Infant and child mortality in Pakistan--some trends and differentials

Data from reproductive histories collected in the Population, Labor Force and Migration Survey (PLM) of 1979 are used to analyze trends and differentials in infant and child mortality in Pakistan. Comparisons with the Pakistan Fertility Survey (PFS) findings are also presented. The main concern is to provide from the latest national data, the PLM, direct measures of infant and child mortality and to demonstrate the relatively static and low chances of survival for children in Pakistan. The apparent trends from the PLM and the PFS are similar and seem to confirm that infant and childhood mortality has ceased to decline, at least rapidly, since 1965-69. Neonatal mortality is higher at levels of 70-85 deaths/1000 compared to postneonatal mortality of 40-60 deaths/1000. Improvements in neonatal rates from 1950 until 1975 are only approximately 1/2 of those for postneonatal rates for that period. The relationship between maternal age and mortality in the PLM data confirms that children of youngest mothers experienced the highest rates of infant mortality; mortality is again higher for children of oldest mothers aged 35 and above. The pattern of mortality in the 2 surveys is similar except that in the PFS there was little variation among births higher than 5th order. Sex differentials in mortality are very clear in both surveys. Boys have higher chances of dying in the 1st month of life but then the probability of their surviving from age 1 to 5 years is higher, reflecting the behavioral preference for the male sex in this society. The data also demonstrate an almost monotonic decline in infant and child mortality associated with longer birth intervals. Childhood mortality shows a less clear association with preceding birth interval than does infant mortality. While neonatal mortality is much higher in rural than in urban areas, there are negligible differences in the postneonatal rate. The urban-rural differential continues into childhood, reflecting lower health care and nutrition of children in rural areas. The data confirm the importance of parental education, particularly that of mothers, as a contributor to the health and mortality of infants. Mortality between age 1 and 5 years for children of the rural educated group is lower than that for the urban uneducated indicating the strong influence that education of mothers can have in preventing child loss. The combined evidence from the PFS and PLM data stresses the importance of improving health facilities in the rural areas, in aneffort to reduce the differences in mortality by area of residence. The data from both surveys also suggest the need to restrict motherhood to between the ages of 20 and 34, when obstetrical and health risks are minimal, and indicate the definite advantages of increasing the spacing between children.     

The Serotype Distribution among Healthy Carriers before Vaccination Is Essential for Predicting the Impact of Pneumococcal Conjugate Vaccine on Invasive Disease

Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD.     

Childhood respiratory infection and adult chronic bronchitis in England and Wales.

The high mortality from chronic bronchitis in England and Wales and the excess of urban over rural mortality are unexplained. On dividing England and Wales into 212 local authority areas a strong geographical relation was found between death rates from chronic bronchitis and emphysema in 1959-78 and infant mortality from bronchitis and pneumonia during 1921-5. It was concluded that this relation provided strong evidence of a direct casual link between acute lower respiratory infection in early childhood and chronic bronchitis in adult life. Regression analysis suggested that infection in early childhood had a greater influence than cigarette smoking in determining the geographical distribution of chronic bronchitis. National time trends reflected the influence of both factors. Chronic air pollution in adult life may be less important a cause of chronic bronchitis than previously supposed.     

Early childhood stress and adult age mortality--a study of dental enamel hypoplasia in the medieval Danish village of Tirup

This study explores how linear enamel hypoplasia (LEH) affects mortality in the village of Tirup (A.D. 1150-1350), Denmark. Data consist of information on 583 skeletons aged 1 year or more. Three partly overlapping subsamples were defined. (1) 104 skeletons of young children aged 1-6 years and 120 skeletons of adults giving information on LEH. (2) 458 skeletons aged 6 years or more. (3) 109 adult skeletons (aged 20 years or more) that provided transition analysis age estimates, sex assessments, and LEH information. Of the 109 skeletons in Subsample 3, 60 had no and 49 had at least one LEH. In Subsample 1, it was found that the case fatality rate for episodes potentially leading to LEH dropped from over 0.5 in 1-year olds to around 0.1 in 3-5-year olds. Only models with heterogeneity of frailty could describe late childhood and adolescent mortality. Further, it was shown that only a model with continuously varying frailty preserved heterogeneity to adulthood. Among young adult females and males in all adult ages, people with LEH experienced a higher mortality than people without it. Among males, the mortality rate ratio (MRR) was 2.28. The analyses indicate that the MRR gives an unbiased estimate for the extra risk of dying for adult males with LEH. The values of the case fatality rates for young children might be slightly biased upward because of a higher than average number of older children and adolescents dying with LEH.     

Quantifying Spatial Disparities in Neonatal Mortality Using a Structured Additive Regression Model

Background

Neonatal mortality contributes a large proportion towards early childhood mortality in developing countries, with considerable geographical variation at small areas within countries.

Methods

A geo-additive logistic regression model is proposed for quantifying small-scale geographical variation in neonatal mortality, and to estimate risk factors of neonatal mortality. Random effects are introduced to capture spatial correlation and heterogeneity. The spatial correlation can be modelled using the Markov random fields (MRF) when data is aggregated, while the two dimensional P-splines apply when exact locations are available, whereas the unstructured spatial effects are assigned an independent Gaussian prior. Socio-economic and bio-demographic factors which may affect the risk of neonatal mortality are simultaneously estimated as fixed effects and as nonlinear effects for continuous covariates. The smooth effects of continuous covariates are modelled by second-order random walk priors. Modelling and inference use the empirical Bayesian approach via penalized likelihood technique. The methodology is applied to analyse the likelihood of neonatal deaths, using data from the 2000 Malawi demographic and health survey. The spatial effects are quantified through MRF and two dimensional P-splines priors.

Results

Findings indicate that both fixed and spatial effects are associated with neonatal mortality.

Conclusions

Our study, therefore, suggests that the challenge to reduce neonatal mortality goes beyond addressing individual factors, but also require to understanding unmeasured covariates for potential effective interventions.     

HUMAN ACTUARIAL AGING INCREASES FASTER WHEN BACKGROUND DEATH RATES ARE LOWER: A CONSEQUENCE OF DIFFERENTIAL HETEROGENEITY?

Many analyses of human populations have found that age-specific mortality rates increase faster across most of adulthood when overall mortality levels decline. This contradicts the relationship often expected from Williams' classic hypothesis about the effects of natural selection on the evolution of senescence. More likely, much of the within-species difference in actuarial aging is not due to variation in senescence, but to the strength of filters on the heterogeneity of frailty in older survivors. A challenge to this differential frailty hypothesis was recently posed by an analysis of life tables from historical European populations and traditional societies that reported variation in actuarial aging consistent with Williams' hypothesis after all. To investigate the challenge, we reconsidered those cases and aging measures. Here we show that the discrepancy depends on Ricklefs' aging rate measure, ω, which decreases as mortality levels drop because it is an index of mortality level itself, not the rate of increase in mortality with age. We also show unappreciated correspondence among the parameters of Gompertz-Makeham and Weibull survival models. Finally, we compare the relationships among mortality parameters of the traditional societies and the historical series, providing further suggestive evidence that differential heterogeneity has strong effects on actuarial aging.     

An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings

Childhood obesity is a global burden affecting millions of children worldwide. It is well-known that the adiposity profile in children is critical for future occurrence of diseases. As a multifactorial disease, obesity is associated with genetic and environmental factors. Epigenetic mechanisms link the plethora of environmental clues to a given phenotype. DNA methylation is the most studied epigenetic mark and its importance in several diseases was acknowledged. In childhood obesity, specifically, the studies show a consistent association between adiposity and methylation at the gene and genome-wide scales. The relationship between DNA methylation and childhood obesity has been proved strong for some genes and pathways. However, the studies are heterogeneous in their design, methodologies, and results. The aim of this review is to discuss this heterogeneity and point out some aspects that should be considered in future studies to clarify the role of DNA methylation in childhood obesity.     

Levels and differentials in childhood mortality in South Africa, 1977-1998

This study uses the 1996 Census and the 1998 Demographic and Health Survey (DHS) to investigate the level of and trend in infant and child mortality and their covariates in South Africa. Census estimates of childhood mortality are higher than those from the DHS. Analysis suggests that the former overestimate mortality while the latter are probably slightly too low. Both inquiries document a reversal of the trend toward lower mortality in the 1990s. Under-five mortality increased by about a third during the five years up to early 1998. By then the infant mortality rate was about 55 per 1000 and under-five mortality 72 per 1000. Other factors may explain the tapering off of the decline in mortality after the late 1980s but AIDS deaths account for its increase. Inequalities in childhood mortality between population groups, rooted in past discriminatory apartheid policies, shrank between the late-1970s and mid-1990s. However, they remain substantial and are largely unaccounted for by province, metropolitan residence and inter-group differences in mothers' education. The HIV/AIDS epidemic is likely to offset the beneficial impact of post-apartheid pro-poor policies and may exacerbate racial differences in childhood mortality in South Africa. There is an urgent need to improve the routine collection of statistics to monitor child mortality so as to assess progress towards the Millennium Development Goals and track inequalities.     

Heterogeneity in Individual Mortality Risk and Its Importance for Evolutionary Studies of Senescence

Mortality was simulated under the assumption of heterogeneity in individual age-specific mortality risk. Heterogeneity was modeled by assigning each individual its own Gompertz mortality function. Means and variances of the Gompertz intercept and slope parameters were based on published data for Drosophila melanogaster. Simulations of large cohorts reproduced mortality plateaus similar to those observed for actual cohorts of flies. Catastrophic late-age mortality was not observed except when heterogeneity was very low and rates of senescence were very high. A second set of simulations was designed to mimic experiments that have investigated age-specific patterns of genetic variance in mortality rates. Within-genotype heterogeneity in mortality risk resulted in a decline in genetic variance of mortality rates at old ages. That result suggests that the decline in genetic variance at old ages that has been observed in some experiments is an artifact of heterogeneity. Mortality rate plateaus, decrease in genetic variance of mortality rates at old ages, and absence of catastrophic late-age mortality all appear to contradict predictions of the evolutionary theory of senescence. Heterogeneity in mortality risk may explain those contradictions.     

Neighbourhood effects influence drought‐induced mortality of savanna trees in Australia

Questions: The following hypotheses of neighbourhood effects on drought‐induced mortality are evaluated: (A) drought‐induced stem death is randomly distributed in space, (B) stems are predisposed to drought‐induced death through negative density‐dependent effects and (C) stems are predisposed to drought‐induced death due to local deficits in plant available resources. Location: Central Queensland, Australia. Methods: Recent mass mortality of woody stems was surveyed and mapped in three 1.21‐ha quadrats within Eucalyptus melanophloia‐dominated savanna. A multi‐faceted analytical approach was adopted including spatial pattern analyses, two logistic regressions of neighbourhood density effects on survival and spatial autocorrelation analyses of model residuals. Results: Mortality was concentrated in stems ≤15‐cm diameter at breast height (DBH). Survival was aggregated or random in quadrats 1 and 3 and random o regular in quadrat 2. Small neighbour density had a negative effect on survival in all quadrats. In addition, the second model identified a positive relationship between survival and living neighbour density in quadrat 3 (indicating a resource patch effect), but a negative relationship in quadrat 2 (density effect). Analysis of model residuals showed that neighbour density explained mortality equally well across quadrat 2, but not across quadrats 1 and 3. Conclusions: There was evidence in support of hypotheses B (neighbour density) and C (resource heterogeneity). We found strong support for an interaction between microsite quality and neighbourhood stem densities, and suggest that this interaction is driven by plant available water.     

How Evolving Heterogeneity Distributions of Resource Allocation Strategies Shape Mortality Patterns

It is well established that individuals age differently. Yet the nature of these inter-individual differences is still largely unknown. For humans, two main hypotheses have been recently formulated: individuals may experience differences in aging rate or aging timing. This issue is central because it directly influences predictions for human lifespan and provides strong insights into the biological determinants of aging. In this article, we propose a model which lets population heterogeneity emerge from an evolutionary algorithm. We find that whether individuals differ in (i) aging rate or (ii) timing leads to different emerging population heterogeneity. Yet, in both cases, the same mortality patterns are observed at the population level. These patterns qualitatively reproduce those of yeasts, flies, worms and humans. Such findings, supported by an extensive parameter exploration, suggest that mortality patterns across species and their potential shapes belong to a limited and robust set of possible curves. In addition, we use our model to shed light on the notion of subpopulations, link population heterogeneity with the experimental results of stress induction experiments and provide predictions about the expected mortality patterns. As biology is moving towards the study of the distribution of individual-based measures, the model and framework we propose here paves the way for evolutionary interpretations of empirical and experimental data linking the individual level to the population level.     

Socioeconomic determinants of age at first marriage in Bangladesh

Using data from the 1976 Bangladesh Fertility Survey, multiple classification analysis was used to evaluate the effect of socioeconomic factors on age at 1st marriage. The independent variables considered were education, childhood and current residence, religion, work status before marriage, and husband's childhood residence, education, and occupation. Analysis was carried out for the total sample as well as for 3 birth cohorts of approximately equal size: 1) those born before 1940, 2) those born between 1940-50, and 3) those born after 1950. Of all the included variables, women's education has the strongest influence on the variation of age at 1st marriage. For all ever-married women, the mean age at marriage for women with primary education is 13.4 years, 0.9 years higher than for women with no education (12.5 years), and 1.2 years lower than for women with a high school education or beyond (14.6 years). Difference in means for cohorts indicate a gradually increasing influence of education on people's decision in marriage. Husband's education does not appear to be as important. Childhood residence has, directly and indirectly, a strong influence in marriage age. Among other factors, women's premarital work participation, as well as region and husband's occupation, are important. Since women's education, childhood residence, and work participation are the strongest socioeconomic variables affecting marriage age, the modernizing influences of education, urbanization, and female work participation should have an effect on the marriage pattern; this effect is consistent with that observed in other societies.     

Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop

We have used cryoelectron tomography of vitreous-ice-embedded HIV-1 virions to compare the envelope (Env) spikes of a wild-type strain with those of a mutant strain in which the V1/V2 loop has been deleted. Deletion of V1/V2 results in a spike with far more structural heterogeneity than is observed in the wild type, likely reflecting greatly enhanced gp120 protomer flexibility. A major difference between the two forms is a pronounced loss of mass from the "peak" of the native Env spike. The apparent loss of contact among three gp120 protomers likely accounts for the more open structure, heterogeneity in configuration, and previous observations that broadly neutralizing epitopes and reactive sites on other structural elements are more exposed in such constructs.     

Childhood cancer mortality in Australia

Aim: To determine current rates of childhood cancer mortality at a national level for Australia and to evaluate recent trends. Methods: Using population-based data from the Australian Paediatric Cancer Registry, we calculated cancer-related mortality counts and rates for the 3-year period 2006-2008 and trends between 1998 and 2008 by sex, age group, and cause of death (defined according to the International Classification of Childhood Cancers, third edition). Rates were directly age-standardised to the 2000 World Standard Population, and linear regression was used to determine the magnitude and significance of trends. The standardised mortality ratio for non-cancer deaths among children with cancer was also estimated. Results: A total of 282 children (23 per million per year) died from cancer in Australia between 2006 and 2008. Large decreases were observed in cancer mortality rates over the study period, particularly for boys (-5.5% per year; p<0.001), children aged 10-14 years old (-5.5% per year; p=0.001), and leukaemia patients (-9.4% per year; p<0.001). However, there was no significant change in mortality due to tumours of the central nervous system. Children with cancer were twice as likely to die from non-cancer causes compared to other children (SMR=2.06; p=0.001). Conclusions: While ongoing improvements in childhood cancer mortality in Australia are generally encouraging, of concern is the lack of a corresponding decrease in mortality among children with certain types of tumours of the central nervous system during the past decade. The results also highlight the need for intensive monitoring of childhood cancer patients for other serious diseases that may subsequently arise.     

Ethnic differentials in early childhood mortality in Nepal

This paper investigates the association of early childhood mortality (between birth and second birthday) with ethnicity in Nepal, based on data from the 1976 Nepal Fertility Survey, which was part of the World Fertility Survey. The approach is through a series of hazard models, which incorporate ethnicity, year of birth, mother's illiteracy, father's illiteracy, rural-urban residence, region, sex, maternal age, survival of previous birth, previous birth interval, and breast-feeding as covariates. Ethnic differentials in early childhood mortality are not explained by the other socioeconomic and demographic covariates, except for a modest effect of illiteracy, but the remaining covariates explain a great deal of variability in early childhood mortality itself. Analysis using an improved specification of breast-feeding as an age-varying covariate indicates, on average, that breast-feeding, relative to not breast-feeding, reduces age-specific mortality risks during the first 2 years of life by 76%, a very large effect.     

Ecological Load and Balancing Selection in Circumboreal Barnacles

Acorn barnacle adults experience environmental heterogeneity at various spatial scales of their circumboreal habitat, raising the question of how adaptation to high environmental variability is maintained in the face of strong juvenile dispersal and mortality. Here, we show that 4% of genes in the barnacle genome experience balancing selection across the entire range of the species. Many of these genes harbor mutations maintained across 2 My of evolution between the Pacific and Atlantic oceans. These genes are involved in ion regulation, pain reception, and heat tolerance, functions which are essential in highly variable ecosystems. The data also reveal complex population structure within and between basins, driven by the trans-Arctic interchange and the last glaciation. Divergence between Atlantic and Pacific populations is high, foreshadowing the onset of allopatric speciation, and suggesting that balancing selection is strong enough to maintain functional variation for millions of years in the face of complex demography.     

Health inequalities: new concerns about the children of single mothers.

OBJECTIVES--To show that the exclusion from conventional class based analyses of child mortality of children whose parents are classified as "unoccupied" produces a misleading picture of health inequalities. DESIGN--Reanalysis of data published in the childhood supplement of the registrar general''s decennial supplement on occupational mortality in England and Wales, which compares numerator data for registrations of deaths in children over the age of 1 but below their 16th birthday in 1979, 1980, 1982, and 1983 with data about children aged 1-15 who were enumerated at the 1981 census. RESULTS--Parents who are classified as "unoccupied" largely consist of economically inactive single mothers. Their children are estimated to represent 89% of the 614,000 aged 1-15 classified as "unoccupied" in the childhood supplement. They have the worst mortality record of all social groups--an age specific death rate of 68.8/100,000 a year, 42% worse than in social class V (48.4/100,000) and worse than that of social class I (22.8) by a factor of 3. At older ages (10-15 years) these children have a relative risk of death of 4.14 relative to classes I and II; the risk is 2.58 in children 0-4 and 2.56 in those 5-9. Relative risks of child mortality in social classes I and II in comparison to classes IV and V suggests a progressive shallowing from 2.08 at ages 1-4 to 1.37 at ages 10-15. When unoccupied parents were combined with classes IV and V and compared with classes I and II, however, inequalities seemed to be pervasive throughout childhood; the relative risks were 2.21 for those aged 1-4 and 1.98 for those aged 10-15. CONCLUSION--Children classified as unoccupied are almost certainly living in poverty as well as experiencing relatively high risks of mortality. Class based analyses which exclude them therefore produce a misleading picture of inequalities in child health. The implications for health policy are profound. Strategies to promote the nation''s health should acknowledge the importance of material and social deprivation more explicitly.     

Anemia and childhood mortality: latitudinal patterning along the coast of pre-Columbian Peru

Hrdlicka ([1914] Smithson. Inst. Misc. Collect. 61:1-69) reported that pre-Columbian skeletal material from the coastal lowland Andean region exhibited a high frequency of porotic hyperostosis, a pathological condition of bone that generally is thought to indicate childhood anemia. While subsequent studies tended to reinforce this conclusion, factors implicated in the condition have yet to be fully explored in the region as a whole. This study explores regional and intravalley variation as one step in establishing biocultural variables that increase the apparent risk of childhood anemia. The study sample includes 1,465 individuals: 512 from Peruvian collections housed at the Field Museum of Natural History, and 953 from systematically excavated contexts from Moquegua, Peru. Environmental stressors, such as parasites and disease, rather than specific dietary practices were found to be more likely associated with childhood anemia in these coastal Andean samples. The study supports cribra orbitalia as an earlier expression of porotic hyperostosis and suggests that porotic hyperostosis, as recorded here, cannot be easily dismissed as a result of cranial shape modification. No clear temporal patterns were observed. Finally, the study establishes that comparing data for children and adults can reveal the relative association between childhood anemia and mortality. Childhood mortality associated with anemia was elevated where the presence of tuberculosis or tuberculosis-like conditions was more common and the presence of water-borne pathogens was negligible. In contrast, those buried at lower altitudes, closer to the coast, and consuming mainly marine resources were less likely to die in childhood with anemia than in the other contexts studied.     

Sex differentials in infant and child mortality in Korea

This paper reports on a study of infant and child mortality in the Republic of Korea, a country known for a strong son preference, using the 1974 World Fertility Survey data. When the age-specific probabilities of dying for ages 0 to 5 are compared for male and female children, an unusual pattern of relatively high female mortality is observed. The higher female mortality is more pronounced during childhood than during infancy. Multivariate analysis of life tables, using a hazard model, shows that covariates influencing the mortality at young ages differ for male and female children and suggests that male and female children receive unequal care by their parents. The analysis also reveals different patterns of interaction between infant and child mortality and mother's fertility control behavior depending on the sex of the child.     

H2 histaminic receptors in rat cerebral cortex. 2. Inhibition of [3H]histamine by H2 antagonists

Sites labeled by [3H]histamine in homogenates of rat cerebral cortex reveal a pharmacological specificity typical of H2 receptors. Fourteen H2 antagonists inhibit the specific binding of the radioligand to the same level; Hill coefficients are near or equal to one for five compounds and markedly lower for nine. The binding patterns of individual antagonists (A) are well described by the empirical expression Y = F1K1/(K1 + [A]) + F2K2/(K2 + [A]), in which F1 and F2 sum to 1; F2 is 0 for those drugs that reveal a Hill coefficient of 1. Concentrations of A that reduce specific binding by 50% (IC50) correlate well (r = 0.991; P less than 0.00001) and show good numerical agreement with potencies reported for inhibition of the response to histamine in H2-mediated systems. The correlation is poorer when IC50 is replaced by either K1 (r = 0.973) or K2 (r = 0.921) for those antagonists that reveal both; the antihistaminic activity of the drug thus appears not to be associated preferentially with one or other class of sites. Since F2 varies from 0.16 to 0.60 among those antagonists that discern heterogeneity, the antagonist appears to determine the distribution of sites between the two classes. Moreover, a correlation among antagonists between values of K1 and K2 (r = 0.975; P = 0.00001) suggests that the apparent heterogeneity reflects different conformers within an otherwise homogeneous population. H2 antagonists appear to be noncompetitive with respect to each other and to the radioligand: one antagonist has relatively little effect on the values of K1, K2, and F2 revealed by another; also, estimates of K1 and K2 are independent of the concentration of [3H]histamine between 1.3 and 10 nM, although the radioligand exhibits an apparent dissociation constant of 3.9 nM [Steinberg, G. H., Eppel, J. G., Kandel, M., Kandel, S. I., & Wells, J. W. (1985) Biochemistry (preceding paper in this issue)].