Summary Background The days immediately after birth are the most risky for human survival, yet neonatal mortality risks are generally not reported by day. Early neonatal deaths are sometimes ...under-reported or might be misclassified by day of death or as stillbirths. We modelled daily neonatal mortality risk and estimated the proportion of deaths on the day of birth and in week 1 for 186 countries in 2013. Methods We reviewed data from vital registration (VR) and demographic and health surveys for information on the timing of neonatal deaths. For countries with high-quality VR we used the data as reported. For countries without high-quality VR data, we applied an exponential model to data from 206 surveys in 79 countries (n=50 396 deaths) to estimate the proportions of neonatal deaths per day and used bootstrap sampling to develop uncertainty estimates. Findings 57 countries (n=122 757 deaths) had high-quality VR, and modelled data were used for 129 countries. The proportion of deaths on the day of birth (day 0) and within week 1 varied little by neonatal mortality rate, income, or region. 1·00 million (36.3%) of all neonatal deaths occurred on day 0 (uncertainty range 0·94 million to 1·05 million), and 2·02 million (73.2%) in the first week (uncertainty range 1·99 million to 2·05 million). Sub-Saharan Africa had the highest risk of neonatal death and, therefore, had the highest risk of death on day 0 (11·2 per 1000 livebirths); the highest number of deaths on day 0 was seen in southern Asia (n=392 300). Interpretation The risk of early neonatal death is very high across a range of countries and contexts. Cost-effective and feasible interventions to improve neonatal and maternity care could save many lives. Funding Save the Children's Saving Newborn Lives programme.
Summary Background Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 ...mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000–15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. Methods We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1–59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. Findings In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million 95% uncertainty range (UR) 0·935–1·179), pneumonia (0·921 million 0·812 −1·117), and intrapartum-related events (0·691 million 0·598 −0·778). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000–15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR. Interpretation In the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target. Funding Bill & Melinda Gates Foundation, WHO.
Summary Background Pakistan faces huge challenges in eradicating polio due to widespread poliovirus transmission and security challenges. Innovative interventions are urgently needed to strengthen ...community buy-in, to increase the coverage of oral polio vaccine (OPV) and other routine immunisations, and to enhance immunity through the introduction of inactivated polio vaccine (IPV) in combination with OPV. We aimed to evaluate the acceptability and effect on immunisation coverage of an integrated strategy for community engagement and maternal and child health immunisation campaigns in insecure and conflict-affected polio-endemic districts of Pakistan. Methods We did a community-based three-arm cluster randomised trial in healthy children aged 1 month to 5 years that resided within the study sites in three districts of Pakistan at high risk of polio. Clusters were randomly assigned by a computer algorithm using restricted randomisation in blocks of 20 by an external statistician (1:1:1) to receive routine polio programme activities (control, arm A), additional interventions with community outreach and mobilisation using an enhanced communication package and provision of short-term preventive maternal and child health services and routine immunisation (health camps), including OPV (arm B), or all interventions of arm B with additional provision of IPV delivered at the maternal and child health camps (arm C). An independent team conducted surveys at baseline, endline, and after each round of supplementary immunisation activity for acceptability and effect. The primary outcome measures for the study were coverage of OPV, IPV, and routine extended programme on immunisation vaccines and changes in the proportion of unvaccinated and fully vaccinated children. This trial is registered with ClinicalTrials.gov , number NCT01908114. Findings Between June 4, 2013, and May 31, 2014, 387 clusters were randomised (131 to arm A, 127 to arm B, and 129 to arm C). At baseline, 28 760 children younger than 5 years were recorded in arm A, 30 098 in arm B, and 29 126 in arm C. 359 clusters remained in the trial until the end (116 in arm A, 120 in arm B, and 123 in arm C; with 23 334 children younger than 5 years in arm A, 26 110 in arm B, and 25 745 in arm C). The estimated OPV coverage was 75% in arm A compared with 82% in arm B (difference vs arm A 6·6%; 95% CI 4·8–8·3) and 84% in arm C (8·5%, 6·8–10·1; overall p<0·0001). The mean proportion of routine vaccine doses received by children younger than 24 months of age was 43% in arm A, 52% in arm B (9%, 7–11) and 54% in arm C (11%, 9–13; overall p<0·0001). No serious adverse events requiring hospitalisation were reported after immunisation. Interpretation Despite the challenges associated with the polio end-game in high-risk, conflict-affected areas of Pakistan, a strategy of community mobilisation and targeted community-based health and immunisation camps during polio immunisation campaigns was successful in increasing vaccine coverage, including polio vaccine coverage. Funding Bill & Melinda Gates Foundation.
Summary Background Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all ...these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. Methods For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. Findings Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12). Interpretation Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality. Funding Bill & Melinda Gates Foundation.
Summary Background Trend data for causes of child death are crucial to inform priorities for improving child survival by and beyond 2015. We report child mortality by cause estimates in 2000–13, and ...cause-specific mortality scenarios to 2030 and 2035. Methods We estimated the distributions of causes of child mortality separately for neonates and children aged 1–59 months. To generate cause-specific mortality fractions, we included new vital registration and verbal autopsy data. We used vital registration data in countries with adequate registration systems. We applied vital registration-based multicause models for countries with low under-5 mortality but inadequate vital registration, and updated verbal autopsy-based multicause models for high mortality countries. We used updated numbers of child deaths to derive numbers of deaths by causes. We applied two scenarios to derive cause-specific mortality in 2030 and 2035. Findings Of the 6·3 million children who died before age 5 years in 2013, 51·8% (3·257 million) died of infectious causes and 44% (2·761 million) died in the neonatal period. The three leading causes are preterm birth complications (0·965 million 15·4%, uncertainty range (UR) 9·8−24·5; UR 0·615–1·537 million), pneumonia (0·935 million 14·9%, 13·0–16·8; 0·817–1·057 million), and intrapartum-related complications (0·662 million 10·5%, 6·7–16·8; 0·421–1·054 million). Reductions in pneumonia, diarrhoea, and measles collectively were responsible for half of the 3·6 million fewer deaths recorded in 2013 versus 2000. Causes with the slowest progress were congenital, preterm, neonatal sepsis, injury, and other causes. If present trends continue, 4·4 million children younger than 5 years will still die in 2030. Furthermore, sub-Saharan Africa will have 33% of the births and 60% of the deaths in 2030, compared with 25% and 50% in 2013, respectively. Interpretation Our projection results provide concrete examples of how the distribution of child causes of deaths could look in 15–20 years to inform priority setting in the post-2015 era. More evidence is needed about shifts in timing, causes, and places of under-5 deaths to inform child survival agendas by and beyond 2015, to end preventable child deaths in a generation, and to count and account for every newborn and every child. Funding Bill & Melinda Gates Foundation.
Summary Background Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0–59 days) according to the presence of ...one or more clinical signs. The recommended treatment is hospital admission with 7–10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify effective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible. Methods We did this randomised, open-label, equivalence trial in four urban hospitals and one rural field site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar efficacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratified randomisation by study site and age (<7 days or 7–59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov , number NCT00844337. Findings Between July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfilled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk difference −1·5%, 95% CI −4·3 to 1·3) and 64 (8%) of 790 infants in group C (−1·7%, −4·5 to 1·1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 2% infants in group A vs 13 2% infants in group B and 10 1% infants in group C). Interpretation Our results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable. Funding USAID , WHO , Save the Children-US , and Bill & Melinda Gates Foundation.
Summary Background Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in ...children younger than 5 years. Methods We used multicause proportionate mortality models to estimate deaths in neonates aged 0–27 days and children aged 1–59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world. Findings Of the estimated 8·795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5·970 million), with the largest percentages due to pneumonia (18%, 1·575 million, uncertainty range UR 1·046 million–1·874 million), diarrhoea (15%, 1·336 million, 0·822 million–2·004 million), and malaria (8%, 0·732 million, 0·601 million–0·851 million). 41% (3·575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1·033 million, UR 0·717 million–1·216 million), birth asphyxia (9%, 0·814 million, 0·563 million–0·997 million), sepsis (6%, 0·521 million, 0·356 million–0·735 million), and pneumonia (4%, 0·386 million, 0·264 million–0·545 million). 49% (4·294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China. Interpretation These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions. Funding WHO, UNICEF, and Bill & Melinda Gates Foundation.
Summary Background Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in ...2010 with time trends since 2000. Methods Updated total numbers of deaths in children aged 0–27 days and 1–59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1–59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates. Findings Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range UR 0·916–1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610–0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252–0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977–1·176), diarrhoea (9·9%; 0·751 million, 0·538–1·031), and malaria (7·4%; 0·564 million, 0·432–0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million 0·339–0·547, 0·363 million 0·283–0·419, and 0·359 million 0·215–0·476, respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4. Interpretation Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010–15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates. Funding The Bill & Melinda Gates Foundation.
Summary Background Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and ...Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates. Methods We searched Medline, Embase, and Wholis databases for studies on invasive early-onset (day 0–6) and late-onset (day 7–89) group B streptococcal disease. Eligible studies were those that described incidence, deaths, or serotypes. We also reviewed reference lists and contacted experts to seek unpublished data and data missed by our search. Random effects meta-analysis was used to pool data. Findings 74 studies met the inclusion criteria; 56 studies reported incidence, 29 case fatality, and 19 serotype distribution. An additional search for studies that reported serotype distribution from Jan 1, 1980, yielded a total of 38 articles. Only five low-income countries were represented in the review and contributed 5% weight to the meta-analysis. 47 (69%) studies reported use of any intrapartum antibiotic prophylaxis. Substantial heterogeneity existed between studies. Mean incidence of group B streptococcus in infants aged 0–89 days was 0·53 per 1000 livebirths (95% CI 0·44–0·62) and the mean case fatality ratio was 9·6% (95% CI 7·5–11·8). Incidence of early-onset group B streptococcus (0·43 per 1000 livebirths 95% CI 0·37–0·49) and case fatality (12·1%, 6·2–18·3) were two-times higher than late-onset disease. Serotype III (48·9%) was the most frequently identified serotype in all regions with available data followed by serotypes Ia (22·9%), Ib (7·0%), II (6·2%), and V (9·1%). Studies that reported use of any intrapartum antibiotic prophylaxis were associated with lower incidence of early-onset group B streptococcus (0·23 per 1000 livebirths 95% CI 0·13–0·59) than studies in which patients did not use prophylaxis (0·75 per 1000 livebirths 0·58–0·89). Interpretation More high-quality studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease. Funding Child Epidemiology Reference Group (CHERG), WHO.
Summary We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote ...complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0·25 (95% CI 0·01–0·49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0·41 (0·05–0·76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0·45, 0·32–0·62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2·93–21·07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0·84, 0·74–0·95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.
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