The sensitivity analyses by excluding one trial at one time showed the same results. This meta-analysis also showed that cervical pessary did not prevent preterm birth <34, 30, 28 weeks and was not associated with respiratory distress syndrome, necrotising enterocolitis, intraventricular haemorrhage, neonatal sepsis, retinopathy of prematurity, fetal death, neonatal death, perinatal death, birth weight <1500 g, birth weight <2500 g, premature preterm rupture of membranes, corticosteroid treatment for fetal maturation, and admission to neonatal intensive care unit. Although this meta-analysis showed cervical pessary placement did not reduce the risk of preterm birth in women with a singleton pregnancy and a short cervix, we could not confirm or refute this conclusion, and large-scale randomised controlled trials are urgently needed.To investigate the efficacy of cervical pessary placement in preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton pregnancy and a short cervix, we searched literature in relevant databases. The meta-analysis of the 3 included trials (1412 women) showed cervical pessary placement did not reduce the risk of spontaneous preterm birth <34 weeks in these women (risk ratio (RR), 0.71; 95% confidence interval (CI), 0.21–2.43, P = 0.59; I Preterm birth is defined as any birth before 37 completed weeks of gestation, or fewer than 259 days of gestation1Spontaneous preterm birth accounts for two thirds of preterm birth, and is also the most common cause of extremely preterm birth, which is any birth before 28 weeks, whereas the rest is medically indicated due to maternal or fetal complications such as preeclampsia, or intrauterine growth restriction78Cervical pessary made of silicone or plastic, which is available in different shapes and sizes, has been used to prevent preterm birth in the past 50 yearsA previous systematic review showed a need for more randomised trials to confirm the beneficial effects of cervical pessary in reducing preterm birthWe conducted a systematic search for the relevant published literature without language restrictions until November 1st 2016 using the following databases: PubMed, the Cochrane Central Register of Controlled Trials, and Embase. The following medical subject heading (MeSH) terms, keywords, and their combinations were used: pessary; premature birth; premature labor. Appropriate suffixes were used for each database. We also manually searched the reference lists of the initially identified articles, previously published meta-analyses and reviews for additional relevant publications.We included randomised controlled trials comparing pessary therapy with expectant treatment for prevention of preterm birth in asymptomatic women with a singleton pregnancy and a short cervical length ≤25 mm as determined by ultrasonography in the mid-trimester. We excluded trials assessing cervical pessary placement in women with premature rupture of membranes, regular uterine contractions, or mid-trimester bleeding. Two independent reviewers screened the titles and abstracts to identify potentially eligible trials and then retrieved and assessed the full texts of the relevant citations for inclusion. The data extracted included the first author, year of publication, population characteristics, intervention details, reported outcomes, and study design. Data extraction was performed independently by two of the reviewers. Any disagreement between the two reviewers was solved unanimously through discussion. The Cochrane risk of bias tool has been used for risk assessment in included studiesThe primary outcome was spontaneous preterm birth <34 weeks of gestation and the secondary outcomes included preterm birth <34, <30 and <28 weeks of gestation; respiratory distress syndrome; necrotising enterocolitis; intraventricular haemorrhage; neonatal sepsis; retinopathy of prematurity; fetal death; neonatal death; perinatal death; birth weight <1500 g and <2500 g; premature preterm rupture of membranes; corticosteroid treatment for fetal maturation; and admission to neonatal intensive care unit.2 statistic. We performed sensitivity analyses to evaluate the effect of risk of bias on the overall results by excluding one trial at one time. All analyses were done using Revman statistical software version 5.We reported the dichotomous data results after pooling estimates across trials with a random effects meta-analysis as RR with 95% CIs. Heterogeneity was assessed with the IOf the 204 citations identified, 29 were duplicates, and 172 were excluded based on title and abstract. After assessing full texts of the remaining 3 citations, we included 3 randomised controlled trials evaluating efficacy and safety of cervical pessary placement for prevention of preterm birth in this meta-analysis1315Baseline characteristics of the 3 included trials is shown in et al.131315All the three trials were designed to evaluate the effect of cervical pessary placement on preterm birth in women with a singleton pregnancy and a short cervix131513132 = 90%)  showed cervical pessary placement had no significant effect on spontaneous preterm birth <34 weeks of gestation in women with a singleton pregnancy and a short cervical length ≤25 mm compared with expectant treatment  .et al.2 = 0%).Due to the high heterogeneity, we performed sensitivity analyses to explore the cause of heterogeneity. When we performed the sensitivity analyses by excluding one trial at one time, the results remained the same. However, when the trial by Goya 2 = 90%), <30 weeks of gestation , <28 weeks of gestation , respiratory distress syndrome , necrotising enterocolitis , intraventricular haemorrhage , neonatal sepsis , retinopathy of prematurity , fetal death , neonatal death , perinatal death , birth weight <1500 g , birth weight <2500 g , premature preterm rupture of membranes , corticosteroid treatment for fetal maturation , and admission to neonatal intensive care unit   .As far as we know, this is the first meta-analysis which combined all the available randomised trials to evaluate the efficacy of cervical pessary in preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton pregnancy and a short cervix. However, this meta-analysis showed that cervical pessary did not reduce the risk of spontaneous preterm birth <34 weeks of gestation in these women compared with expectant treatment. The sensitivity analyses by excluding one trial at one time showed the same results. This meta-analysis also showed that cervical pessary did not prevent preterm birth <34, 30, 28 weeks of gestation and had no significant adverse effects on perinatal morbidity and mortality.et al.et al.et al.171819Cervical pessary is a device which is easily placed and removed without anesthesia, and is inexpensive compared with progesterone and cerclage. Unfortunately, this meta-analysis of the 3 trials showed cervical pessary had no beneficial efficacy in preventing preterm birth in women with a singleton pregnancy and a short cervix, but the heterogeneity is high. Therefore we analysed these trials in detail. First, we noticed that the preterm birth rates in the pessary group were similar in the three trials131513et al.This meta-analysis showed that cervical pessary had no significant adverse effects on respiratory distress syndrome, necrotising enterocolitis, intraventricular haemorrhage, neonatal sepsis, and perinatal death, among others. No serious side effects were reported in these trials1315This meta-analysis has its limitations. The open-label nature of the trials could result in risk of bias for blinding of participants and personnel and outcome assessment, which hampers the validity of research of cervical pessary. Because of the inconsistence and scarcity of trials, we were unable to explore the effects of maternal age, ethnicity, obstetric history, body mass index, and cervical length on the results. In addition, none of the trials had the power to assess the treatment effect of cervical pessary.To confirm the efficacy of cervical pessary in preventing preterm birth, future researches may focus on the following respects. First, as progesterone has been suggested to be effective in preventing preterm birth171819In conclusion, although this meta-analysis showed cervical pessary did not reduce the risk of preterm birth in women with a singleton pregnancy and a short cervix, we could not confirm or refute this conclusion, and large-scale randomised controlled trials are urgently needed.How to cite this article: Jin, X.-H. et al. Cervical Pessary for Prevention of Preterm Birth: A Meta-Analysis. Sci. Rep.7, 42560; doi: 10.1038/srep42560 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Cerebrovascular disease (CVD) is often present in old age and may be associatedwith microstructural pathology of white matter (WM) and cognitive dysfunction.The current review investigated the relationship between CVD, cognitive statusand WM integrity as assessed by diffusion tensor imaging (DTI).DTI studies were searched on ISI and Pubmed databases from 2002 to 2012.Studies evidenced DTI changes in WM as associated with vascular disease andprovide increasing support for DTI as a valuable method for early detectionof CVD.DTI parameters can serve as important biomarkers in monitoring vasculardisease progression and treatment response and may represent a surrogatemarker of WM tract integrity. Depending on thesite, intensity, and severity, CVD may either cause or contribute to furthercognitive decline.2 Earlier reportsdescribe CVD pathology as a consequence of blood perfusion deficits generated byhypoxia, hypoperfusion and hemorrhage which in turn result in neuronal injury,necrosis, apoptosis and ischaemic penumbra.2 The presence and severity of CVD hinge on non-modifiablerisk factors such as ageing, gender and genetics but also on several other variablessuch as smoking, systemic arterial hypertension, diet and metabolic diseases.Structural studies have identified subcortical hyperintensities as macroscopic whitematter (WM) changes which have been cited by several reports as associated with CVD,mood disorders, executive dysfunction and higher conversion to dementia. Morerecently, the underlying pathology associated with normal-appearing WM as well asits clinical significance has become the main focus of investigation.3Cerebrovascular disease (CVD) occurs in one third of the populationin vivo.6 One of themost useful of these techniques is diffusion tensor imaging (DTI), which issensitized to the motion of water molecules as they interact within tissues, thusreflecting characteristics of their immediate structural surroundings.8 Earlier DTI studies used a region-of-interest (ROI) analysisapproach, with brain areas being delineated manually or with semi-automatedmethods.11 However the ROI approach has a number ofdrawbacks, such as difficulty precisely replicating and delineating anatomicalregions as well as the use of pre-selected brain areas rather than consideringdiffusion changes in the whole brain.12 To improve the objectivity and interpretability of DTI studies,Tract-Based Spatial Statistics (TBSS) was developed to enable DTI scans to becompared across subjects more robustly.13 TBSS is based on voxel-wise analysis, which approaches thewhole brain without any a priori selection of regions. Anotheradvantage of TBSS is that it minimizes the problem of misalignment.14 To date, the vast majority ofstudies have concentrated on the role of FA in cognitive disorders.17 However, a rangeof factors influence FA decreases, including myelination, axon density, axondiameter and intra-voxel coherence of fiber orientation.19Therefore, there is an increasing awareness of the limitations of single FAmeasurements, and of the need to investigate how other DTI indices  change over the course of bothvascular and neurodegenerative diseases.15In recent years, novel methods of neuroimaging have enabled WM microstructureintegrity to be investigated 2 the influence ofmilder vascular risk factors such as controlled hypertension, or high normal bloodpressure is largely unknown.2Another promising topic of DTI investigation is the common pathological routesbetween CVD and Alzheimer's Dementia (AD), especially the landscape involvingneurodegenerative and vascular changes. Cerebral atherosclerosis is associated witha higher risk of AD while cardiovascular risk factors are associated withclinically-diagnosed AD and vascular dementia (VaD).20 Thesimilarities in association between cardiovascular risk factors and dementiadiagnosed as AD or VaD underline the relevance of CVD for aging-related cognitivedecline in general and the flaws in simplistic diagnostic categories.20 Although vascular and degenerationprocesses often overlap, relatively few studies have focused on the interactionbetween these two pathologies. Conversely, no serum or plasma biomarker has beenestablished as a reliable biomarker of CVD compared to other types of dementia andnon-demented individuals.20There is an open field of investigation on DTI and CVD. To date, the majority ofstudies conducted have investigated only WM abnormalities in relation toneurodegeneration predominantly among AD patients but the pathological processes ofWM associated with vascular disease are not yet fully understood. In contrast to thedamaging effects of CVD and untreated hypertension on diffusion-based parameters ofWM,This review investigated the main results of DTI studies in patients with CVD. Weaimed to discuss these results and the integration of diffusion findings withstructural data and WM microscopic pathology and progression of cognitive impairmentin relation to vascular disease.A systematic review of DTI studies on CVD was performed by searching data from ISIand Pubmed web databases from the first DTI studies in 2002 (January) to 2012 (May).The search strategy included key words aimed at investigating a broader spectrum ofprimary vascular disorders affecting subcortical areas, particularly white-matterlesions: DTI, vascular dementia, subcortical disease, white-matter, neuroimaging,dementia, MCI, blood vessels.All abstracts were independently read by six authors and those studies which complied with the inclusion criteria were selected forfurther reading. A manual search was also performed to retrieve articles related tothis subject found among the references of the selected studies. The articles whichsatisfied all the following criteria were included for further reading and analysis.For inclusion, articles had to:[1] have at least one DTI parameter, such as FA;21[2] be cohort, cross-sectional, or case-control studies with at least onecriterion for vascular dementia  and mild cognitive impairment, vascular type as developed by theNINDS research group;4 and[3] provide data on cognitively impaired patients ≥60 years ofage, with or without clinical diagnosis of dementia;[4] include a comprehensive neuropsychological assessment.The Pubmed electronic search retrieved 156 articles. Only 12 remained eligible forfurther analysis. 22 The classical viewin which vascular disease was related to WM hyperintensity (WMH) burden has beenprogressively substituted by new insights on the pathological development of brainvascular disease and its dynamic interaction with neurodegeneration. DTI paperssupport previous evidence from genetics and biomarkers25 showingthat vascular disease plays an important role in the development and clinical courseof AD.26 The ensuing topics coveraspects of the pathology and clinical features of the studies.The majority of studies evidenced diffusion changes in WM as associated with vasculardisease and supported DTI as a valuable method for the early diagnosis ofCVD.The pathological basis of vascular changes. There is growing evidencefrom DTI studies demonstrating that macroscopic and microscopic changes in WM resultfrom distinct pathological processes which have been described by some authors as WMlesion formation and WM atrophy.27Both processes result from a complex combination of independent factors such as age,hypertension, metabolic and degeneration, but there is no established modelexplaining these underlying changes.2826 whereas temporal and occipital lobes weredescribed by another study.29 In athird study, periventricular areas were described as more susceptible to ischemicinjury.30The territorial pattern of progression of WM changes has been discussed in somepapers with equivocal findings. Parietal WM and the centrum semiovale were reportedas the regions most associated with the vascular pathology27 Additionally,one study showed that atrophy of the corpus callosum was significantly associatedwith changes in diffusion in deep WM hyperintensities. According to Schimidt etal.,31 such findings canfurther etiologic understanding of age-related WM damage because they argue againsta diffuse pathological process as the origin of WMH.Among the WM tracts most susceptible to damage due to atrophy of WM were thosecomponents of the limbic system (which comprise the anatomic substrate ofAlzheimer's disease) such as the fornix, the cingulum tracts and in the region ofthe hippocampus.Correlation of WM changes with clinical variables. Diabetes andhypertension32 have beencited as the most important clinical variables associated with CVD. Hypertension hasbeen associated with reduction in WM volume35 and increase in WMH burden.38 In a recentinvestigation,39 theeffects of Mean Blood Pressure were present both in subjects with mildcardiovascular risk and those with established hypertension. Hence, significanteffects of cognitive decline were present even in individuals outside thehypertensive range.39 Takentogether, these findings support that systemic vascular function is an importantvariable to be considered in the investigation of cognitive changes also in thecontext of patients without known vascular disease or overt brain vascularchanges.Use of overlapping DTI indices in the differential diagnosis between vasculardisease and neurodegeneration. Contrasting with earlier reports, recentevidence in vascular disease has attempted to investigate WM pathology through thecombination of FA and non FA indices15 thus following a general tendency seen in otherstudies, e.g. those with Alzheimer individuals.40 The overlap between axial and radial diffusionincreases was associated with atrophy of WM in different regions , while acuteaxonal injury results in a decrease in diffusion parallel to the fibers .27 Theseincreases suggest decreased packing within a voxel.43 An alternative explanation is that apparentincreases in axial diffusion may stem from a loss in fiber coherence among regionswith fiber crossing.44 Early reports characterize thevascular pathology of subcortical areas by extensive occlusion of arterioles andmicro-atherosclerosis. One study28showed statistically significant FA and MD differences in areas of WMH burden andthose with apparent normal WM. FA-MD and MD-DR overlaps may thus reflectdemyelination and axonal loss within the fibers and early vascular disease. However,as the interpretation of multiple indices is not clearly established, furtherstudies should comprehensively analyze the application of DTI indices to theunderstanding of complex interactions between vascular disease and degeneration. regions  and coulCorrelation between DTI and neuropsychological testing. One outpatientstudy20 analyzed theassociation of brain structural parameters and cognitive tasks and found a greatercoefficient of correlation with diffusion indices than with WM volume or WM burdenrated by the Fazekas scale.20 In alarge multicenter study conducted by the LADIS multicenter group,31 which included 340 patients withvarying degree of macroscopic WMH (leukoaraiosis), the correlation of microscopicchanges in normal-appearing brain tissue was more strongly related to executive andmemory impairment than WM volume and WMH burden. A similar conclusion was found bythe Rotterdam study (28 Findings from these three studies31 evidence agreater variability of WM microscopic pathology and support non-FA indices assensitive biomarkers for assessing the integrity of WM independently of otherstructural measurements such as atrophy of white and gray matter or WM burden.Future studies should evaluate the usefulness of multiple diffusion parameters asbiomarkers of cognitive decline in research and their applicability in monitoringresponses to therapeutic interventions and treatment success.am study  in whicham study .28 Findi39 DTI parameterscan serve as important biomarkers in monitoring vascular disease progression andtreatment response and may represent a surrogate marker of WM tract integrity.Therefore, the studies discussed in the current review encourage the use of multiplediffusion indices as important tools for the diagnosis of microscopic changes in WMassociated with early-onset vascular disease.This summary of findings demonstrates that loss of integrity in normal-appearing WMpoints to an independent process of WMH burden and may reflect a constellation ofpathophysiological interactions, including ageing, neurodegenerative mechanisms andalso vascular disease. Current evidence highlights the increasing importance ofvascular health as a major component of general neural aging as demonstrated byprevious studies.


Child mortality is almost twice as high in England compared with Sweden. We aimed to establish the extent to which adverse birth characteristics and socioeconomic factors explain this difference.We developed nationally representative cohorts of singleton livebirths between Jan 1, 2003, and Dec 31, 2012, using the Hospital Episode Statistics in England, and the Swedish Medical Birth Register in Sweden, with longitudinal follow-up from linked hospital admissions and mortality records. We analysed mortality as the outcome, based on deaths from any cause at age 2–27 days, 28–364 days, and 1–4 years. We fitted Cox proportional hazard regression models to estimate the hazard ratios (HRs) for England compared with Sweden in all three age groups. The models were adjusted for birth characteristics , and for socioeconomic factors .The English cohort comprised 3 932 886 births and 11 392 deaths and the Swedish cohort comprised 1 013 360 births and 1927 deaths. The unadjusted HRs for England compared with Sweden were 1·66 (95% CI 1·53–1·81) at 2–27 days, 1·59 (1·47–1·71) at 28–364 days, and 1·27 (1·15–1·40) at 1–4 years. At 2–27 days, 77% of the excess risk of death in England was explained by birth characteristics and a further 3% by socioeconomic factors. At 28–364 days, 68% of the excess risk of death in England was explained by birth characteristics and a further 11% by socioeconomic factors. At 1–4 years, the adjusted HR did not indicate a significant difference between countries.Excess child mortality in England compared with Sweden was largely explained by the unfavourable distribution of birth characteristics in England. Socioeconomic factors contributed to these differences through associations with adverse birth characteristics and increased mortality after 1 month of age. Policies to reduce child mortality in England could have most impact by reducing adverse birth characteristics through improving the health of women before and during pregnancy and reducing socioeconomic disadvantage.The Farr Institute of Health Informatics Research . The UK has one of the highest child mortality rates in western Europe. In 2013, mortality in children aged less than 5 years was 4·9 per 1000 births in the UK, which was around 25% higher compared with France, Germany, Italy, or Spain, and almost twice as high compared with Sweden (2·7 per 1000 births).5Policy makers and child health professionals have called for improvements in child health services to reduce child mortality in the UK relative to Sweden, including more efficient general practitioner (GP) responses to sick children through better integration of GP and paediatric services and enhanced training.9Policy makers need evidence from a comparison of child mortality between the UK and Sweden that accounts for between-country differences in birth characteristics  and socioeconomic circumstances to guide policies to reduce child mortality. Such evidence could inform policy decisions on whether to focus preventive strategies on health care for children after birth or on improving the health of women before and during pregnancy to reduce risk factors present at birth.We compared child mortality in England, which accounts for 85% of all births in the UK,Evidence before the studyWe searched PubMed for international comparisons of child mortality published from Jan 1, 2000, to Jun 30, 2017, which included England or the UK and Sweden in the analyses. We used the search terms “((England OR English OR United Kingdom OR UK) AND (Sweden OR Swedish))” AND “(infan* OR neonat* OR post-neonat* OR child OR childhood OR under-5)” AND “” in titles and abstracts, and checked reference lists of identified papers to find additional relevant studies. We excluded studies which only used data from before the year 2000, and included only studies in English. We identified seven studies. Global comparisons of trends in child mortality show that rates in the UK have remained almost twice those in Sweden. Potential explanations are the UK's higher prevalence of preterm birth and congenital anomalies and that the UK has one of the most unequal distributions of income of all western countries. In 2003–05, the most deprived 20% of the population had a seven-times lower income than did the least deprived 20%, compared with a four-times difference in Sweden. Additionally, differences in health-care provision might contribute to increased health-care amenable mortality in the UK relative to Sweden. However, no previous study has adequate data to identify the relative contribution of birth characteristics or socioeconomic status to the excess in child mortality in the UK compared with Sweden.Added value of this studyWe developed representative birth cohorts in England and Sweden using individual-level administrative health databases with detailed information on child characteristics at birth  and socioeconomic factors . We compared mortality in England and Sweden adjusted for these risk factors at birth. At 2–27 days, 77% of the excess mortality in England relative to Sweden was due to differences in birth characteristics and 3% due to an independent effect of socioeconomic factors. For mortality at 28–364 days, these proportions were 68% for birth characteristics and 11% for socioeconomic factors. Small but significant differences remained after adjustment in the first year of life. At 1–4 years, the differences in mortality were negligible after adjusting for birth characteristics and socioeconomic factors.Implications of all the available evidenceThe largest improvements in child mortality in England relative to Sweden could be achieved by reducing the prevalence of low birthweight, prematurity, and congenital anomalies. The risk of child mortality in England relative to Sweden declined by 70–80% when adjusted for birth characteristics in the two populations. Socioeconomic disadvantage contributes to child mortality through its association with adverse birth characteristics, and in our study socioeconomic factors independently led to a further 10% reduction in mortality beyond the first month of life. These findings suggest that the biggest reductions in child mortality in England relative to Sweden could be achieved by reducing the prevalence of adverse birth characteristics through universal programmes to improve the health of women and reduce health inequalities before and during pregnancy.In this population-based birth cohort study, we developed nationally representative birth cohorts using birth records linked to hospital admission data and mortality registration databases in England and Sweden. These databases captured 97% of all births and 98–99% of all hospital admissions in England,We received ethical approval to use the Swedish national registers from the Regional Committee of Stockholm . We have a data sharing agreement with National Health Service (NHS) Digital to use a de-identified extract of Hospital Episode Statistics linked to Office for National Statistics death registration data for research on child mortality; therefore, we did not require ethical approval to use English datasets.In England, entry to the birth cohort was based on birth admissions recorded in Hospital Episode Statistics, which is a hospital discharge database containing all admissions to NHS hospitals and 97% of all births in England.In Sweden, entry to the birth cohort was based on data recording in the Swedish Medical Birth Register, a mandatory database containing details of antenatal, obstetric, and neonatal care for all births in Sweden to resident mothers.Information about birthweight, gestational age, and sex was obtained from the Swedish Medical Birth Register and from Hospital Episode Statistics.We categorised gestational age as 24–27 weeks, 28–31 weeks, 32–34 weeks, 35–36 weeks, 37–38 weeks, and 39 weeks and longer, and birthweight as 500–999 g, 1000–1499 g, 1500–2499 g, 2500–3499 g, and 3500 g and higher. To minimise bias from intercountry differences in recording of stillbirths and early neonatal deaths, we excluded all babies weighing less than 500 g at birth or born at less than 24 weeks of gestation in both England and Sweden.No directly comparable measure of socioeconomic status was available in the two countries. Instead, in Sweden we used quintiles of disposable household income in the year before childbirth, obtained via linkage to the Longitudinal Integration Database for Health Insurance and Labour Market Studies.As young maternal age (<20 years) is strongly associated with social disadvantageWe analysed mortality as the outcome, based on deaths from any cause at age 2–27 days, 28–364 days, and 1–4 years. We excluded deaths on days 0–1 because of under-reporting of risk factors at birth for these deaths in the English cohort  and to mWe derived the numbers and proportions of livebirths and deaths according to each birth characteristic  and socioeconomic factor  in England and Sweden. We calculated unadjusted mortality rates per 100 000 child-years by country and each risk factor category. We plotted Kaplan-Meier failure curves to illustrate between-country differences in the distribution of deaths by age, according to gestational age and presence of congenital anomalies. For each plot, we calculated the number of excess deaths in England relative to Sweden by multiplying the number of singleton livebirths in all of England (before applying exclusion criteria) between Jan 1, 2003, and Dec 31, 2012 (n=6 100 404), by the difference in the proportion of children who died in England and Sweden (by their first and fifth birthdays). We also listed the ten most common congenital anomalies recorded in hospital records and death certificates in each country.We fitted Cox proportional hazards regression models to estimate hazard ratios (HRs), comparing mortality in England relative to Sweden (the baseline). We fitted separate models for deaths at 2–27 days, 28–364 days, and 1–4 years. We first fitted unadjusted models including only country of birth. We then added birth characteristics and socioeconomic factors a priori. To estimate the extent to which the differences in birth characteristics and socioeconomic factors contributed to the increased risk of death in England relative to Sweden, we calculated the percentage of excess risk mediated (abbreviated as PERM)Percentage of excess risk mediated was calculated only for models with a statistically significant adjusted HR for England compared with Sweden, when the Wald test result for the country parameter was p<0·05. For all models, the proportional hazards assumption was assessed using Schoenfeld residual plots.As England and Sweden might differ in the recording of congenital anomalies, we used a stricter definition, indicating only severe congenital anomalies in sensitivity analyses.The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.The English cohort comprised 3 932 886 births and 11 392 deaths and the Swedish cohort comprised 1 013 360 births and 1927 deaths . This reIn general, children born in England weighed less at birth and were born at earlier gestational ages than were children born in Sweden . In EnglThe unadjusted child mortality rate was almost twice as high in England compared with Sweden , accountDisparities in child mortality by socioeconomic status were wider in England than in Sweden ; howeverAt 2–27 days of age, the unadjusted HR for England relative to Sweden was 1·66  and Sweden . Maternal education is the most comparable and consistent socioeconomic status indicator for international studies of child health outcomes,Our study would have benefited from analysis of additional maternal risk factors, such as smoking during pregnancy and body-mass index (BMI), which are recorded in the Swedish Medical Birth Register,vs 6·5% in 2010), and a higher proportion of women are obese .Disparities in child mortality rates in England compared with Sweden were largely driven by differences in distribution of birth characteristics in the two countries. A child's birth characteristics are associated with maternal characteristics, health, and socioeconomic circumstances before and during pregnancy. For example, young or old maternal age, smoking during pregnancy, and obesity are associated with increased prevalence of preterm birth,Efforts to reduce the prevalence of adverse birth characteristics would not only reduce child mortality, but could improve many other serious and more prevalent health problems. Preterm birth and low birthweight are associated with increased risk of chronic illness ,vs 7·3% in Sweden in 2009) or in deprived households (5·5% vs 1·3% in Sweden in 2009).Further research needs to focus on differences in the prevalence of adverse birth characteristics within each country according to maternal health indicators , health behaviours , ethnic group, and measures of health inequalities and socioeconomic disadvantage of the mother to evaluate policy interventions to improve maternal health and reduce adverse birth characteristics. Welfare policies that reduce socioeconomic disparities in England should be an important part of a strategy to lower child mortality in England. Socioeconomic disadvantage is an important determinant of preterm birth,Some of the increased prevalence of congenital anomalies in England might be attributable to differences in provision of prenatal care. For example, the number of terminations of pregnancies is higher in Sweden than in England because of more terminations for women aged 35 years and older (numbers are comparable for women aged <20 years)Further research is needed to identify the origins of the small but significant differences in the risk of death, which remained after adjustment for characteristics at birth and socioeconomic factors. First, some of these differences could reflect variation in the prevalence or severity of chronic conditions not measured in our study that are associated with increased mortality . Second, differences between England and Sweden might reflect differences in family policy between these countries. For example, both provide comparable amounts of universal child benefit;The increased child mortality in England relative to Sweden was largely explained by differences in the distribution of birth characteristics between the two countries. Adverse birth characteristics are strongly associated with maternal health. Therefore, the largest reductions in child mortality in England relative to Sweden could be achieved through universal programmes to improve the health of women and reduce health inequalities before and during pregnancy.


Prelacteal feeding (PLF) is a barrier to exclusive breast feeding.To determine factors associated with PLF in rural and urban Nigeria.We utilized data from the 2013 Nigerian Demographic and Health Survey. Bivariate and multivariate analyses were used to test for association between PLF and related factors.Prevalence of PLF in urban Nigeria was 49.8%, while in rural Nigeria it was 66.4%. Sugar or glucose water was given more in urban Nigeria (9.7% vs 2.9%), plain water was given more in rural Nigeria (59.9% vs 40.8%). The multivariate analysis revealed that urban and rural Nigeria shared similarities with respect to factors like mother's education, place of delivery, and size of child at birth being significant predictors of PLF. Mode of delivery and type of birth were significant predictors of PLF only in urban Nigeria, whereas, mother's age at birth was a significant predictor of PLF only in rural Nigeria. Zones also showed variations in the odds of PLF according to place of residence.Interventions aimed at decreasing PLF rate should be through a tailored approach, and should target at risk sub-groups based on place of residence. Exclusive breast feeding (EBF) from birth through six months of age has long-term health and emotional benefits for both mother and child and is associated with lower infant morbidity and mortality as well as better growthThe World Health Organisation (WHO) and the United Nations Children's Fund (UNICEF) during the Innocenti Declaration in 1990 called for policies that would cultivate breast feeding culture and encourage women to breastfeed their infants exclusively for the first six months of lifeAmong the 10 steps to successful breast feeding is giving infants no food or drink other than breast milk, unless medically indicatedNigeria became a fully independent country in October 1960Previous literature has shown that the determinant of PLF are multi-factorial in nature and includes factors such as mode of delivery, type of birth, occupation, education, place of delivery, size at birth, and regionsBreast feeding practices such as Early Initiation of Breast Feeding (EIBF) and EBF are the key and easiest intervention to reducing child death and morbidityThis was a cross-sectional study using nationally representative data from the 2013 Nigeria Demographic and Health Survey (NDHS) and authorization to use the data was given by Measure DHS. The 2013 NDHS was implemented by the National Population Commission and it is the fifth in the series of Demographic and Health Surveys conducted so far in Nigeria. NDHS have the approval of the National Health Research Ethics Committee.Administratively, Nigeria is divided into 36 states, and the Federal Capital Territory, Abuja. Each state is sub-divided into local government areas (LGAs), and each LGA is divided into localities.The sample for the 2013 NDHS was a stratified sample, selected independently in three stages. Stratification was achieved by separating each state into urban and rural areas. In the first stage, 893 localities were selected with probability proportional to size. In the second stage, one cluster was selected by simple random sampling. In a few larger localities, more than one cluster was selected. In total, 904 clusters  were selected. In the third stage of selection, a fixed number of 45 households were selected in every urban and rural cluster through equal probability systematic sampling.All women aged 15–49 years who were either permanent residents of the households in the 2013 NDHS sample or visitors present in the households on the night before the survey were eligible to be interviewed. Three sets of validated questionnaires were utilized to collect data and included; a household questionnaire, a woman's questionnaire and a man's questionnaire.A four-week-long training course in January and February 2013 was conducted for the field staff and the fieldwork was conducted from February 15, 2013, to the end of May .In the interviewed households, a total of 39,902 women aged 15–49 years  were identified as eligible for individual interviews, and 98 percent of them were successfully interviewedAnalysis for this study was restricted to last-born ever breastfed children born in the past two years preceeding the survey and the total sample size was 3879 for urban and 7888 for rural residence. After accounting for sample weights, this corresponded to a sample size of 4172 for urban and 7637 for rural areas.In the NDHS woman's questionnaire, mothers were asked “In the first three days after delivery, was (NAME) given anything to drink other than breast milk? What was (NAME) given to drink? (Options were: milk (other than breast milk); plain water; sugar or glucose water, gripe water, sugar salt water solution; fruit juice; infant formula; tea infusion; coffee, honey; and/others)The explanatory factors were chosen based on previous studiesMaternal socio-demographic factors; Ungrouped mothers age at birth was recoded into <=19, 20–24, 25–29, 3034 and >=35 years. Mother's education was categorized as no education, primary, secondary and above. Mother's occupation was re-grouped into not working and working. DHS wealth index was categorized into lowest (poorest), second (poorer), middle, fourth (richer) and highest (richest) wealth quintile, the index was constructed using household asset data via a principal components analysis. All the six geopolitical zones were included in the study.(i) Antenatal and postnatal factors; We created a new variable combined birth interval and birth rank to compare the effect of birth order and subsequent birth interval with PLF, this variable was categorized into 5 categories namely; 1st birth rank, 2nd–3rd birth rank and preceding birth interval < =23 month, 2nd–3rd birth rank and preceding birth interval 24 month and above, 4th and above birth rank and preceding birth interval < =23 months, 4th and above and preceding birth interval 24 month and above. Number of antenatal care (ANC) visits was recoded into 0, 1–3, 4 and above visit. Place of delivery was categorized as home and health facility. Also considered was mode of delivery . Birth type was recoded into singleton or twin/multiple, sex of child was as reported in the 2013 NDHS , size of child at birth based on mothers perception (subjective birth weight) and was categorized into three groups namely; large, average and small.(ii) Chi square tests were performed to evaluate the association of the independent variables with PLF. Rate of PLF and distribution by different independent variables were reported as weighted percentages and 95 % CI using Stata version 13.0 . Before running the multivariate analysis, we examined the correlation between explanatory variables that had high potential for collinearity. Binary logistic regression was used to examine the likely predictors of PLF in Nigeria. Factors considered for the multivariable model were based from previous literature. The logistic regression analysis consisted of 2 models. Model 1 was the maternal socio-demographic model while model 2 included model 1+ antenatal and postnatal factors. Adjusted odds ratios (AOR) with their 95% confidence interval (CI) were reported. The multivariate analysis accounted for the sample design and sample weight using Statistical Package for Social Sciences (SPSS) complex sample analysis method (SPSS version 21).A higher proportion of urban and rural mothers at the time of birth were within the ages of 25–29 years . 60.0% of urban mothers had secondary and above education, on the other hand, 57.8% of rural mothers had no education. The percentages of male and female children were more or less equal in both settings .The overall prevalence of PLF in Nigeria was 60.5% (95 % CI: 59.6%–61.4%). The prevalence of PLF observed in urban area was 49.8%, (95 % CI: 48.2%–51.3%). while in rural areas it was 66.4% (95 % CI: 65.3%–67.5%) .Sugar or glucose water (9.7 vs 2.9%) and honey (2.1 vs 1.5%) were predominatly given in urban Nigeria, whereas plain water (59.9 vs 40.8%), milk other than breast milk (14.3% vs 3.9%) and other pre-lacteal feeds (2.5 vs 2%) were commonly given in rural Nigeria. Gripe water was evenly given in both urban and rural Nigeria .Urban Nigeria: In urban Nigeria, the explanatory variables that were significantly associated with higher PLF rates included: Mothers age at birth being <=19 years, no education, non-working mothers, belonging to the lowest wealth quartile, all geopolitical zones as compared to the South Western zone, 4th birth rank and above with preceding birth interval of less than or equal to 23 months, no ANC visits, home delivery, multiple births, and small size of baby at birth , urban mothers with no education and primary educational status had significantly 48 and 31% higher odds of PLF as compared to mothers with secondary and above educational status (Adjusted Odd Ratio (AOR)=1.48, 95% CI=1.07–2.04 and AOR=1.31, 95% CI=1.02–1.69, respectively). Also, compared to the South Western geopolitical zone, urban mothers, who lived in the following geopolitical zones of Nigeria, were significantly more likely to give prelacteal feeds: North East ; North West ; and South East . Urban mothers who delivered at home had significantly higher odds of PLF as compared to urban mothers whose place of delivery were health facility . The odds of PLF was 1.87 times higher for urban mothers who had caesarean section as compared to urban mothers who had spontaneous vaginal delivery . In addition, urban mothers with multiple births had a 2.37 times the odds of PLF as compared to mothers with singleton birth . We further observed that urban mothers who perceived the size of their child at birth to be small or average had significantly higher odds for PLF as compared to urban mothers who perceived the size of their child at birth to be large .Rural Nigeria: In rural Nigeria, Model 2 showed that mothers who were aged <=19 years at birth were significantly more likely to give pre-lacteal feeds as compared to those aged 35 years and above at birth . Also, rural mothers with no education  and primary educational status  were significantly more likely to give pre-lacteal feeds as compared to mothers with secondary and above educational status. Compared to the South Western geopolitical zone, rural mothers, who lived in the following geopolitical zones of Nigeria, were significantly more likely to give prelacteal feeds: North East ; North West ; South East  and South South . The odds of PLF was 2.05 times higher for rural mothers who delivered at home as compared to mothers who delivered in a health facility . Rural mothers who perceived their babies as small  or average sized  at birth were more likely to give pre-lacteal feeds as compared to rural mothers who perceived their child to be large at birth.The main finding of this study was that PLF practice was more common in rural Nigeria (66.4%) as compared to urban Nigeria (49.8%). Prevalence of PLF was also higher in rural as compared to urban areas in India and MalawiThe commonest prelacteal feeds in Nigeria were plain water, sugar or glucose water and milk other than breast milk. This agrees with previous studies done in countries like KenyaIn the full model, urban and rural Nigeria shared similarities with respect to factors like mothers education, place of delivery, and size of child at birth being significant predictors of PLF, however some factors such as mode of delivery, type of birth, and mother's age at birth, showed variation in terms of significance according to place of residence. Mode of delivery, and type of birth were significant predictors of PLF only in urban Nigeria, whereas, mother's age at birth was a significant predictors of PLF only in rural Nigeria. Zones also showed variations in the odds of PLF according to place of residence. In urban Nigeria, caesarean section contributed significantly to a higher likelihood of PLF. The high rates of PLF among women who had caesarean section as compared to spontaneous vaginal deliveries could be linked to the fact that caesarean section (CS) is associated with prolonged maternal-infant separation, antibiotics safety concern on the child, pain and discomfort, and longer stay in the hospitalThe result of this study showed that urban mothers who had multiple births were more likely to give PLF as compared to urban mothers who had singleton births. This result is in consonance with findings of a previous study that report that establishment of breastfeeding after multiple births is extremely difficultIn rural Nigeria, mothers aged less than or equal to 19 years were significantly more likely to offer pre-lacteal feed as compared to older mothers aged 35 years and above. The reason could be that younger mothers may lack knowledge or experience about appropriate breastfeeding practicesMaternal education was an important determinant of PLF, although not strongly so, in both settings. The odds of PLF were higher for mothers with no education or primary education as compared to mothers with secondary and above educational status. A probable reason could be that the longer time spent in formal education put mothers in a better position to self-educate themselves on infant nutritionOur study findings showed that place of delivery was significantly associated with PLF practice in both urban and rural Nigeria. Mothers who delivered at home were more likely to give pre-lacteal feeds as compared to mothers who delivered in a health facility. This is in consonance with a study done in EthopiaMothers in both urban and rural Nigeria, mothers who perceived their infant to be small or average sized at birth were more likely to introduce pre-lacteal feeds as compared to mothers who perceived their infants to be large sized. In consonance, Flaherman and colleagues found that higher birth weight was strongly associated with exclusive breastfeedingThe current study observed significant zonal variations in PLF odds in both urban and rural Nigeria. Regional differences in PLF in both urban and rural Nigeria could be in part a function of access to health service, inequitable distribution of health services, health information, resources and other geographic differences, as shown in another studyThis study is not without some limitations, the study limitation relates to the fact that the data was based on a cross-sectional study and is subject to recall bias. In addition, due to the cross-sectional nature of the data, caution must be exercised in making causal influence of the identified determinants of PLF. On the other hand, the study has strength of being a nationally representive study with a high response rate, in addition, complex sample analysis was performed to account for the sampling strategy and sample weight, thus, the findings are generalizable to the entire country. Future studies using qualitative approaches such as in-depth interview of some key informants will help in enriching the knowledge on PLF in Nigeria.We observed differences in PLF between urban and rural areas, with factors affecting PLF showing variation in terms of significance according to place of residence. Interventions aimed at decreasing PLF rate should be through a tailored approach, targeting at risk sub groups discovered in our study.


Mortality associated with in-utero HIV infection rises rapidly within weeks after birth. Very early infant diagnosis of HIV (VEID)–testing within 2 weeks of birth–followed by immediate initiation of antiretroviral therapy has potential to avert mortality associated with in-utero transmission. However, our understanding of acceptability and feasibility of VEID is limited.VEID was piloted in an observational prospective cohort of HIV-positive pregnant women and their infants in 13 Lesotho health facilities. Between March-July 2016, semi-structured interviews were conducted with HIV-positive women attending 6-week or 14-week postnatal visits and health workers (HWs) in 8 study facilities in 3 districts as well as with district and central laboratory staff. Interview themes included acceptability of birth and subsequent HIV testing and early treatment, perceived VEID challenges, and HIV birth testing procedures and how well they were performed.Interviews were conducted with 20 women, 18 HWs and 9 district/central laboratory staff. Nearly all mothers perceived knowing their child’s HIV status at birth positively. Mothers and HWs did not indicate that birth testing affected subsequent acceptance of infant HIV testing or clinic attendance. HWs and laboratory staff reported weak follow-up systems for mothers with home deliveries, and concern regarding the increased workload associated with additional testing requirements. All groups reported turnaround time delays for EID, and that sometimes results were never received.Women, HWs, and laboratory staff found VEID acceptable and were supportive of national implementation of birth testing. However, they identified challenges within the EID system that could be exacerbated by adding a test to the diagnostic algorithm, such as delays in receiving test results, suggesting VEID may not be feasible in certain settings. Policymakers will need to consider whether adding birth testing or strengthening the current clinic and laboratory system is the most appropriate course of action. Perinatally HIV-infected infants face rapid disease progression and mortality as high as 68% by age 2 years without antiretroviral therapy (ART) –2. Mortain utero transmissions when mothers are receiving antepartum ART, and hence HIV can be detectable on day 1 of life in a significant percentage of infected infants  2–9). Five district and 4 central laboratory staff were interviewed; 5 were laboratory technicians and 4 were laboratory technologists.VEID acceptability was defined by the perceived benefits and challenges of early testing and treatment initiation, acceptability of treatment and subsequent infant testing after birth, and perspectives on national policy, including selective (“high risk”) versus universal testing. Quotes illustrating the acceptability thematic areas are presented in Respondents from all 3 groups agreed that birth testing was important. Nearly all women positively perceived having their child tested or knowing their child’s HIV status at birth. The primary benefit of VEID cited by women and HWs was earlier knowledge of children’s HIV status. Women felt this knowledge was important, for reasons such as being able to provide the appropriate care for the child and so that the child does not become ill later. Both HWs and laboratory staff highlighted earlier treatment initiation as a key benefit leading to reduced infant mortality. HWs also noted that earlier receipt of test results allowed them to alleviate caregiver uncertainty and guide proper care for the child. Birth testing refusal was rare; the main reasons were fear of hurting the newborn, long waiting time for blood draw, and fear that their child could be HIV-positive. While most women had no negative perceptions of birth testing, VEID acceptance was sometimes the result of extensive counseling and the existing, trusting relationship between study nurse and patient.HWs reported that treatment acceptance was not felt to be different between mothers learning their child was infected at birth versus other time points. Counseling and individual personalities were more relevant to treatment acceptability for children. Women and HWs also did not indicate that birth testing affected subsequent infant HIV testing acceptance nor did it negatively influence women’s motivations to attend postnatal services. The few HWs who encountered women who refused birth testing indicated that those women still accepted subsequent infant tests.While women felt birth testing was important, they still expressed concerns about infant testing not specific to test timing, such as possible infant transmission. Two women also expressed discomfort with pricking their newborn to obtain blood. Women, HWs, and laboratory staff cited that turnaround time (TAT) for result receipt was a challenge for all DNA-PCR tests. HWs estimated TAT to receive results at the MCH clinic was 2 weeks to 3 months at both health centers and hospitals, with some results never received by health facilities. A woman raised the issue of her child being tested again at 6 weeks, though she had not yet received results from the birth test. While not all HWs perceived a significant increase in resource burden as part of the birth testing pilot, those who were counselors and all laboratory staff felt that a national roll-out of VEID would result in increased workloads and further delays in TAT. Laboratory staff suggested that additional laboratory technologists, or data clerks to assist with sample registration and packaging, could help address the workload challenge at laboratories.Despite challenges, HWs felt that birth testing was important and the majority recommended nationwide implementation. Most HWs and laboratory staff preferred universal birth testing for HIV-exposed children, rather than selective ‘high risk’ testing. They reasoned that all HIV-positive women should be considered high risk and assessing risk in clinic settings would be difficult. While in favor of broader implementation, one laboratory respondent suggested that VEID rollout be staggered, starting with hospitals and then to lower-level facilities, to better understand the extent of the added burden to the laboratory/health system and plan accordingly.VEID feasibility was defined as the procedures used for the HIV birth testing pilot and how well they were performed and could be practicably implemented on a national scale, including counselling on and understanding of birth testing, birth testing following home deliveries, communicating test results, and perceived challenges with VEID scale-up. Quotes illustrating the feasibility thematic areas are presented in Most women understood the purpose of birth testing, felt that HWs had answered their questions, and first learned about birth testing in ANC. However, a significant number described the time spent in counseling as too short. Among these women, the amount of time being counseled varied from 5 to 35 minutes in ANC and at delivery combined. The majority of HWs estimated that counseling lasted 15–30 minutes, depending on women’s level of understanding and questions. HWs reported that women’s questions included whether the child was too young to have blood drawn or was being hurt unnecessarily, what to do if the child’s result was positive, and when results could be expected.Home deliveries were cited as a significant challenge to universal birth testing, particularly in more remote facilities. Women who deliver at home or in South Africa may not return to the facility within the 2-week window to have their infants tested. In order to help ensure a birth test was conducted, village or community health workers would accompany women and their newborns to a facility if possible or report home deliveries to the MCH clinic for follow-up. Other strategies employed by HWs included asking women to notify them in case of home delivery, and following up with women via phone around the time of their estimated delivery date.Nearly all HWs described using mechanisms to fast-track HIV-positive results to mothers or other caregivers. Typically, they called mothers on the same day the result was returned and enlisted community or village health workers to locate them and facilitate their return to the facility if needed. This presented challenges when women lived outside the surrounding villages and when there was poor mobile network coverage or unavailable phone numbers. HWs described waiting to share HIV-negative infant results until women attended their regularly scheduled clinic visits, occurring every 1 to 2 months. Women also described receiving their child’s results at scheduled visits.No formal fast-tracking mechanisms for HIV-positive results existed at the laboratory level, however some laboratory staff reported hand-delivering results to clinics (for those on the same campus) or calling health centers if there was a positive result. The reason given for results not typically being relayed by phone was so that the results can be properly documented in patients’ health booklets.While nearly all respondents from the 3 groups felt birth testing should be rolled out nationally, they anticipated challenges moving from pilot-testing to national implementation. HWs and laboratory staff described even longer TAT for results with an additional burden on staff. Laboratory respondents were concerned that having samples collected at any time for deliveries versus having scheduled days for blood draws would affect transportation schedules at health centers. Other challenges included the limited capacity of machines to perform additional tests and the greater likelihood of reagent stock-outs at central level. HWs also described issues that were reflective of the pilot nature of birth testing, such as the lack of birth testing information in standard facility registers and group counseling messages that omitted birth testing and failed to emphasize the 7-day visit for infants not tested at birth. They felt these issues would be addressed if the algorithm is updated in the national guidelines.Given the delay of transporting samples and results, several HWs and laboratory respondents suggested DNA-PCR machines be placed in districts to bring EID services closer to women. Other recommendations to reduce TAT included improving communication from the district and central laboratories to MCH clinics, so positive test results could be immediately communicated and documentation errors could be swiftly resolved, and ensuring the laboratory information system and short message service (SMS) printers are functional to expedite result transfer. It was also suggested to communicate HIV-negative results to women via text messaging and include prevention strategies for keeping their child negative.Our study provides some of the first published qualitative findings on acceptability of birth testing. We found that birth testing was acceptable to women, HWs, and laboratory staff and that there was support for national implementation of birth testing. However, they identified EID system challenges that could be exacerbated by adding a test to the diagnostic algorithm, suggesting VEID may not be feasible in certain settings, unless systems were strengthened. Respondents felt that adding birth testing to the current EID specimen and result transfer system would likely increase workloads and result in further delays in TAT. In addition, ensuring HIV-exposed infants delivered at home were tested soon after birth would be a challenge due to weak follow-up systems for tracing HIV-exposed infants and limited attendance at 7-day postnatal visits.Interviewed women regarded knowing their child’s status around the time of delivery positively. Birth test refusals were rare, similar to another study reporting 100% uptake of birth testing . HIV-posImprovements along the EID pathway would be critical to a successful VEID rollout. Decentralization of testing to the district level and use of point-of-care (POC) HIV diagnostic machines could permit more timely treatment initiation for infants identified as HIV-positive. It would help to address some challenges related to transportation of samples and results, laboratory staff shortages by task shifting of testing, and the limited capacity of a small number of machines at central level. However, this strategy would need to be evaluated for cost-effectiveness and feasibility of “hub and spoke” models. While POC diagnostics has demonstrated promise for other tests, such as CD4, it is not without challenges, including increased provider workload ,18.Strengthening clinic and laboratory systems to improve EID at 6 weeks of life rather than the addition of birth testing should also be considered. A study in South Africa suggests that, under certain conditions, focusing on DNA-PCR testing at 6 weeks would be more effective. A 6-week plus birth testing scenario with 50% testing coverage and 50% of results returned, yielded a lower infant survival gain than if 6-week testing coverage and result return frequency was increased to 75% for 6-week testing alone . In counIf birth testing were to be implemented nationally, follow-up systems for women delivering at home would need to be strengthened. Counselling messages would need to emphasize the importance of birth testing and the 7-day visit. Given that the Lesotho Demographic and Health Survey found that nearly a quarter of women delivered at home , the potin utero infection might be a cost-effective way to implement birth testing, particularly when risk of MTCT is low. However, a targeted program may be more complex to implement, and could result in high-risk infants not being identified and hence missing birth testing. A study on birth testing in South Africa estimated that targeted testing, based on risk factors such as short maternal ART duration, poor adherence, and infant low birth weight, would miss 36% of infected newborns [While respondents favored universal testing, a targeted testing program of infants at high risk of newborns .The study had limitations. Due to low numbers of HIV-infected children during the study period, no women who had a child infected at birth were interviewed, despite efforts to include them. No interviews were conducted with clinic (non-study) nurses. These nurses were not involved in VEID as it was only a pilot, though they may have viewed VEID less favorably. While they would certainly be involved if VEID were rolled out nationally, counselors, who were interviewed as part of this study, would be primarily responsible for performing infant HIV counseling and testing. Finally, given the qualitative nature of the study and the limited perspectives permitted by the pilot, we are not positioned to make a recommendation regarding widespread implementation. However, this is one of the first qualitative studies on VEID and offers some lessons learned for how to optimize success should birth testing be rolled out nationally.


Despite evidences indicating the superiority of breastfeeding and recent advances in the indicators of breastfeeding in Brazil, exclusive breastfeeding (EBF) during the first six months after birth continues to be an infrequent practice in the country. The objective of the present study was to determine which gestational, perinatal, and postnatal factors of the mother-baby dyad might be associated with the cessation of EBF by six months after birth.Data were collected at the rooming-in facility of the Reference Center of Women’s Health of Ribeirão Preto-Mater (CRSM-Mater) during the postpartum period (24 to 72 h after birth) from December 2012 to April 2013 and by telephone contact between the researcher and participating mothers by six months after birth.Questionnaires were applied to collect data, such as the practice of EBF in the last 24 h in the sixth month after birth. The hierarchical theoretical model was proposed and data were analyzed statistically by log-binomial regression models using SAS 9.3.The study involved 283 mother-baby dyads in which the mother evaluated did not present pregnancy-puerperal complications that could impede breastfeeding and confirmed the interest in breastfeeding her child. After the telephone contact in the exact sixth month after the birth of each participating baby, 84.8% of the participating mothers reported that they were no longer exclusively breastfeeding their babies. After statistical analysis, we found that there was a significant association between cessation of EBF and maternal report of previous experience with EBF for one month  and six months . These practices were associated with the maintenance of EBF and, even after adjustment for maternal socio-demographic variables, this association was maintained . Thus, there is a greater chance of practicing and maintaining EBF by six months after birth when mother had previous experience with it.The identification of the risk variables associated with cessation of EBF by six months postpartum, such as previous experience with exclusive breastfeeding, may contribute to the effectiveness of EBF intervention and support measures during the first six months after birth.The online version of this article (10.1186/s13006-017-0132-y) contains supplementary material, which is available to authorized users. Despite scientific evidence regarding the benefits and superiority of human milk (HM) as well as the harmful effects of infant formulas, the practice of exclusive breastfeeding (EBF) is still infrequent in Brazil. Even with the consolidation of numerous strategies to promote breastfeeding (BF) and the general public health recommendation that infants should be exclusively breastfed during the first six months of life in order to achieve good growth and development, the percentage of infants exclusively breastfed for the first six months of life is still low and worrisome –11.A cross-sectional study conducted in the late 1990s in Brazil found alarming data on the estimated prevalence of EBF in the last 24 h by age of the child, showing that of 1259 children aged between 15 and 45 days of life, only 47.5% were In EBF [In addition to this previous study, an important national survey entitled “National Survey of Demography and Health of Children and Women (PNDS) 2006” evaluated a sample of 4817 children considered to be representative of the Brazilian population and found that 42.9% were breastfed up to one hour after And that 48.3% of children aged 2–3 months were in EBF in the last 24 h [The low EBF prevalence can be explained by sociocultural influences related to the industrialization process, such as the increasing commercialization of breast milk substitutes and the increase in female participation in the labor market. With the absence of women, the resources used to feed their children include bottles; milk from animal sources, such as cows; and industrialized infant formulas , 13–15. In addition, the low prevalence of BF in Brazil can be explained by the fact that BF is a biologically determined, yet culturally and socially conditioned, practice that makes the BF experience complex because it involves biological, psychological, and social factors related to both mother and their child –25. ThusConsidering the above considerations, the objective of the present study was to determine which gestational, perinatal, and postnatal factors of the mother-baby dyad might be associated with the cessation of EBF by six months after birth. It is speculated that if such associations are confirmed, it will be possible to enrich prenatal and postnatal counseling to encourage EBF for a period of six months postpartum. Finally, we also sought to identify information that may help increase the prevalence of EBF in Brazil.Data from this observational, analytical, and longitudinal study were collected in two stages. The baseline data collection involved the inpatient facility of the CRSM-Mater from December 2012 to April 2013. The follow-up data collection consisted of telephone contact between researchers and the participating mothers in the six months completed after the birth date .In baseline data collection, clinical and sociodemographic information of the mother-baby dyad were collected through the application of a previously established questionnaire composed of open questions  of the 283 mothers being 20 years of age or older; 203 (71.7%) reporting schooling of more than 8 years, and 167 (59.0%) reporting that they did not perform any type of remunerated activity until birth.Clinical data collected immediately after childbirth revealed that 162 (57.2%) of the participating puerperal women were multigestae, 152 (53.7%) had no experience with EBF for at least one month, and 216 (76.3%) had no experience with EBF for at least six months.In addition, 197 (69.6%) of the puerperal woman had not planned the last pregnancy, 245 (86.6%) participated in six or more prenatal visits, and 147 (51.9%) reported having received no guidance regarding BF during their prenatal care.Perinatal clinical data showed that 143 (50.5%) neonates were born during the daytime period, 172 (60.8%) were born by vaginal birth, and 174 (61.5%) were breastfed for the first time only after the first hour of life.A total of 206 (72.8%) did not report initial difficulties with BF and 271 (95.8%) reported having received BF instructions after birth.After the telephone contact in the exact sixth month after the birth date of each participating baby, 43 (15.2%) mothers reported practicing EBF, however 240 (84.8%) mothers reported no more exclusively breastfeeding.After statistical analysis of the data, the unadjusted logistic regression analysis indicated that the factors “Multigestae,” “experience with EBF for at least one month,” “experience with EBF for at least six months,” and “birth during the nighttime period” were associated with cessation of EBF by six months after birth; however, they behaved as protective factors for EBF, as presented in Table Statistical analysis using the proposed theoretical hierarchical model Table  revealedThe present study was conducted in the city of Ribeirão Preto (SP) from 2012 to 2013 to evaluate 283 mother-baby dyads. In doing so, we detected a 15.2% prevalence of EBF among six-month-old babies  and six months . These practices were associated with the maintenance of EBF and, even after adjustment for maternal socio-demographic variables, this association was maintained , as presented in Table Despite the evidence obtained in the present study, a systematic review of epidemiological studies conducted in Brazil between 1998 and 2010, specifically 20 cross-sectional studies and 7 cohort studies, identified 36 factors associated with EBF. However, only two studies reported the association between prior maternal experiences with EBF by six months after birth . In addiHowever, in addition to what has already been advocated, a recent study found that previous maternal experience with BF of the first child might determine the practice of BF the second child. However, the authors emphasized that mothers who had initial difficulties with BF their first child were less likely to initiate BF of the second child. Therefore, it is necessary to deal with the difficulties and quality of BF practice of their first child to ensure that the next child will be properly breastfed .Therefore, we believe that it is important to emphasize that 152 and 216 mothers participating in our study reported that they did not have prior experience with EBF for one and six months, respectively. Because our sample comprised 121 primiparous women, who did not really have the possibility of previous BF experience, a higher number of mothers interviewed reported that they did not have such experience, which shows that some of the multigestae had no previous experience with EBF. Thus, we believe that previous experience with EBF influences BF practice and that the evaluation of the quality of this experience is necessary. Furthermore, it is important to evaluate the difficulties related to the process of BF previous children.Regarding difficulties with BF, we did not question the reported previous difficulties with BF because its reporting was subjective and could have biased this study. However, we questioned the mother about initial difficulties with the current child’s BF but without detailing such a variable. After performing the unadjusted analysis of the data, responses to “initial maternal difficulty with BF” was associated with cessation of EBF by six months after birth Table . DifficuFinally, based on previous reports, the specialized support of health care professionals and the support of family members are fundamental to the practice of BF , 58. StuWe found an interesting association between the variable “period of birth” and the cessation of EBF. Possible speculation about night time birth as a protective factor for EBF could be the nature of the hospital environment, which is routinely calmer at night. This could more easily allow for skin-to-skin contact and BF during the first hour of life. In addition, visitors are only allowed to visit during the day, which may interfere with BF practice , 63.The study presented some limitations such as the fact that information needed to justify the findings had not been collected, since there were dyads invited to participate in the study who refused the invitation after being informed of the procedures. In addition, the relatively small sample size and the restriction to a single data collection site can also be considered limiting factors of this study.The support of health professionals and society at large is essential to advocate the importance of EBF practice. However, being aware of the benefits and advantages of BF and opting for this practice are not enough to establish and maintain BF for an appropriate period.It is important not to generalize the ability to breastfeed and to consider the variables involved in the BF process. Therefore, it is essential to promptly identify the risk variables associated with the early interruption of EBF, thereby contributing to the efficacy of intervention measures for the support of EBF during the first six months after birth. Our study allowed the identification of risk variables associated with the cessation of EBF by six months after birth, such as the previous experience with exclusive breastfeeding. We believe that the identification and consideration of variables associated with EBF cessation may contribute to the effectiveness of intervention and support measures related to breastfeeding.When favorable interventions that promote BF are performed with consideration of different determinants of BF practice, EBF is more frequently practiced. This fact can provide economic and environmental advantages for children, women, and society, such as the reduction in health care costs .Additional file 1:Description of data: Clinical and sociodemographic information of the mother-baby dyad were collected through the application of this previously established questionnaire composed of open questions. (DOCX 13 kb)Additional file 2:Questionnaire used in the sixth month. Description of data: In follow-up data collection, this survey used this questionnaire composed of two questions to identify the type of feeding practiced at that time. (DOCX 17 kb)


Tracking progress towards global newborn health targets depends largely on maternal reported data collected through large, nationally representative surveys. We evaluated the validity, across a range of recall period lengths (1 to 24 months post-delivery), of maternal report of birthweight, birth size and length of pregnancy.We compared maternal reports to reference standards of birthweights measured within 72 hours of delivery and gestational age generated from reported first day of the last menstrual period (LMP) prospectively collected as part of a population-based study (n = 1502). We calculated sensitivity, specificity, area the under the receiver operating curve (AUC) as a measure of individual-level accuracy, and the inflation factor (IF) to quantify population-level bias for each indicator. We assessed if length of recall period modified accuracy by stratifying measurements across time bins and using a modified Poisson regression with robust error variance to estimate the relative risk (RR) of correctly classifying newborns as low birthweight (LBW) or preterm, adjusting for child sex, place of delivery, maternal age, maternal education, parity, and ethnicity.The LBW indicator using maternally reported birthweight in grams had low individual-level accuracy (AUC = 0.69) and high population-level bias (inflation factor IF = 0.62). LBW using maternally reported birth size and the preterm birth indicator had lower individual-level accuracy  and higher population-level bias  up to 24 months following birth. Length of recall time did not affect accuracy of LBW indicators. For the preterm birth indicator, accuracy did not change with length of recall up to 20 months after birth and improved slightly beyond 20 months.The use of maternal reports may underestimate and bias indicators for LBW and preterm birth. In settings with high prevalence of LBW and preterm births, these indicators generated from maternal reports may be more vulnerable to misclassification. In populations where an important proportion of births occur at home or where weight is not routinely measured, mothers perhaps place less importance on remembering size at birth. Further work is needed to explore whether these conclusions on the validity of maternal reports hold in similar rural and low-income settings. Approximately 20 million low birth weight LBW, <2500 grams) infants are born annually, the vast majority from low and middle income countries . In Sout00 grams One challenge to accurately tracking LBW is that more than half of children globally, and up to 69% of children in South Asia, are not weighed at birth. Despite substantial progress, many births still occur at home ,2,4 and Thus, maternally-reported information collected through national surveys, like the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), is often utilized to generate birth indicators in low-income countries . Recall The study was conducted in Sarlahi district of Nepal, bordering Bihar, India to the south. Among approximately 800 000 predominantly Hindu residents, 40% are less than 15 years of age . GovernmBetween November 2010 and January 2017, a randomized community-based trial enrolled pregnant women and their babies in 34 Village Development Committees in the rural district of Sarlahi, Nepal to investigate the impact of full-body newborn massage with sunflower seed oil on newborn deaths and infections. The trial was registered at ClinicalTrials.gov (NCT01177111). Locally-resident female study staff visited married women 15-35 years of age at home every 5 weeks and asked about date of last menstrual period in the past 5 weeks. If they had not menstruated in the past 5 weeks, they were offered a pregnancy test and if found to be pregnant, were asked if they would consent to enroll in the study. Enrolled women were followed through delivery; study staff visited as soon as possible after delivery and through the first month . At the visit following birth, workers recorded date/time of delivery, circumstances of labor and delivery, health status of mother and newborn, and the median of three measures of baby’s weight using a digital scale precise to 10g (Tanita BD-585). The date, time of birth and weight of the newborn were also provided to the mother/caretaker on a small 10 × 8 centimeter card. Subsequent visits focused on maternal report and directly observed aspects of newborn health.Between April and September 2016, mother/child pairs that had participated in the parent trial were selected for one additional follow-up visit to ask mothers to report on events during labor and delivery, immediate newborn care, postnatal care, and cases of illness and care sought in the first 7 days of life. Mothers who had a singleton live birth and whose visit following birth had been conducted within 72 hours after delivery were eligible. Given that a relatively low (i.e. <10%) proportion of newborns would have experienced illness or received postnatal care in the first week of life, we oversampled mother/child pairs with these characteristics. We defined illness as death or having two or more of the following signs in the same visit in the first week of life: difficulty sucking, difficulty breathing, stiffening of the back or convulsions, rapid breathing (a respiratory rate of 60 breaths per minute or faster), chest in-drawing, hyperthermia (100.4°F or higher), hypothermia (lower than 95.9°F), lethargy, or pus or redness at the base of the cord stump. We categorized newborns into four groups: those who experienced an illness, did not experience an illness, had a postnatal visit with a health provider outside of the study, and did not have a postnatal visit. All newborns enrolled in the study were visited (i.e. as part of the parent study procedures) in the immediate postnatal period by study staff, but not all had postnatal care visits with non-study providers. We sampled all newborns who experienced an illness and/or had a non-study postnatal care visit, and randomly sampled additional newborns without an illness and/or without a non-study postnatal visit. Rather than aim to produce a representative sample of the larger community, our intent was to ensure we could evaluate the accuracy of maternal recall for rarer events such as care seeking for newborn illness. We aimed to interview approximately equal numbers of different mothers at each of seven follow-up time periods: 1, 3, 6, 9, 12, 18, or 24 months after birth.Online Supplementary Document(Online Supplementary Document)) in addition to questions about newborn care practices, morbidity and care seeking (results for those indicators will be published separately).Study staff visited selected mothers and requested participation through an oral consent process in Nepali or Maithili, followed by collection of signature or thumbprint. Those agreeing were asked questions specific to this analysis . In Nepal, approval was received from the Tribhuvan University Institute of Medicine, Kathmandu  and the Nepal Health Research Council, Kathmandu (substudy).Here we focus on assessing the validity of maternal reports of A) birthweight and B) birth size in correctly categorizing newborns as LBW, and C) a shortened length of pregnancy in identifying preterm births. Maternal classification of LBW included a reported birthweight <2500 grams  or birth size of “small” or “very small.” Maternal classification of preterm birth was defined as a reported time of delivery of “early” or “very early.” We compared the percent of babies classified as LBW using these maternal reports of birthweight and birth size, to the proportion so classified using weight data collected using the digital scale (i.e. within 72 hours of birth). Similarly, we compared maternal classification of preterm birth with our “gold standard” estimate of pregnancy length estimated by calculating the difference in days between delivery date and reported first day of the LMP, collected through prospective surveillance as described above.Sensitivity, specificity, area under the curve (AUC), and the inflation factor (IF) were calculated. AUC is the area under the receiver operating characteristic curve (plot of 1 – specificity vs. sensitivity). An AUC of 1 represents a perfect test while a score of 0.5 suggests the test is no better than a random guess. The IF is the ratio of the survey-based prevalence of the indicator (given the estimated sensitivity and specificity) and the ‘true’ prevalence based on a gold standard, and thus quantifies the extent to which the indicator is over- or underestimated in a survey. The observed prevalence of an indicator in a population-based survey is equal to the true prevalence × (Sensitivity + Specificity – 1) + (1 – Specificity) . Bootstra priori high individual-level accuracy as AUC>0.70, and low population-level bias as 0.75<IF<1.25 [We stratified sensitivity, specificity, AUC, and IF by child sex, birth location (facility vs. home), maternal education (any vs. none), maternal age (<20 vs. ≥20 years) and parity (primiparous vs. multiparous). To examine whether accuracy of maternal reports erodes with longer recall periods, sensitivity, specificity, AUC, and IF were calculated within each of the seven bins of recall time. Comparable to other studies that have assessed validity of indicators, we defined <IF<1.25 -17.Finally, to control for possible differences in the types of mothers interviewed across recall periods, we used a modified Poisson regression with robust error variance to estimate relative risk ratios (RR)  to assesOnline Supplementary Document). More than half of newborns were male (55.5%) and a majority of these births occurred in the home (53.7%). The mean age of mothers at follow up was 23.8 years; most had no schooling (68.2%) and had prior children (71.4%). Participants were nearly universally (96.2%) of Madhesi ethnic origin, frequently lacked a household latrine (71.2%), had electricity (80.5%), and owned some type of land (97.4%). Our sample was largely comparable to the parent trial sample; one difference was that the parent trial sample was more balanced by child sex . The median gestational age at the time pregnancy was first identified was comparable between the parent trial and this substudy: 14.3 weeks (interquartile range IQR = 9.7-23.9 weeks) and 14.6 weeks (IQR = 9.9-23.1 weeks), respectively.Of the 1892 households visited, 363 (19%) mothers were not met at their homes. We consented and interviewed 1517 mothers , parental refusal of weight measurement (n = 1), and missing weight measurement (n = 1); the latter exclusions included pairs where mothers reported the child was not weighed (n = 21), was uncertain if child was weighed (n = 6), or was weighed but could not respond (n = 47). A further six mothers without LMP data were excluded. Online Supplementary Document(Online Supplementary Document)). Of the total of 127 cards presented, 22 were from a facility and 105 were from the parent study. Of the 22 facility cards, all had reported delivering at a facility, and of the 105 birth cards distributed during the parent trial, 70.5% delivered in the home and 29.5% delivered in a facility. Comparing the percent of newborns that would be categorized as low birthweight based on birthweight measurements taken during the parent trial versus the birth cards produced at the follow up visit, fewer would be categorized as low birthweight for home births (17.6% vs. 20.3%) and more would be identified as low birthweight among facility births (26.4% vs. 22.6%). This observation is purely descriptive as no statistical test was performed with so few birth cards presented.Of the 1476 mothers who were asked if they had a card with a birthweight record, only 74 (9.4%) of those who delivered at home and 53 (7.7%) of those who delivered at a facility were able to produce one (Table S3 in Online Supplementary Document(Online Supplementary Document)). Sensitivity for all three indicators was low while specificity was high. LBW, estimated from maternal reports of birthweight, had low individual reporting accuracy  and high population-level bias . Using reports of birth size and pregnancy length to estimate LBW and preterm birth prevalence also resulted in low individual-level accuracy  and high population-level bias , respectively.Sensitivity, specificity, AUC, and IF are presented in Online Supplementary Document(Online Supplementary Document)) [Online Supplementary Document(Online Supplementary Document)).To further investigate population-level bias, we plotted the values of the predicted survey prevalence of each of the three indicators across all possible prevalences of LBW and preterm births within our reference standard ) . We woulOnline Supplementary Document(Online Supplementary Document)). These findings were consistent with our estimated RR for the proportions accurately categorized as LBW and preterm against recall length, controlling for child sex, place of delivery, maternal age, maternal education, parity, and ethnicity (P = 0.004), adjusting for other factors. In Model B, the estimated RR for the proportion of newborns correctly identified as LBW by maternally-reported birth size similarly decreased only slightly with increasing length of recall time but was not statistically significant , controlling for other variables. For both models, mothers’ reports were less likely to accurately identify newborns as LBW if their child was female, and were more likely to accurately categorize the child if the mother reported having had any education and if the mother had one or more children prior to the child of interest. Model C included an inflection point at 20 months in the time since birth. Up to 20 months after birth, the estimated RR for the proportion of newborns correctly identified as preterm by maternally reported length of gestation was not associated with time , adjusting for other variables. After 20 months since birth, the estimated RR for the proportion of newborns correctly identified as preterm by maternally reported length of gestation improved slightly with increasing time since birth and was statistically significant . Maternal age, parity, and ethnicity were also predictive of correct categorization of preterm birth.We observed no significant differences in the measures of accuracy by binned recall time for any of the three indicators  compared to that described in a study in Uganda  . Other sWe observed both low individual-level accuracy and high population-level bias for the preterm birth indicator generated from maternal reports of length of gestation at birth. Several studies have reported high degrees of accuracy of gestational age reports from mothers in developed countries ,22,34,35Contrary to our hypothesis, the length of time since delivery did not affect the validity of maternal report for LBW and longer length of time among mothers we visited 20 months since birth and later resulted in improved accuracy for preterm birth. Some studies have reported improved accuracy and agreement between medical records and maternal report for birthweight and gestational age associated with shorter length of recall ,34,36 whA strength of our study is the inclusion of home births in a population with relatively high prevalence of LBW and preterm birth. In the South Asian region, where around 69% of newborns are not weighed at birth, perhaps mothers place less importance on remembering and documenting birthweight, as evidenced by very few mothers who were able to present a birthweight card. Also, our study used accurate and calibrated scales of research quality and trained and supervised data collectors, in contrast to many delivery facilities. We also demonstrated that these indicators may be increasingly vulnerable to being underestimated in populations with higher prevalences. A limitation of our birthweight measurements used as the gold standard is that newborns were weighed up to 72 hours after birth. In this time period, newborns normally lose weight before patterns of growth and weight gain are observed. Therefore, our measurements were likely taken at a nadir and overestimate the prevalence of LBW; however, our intention was to validate maternal report rather than provide an estimate of prevalence. In addition, for home births, we are fairly confident that mothers were reporting the birthweight measured during the parent trial since this would have been the only birthweight provided to them. However, mothers who delivered in a facility may have had their child weighed both at the facility and during participation in the parent trial. For facility births, we assumed the mother was reporting the weight measurement during the parent trial. Lastly, we did not ask mothers to report birthweight immediately after the measurement taken, which would have provided more information about whether mothers could retain birthweight information if the event occurred just prior to our interview.Our conclusions regarding appropriate classification of preterm birth are limited since we did not ask mothers to report a numerical length of gestational age. Our categories of gestational length at birth were adapted from the DHS and MICS birth size question and have only been used in this study. Additionally, our gold standard for gestational age is based only on reported LMP, which frequently overestimates gestational age by a few days when compared to the gold standard of ultrasound measurements taken in the first trimester . Our relThe use of maternal reporting may underestimate and bias indicators for LBW and preterm birth. Additional approaches may be needed to correct for these inaccuracies in large surveys and improve methods to monitor and track progress towards global newborn health targets. The findings of this study may have limited generalizability to settings with high prevalence of LBW and preterm births and where the majority of births take place in the home. Further work is needed to explore whether these conclusions on the validity of maternal reporting hold in similar rural and low-income settings. Additional studies may be needed to understand the range of likely individual-level accuracy and population bias for these indicators in settings where women more commonly deliver in facilities and health cards are more frequently retained.