Why Are Babies Dying in the First Month after Birth? A 7-Year Study of Neonatal Mortality in Northern Ghana

Objectives

To determine the neonatal mortality rate in the Kassena-Nankana District (KND) of northern Ghana, and to identify the leading causes and timing of neonatal deaths.

Methods

The KND falls within the Navrongo Health Research Centre’s Health and Demographic Surveillance System (HDSS), which uses trained field workers to gather and update health and demographic information from community members every four months. We utilized HDSS data from 2003–2009 to examine patterns of neonatal mortality.

Results

A total of 17,751 live births between January 2003 and December 2009 were recorded, including 424 neonatal deaths 64.8%(275) of neonatal deaths occurred in the first week of life. The overall neonatal mortality rate was 24 per 1000 live births (95%CI 22 to 26) and early neonatal mortality rate was 16 per 1000 live births (95% CI 14 to 17). Neonatal mortality rates decreased over the period from 26 per 1000 live births in 2003 to 19 per 1000 live births in 2009. In all, 32%(137) of the neonatal deaths were from infections, 21%(88) from birth injury and asphyxia and 18%(76) from prematurity, making these three the leading causes of neonatal deaths in the area. Birth injury and asphyxia (31%) and prematurity (26%) were the leading causes of early neonatal deaths, while infection accounted for 59% of late neonatal deaths. Nearly 46% of all neonatal deaths occurred during the first three postnatal days. In multivariate analysis, multiple births, gestational age <32 weeks and first pregnancies conferred the highest odds of neonatal deaths.

Conclusions

Neonatal mortality rates are declining in rural northern Ghana, with majority of deaths occurring within the first week of life. This has major policy, programmatic and research implications. Further research is needed to better understand the social, cultural, and logistical factors that drive high mortality in the early days following delivery.     

Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats

Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.     

Association between Gestational Weight Gain and Postpartum Diabetes: Evidence from a Community Based Large Cohort Study

We have investigated the prospective association between excess gestational weight gain (GWG) and development of diabetes by 21 years post-partum using a community-based large prospective cohort study in Brisbane, Australia. There were 3386 mothers for whom complete data were available on GWG, pre-pregnancy BMI and self-reported diabetes 21 years post-partum. We used The Institute of Medicine (IOM) definition to categorize GWG as inadequate, adequate and excessive. We found 839 (25.78%) mothers gained inadequate weight, 1,353 (39.96%) had adequate weight gain and 1,194 (35.26%) had gained excessive weight during pregnancy. At 21 years post-partum, 8.40% of mothers self-reported a diagnosis of diabetes made by their doctor. In the age adjusted model, we found mothers who gained excess weight during pregnancy were 1.47(1.11,1.94) times more likely to experience diabetes at 21 years post-partum compared to the mothers who gained adequate weight. This association was not explained by the potential confounders including maternal age, parity, education, race, smoking, TV watching and exercise. However, this association was mediated by the current BMI. There was no association for the women who had normal BMI before pregnancy and gained excess weight during pregnancy. The findings of this study suggest that women who gain excess weight during pregnancy are at greater risk of being diagnosed with diabetes in later life. This relationship is likely mediated through the pathway of post-partum weight-retention and obesity. This study adds evidence to the argument that excessive GWG during pregnancy for overweight mothers has long term maternal health implications.     

Techniques for Processing Eyes Implanted With a Retinal Prosthesis for Localized Histopathological Analysis

With the recent development of retinal prostheses, it is important to develop reliable techniques for assessing the safety of these devices in preclinical studies. However, the standard fixation, preparation, and automated histology procedures are not ideal. Here we describe new procedures for evaluating the health of the retina directly adjacent to an implant. Retinal prostheses feature electrode arrays in contact with eye tissue. Previous methods have not been able to spatially localize the ocular tissue adjacent to individual electrodes within the array. In addition, standard histological processing often results in gross artifactual detachment of the retinal layers when assessing implanted eyes. Consequently, it has been difficult to assess localized damage, if present, caused by implantation and stimulation of an implanted electrode array. Therefore, we developed a method for identifying and localizing the ocular tissue adjacent to implanted electrodes using a (color-coded) dye marking scheme, and we modified an eye fixation technique to minimize artifactual retinal detachment. This method also rendered the sclera translucent, enabling localization of individual electrodes and specific parts of an implant. Finally, we used a matched control to increase the power of the histopathological assessments. In summary, this method enables reliable and efficient discrimination and assessment of the retinal cytoarchitecture in an implanted eye.     

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants'' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one''s own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one''s own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.     

A two‐dimensional proteome map of the aflatoxigenic fungus Aspergillus flavus

The filamentous fungus Aspergillus flavus is an opportunistic soil‐borne pathogen that produces aflatoxins, the most potent naturally occurring carcinogenic compounds known. This work represents the first gel‐based profiling analysis of A. flavus proteome and establishes a 2D proteome map. Using 2DE and MALDI‐TOF‐MS/MS, we identified 538 mycelial proteins of the aflatoxigenic strain NRRL 3357, the majority of which were functionally annotated as related to various cellular metabolic and biosynthetic processes. Additionally, a few enzymes from the aflatoxin synthesis pathway were also identified.     

Potential fluid mechanic pathways of platelet activation

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.     

Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling Based on Demographics,Excess Mortality,and Interventions

Background

The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.

Methods and Findings

First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400–398,800) in 2010 to 404,200 (CI: 242,500–657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900–106,100]; 2050: 140,800 [CI: 95,500–200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600–48,800]; 2050: 44,700 [CI: 27,100–70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700–59,100]; 2050: 33,900 [CI: 15,900–64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800–6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800–14,232,700) newborns with SCA globally, 85% (CI: 81%–88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.

Conclusions

Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors'' Summary     

Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans

Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage.