Early Infant Mortality Research Articles

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) diagnosed in children and adolescents

BackgroundAnomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially fatal congenital coronary anomaly associated with early infant mortality and sudden adult death. By the development or lack of coronary collateral, it can be classified as infantile or adult type. However, even with the compensatory mechanism in adult patients, there is an estimated 80 to 90% incidence of sudden death at the mean age of 35 years.MethodsWe enrolled 9 patients with ALCAPA within the age group 5 to 16 years.ResultsOnly one patient developed symptoms (apsychia), whereas other patients were asymptomatic, and there was no evident left ventricular dysfunction found in any of the cases.ConclusionWith the development of imaging techniques, asymptomatic adult-type ALCAPA patients could be identified and diagnosed in childhood or adolescence. As a potential cause of sudden death, ALCAPA should be surgically repaired soon after the diagnosis.

The Effect of Maternal Multiple Micronutrient Supplementation on Female Early Infant Mortality Is Fully Mediated by Increased Gestation Duration and Intrauterine Growth

Background:Maternal micronutrient supplementation in pregnancy (MMS) has been shown to improve birth weight among infants in low- and middle-income countries. Recent evidence suggests that the survival benefits of MMS are greater for female infants compared to male infants, but the mechanisms leading to differential effects remain unclear. Objective:The objective of this study was to examine the potential mechanisms through which MMS acts on infant mortality among Tanzanian infants. Methods:We used data collected from pregnant women and newborns in a randomized, double-blind, placebo-controlled trial of MMS conducted in Tanzania to examine mediators of the effect of MMS on 6-wk infant mortality (NCT00197548). Causal mediation analyses with the counterfactual approach were conducted to assess the contributions of MMS on survival via their effects on birth weight, gestational age, weight-for-gestational age, and the joint effect of gestational age and weight-for-gestational age. The weighting method allowed for interaction between gestational age and weight-for-gestational age. Results:Among 7486 newborns, the effect of MMS on 6-wk survival was fully mediated (100%) through the joint effect of gestational age and weight-for-gestational age. MMS was also found to have a significant natural indirect effect through increased birth weight (P-value < 0.001) that explained 75% of the total effect on 6-wk mortality. When analyses were stratified by sex, changes in gestational age and weight-for-gestational age fully mediated the mortality effect among female infants (n = 3570), but these mediators only explained 34% of the effect among males (n = 3833). Conclusions:The potential sex-specific effects of MMS on mortality may be a result of differences in mechanisms related to birth outcomes. In the context of the Tanzanian trial, the observed effect of MMS on 6-wk mortality for female infants was entirely mediated by increased gestation duration and improved intrauterine growth, while these mechanisms did not appear to be major contributors among male infants.

Adult-Type Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery Syndrome

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare cardiac malformation accounting for 0.25% of congenital heart diseases with reported incidence of 1 in 300,000 live births. It frequently occurs as an isolated defect and is associated with early infant mortality and sudden death in adults. Surgical repair is the treatment of choice and should be done soon after diagnosis. We report the case of a 38-year-old female, presenting as cardiac arrest and being finally diagnosed as adult ALCAPA. Successful surgical repair was performed using the trap door technique. The patient had an uneventful recovery.

Alternative Treatments for Syphilis During Pregnancy.

Alternative Treatments for Syphilis During Pregnancy.

Unmet need for health care during pregnancy: A French – Romanian comparison

ABSTRACTHealth inequalities emerge from birth, the early neonatal mortality and infant mortality rates being different between countries. These differences may be related to inequalities in use of health care during pregnancy. The aim of this research is to identify and compare the profiles of women who do not follow pregnancy health care recommendations in two European countries with different health systems and indicators: namely France and Romania. However, health care recommendations for pregnant women are free in the two countries. Firstly, unmet need for health care during pregnancy is observed. Secondly, our results reveal that there is a relationship between perinatal health care abandonment and several forms of inequalities (social, informational and psychological). Thirdly, the much higher probability of forgoing perinatal health care for Romanian women could be associated with financial or informational problems which seems counterintuitive because perinatal health care recommendations are free. Free coverage is too insufficient to ensure the efficiency of the perinatal health care system.

Can earlier BCG vaccination reduce early infant mortality? Study protocol for a cluster randomised trial in Guinea-Bissau

IntroductionThe BCG vaccine is designed to protect against tuberculosis, but the vaccine may have broader effects. In 2014, the Strategic Advisory Group of Experts on Immunization reviewed the literature on...

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

ABSTRACTBackgroundThe Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.ObjectiveThe aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).MethodsWe used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.ResultsIn both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = −4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = −7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = −7.39, P = 0.017).ConclusionMaternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Effects of Early Initiation of Breastfeeding on Exclusive Breastfeeding Practices of Mothers in Rural Haiti

Rates and relationships of early initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) of mothers in rural Haiti were examined. Prelacteal and complementary feedings were identified. With a cross-sectional descriptive design, survey data from mothers (N = 195) were collected at three intervals after birth. Data were analyzed for indicators of EIBF, EBF, and complementary feedings. Overall, 148 (75.9%) mothers reported EIBF, and 75 (38.5%) reported EBF. EIBF was associated with EBF, with an adjusted relative risk 1.35 (95% confidence interval = [0.84, 2.18]). Several nutritive and nonnutritive substances interrupted EBF during the first 6 months of life. Haiti has an under-five mortality rate of 67.0/1,000 live births, exceeding the mean of 46.5/1,000 live births for developing regions. Both EIBF and EBF are associated with decreased neonatal and early infant mortality. Country-specific data are needed to inform and develop breastfeeding initiatives and community-level campaigns to improve the prevalence of EIBF and EBF in Haiti.

Сongenital diseases of the heart among newborn children: genetic aspects

Congenital heart defects are a heterogeneous group of diseases that occur as isolation or a part of multiple birth defects, gene disorders or chromosomal abnormalities. Chromosomal abnormalities and its underlying syndromes are the cause of 6 to 36% of cases of congenital heart defects. Monogenic etiology is proven in about 8% of cases, and the main group - about 90% of the congenital heart defects is the result of an unfavorable combination of genetic predisposition and external factors. The causes of early neonatal infant mortality are dominated by incompatible birth defects: almost 26% of perinatal and neonatal deaths are associated with congenital child pathology. Heart defects compose about 30% of all birth defects. They rank first place among the diseases that lead to perinatal mortality and early disability. World statistics show that the incidence of birth defects in the world is 9 per 1000 newborns, in Europe - 8/1000, which is 4 times more frequent than neural tube defects and 6 times higher than chromosomal abnormalities. In Ukraine, about 5,000 children with congenital heart defects are born each year, and the total number of those children on dispensary records reaches more than 45,000. Knowledge about the prevalence of birth defects in the region is needed to develop new information markers of the risk of congenital pathology of the circulatory system for women of reproductive age. Data on the incidence of congenital heart defects of fetuses and newborns in the region will allow the creation of a database for follow-up studies, which will facilitate the timely identification of pregnant women at risk. This will improve the prognosis of pregnancy, reduce the level of perinatal pathology, which will have a significant medical and social effect. The data obtained will allow to create preconditions for improvement of approaches to the definition of risk groups of perinatal pathology, perfection of specialized care for pregnant women with risk of congenital heart defects of the fetus.

Emerging trends in the prenatal diagnosis of complex CHD and its influence on infant mortality in this cohort.

Fetal echocardiography is the main modality of prenatal diagnosis of CHD. This study was done to describe the trends and benefits associated with prenatal diagnosis of complex CHD at a tertiary care centre. Retrospective chart review of patients with complex CHD over an 18-year period was performed. Rates of prenatal detection along with early and late infant mortality outcomes were studied. Of 381 complex CHD patients born during the study period, 68.8% were diagnosed prenatally. Prenatal detection rate increased during the study period from low-50s in the first quarter to mid-80s in the last quarter (p=0.001). Rate of detection of conotruncal anomalies increased over the study period. No infant mortality benefit was noted with prenatal detection. Improved obstetrical screening indications and techniques have contributed to higher proportions of prenatal diagnosis of complex CHD. However, prenatal diagnosis did not confer survival benefits in infancy in our study.

Early neonatal vitamin A supplementation and infant mortality: an individual participant data meta-analysis of randomised controlled trials

BackgroundBiannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on...

Reducing early infant mortality in India: results of a prospective cohort of pregnant women using emergency medical services

ObjectivesTo describe the demographic characteristics and clinical outcomes of neonates born within 7 days of public ambulance transport to hospitals across five states in India.DesignProspective observational study.SettingFive Indian states using...

Hemodynamic monitoring on the background of intensive therapy in newborns

The article deals with the problem of early neonatal and infant mortality. It is pointed out that recent advances in emergency and intensive care therapy have provided decline in early neonatal and infant mortality. Hemodynamic disorders are reported to be associated with any severe pathology in patients of all age groups including newborns, significantly influence quality of life of patients having experienced a critical condition. Clinical manifestations of hemodynamic disorders in infants are not considered to be specific; they are critically delayed and are not timely recognized. The article describes peculiarities of the cardio-vascular system of newborns that are responsible for the necessity of thorough hemodynamic profile monitoring in order to provide detection of vital function alterations at the early stages, ensure timely onset of intensive therapy and its qualitative performance. Special attention is paid to current methods of determination of central hemodynamic parameters, which are stated to be divided into invasive and non-invasive. The paper also highlights some peculiarities of evaluation of hemodynamic findings using specific monitoring methods and factors influencing the outcome. The article specifies increased interest towards non-invasive monitoring tools of hemodynamic profile in recent years; their relevance is stated to be doubtless in both pediatric and neonatal practice. The main task of any monitoring procedure is reported to be hemodynamic findings analysis, “trend tracking” in the process of monitoring a patient and intensive therapy performance.

Designing and assessing wheel/rail profiles for improved rolling contact fatigue and wear performance

A quick survey of wheel and rail profiles used around the world reveals a huge range of options. Wheels come in cylindrical, conical, and concave variations, while rails range in shape from a very flat 14 in. (350 mm) head radius to a tightly crowned 6 in. (150 mm) head radius. The rationale for implementing one or the other is often institutional inertia—a strong tendency to continue doing what has been done in the past. But the impacts of wheel and rail profiles on the performance of the vehicle/track interaction are large and the decision should not be made lightly. Unfortunately, there are few well-matched “off-the-shelf” solutions from the existing commercially available profiles, such that new rails and wheels often suffer early failures or infant mortality. Through examples and case studies, this paper discusses the significant role that wheel and rail profiles play with respect to performance and safety and makes the case for wheel and rail profiles specifically suited to the needs of each railway. Various techniques for assessing the performance of systems of wheels and rails are reviewed and discussed.

There’s a World Going on Underground—Infant Mortality and Fracking in Pennsylvania

Background: There has been a rapid global development of the horizontal drilling and hydraulic fracturing process termed fracking. This involves the dispersion of “produced water” which contains naturally occurring radioactive material (NORM) which may contaminate surface water and pose a health risk. Objectives: To investigate association between early (0-28 days) infant mortality by county in Pennsylvania and fracking. Methods: We compared early infant mortality for 2007-2010 after fracking developed with a control period 2003-2006, contrasting a group of the 10 most heavily fracked counties with the rest of Pennsylvania. Results: Whilst early infant deaths decreased by 2.4% in the State over the period, in the 82,558 births in the 10 fracked counties there was a significant increase in mortality (238 vs 193; RR = 1.29; 95% CI 1.05, 1.55; p = 0.011). For the five north east fracked counties Bradford, Susquehanna, Lycoming, Wyoming and Tioga the combined early infant mortality increased from 34 deaths to 60 (RR 1.66; 1.05, 2.51; p = 0.014), whereas in the south western 5 counties Washington, Westmoreland, Fayette, Butler and Greene the increase was modest, 157 to 178 (RR 1.18; 0.95, 1.46; p = 0.13). Increased risk was associated with exposure to groundwater, expressed as the county ratio of water wells divided by the number of births. Conclusions: Fracking appears to be associated with early infant mortality in populations living in counties where the process is carried out. There is some evidence that the effect is associated with private water well density and/or environmental law violations.

Aborted sudden cardiac death in a young male with anomalous left coronary artery arising from the pulmonary artery

Anomalous left coronary artery arising from the pulmonary artery (ALCAPA) is a rare type of congenital coronary abnormality that may be associated with early infant mortality and sudden adult cardiac death. We report a case regarding a 23-year-old male who collapsed during a marathon race and was resuscitated with cardiopulmonary resuscitation. Subsequent workups verified the diagnosis of ALCAPA. The patient underwent surgical intervention with obliteration of the ALCAPA orifice and coronary artery bypass grafting with left internal mammary artery to left anterior descending coronary artery. The procedure was done smoothly, and he was discharged uneventfully.

Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho.

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants' HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January–June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems.

Impact of Malaria Control on Late and Early Infant Mortality in Senegal

AbstractOne of the greatest achievements of the twenty‐first century has been the dramatic decline in malaria prevalence notably in endemic developing countries. In this study, we estimate the impact of recent scale up in malaria control in Senegal on neonatal, postnatal and infant mortality. We exploit natural preintervention variation in malaria prevalence to estimate the impact of recent malaria control policy in Senegal. In a difference in differences design, we find a negative and significant effect on neonatal and infant mortality in malaria endemic regions while the impact on postnatal mortality is inconclusive. We rule out competing explanations such as contemporaneous health campaigns, general improvement in health care delivery and pre‐existing regional time trends. We identify a 26.9% and 16.3% reduction in neonatal and infant mortality, respectively, in malaria endemic regions during 2005–2014. We argue that increase in donor funding for malaria control as well as greater involvement of local communities and civil society organization has proven to be effective. However, the impact of malaria control on mortality may vary substantially depending on early or late infant mortality.

Iron Supplementation Affects Hematologic Biomarker Concentrations and Pregnancy Outcomes among Iron-Deficient Tanzanian Women

Background: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes.Objective: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women.Methods: We identified 600 iron-deficient (serum ferritin ≤12 μg/L) pregnant women, aged 18–45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 μg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 μg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes.Results: There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 μg/L; 95% CI: 49.5, 58.8 μg/L), and serum hepcidin (14.0 μg/L; 95% CI: 12.4, 15.6 μg/L) and decreases in sTfR (−1.7 mg/L; 95% CI: −2.0, −1.3 mg/L) and ZPP (−17.8 mmol/L; 95% CI: −32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline – up to 12.1 g/L and 14.5 μg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76).Conclusion: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits.

284. Long-Term Therapeutic Immune Reconstitution in XSCID Canine Model via In Vivo Foamy Virus Delivery of Common Gamma Chain

X-linked combined immunodeficiency disease (XSCID) is caused by mutation in the common gamma chain, γC (interleukin-2 receptor subunit gamma, IL2RG) in both humans and canines. It is characterized by the inability of T-cell development leading to absence of T-cells in peripheral blood, lack of T-cell mediated immune response, low IgA and IgG levels, and early infant mortality. In the 1990s, human XSCID clinical trials utilizing gamma-retroviral vectors to deliver the IL2RG gene caused leukemia in 5 out of 20 patients due to vector integration in or near proto-oncogenes. Recent studies showed Foamy virus based vectors as an excellent alternative for in vivo gene-therapy because it is non-pathogenic in humans while exhibiting increased serum stability and favorable integration pattern. Previously, we have demonstrated CD3+ T-cell reconstitution in the canine model via intravenous injection of foamy virus expressing human elongation factor-1 alpha promoter (Ef1α)-yC. Unfortunately, the treated animals contained a low number of gene corrected progenitors at a sub-therapeutic level. Here, we achieved long-term therapeutic immune-reconstitution by intravenous delivery of a human phosphoglycerate kinase promoter (Pgk)-mediated γC foamy viral vector into XSCID neonatal canines. Long-term (2 years) post-injection follow-up demonstrated therapeutic levels of CD3+ T-cell expansion. Within the T-cell population, gene correction with Pgk-γC stabilized at ~80%. We validated T-cell functionality by using spectratyping analysis, which exhibited a diverse repertoire of receptor gene rearrangement. Retroviral integration site analysis (RIS) indicated polyclonal contribution to the reconstituted T-cells. Immunoglobulin ELISA assays showed that IgA and IgG levels in peripheral blood are comparable to normal healthy controls. We immunized the gene-corrected canine recipients with bacteriophage ϕx174 and confirmed production of specific IgG antibodies, showing the ability for isotype switching in B-lymphocytes. Currently, the gene-corrected canines exhibit comparable health and physical attributes to normal controls. Furthermore, semen from the gene-corrected male canine was used via artificial insemination to produce a litter of viable offsprings. In summary, our data demonstrate that Pgk-γC foamy viral vector delivered long-term therapeutic gene correction in a large-animal model for XSCID gene therapy. Most importantly, these results indicate that in vivo Pgk-γC foamy vector administration is a viable option for long-term immune reconstitution in future XSCID human clinical trials.