countries. We examined the performance of new questions to measure GA in household surveys, a subset of which had linked early pregnancy ultrasound GA data. METHODS: The EN-INDEPTH population-based survey of 69,176 women was undertaken (2017-2018) in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda. We included questions regarding GA in months (GAm) for all women and GA in weeks (GAw) for a subset; we also asked if the baby was 'born before expected' to estimate preterm birth rates. Survey data were linked to surveillance data in two sites, and to ultrasound pregnancy dating at <24 weeks in one site. We assessed completeness and quality of reported GA. We examined the validity of estimated preterm birth rates by sensitivity and specificity, over/under-reporting of GAw in survey compared to ultrasound by multinomial logistic regression, and explored perceptions about GA and barriers and enablers to its reporting using focus group discussions (n = 29). RESULTS: GAm questions were almost universally answered, but heaping on 9 months resulted in underestimation of preterm birth rates. Preference for reporting GAw in even numbers was evident, resulting in heaping at 36 weeks; hence, over-estimating preterm birth rates, except in Matlab where the peak was at 38 weeks. Questions regarding 'born before expected' were answered but gave implausibly low preterm birth rates in most sites. Applying ultrasound as the gold standard in Matlab site, sensitivity of survey-GAw for detecting preterm birth (GAw <37) was 60% and specificity was 93%. Focus group findings suggest that women perceive GA to be important, but usually counted in months. Antenatal care attendance, women's education and health cards may improve reporting. CONCLUSIONS: This is the first published study assessing GA reporting in surveys, compared with the gold standard of ultrasound. Reporting GAw within 5 years' recall is feasible with high completeness, but accuracy is affected by heaping. Compared to ultrasound-GAw, results are reasonably specific, but sensitivity needs to be improved. We propose revised questions based on the study findings for further testing and validation in settings where pregnancy ultrasound data and/or last menstrual period dates/GA recorded in pregnancy are available. Specific training of interviewers is recommended.

Complete and on-time routine childhood immunisation: determinants and association with severe morbidity in urban informal settlements, Nairobi, Kenya.

Background: Completion of the full series of childhood vaccines on-time is crucial to ensuring greater protection against vaccine-preventable diseases.Aim: To examine determinants of complete and on-time vaccination and evaluate the relationship between vaccination patterns and severe morbidity outcomes.Subjects and methods: Vaccination information from infants in Nairobi Urban Health and Demographic Surveillance System was used to evaluate full and on-time vaccination coverage of routine immunisation. Logistic regression was used to identify determinants of full and on-time vaccination coverage. Cox regression model was used to evaluate the relationship between vaccination status and subsequent severe morbidity. A shared frailty cox model was fitted to account for the heterogeneity in hospitalisation episodes.Results: Maternal age, post-natal care, parity, ethnicity, and residence place were identified as determinants of vaccination completion. Institutional deliveries and residence place were identified as the determinants of on-time vaccination. A significant 58% (confidence interval [CI]: 15-79%) (p = .017) lower mortality was observed among fully immunised children compared with not fully immunised. Lower mortality was observed among on-time immunised children, 64% (CI: 20-84%) compared to those with delays.Conclusions: Improving vaccination timeliness and completion schedule is critical for protection against vaccine preventable diseases and may potentially provide protection beyond these targets.

Differences in barriers to birth and death registration in Guinea-Bissau: implications for monitoring national and global health objectives.

OBJECTIVE: Improving civil registration and vital statistics (CRVS) systems is essential to monitoring health objectives locally and globally. The barriers to birth and particularly death registration in low- and middle-income countries are however poorly understood. METHODS: We conducted a survey among women of reproductive age in Bissau, the capital of Guinea-Bissau. We asked women with a birth in the past two years whether their child had been registered and had obtained a birth certificate. We elicited the sources of information about birth registration and asked respondents to list their reasons for (not) registering a birth. If their child had died, we asked similar questions about death registration. RESULTS: Most women (86%) had received messages about birth registration, but few women whose child had died had heard about the need to register deaths (22%). The primary sources of information about birth registration were messages broadcast on the radio or displayed at health facilities. Information about death registration was primarily obtained through informal social networks. Only 16% of births, and 2% of deaths, had been registered. The main barriers to birth registration were administrative pre-requisites and paternal absence. The main reasons for not registering a death were lack of knowledge about death registration and lack of perceived benefits. CONCLUSION: Strengthening CRVS systems requires addressing the specific barriers preventing birth and death registration. In Bissau, interventions to improve knowledge about death registration are needed. Simplifying registration procedures, as well as providing additional incentives, might help improve the coverage of birth registration.

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.

Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival.

BACKGROUND: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. METHODS: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4-6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination. RESULTS: In trial I (1993-1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09-.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4-6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years. CONCLUSIONS: Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4-6 months (earlier than currently recommended) and a booster dose at 9-12 months of age. CLINICAL TRIALS REGISTRATION: NCT00168558.

Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial.

Whether neonatal vitamin A supplementation (NVAS) should be policy in areas with vitamin A deficiency is debated. We observed that a smaller dose of vitamin A may decrease mortality more than a larger dose and conducted a randomized, double-blind, placebo-controlled trial in Guinea-Bissau with the primary aim of comparing the effect of 50,000 with 25,000 IU neonatal vitamin A on infant mortality. The secondary aim was to study the effect of NVAS vs. placebo, including a combined analysis of NVAS trials. Between 2004 and 2007, normal-birth-weight neonates were randomly assigned in a 1:1:1 ratio to be administered 2 different doses of vitamin A (50,000 or 25,000 IU) or placebo. Infant mortality rates (MRs) were compared in Cox models providing MR ratios (MRRs). Among 6048 children enrolled, there were 160 deaths in 4125 person-years (MR = 39/1000). There was no difference in mortality between the 2 dosage groups: the MRR for 25,000 vs. 50,000 IU was 0.96 (95% CI: 0.67, 1.38). Neither dose of NVAS was associated with lower mortality than placebo (MRR = 1.28; 95% CI: 0.91, 1.81). In a combined analysis of the present trial and 2 previous NVAS trials in Guinea-Bissau, the effect of receiving NVAS (any dose) vs. placebo was 1.13 (95% CI: 0.94, 1.36) and differed significantly (P = 0.01) between boys (0.80; 95% CI: 0.58, 1.09) and girls (1.35; 95% CI: 1.04, 1.75). We could not confirm that a smaller dose of neonatal vitamin A reduces mortality more than a larger dose. We confirmed 2 other trials in Guinea-Bissau that showed no beneficial effect of NVAS. This trial was registered at clinicaltrials.gov as NCT00168610.

Effect of distributing locally produced cloth facemasks on COVID-19-like illness and all-cause mortality-a cluster-randomised controlled trial in urban Guinea-Bissau.

Facemasks have been employed to mitigate the spread of SARS-CoV-2. The community effect of providing cloth facemasks on COVID-19 morbidity and mortality is unknown. In a cluster randomised trial in urban Bissau, Guinea-Bissau, clusters (geographical areas with an average of 19 houses), were randomised to an intervention or control arm using computer-generated random numbers. Between 20 July 2020 and 22 January 2021, trial participants (aged 10+ years) living in intervention clusters (n = 90) received two 2-layer cloth facemasks, while facemasks were only distributed later in control clusters (n = 91). All participants received information on COVID-19 prevention. Trial participants were followed through a telephone interview for COVID-19-like illness (3+ symptoms), care seeking, and mortality for 4 months. End-of-study home visits ensured full mortality information and distribution of facemasks to the control group. Individual level information on outcomes by trial arm was compared in logistic regression models with generalised estimating equation-based correction for cluster. Facemasks use was mandated. Facemask use in public areas was assessed by direct observation. We enrolled 39,574 trial participants among whom 95% reported exposure to groups of >20 persons and 99% reported facemasks use, with no difference between trial arms. Observed use was substantially lower (~40%) with a 3%, 95%CI: 0-6% absolute difference between control and intervention clusters. Half of those wearing a facemask wore it correctly. Few participants (532, 1.6%) reported COVID-19-like illness; proportions did not differ by trial arm: Odds Ratio (OR) = 0.81, 95%CI: 0.57-1.15. 177 (0.6%) participants reported consultations and COVID-19-like illness (OR = 0.83, 95%CI: 0.56-1.24); 89 participants (0.2%) died (OR = 1.34, 95%CI: 0.89-2.02). Hence, though trial participants were exposed to many people, facemasks were mostly not worn or not worn correctly. Providing facemasks and messages about correct use did not substantially increase their use and had limited impact on morbidity and mortality. Trial registration: clinicaltrials.gov: NCT04471766.

The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau.

Vitamin A supplementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria-tetanus-pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and supplementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95 % CI 1·07, 1·49, P=0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P=0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P=0·03 and P=0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.

Trends and determinants of mortality in women of reproductive age in rural Guinea-Bissau, West Africa--a cohort study.

BACKGROUND: There are few studies reporting mortality of women of reproductive age (WRA) in developing countries. The trend and patterns of their mortality may be important for documenting the health status of the population in general. METHODS: We used a prospective open cohort of women aged 12 to 49 years living in the Bandim Health Project's rural Health and Demographic Surveillance System (HDSS) in 5 regions of Guinea-Bissau from 1996 to 2007. Information on in- and out-migration and deaths were collected through the HDSS routine procedures. We assessed the trends in mortality and the associated determinants using Cox regression models. RESULTS: We followed 27,185 WRA for 141,693 person-years-at-risk (PYO) among whom 9,093 moved out and 1,006 died. Overall standardized mortality rate was 759 per 100,000 PYO. WRA mortality did not decline, but three periods could be distinguished: a stable mortality between 1996-2000 followed by 14% increase in mortality [Hazard rate ratio (HRR) = 1.14; 95% confidence interval (CI): 0.98-1.32; p = 0.08] between 2001-2003, and then in the last period from 2004-2007 a 25% decline (HRR = 0.75; 95% CI: 0.64-0.87; p < 0.001) in relation to the first period. Compared with the years 1990-1996 mortality increased in the first two periods until 2003; only in the last period did mortality reach the same level as in 1990-1996 (HRR = 0.96; 95% CI: 0.82-1.13; p = 0.62). The level of mortality differed between regions. In the adjusted analysis the eastern regions Bafata (HRR = 1.79; 95% CI: 1.38-2.32; p < 0.001) and Gabu (HRR = 1.70; 95% CI: 1.28-2.26; p < 0.001) had significantly higher mortality, but the hazard rate did not differ by ethnic group. As expected the rate increased with increasing age. CONCLUSIONS: Over the twelve-year period mortality of WRA did not decline. A stable mortality in the beginning was followed by an increase and then a return to the previous levels. Further monitoring of mortality is needed to identify the risk factors for the striking regional differences. Advantage should be taken of the HDSS to monitor progress towards the MDGs and beyond.

Provider-mother interactions are associated with birth outcome misclassifications in household surveys: A case-control study in Guinea-Bissau.

Background: Approximately 4.4 million children die peripartum annually, primarily in low- and middle-income countries. Accurate mortality tracking is essential to prioritising prevention efforts but is undermined by misclassification between stillbirths (SBs) and early neonatal deaths (ENNDs) in household surveys, which serve as key data sources. We explored and quantified associations between peripartum provider-mother interactions and misclassification of SBs and ENNDs in Guinea-Bissau. Methods: Using a case-control design, we followed up on women who had reported a SB or ENND in a retrospective household survey nested in the Bandim Health Project's Health and Demographic Surveillance Systems (HDSS). Using prospective HDSS registration as the reference standard, we linked the survey-reported deaths to the corresponding HDSS records and cross-tabulated SB/ENND classification to identify cases (discordant classification between survey and HDSS) and controls (concordant classification). We further interviewed cases and controls on peripartum provider-mother interactions and analysed data using descriptive statistics and logistic regressions. Results: We interviewed 278 women (cases: 63 (23%); controls: 215 (77%)). Most cases were SBs misclassified as ENNDs (n/N = 49/63 (78%)). Three-fourths of the interviewed women reported having received no updates on the progress of labour and baby's health intrapartum, and less than one-fourth inquired about this information. In comparison with births where women did inquire for information, misclassification was less likely when women did not inquire and recalled no doubts about progress of labour (odds ratio (OR) = 0.51; 95% confidence interval (CI) = 0.28-0.91), or baby's health (OR = 0.54; 95% CI = 0.30-0.97). Most women reported that service providers' death notifications lasted <5 minutes (cases: 23/27 (85%); controls: 61/71 (86%)), and most often encompassed neither events leading to the death (cases: 19/27 (70%); controls: 55/71 (77%)) nor causes of death (cases: 20/27 (74%); controls: 54/71 (76%)). Misclassification was more likely if communication lasted <1 compared to 1-4 minutes (OR = 1.83; 95% CI = 1.10-3.06) and if a formal service provider had informed the mother of the death compared to a family member (OR = 1.57; 95% CI = 1.04-2.36). Conclusions: Peripartum provider-mother interactions are limited in Guinea-Bissau and associated with birth outcome misclassifications in retrospective household surveys. In our study population, misclassification led to overestimated neonatal mortality.

Overall effect of a campaign with measles vaccine on the composite outcome mortality or hospital admission: A cluster-randomized trial among children aged 9-59 months in rural Guinea-Bissau.

OBJECTIVES: Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%. METHODS: Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers. RESULTS: Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies. CONCLUSION: C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up.

Health effects of utilising hospital contacts to provide measles vaccination to children 9-59 months-a randomised controlled trial in Guinea-Bissau.

BACKGROUND: Measles vaccination coverage in Guinea-Bissau is low; fewer than 80% of children are currently measles vaccinated before 12 months of age. The low coverage hampers control of measles. Furthermore, accumulating evidence indicates that measles vaccine has beneficial non-specific effects, strengthening the resistance towards other infections. Thus, even if children are not exposed to measles virus, measles-unvaccinated children may be worse off. To increase vaccination coverage, WHO recommends that contacts with the health system for mild illness are utilised to vaccinate. Currently, in Guinea-Bissau, curative health system contacts are not utilised. METHODS: Bandim Health Project registers out-patient consultations and admissions at the paediatric ward of the National Hospital in Guinea-Bissau. Measles-unvaccinated children aged 9-59 months consulting for milder illness or being discharged from the paediatric ward will be invited to participate in a randomised trial. Among 5400 children, randomised 1:1 to receive standard measles vaccine or a saline placebo, we will test the hypothesis that providing a measles vaccine at discharge lowers the risk of admission/mortality (composite outcome) during the subsequent 6 months by 25%. All enrolled children are followed through the Bandim Health Project registration system and through telephone follow-up. The first 1000 enrolled children are furthermore followed through interviews on days 2, 4, 7 and 14 after enrolment. DISCUSSION: Utilising missed vaccination opportunities can increase vaccination coverage and may improve child health. However, without further evidence for the safety and potential benefits of measles vaccination, these curative contacts are unlikely to be used for vaccination in Guinea-Bissau. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT04220671 . Registered on 5 January 2020.

Oral Polio Vaccine to Mitigate the Risk of Illness and Mortality During the Coronavirus Disease 2019 Pandemic: A Cluster-Randomized Trial in Guinea-Bissau.

Background: Oral polio vaccine (OPV) may improve resistance to non-polio-infections. We tested whether OPV reduced the risk of illness and mortality before coronavirus disease 2019 (COVID-19) vaccines were available. Methods: During the early COVID-19 pandemic, houses in urban Guinea-Bissau were randomized 1:1 to intervention or control. Residents aged 50+ years were invited to participate. Participants received bivalent OPV (single dose) or nothing. Rates of mortality, admissions, and consultation for infections (primary composite outcome) during 6 months of follow-up were compared in Cox proportional hazards models adjusted for age and residential area. Secondary outcomes included mortality, admissions, consultations, and symptoms of infection. Results: We followed 3726 participants (OPV, 1580; control, 2146) and registered 66 deaths, 97 admissions, and 298 consultations for infections. OPV did not reduce the risk of the composite outcome overall (hazard ratio [HR] = 0.97; 95% confidence interval [CI], .79-1.18). OPV reduced the risk in males (HR = 0.71; 95% CI, .51-.98) but not in females (HR = 1.18; 95% CI, .91-1.52) (P for same effect = .02). OPV also reduced the risk in Bacillus Calmette-Guérin scar-positive (HR = 0.70; 95% CI, .49-.99) but not in scar-negative participants (HR = 1.13; 95% CI, .89-1.45) (P = .03). OPV had no overall significant effect on mortality (HR = 0.96; 95% CI, .59-1.55), admissions (HR = 0.76; 95% CI, .49-1.17) or recorded consultations (HR = 0.99; 95% CI, .79-1.25), but the OPV group reported more episodes with symptoms of infection (6050 episodes; HR = 1.10 [95% CI, 1.03-1.17]). Conclusions: In line with previous studies, OPV had beneficial nonspecific effects in males.

Stopping Oral Polio Vaccine (OPV) After Defeating Poliomyelitis in Low- and Middle-Income Countries: Harmful Unintended Consequences? Review of the Nonspecific Effects of OPV.

Background: The live vaccines bacille Calmette-Guérin (BCG) and measles vaccine have beneficial nonspecific effects (NSEs) reducing mortality, more than can be explained by prevention of tuberculosis or measles infection. Live oral polio vaccine (OPV) will be stopped after polio eradication; we therefore reviewed the potential NSEs of OPV. Methods: OPV has been provided in 3 contexts: (1) coadministration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine at 6, 10, and 14 weeks of age; (2) at birth (OPV0) with BCG; and (3) in OPV campaigns (C-OPVs) initiated to eradicate polio infection. We searched PubMed and Embase for studies of OPV with mortality as an outcome. We used meta-analysis to obtain the combined relative risk (RR) of mortality associated with different uses of OPV. Results: First, in natural experiments when DTP was missing, OPV-only compared with DTP + OPV was associated with 3-fold lower mortality in community studies (RR, 0.33 [95% confidence interval {CI}, .14-.75]) and a hospital study (RR, 0.29 [95% CI, .11-.77]). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than DTP + OPV (RR, 3.23 [95% CI, 1.27-8.21]). Second, in a randomized controlled trial, BCG + OPV0 vs BCG + no OPV0 was associated with 32% (95% CI, 0-55%) lower infant mortality. Beneficial NSEs were stronger with early use of OPV0. Third, in 5 population-based studies from Guinea-Bissau and Bangladesh, the mortality rate was 24% (95% CI, 17%-31%) lower after C-OPVs than before C-OPVs. Conclusions: There have been few clinical polio cases reported in this century, and no confounding factors or bias would explain all these patterns. The only consistent interpretation is that OPV has beneficial NSEs, reducing nonpolio child mortality.