Search

BACKGROUND: In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above 90% by 2014. In other settings, PCV introduction has been followed by an increase in carriage or disease caused by non-vaccine serotypes, including some serotypes with a high prevalence of antibiotic resistance. METHODS: We characterized the serotype epidemiology and antibiotic resistance of pneumococcal isolates cultured from nasopharyngeal samples collected from infants (≤12 months) in southeastern Botswana between 2016 and 2019. Capsular serotyping was performed using the Quellung reaction. E-tests were used to determine minimum inhibitory concentrations for common antibiotics. RESULTS: We cultured 264 pneumococcal isolates from samples collected from 150 infants. At the time of sample collection, 81% of infants had received at least one dose of PCV-13 and 53% had completed the three-dose series. PCV-13 serotypes accounted for 27% of isolates, with the most prevalent vaccine serotypes being 19F (n = 20, 8%), 19A (n = 16, 6%), and 6A (n = 10, 4%). The most frequently identified non-vaccine serotypes were 23B (n = 29, 11%), 21 (n = 12, 5%), and 16F (n = 11, 4%). Only three (1%) pneumococcal isolates were resistant to amoxicillin; however, we observed an increasing prevalence of penicillin resistance using the meningitis breakpoint (2016: 41%, 2019: 71%; Cochran-Armitage test for trend, p = 0.0003) and non-susceptibility to trimethoprim-sulfamethoxazole (2016: 55%, 2019: 79%; p = 0.04). Three (1%) isolates were multi-drug resistant. CONCLUSIONS: PCV-13 serotypes accounted for a substantial proportion of isolates colonizing infants in Botswana during a four-year period starting four years after vaccine introduction. A low prevalence of amoxicillin resistance supports its continued use as the first-line agent for non-meningeal pneumococcal infections. The observed increase in penicillin resistance at the meningitis breakpoint and the low prevalence of resistance to ceftriaxone supports use of third-generation cephalosporins for empirical treatment of suspected bacterial meningitis.

Early life environmental exposures, even those experienced before conception, can shape health and disease trajectories across the lifespan. Optimizing the detection of the constellation of exposure effects on a broad range of child health outcomes across development requires considerable sample size, transdisciplinary expertise, and developmentally sensitive and dimensional measurement. To address this, the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Cohort Study is an observational longitudinal pediatric cohort study. In the first phase from 2016-2023, the ECHO Program built a robust platform for investigating prenatal and early life environmental exposures on child health outcomes. Now, the ECHO Program is extending longitudinal follow-up of existing ECHO participants

BACKGROUND & AIMS: Steatotic liver disease affects approximately 1 in 10 children in the U.S. and increases the risk of cirrhosis, diabetes, and cardiovascular disease. Lifestyle modification centered on increased physical activity and dietary improvement is the primary management approach. However, significant gaps in the literature hinder the establishment of exercise as a targeted therapeutic strategy for pediatric metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of studies assessing the impact of exercise interventions on validated hepatic outcomes in children with NAFLD. METHODS: We searched CENTRAL, PubMed, Embase, Web of Science, CINAHL, and Google Scholar on June 5 and 6, 2023, for studies in English involving children aged 0 to 19 years diagnosed with NAFLD or at increased risk for NAFLD due to overweight or obesity. We updated the search on August 8, 2024. Eligible studies were required to examine the impact of exercise interventions on hepatic steatosis or liver chemistry. The risk of bias was assessed with RoB2 and ROBINS-I. Data extraction was performed by two independent reviewers. RESULTS: After screening 1578 unique records, 16 studies involving 998 children were included. This comprised seven studies comparing exercise intervention with non-exercising controls, three uncontrolled studies of exercise intervention, two studies comparing exercise plus lifestyle interventions with lifestyle interventions alone, and nine studies comparing different types of exercise interventions. Five of the 11 studies that evaluated hepatic steatosis reported an absolute decrease of 1% to 3%. In the nine studies that evaluated liver chemistry, no significant changes were observed. CONCLUSIONS: Evidence supporting exercise intervention for the treatment of pediatric MASLD is limited. Existing studies were constrained by their methodological approaches; thus, there is a pressing need for high-quality future research. This will enable the development of precise, evidence-based exercise guidelines crucial for the effective clinical management of this condition.

BACKGROUND: Preventing Adverse Childhood Experiences (ACEs) is a public health priority, and the perinatal period is a sensitive life stage when preventive interventions could be particularly effective. Protecting and buffering pregnant persons and infants from exposure to adversity can optimize childrens development and health trajectories, reduce future morbidity and mortality, and even break intergenerational cycles of adversity, but no study has synthesized experimental evidence on effectiveness of interventions to address ACEs in the perinatal period. OBJECTIVES: To (1) identify perinatal ACE prevention interventions, tested in high quality randomized control trials, with a dyadic perspective examining outcomes for mother and child; (2) describe their (a) place on the public health prevention continuum and (b) incorporation of life course characteristics that aim to optimize life health trajectories; and (3) determine which interventions show evidence of effectiveness. METHODS: We undertook a scoping review, using a modified PRISMA-Sc approach, of articles published in English between January 2000 and November 2023 identified through Psych info and PubMed using search terms for a broad range of adversities, with additional capture of articles from relevant reference lists. Interventions were included if they targeted an identified ACEs exposure or risk; were tested in randomized controlled trials (RCTs); reported outcome measures for both mother and child and were initiated during pregnancy. Interventions were further analyzed using the public health prevention continuum and Life Course Intervention Research (LCIR) characteristics frameworks. A two-tailed t test was used to ascertain the association between LCIR characteristics, and the outcomes achieved. RESULTS: Of 2148 articles identified, 57 were in scope for detailed analysis, yielding 53 unique interventions. Overall, 42 (74%) reported some positive impact; 37 (65%) for mothers; 37 (65%) for the child, and 32 (56%) for both. Interventions with the strongest evidence based on study quality and reported outcomes were co-parenting programs designed to improve the quality and function of the co-parenting relationship, home visiting interventions, and integrative health interventions incorporating baby massage and/or yoga. Half of effective interventions were secondary prevention focused. The mean number of life course characteristics was significantly higher in the studies that reported a positive impact on the mother and/or child (p = 0.003). CONCLUSIONS: Few studies specifically addressed ACEs as a defined set of adversities, yet a range of perinatal interventions showed positive impacts on individual ACE risks or exposures. Intentional incorporation of life course characteristics and bundling of evidence-based components into comprehensive perinatal interventions hold promise for future ACEs prevention.

BackgroundDisease prevalence and distribution by patient characteristics data are needed to guide "representative" patient enrollment in clinical trials and assess relevance of results to patient populations. Our objective was to describe disease prevalence, and age/sex distribution of patients with common chronic conditions from a large population sample.MethodsA cross-sectional study of all members of Clalit Health Services, alive on January 1, 2020. Included were 26 chronic diseases, and 21 types of malignancies regarded as active by being diagnosed between January 1, 2018- to January 1, 2020, or by prescription of oncologic treatment medications January 1, 2018 and January 1, 2020.ResultsData from 4,627,183 individuals, 2,274,349 males and 2,352,834 females from newborn to 110 years. Obesity (19%), hypertension (13%), diabetes mellitus (9%), esophagitis-gastritis (5.5%), thyroid disease (5.3%), asthma (5.1%), ischemic heart disease (4.5%), depression (4.5%), osteoporosis (3.8%), and atopic dermatitis (3.6%) were the ten most prevalent conditions. Proportions of age groups varied between conditions (67% of hypertensives were ≥65 years old, 24% ≥80 years; 73% with ischemic heart disease were ≥65 years, 29% ≥80 years; 59% of diabetics were ≥65 years, 17% ≥80 years; 42% of atrial fibrillation patients were ≥80 years; 40% of heart failure patients were ≥80 years). Proportions of males and females for most conditions paralleled prevalence except proportions of women increased after age 80 for cardiovascular diseases, and for diabetes after age 75. The five most frequent active cancers were breast, prostate, colon/rectal, lymphoma and melanoma. The prevalence of cancers increased with age beginning in the middle-aged groups and peaking at very old ages. Women had lower prevalence of lung cancers and accounted for lower percentages of patients with lung cancers (45 vs 55%) but similar percentages for women and men were seen in the patients with colon and rectal cancer (50.4 vs. 49.6% in women) and lymphoma (50.7 vs. 49.3% in women).ConclusionsPrevalence of medical conditions and distributions differ by age and sex. This information serves as an example and resource for data needed to describe a "representative" clinical population.

BACKGROUND: Children from families with low socioeconomic status (SES), as determined by income, experience several negative outcomes, such as higher rates of newborn mortality and behavioral issues. Moreover, associations between DNA methylation and low income or poverty status are evident beginning at birth, suggesting prenatal influences on offspring development. Recent evidence suggests neighborhood opportunities may protect against some of the health consequences of living in low income households. The goal of this study was to assess whether neighborhood opportunities moderate associations between household income (HI) and neonate developmental maturity as measured with DNA methylation. METHODS: Umbilical cord blood DNA methylation data was available in 198 mother-neonate pairs from the larger CANDLE cohort. Gestational age acceleration was calculated using an epigenetic clock designed for neonates. Prenatal HI and neighborhood opportunities measured with the Childhood Opportunity Index (COI) were regressed on gestational age acceleration controlling for sex, race, and cellular composition. RESULTS: Higher HI was associated with higher gestational age acceleration (B = .145, t = 4.969, p = 1.56x10-6, 95% CI [.087, .202]). Contrary to expectation, an interaction emerged showing higher neighborhood educational opportunity was associated with lower gestational age acceleration at birth for neonates with mothers living in moderate to high HI (B = -.048, t = -2.08, p = .03, 95% CI [-.092, -.002]). Female neonates showed higher gestational age acceleration at birth compared to males. However, within males, being born into neighborhoods with higher social and economic opportunity was associated with higher gestational age acceleration. CONCLUSION: Prenatal HI and neighborhood qualities may affect gestational age acceleration at birth. Therefore, policy makers should consider neighborhood qualities as one opportunity to mitigate prenatal developmental effects of HI.

This study evaluated the effect of Momentum-an integrated family planning, maternal and newborn health, and nutrition intervention-on postpartum family planning norms and behaviors among ever married and never-married first-time mothers age 15-24 in Kinshasa, Democratic Republic of the Congo. Using data collected in 2018 and 2020, we conducted an intent-to-treat analysis among 1,927 first-time mothers who were about six-months pregnant at enrollment. Difference-in-differences models were run for panel data and treatment effects models with inverse-probability weighting for endline-only outcomes. Average treatment effects (ATE) were estimated. Momentum had positive effects on partner discussion of family planning in the early postpartum period (ever married 15-19: ATE = 0.179, 95% CI = 0.098, 0.261; never married 15-19: ATE = 0.131, 95% CI = 0.029, 0.232; ever married 20-24: ATE = 0.233, 95% CI = 0.164, 0.302; never married 20-24: ATE = 0.241, 95% CI = 0.121, 0.362) and discussion with a health worker, and on obtaining a contraceptive method in the early postpartum period, except among never married adolescents. Among adolescents, intervention effects on modern contraceptive use within 12 months of childbirth/pregnancy loss were larger for the never married (ATE = 0.251, 95% CI = 0.122, 0.380) than the ever married (ATE = 0.114, 95% CI = 0.020, 0.208). Full intervention exposure had consistently larger effects on contraceptive behaviors than partial exposure, except among ever married adolescents. Momentum had no effect on normative expectations about postpartum family planning use among adolescents, and on descriptive norms and personal agency among those who were never married. Results for normative outcomes and personal agency underscored the intersectionality between young maternal age and marital status. Future programs should improve personal agency and foster normative change in support of postpartum family planning uptake and tailor interventions to different age and marital status subsets of first-time mothers.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

BACKGROUND: In the US, non-Hispanic (NH) Black birthing persons show a two-fold greater risk of fetal death relative to NH white birthing persons. Since males more than females show a greater risk of fetal death, such loss in utero may affect the sex composition of live births born preterm (PTB;

OBJECTIVE: To describe the characteristics of patients who received outpatient therapy services through an infant bridge program using telehealth mode of service delivery and to identify if attendance rates vary by mode of service delivery. We hypothesized that telehealth visits will increase attendance rates. DESIGN: Retrospective, cross-sectional study. SETTING: UCSF Benioff Childrens Hospital outpatient infant bridge program. PARTICIPANTS: Eighty infants with a history of NICU admission and scheduled for a therapy appointment between June 1, 2019 and December 31, 2020 were included in the study. Participants had an average(SD) gestational age of 34.63(4.41) weeks and length of stay was 43.55(56.03) weeks. The majority were English-speaking (96.3%), White (37.5%), and had commercial insurance (72.5%). MAIN OUTCOME MEASURE: Descriptive analyses were conducted across the entire group along with service delivery model subgroup analysis. Logistic regression was performed to assess patient characteristics associated with attendance and if service delivery model influences attendance. RESULTS: In the analysis of 596 scheduled visits, there were more completed telehealth sessions than for in-person sessions (90.0% versus 84.1%, p = .011). For in-person sessions, infants (N = 40) with lower birth gestational ages (p = .009), longer length of stay (p = .041), and Medi-Cal insurance (p = .006) were more likely to have ≥2 missed appointments. For the telehealth sessions, infants (N = 40) who had longer length of stay (p = .040) were more likely to have ≥2 missed appointments. There is a higher likelihood of ≥2 missed appointments for patients with a longer length of stay (OR = 1.02, 95% CI [1.01, 1.03]) and for in-person service delivery when compared to telehealth (OR = 6.25, 95% CI [1.37, 28.57]). CONCLUSIONS: Telehealth was associated with higher likelihood of attendance, revealing that telehealth has the potential to increase access to early therapy services for certain populations. Future studies with larger sample sizes to determine which populations benefit from telehealth is recommended.

BackgroundWhile early autism intervention can significantly improve outcomes, gaps in implementation exist globally. These gaps are clearest in Africa, where forty percent of the world's children will live by 2050. Task-sharing early intervention to non-specialists is a key implementation strategy, given the lack of specialists in Africa. Naturalistic Developmental Behavioral Interventions (NDBI) are a class of early autism intervention that can be delivered by caregivers. As a foundational step to address the early autism intervention gap, we adapted a non-specialist delivered caregiver coaching NDBI for the South African context, and pre-piloted this cascaded task-sharing approach in an existing system of care.ObjectivesFirst, we will test the effectiveness of the caregiver coaching NDBI compared to usual care. Second, we will describe coaching implementation factors within the Western Cape Department of Education in South Africa.MethodsThis is a type 1 effectiveness-implementation hybrid design; assessor-blinded, group randomized controlled trial. Participants include 150 autistic children (18-72 months) and their caregivers who live in Cape Town, South Africa, and those involved in intervention implementation. Early Childhood Development practitioners, employed by the Department of Education, will deliver 12, one hour, coaching sessions to the intervention group. The control group will receive usual care. Distal co-primary outcomes include the Communication Domain Standard Score (Vineland Adaptive Behavior Scales, Third Edition) and the Language and Communication Developmental Quotient (Griffiths Scales of Child Development, Third Edition). Proximal secondary outcome include caregiver strategies measured by the sum of five items from the Joint Engagement Rating Inventory. We will describe key implementation determinants.ResultsParticipant enrolment started in April 2023. Estimated primary completion date is March 2027.ConclusionThe ACACIA trial will determine whether a cascaded task-sharing intervention delivered in an educational setting leads to meaningful improvements in communication abilities of autistic children, and identify implementation barriers and facilitators.Trial registrationNCT05551728 in Clinical Trial Registry (https://clinicaltrials.gov).

PURPOSE: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing. DESIGN: Pilot study using ex vivo human eyes. METHODS: Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors. RESULTS: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 μL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx. CONCLUSIONS: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is related to developing lung and liver disease, but no large-scale studies examine its association with birth outcomes. OBJECTIVE: We investigated the risk of pregnancy complications and adverse birth outcomes in mothers and children with AATD. METHODS: Using a large cohort data of Danish mothers and children with AATD from 1973 to 2013 (n = 2,027,229), with 559 cases (305 mothers and 254 children). We conducted Poisson regression to examine associations between alpha-1 antitrypsin deficiency, adverse birth outcomes, and pregnancy complications in mothers and children. RESULTS: AATD was related to term low birth weight [

OBJECTIVE: To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome. METHODS: This retrospective cohort study included 4,348,226 children enrolled in six U.S. integrated healthcare systems from 1996-2016, 3,095 of whom were diagnosed with Down syndrome. We calculated imaging rates per 100 person years and associated red bone marrow dose (mGy). Relative rates (RR) of imaging in children with versus without Down syndrome were estimated using overdispersed Poisson regression. RESULTS: Compared to other children, children with Down syndrome received imaging using ionizing radiation at 9.5 times (95% confidence interval[CI] = 8.2-10.9) the rate when age

IntroductionAntenatal depression is highly prevalent and is associated with negative birth and neonatal outcomes. However, the mechanisms and causality behind these associations remain poorly understood as they are varied. Given the variability in whether associations are present, there is need to have context-specific data to understand the complex factors that go into these associations. This study aimed to assess the associations between antenatal depression and birth and neonatal outcomes among women attending maternity care in Harare, Zimbabwe.MethodsWe followed 354 pregnant women in second or third trimester, attending antenatal care services in two randomly selected clinics in Harare, Zimbabwe. Antenatal depression was assessed using the Structured Clinical Interview for DSM-IV. Birth outcomes included birth weight, gestational age at delivery, mode of delivery, Apgar score, and initiation of breastfeeding within one-hour postdelivery. Neonatal outcomes at six weeks postdelivery included infant's weight, height, illness, feeding methods and maternal postnatal depressive symptoms. The association between antenatal depression and categorical and continuous outcomes were assessed by logistic regression and point-biserial correlation coefficient, respectively. Multivariable logistic regression determined the confounding effects on statistically significant outcomes.ResultsPrevalence of antenatal depression was 23.7%. It was associated with low birthweight [AOR = 2.30 (95% CI: 1.08-4.90)], exclusive breastfeeding [AOR = 0.42 (95%CI: 0.25-0.73)] and postnatal depressive symptoms [AOR = 4.99 (95%CI: 2.81-8.85)], but not with any other birth or neonatal outcomes measured.ConclusionsThe prevalence of antenatal depression in this sample is high with significant associations demonstrated for birth weight, maternal postnatal depressive symptoms and infant feeding methods Effective management of antenatal depression is thus crucial to the promotion of maternal and child health.

BackgroundGlobally, almost 15 million infants are born prematurely each year, disproportionately affecting low and middle-income countries. In the absence of mother's milk, the World Health Organization recommends using donor human milk (DHM) due to its protective effect against necrotizing enterocolitis, a life-threatening intestinal disorder. The use of DHM is increasing globally, with many low and middle-income countries integrating donor milk banks into their public health strategies to reduce neonatal mortality, yet very little is known about the nutritional composition of DHM. Additional knowledge gaps include how DHM composition is influenced by milk banking practices, and whether preterm nutrient recommendations are achieved when DHM is used with commercially available fortifiers.MethodsWe designed a multi-site study with eight geographically diverse milk bank partners in high, middle, and low-income settings that will examine and compare a broad range of nutrients and bioactive factors in human milk from 600 approved milk bank donors around the world to create comprehensive, geographically diverse nutrient profiles for DHM. We will then simulate the random pooling of 2 to 10 donors to evaluate the impact of pooling as a potential strategy for milk banks to manage nutrient variability in DHM. Finally, we will evaluate whether commercially available fortifiers meet nutrient recommendations when used with DHM.DiscussionWe expect that results from this study will improve nutritional care globally for the growing number of preterm infants who receive donor human milk.

Long-duration space exploratory missions to the Earth's moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.

Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls where the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples display a hypermature methylation signature than expected given their respective gestational age which likely impacts birth timing.

IntroductionAneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. The optimal treatment strategy and clinical outcome of aSAH in pregnancy remains unclear. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnant people.MethodsUsing the 2010-2018 National Inpatient Sample, we identified all birth hospitalizations of women between ages of 18 to 45 associated with subarachnoid hemorrhage and aneurysm treatment were included. Multivariate analyses were used to evaluate the effect of pregnancy state, mode of treatment of aneurysms, severity of subarachnoid hemorrhage on mortality and discharge destination of this cohort. Trends in mode of treatment utilized for aneurysmal treatment in this time interval was evaluated.Results13,351 aSAH with treatment were identified, of which 440 were associated with pregnancy. There was no significant difference in mortality or rate of discharge to home in pregnancy related hospitalization. Worse aSAH severity, chronic hypertension, and smaller hospital size was associated with significantly higher rate of mortality from aSAH during pregnancy. Worse aSAH severity was associated with lower rate of discharge to home. Like the non-pregnant cohort, the treatment of ruptured aneurysms in pregnancy are increasingly through endovascular approaches. The mode of treatment does not change the mortality or discharge destination.ConclusionsPregnancy does not alter mortality or the discharge destination for aSAH. Ruptured aneurysms during pregnancy are increasingly treated endovascularly. Mode of aneurysm treatment does not affect mortality or discharge destination in pregnancy.

IntroductionIn Nepal, abortion is legal on request through 12 weeks of pregnancy and up to 28 weeks for health and other reasons. Abortion is available at public facilities at no cost and by trained private providers. Yet, over half of abortions are provided outside this legal system. We sought to investigate the extent to which patients are denied an abortion at clinics legally able to provide services and factors associated with presenting late for care, being denied, and receiving an abortion after being denied.MethodsWe used data from a prospective longitudinal study with 1835 women aged 15-45. Between April 2019 and December 2020, we recruited 1,835 women seeking abortions at 22 sites across Nepal, including those seeking care at any gestational age (n = 537) and then only those seeking care at or after 10 weeks of gestation or do not know their gestational age (n = 1,298). We conducted interviewer-led surveys with these women at the time they were seeking abortion service (n = 1,835), at six weeks after abortion-seeking (n = 1523) and six-month intervals for three years. Using descriptive and multivariable logistic regression models, we examined factors associated with presenting for abortion before versus after 10 weeks gestation, with receiving versus being denied an abortion, and with continuing the pregnancy after being denied care. We also described reasons for the denial of care and how and where participants sought abortion care subsequent to being denied. Mixed-effects models was used to accounting clustering effect at the facility level.ResultsAmong those recruited when eligibility included seeking abortion at any gestational age, four in ten women sought abortion care beyond 10 weeks or did not know their gestation and just over one in ten was denied care. Of the full sample, 73% were at or beyond 10 weeks gestation, 44% were denied care, and 60% of those denied continued to seek care after denial. Nearly three-quarters of those denied care were legally eligible for abortion, based on their gestation and pre-existing conditions. Women with lower socioeconomic status, including those who were younger, less educated, and less wealthy, were more likely to present later for abortion, more likely to be turned away, and more likely to continue the pregnancy after denial of care.ConclusionDenial of legal abortion care in Nepal is common, particularly among those with fewer resources. The majority of those denied in the sample should have been able to obtain care according to Nepal's abortion law. Abortion denial could have significant potential implications for the health and well-being of women and their families in Nepal.

BackgroundThere is a dearth of studies assessing the effects of SARS-CoV-2 on the healthcare system and access to care, especially in lower- and middle-income countries such as Malawi. We aimed to assess the impacts of COVID-19 on reported maternal and neonatal complications as well as potential changes in maternal care access to care among five primary care health facilities in Blantyre, Malawi.MethodsThis retrospective cohort study assessed maternal and neonatal register data from five participating health centers in Blantyre, Malawi using the Malawi District Health Information Software 2 (DHIS2) to compare outcomes from 15 months before COVID-19 emerged, defined as the pre-Covid period (January 2019 -March 2020) with nine months after COVID-19 (April 2020 -December 2020).ResultsThere was a significant decrease in reported use of vacuum extraction, which went from

An infants everyday visual environment is composed of a complex array of entities, some of which are well integrated into their surroundings. Although infants are already sensitive to some categories in their first year of life, it is not clear which visual information supports their detection of meaningful elements within naturalistic scenes. Here we investigated the impact of image characteristics on 8-month-olds search performance using a gaze contingent eye-tracking search task. Infants had to detect a target patch on a background image. The stimuli consisted of images taken from three categories: vegetation, non-living natural elements (e.g., stones), and manmade artifacts, for which we also assessed target background differences in lower- and higher-level visual properties. Our results showed that larger target-background differences in the statistical properties scaling invariance and entropy, and also stimulus backgrounds including low pictorial depth, predicted better detection performance. Furthermore, category membership only affected search performance if supported by luminance contrast. Data from an adult comparison group also indicated that infants search performance relied more on lower-order visual properties than adults. Taken together, these results suggest that infants use a combination of property- and category-related information to parse complex visual stimuli.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (

A 3-months old Chinese shar-pei puppy with ichthyosis was investigated. The dog showed generalized scaling, alopecia and footpad lesions. Histopathological examinations demonstrated a non-epidermolytic hyperkeratosis. The parents of the affected puppy did not show any skin lesions. A trio whole genome sequencing analysis identified a heterozygous de novo 3 bp deletion in the KRT1 gene in the affected dog. This variant, NM_001003392.1:c.567_569del, is predicted to delete a single asparagine from the conserved coil 1A motif within the rod domain of KRT1, NP_001003392.1:p.(Asn190del). Immunohistochemistry demonstrated normal levels of KRT1 expression in the epidermis and follicular epithelia. This might indicate that the variant possibly interferes with keratin dimerization or another function of KRT1. Missense variants affecting the homologous asparagine residue of the human KRT1 cause epidermolytic hyperkeratosis. Histologically, the investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. To the best of our knowledge, this is the first description of a KRT1-related non-epidermolytic ichthyosis in domestic animals.

BackgroundTetanus is a potentially fatal disease that is preventable through vaccination. While the Democratic Republic of the Congo (DRC) has continued to improve implementing routine vaccination activities throughout the country, they have struggled to maintain high childhood vaccine coverage. This study aims to examine the seroprevalence of tetanus in children 6 to 59 months to identify areas for intervention and improvement of vaccination coverage.MethodsIn collaboration with the 2013-2014 Demographic and Health Survey, we assessed the seroprevalence of tetanus antibodies among children in the DRC. Dried blood spot samples collected from children 6-59 months of age were processed using a prototype DYNEX Multiplier® chemiluminescent automated immunoassay instrument with a multiplex measles, mumps, rubella, varicella and tetanus assay. Multivariable logistic regression was used to determine factors associated with tetanus vaccination and seroprotection.ResultsOverall, 36.1% of children 6-59 months of age reported receiving at least 1 dose of tetanus vaccine while 28.7% reported receiving 3 doses; tetanus seroprotection was 40%. Increasing age in children was associated with decreased tetanus seroprotection, but increased number tetanus vaccinations received. Factors related to increased tetanus seroprotection included number of children in the household, wealth index of the family, urban residence compared to rural, level of maternal education, and province and geography.ConclusionsOur findings in this nationally representative sample indicate that serology biomarkers may help identify children who are not fully immunized to tetanus more accurately than reported vaccination. While children may be captured for routine immunization activities, as children age, decreasing seroprevalence may indicate additional need to bolster routine vaccination activities and documentation of vaccination in school aged children. Additionally, the study highlights gaps in rural residential areas and vaccination coverage based on maternal education, indicating that policies targeting maternal education and awareness could improve the coverage and seroprevalence of tetanus antibodies in the DRC.

Neonatal brain injury may impact brain development and lead to lifelong functional impairments. Hypoxic-ischemic encephalopathy (HIE) and congenital heart disease (CHD) are two common causes of neonatal brain injury differing in timing and mechanism. Maturation of whole-brain neural networks can be quantified during development using diffusion magnetic resonance imaging (dMRI) in combination with graph theory metrics. DMRI of 35 subjects with CHD and 62 subjects with HIE were compared to understand differences in the effects of HIE and CHD on the development of network topological parameters and functional outcomes. CHD newborns had worse 12-18 month language (P

BackgroundIn populations at high risk of HIV infection, rates of depression can be elevated with far-reaching effects on overall well-being. There is limited research on depression among young women engaged in high-risk sexual behaviour in low and middle-income settings. We investigated the prevalence, correlates and factors associated with mean HSCL depression score among young women at high risk (aged 15-24 years old) in Kampala, Uganda.MethodsWe conducted a baseline analysis of a randomized controlled trial. Probable depression was measured using the 15-item Hopkins Symptoms Checklist for depression (HSCL). This checklist has been validated in Ugandan populations, and our reliability test gave a Cronbach alpha coefficient of 0.89. The test was administered to all the participants. Participants whose HSCL mean score was greater than 1.75 were categorized as having probable depression. Socio-demographics and behaviour data were collected and factors associated with mean HSCL depression score were analysed using multiple linear regression.ResultsData was available for 600 participants, mean age 20.4 (SD±2.44) years. The prevalence of probable depression was 56% (95% CI, 52%-60%). Probable depression symptoms were most prevalent among those who reported ever-experiencing violence from a sexual partner (64.7%), those aged between 20-24 years (58.2%) and those who reported more than 10 sexual exposures in the month prior to the interview (56.8%). At the adjusted analysis level, condom use during their last sexual intercourse prior to the survey decreased probable depression symptoms by 0.147 units compared to those who never used condoms (β = -0.147, 95% CI -0.266-0.027). Having experienced physical violence by a sexual partners increased mean HSCL depression score by 0.183 units compared to those who have never experienced violence (β = 0.183, 95% CI 0.068-0.300). Participants who reported ever using drugs of addiction had their mean HSCL depression scoreincrease by 0.20 units compared to those who have never used (β = 0.20,95% CI 0.083-0.317).ConclusionsProbable depression is high in this population and increased mean HSCL depression score is related to violence. Periodic screening for depression and interventions targeting depression, partner violence and risky sexual behaviours are recommended.

Angiogenesis is vital during pregnancy for remodeling and enhancing vasodilation of maternal uterine arteries, and increasing uterine blood flow. Abnormal angiogenesis is associated with decreased uteroplacental blood flow and development of pregnancy disorders such as gestational hypertension, preeclampsia, fetal growth restriction, preterm delivery, stillbirth, and miscarriage. The mechanisms that contribute to normal angiogenesis remain obscure. Our previous studies demonstrated that expression of the angiotensin type 2 receptor (AT2R) is increased while the angiotensin type 1 receptor (AT1R) is unchanged in the endothelium of uterine arteries, and that AT2R-mediated pregnancy adaptation facilitates enhanced vasodilation and uterine arterial blood flow. However, the role of AT2R in regulating angiogenesis during pregnancy has never been studied. This study examines whether or not AT2R activation induces angiogenesis and, if so, what mechanisms are involved. To this end, we used primary human uterine artery endothelial cells (hUAECs) isolated from pregnant and nonpregnant women undergoing hysterectomy. The present study shows that Compound 21, a selective AT2R agonist, induced proliferation of pregnant-hUAECs, but not nonpregnant-hUAECs, in a concentration-dependent manner, and that this C21-induced mitogenic effect was blocked by PD123319, a selective AT2R antagonist. The mitogenic effects induced by C21 were inhibited by blocking JNK-but not ERK, PI3K, and p38-signaling pathways. In addition, C21 concentration dependently increased cell migration and capillary-like tube formation in pregnant-hUAECs. The membrane-based antibody array showed that C21 increased expression of multiple angiogenic proteins, including EGF, bFGF, leptin, PLGF, IGF-1, and angiopoietins. Our qPCR analysis demonstrates that C21-induced increase in expression of these angiogenic proteins correlates with a proportional increase in mRNA expression, indicating that AT2R activates angiogenic proteins at the transcriptional level. In summary, the present study shows that AT2R activation induces angiogenesis of hUAECs in a pregnancy-specific manner through JNK-mediated pathways with associated transcriptional upregulation of multiple proangiogenic proteins.

Childhood undernutrition is a major health burden worldwide that increases childhood morbidity and mortality and causes impairment in infant growth and developmental delays that can persist into adulthood. The first weeks and months after birth are critical to the establishment of healthy growth and development during childhood. The World Health Organization recommends immediate and exclusive breastfeeding (EBF). In infants for whom EBF may not meet nutritional and caloric demands, early, daily, small-volume formula supplementation along with breastfeeding may more effectively avoid underweight wasting and stunting in early infancy than breastfeeding alone. The primary objective of this randomized controlled trial is to evaluate the efficacy of formula for 30 days among low birth weight (LBW) infants

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Pediatric firearm-related injuries pose a significant public health problem in the United States, yet the associated financial burden has not been well described. This is the first study examining national data on the cost of initial hospitalization for pediatric firearm-related injuries. In this retrospective review, the Healthcare Cost and Utilization Project Kids Inpatient Database from the years 2003, 2006, 2009, and 2012 was used to identify all patients 18 years of age and under who were admitted with firearm-related injuries. We compared demographic and discharge-level data including injury severity score, hospital length of stay, income quartile, injury intent, and inflation-adjusted hospital costs across age groups (0-5, 6-9, 10-15, 16-18 years). There were approximately 4,753 pediatric firearm-related admissions each year, with a median hospitalization cost of $12,984 per patient. Annual initial hospitalization costs for pediatric firearm injuries were approximately $109 million during the study period. Pediatric firearm-related injuries predominately occured among older teenagers (74%, 16-18 years), males (89%), black individuals (55%), and those from the lowest income quartile (53%). We found significant cost variation based on patient race, income quartile, injury severity score, intent, hospital length of stay, disposition, and hospital region. Inflation-adjusted hospitalization costs have increased significantly over the study period (p < 0.001). Pediatric firearm-related injuries are a large financial burden to the United States healthcare system. There are significant variations in cost based on predictable factors like hospital length of stay and injury severity score; however, there are also substantial discrepancies based on hospital region, patient race, and income quartile that require further investigation.

ObjectiveThis population-based, matched cohort study aimed to evaluate utilization of health care services by mothers of children with major congenital anomalies (MCAs), compared to mothers of children without MCAs over a 20-year post-birth time horizon in Denmark.MethodsOur analytic sample included mothers who gave birth to an infant with a MCA (n = 23,927) and a cohort of mothers matched to them by maternal age, parity and infant's year of birth (n = 239,076). Primary outcomes were period prevalence and mothers' quantity of health care utilization (primary, inpatient, outpatient, surgical, and psychiatric services) stratified by their child's age (i.e., ages 0-6 = before school, ages 7-13 = pre-school + primary education, and ages 14-18 = secondary education or higher). The secondary outcome measure was length of hospital stays. Outcome measures were adjusted for maternal age at delivery, parity, marital status, income quartile, level of education in the year prior to the index birth, previous spontaneous abortions, maternal pregnancy complications, maternal diabetes, hypertension, alcohol-related diseases, and maternal smoking.ResultsIn both cohorts the majority of mothers were between 26 and 35 years of age, married, and employed, and 47% were primiparous. Mothers of infants with anomalies had greater utilization of outpatient, inpatient, surgical, and psychiatric services, compared with mothers in the matched cohort. Inpatient service utilization was greater in the exposed cohort up to 13 years after a child's birth, with the highest risk in the first six years after birth [adjusted risk ratio, 1.13; 95% confidence interval (CI), 1.12-1.14], with a decrease over time. Regarding the quantity of health care utilization, the greatest difference between the two groups was in inpatient service utilization, with a 39% increased rate in the exposed cohort during the first six years after birth (adjusted rate ratio, 1.39; 95% CI, 1.37-1.42). During the first 6 years after birth, mothers of children with anomalies stayed a median of 6 days (interquartile range [IQR], 3-13) in hospital overall, while the comparison cohort stayed a median of 4 days (IQR, 2-7) in hospital overall. Rates of utilization of outpatient clinics (adjusted rate ratio, 1.36; 95% CI, 1.29-1.42), as well as inpatient (adjusted rate ratio, 1.77; 95% CI, 1.68-1.87), and surgical services (adjusted rate ratio, 1.33; 95% CI, 1.26-1.41) was higher in mothers of children with multiple-organ MCAs during 0 to 6 years after birth. Among mothers at the lowest income levels, utilization of psychiatric clinic services increased to 59% and when their child was 7 to 13 years of age (adjusted rate ratio, 1.59; 95% CI, 1.24-2.03).ConclusionMothers of infants with a major congenital anomaly had greater health care utilization across services. Health care utilization decreased over time or remained stable for outpatient, inpatient, and surgical care services, whereas psychiatric utilization increased for up to 13 years after an affected child's birth. Healthcare utilization was significantly elevated among mothers of children with multiple MCAs and among those at the lowest income levels.

BackgroundMost evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue.MethodsWe conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980-2016), Finland (1987-2017), Norway (1980-2016) and the United States (California) (1991-2012). IPI was calculated based on the time difference between two dates-the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR).ResultsCompared to an IPI of 18-23 months, there was insufficient evidence for an association between IPI 24 month IPIs.ConclusionsWe found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.

Trauma is a leading cause of morbidity and mortality worldwide. Data characterizing the burden of injury in rural Uganda is limited. Hospital-based trauma registries are a critical tool in illustrating injury patterns and clinical outcomes. This study aims to characterize the traumatic injuries presenting to Soroti Regional Referral Hospital (SRRH) in order to identify opportunities for quality improvement and policy development. From October 2016 to July 2019, we prospectively captured data on injured patients using a locally designed, context-relevant trauma registry instrument. Information regarding patient demographics, injury characteristics, clinical information, and treatment outcomes were recorded. Descriptive, bivariate, and multivariate statistical analyses were conducted. A total of 4109 injured patients were treated during the study period. Median age was 26 years and 63% were male. Students (33%) and peasant farmers (31%) were the most affected occupations. Falls (36%) and road traffic injuries (RTIs, 35%) were the leading causes of injury. Nearly two-thirds of RTIs were motorcycle-related and only 16% involved a pedestrian. Over half (53%) of all patients had a fracture or a sprain. Suffering a burn or a head injury were significant predictors of mortality. The number of trauma patients enrolled in the study declined by five-fold when comparing the final six months and initial six months of the study. Implementation of a context-appropriate trauma registry in a resource-constrained setting is feasible. In rural Uganda, there is a significant need for injury prevention efforts to protect vulnerable populations such as children and women from trauma on roads and in the home. Orthopedic and neurosurgical care are important targets for the strengthening of health systems. The comprehensive data provided by a trauma registry will continue to inform such efforts and provide a way to monitor their progress moving forward.

Maternal and neonatal mortality in Bihar, India was far higher than the aspirational levels set out by the Sustainable Development Goals. Provider training programs have been implemented in many low-resource settings to improve obstetric and neonatal outcomes. This longitudinal investigation assessed diagnoses and management of postpartum hemorrhage (PPH), hypertensive disorders of pregnancy, birth asphyxia (BA), and low birth weight (LBW), as part of the CARE's AMANAT program in 22 District Hospitals in Bihar, between 2015 and 2017. Physicians and nurse mentors conducted clinical instruction, simulations and teamwork and communication activities, infrastructure and management support, and data collection for 6 consecutive months. Analysis of diagnosis included 11,259 non-referred and management included 11,800 total (non-referred and referred) admissions that were observed. Data were analyzed using the chi-square test for trend. PPH was diagnosed in 3.7% with no significant trend but diagnosis of hypertensive disorders increased from 1.0% to 1.7%, (ptrend = 0.04), over the 6 months. BA was diagnosed in 5.8% with no significant trend but LBW diagnoses increased from 11% to 16% (ptrend

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

Keratinocyte migration into skin wounds is the step of the healing process that correlates with the wound closure rate. Keratinocyte migration, and wound epithelialization are decreased when beta 2-adrenergic receptors (B2AR) are activated by 1 μM epinephrine/adrenaline, resulting in delayed wound healing in human and mouse skin. In the present study, we found paradoxically, that in a subset of keratinocyte strains exposure to low concentrations of epinephrine (0.1 nM) increased, rather than decreased, their migratory rate. We find that both the alpha- and the beta-adrenergic receptors are expressed in human keratinocytes, and expression of alpha-2 AR subtypes demonstrated for the first time. Therefore, we tested if the alpha-AR could be modulating the increased migratory response observed in these cell strains. By using specific inhibitors to alpha-AR, we demonstrated that blocking A2B-AR could reverse the rapid cell migration induced by the 0.1 nM epinephrine. Phosphorylation of ERK was elevated after 1-10 minutes of the low epinephrine treatment and the A2B-AR inhibitor blocked the ERK phosphorylation. The results suggest that both the A2B-AR and B2AR mediate keratinocyte migration, in which with a low level of epinephrine treatment, A2B-AR could alter the B2AR signals and regulate the migration rate.

BackgroundChildren with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis.ProcedureWe conducted a retrospective cohort study of children aged 0-20 years diagnosed with CNS tumors between 1996-2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade.ResultsWe observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09-1.13) and 2.14 MRIs (95%CI 2.12-2.16) in the U.S., and 1.67 CTs (95%CI 1.65-1.68) and 1.86 MRIs (95%CI 1.85-1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities.ConclusionsMRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

BackgroundHumans life histories have been described as "slow", patterned by slow growth, delayed maturity, and long life span. While it is known that human life history diverged from that of a recent common chimpanzee-human ancestor some ~4-8 mya, it is unclear how selection pressures led to these distinct traits. To provide insight, we compare wild chimpanzees and human subsistence societies in order to identify the age-specific vital rates that best explain fitness variation, selection pressures and species divergence.MethodsWe employ Life Table Response Experiments to quantify vital rate contributions to population growth rate differences. Although widespread in ecology, these methods have not been applied to human populations or to inform differences between humans and chimpanzees. We also estimate correlations between vital rate elasticities and life history traits to investigate differences in selection pressures and test several predictions based on life history theory.ResultsChimpanzees' earlier maturity and higher adult mortality drive species differences in population growth, whereas infant mortality and fertility variation explain differences between human populations. Human fitness is decoupled from longevity by postreproductive survival, while chimpanzees forfeit higher potential lifetime fertility due to adult mortality attrition. Infant survival is often lower among humans, but lost fitness is recouped via short birth spacing and high peak fertility, thereby reducing selection on infant survival. Lastly, longevity and delayed maturity reduce selection on child survival, but among humans, recruitment selection is unexpectedly highest in longer-lived populations, which are also faster-growing due to high fertility.ConclusionHumans differ from chimpanzees more because of delayed maturity and lower adult mortality than from differences in juvenile mortality or fertility. In both species, high child mortality reflects bet-hedging costs of quality/quantity tradeoffs borne by offspring, with high and variable child mortality likely regulating human population growth over evolutionary history. Positive correlations between survival and fertility among human subsistence populations leads to selection pressures in human subsistence societies that differ from those in modern populations undergoing demographic transition.

BackgroundActive parent participation in neonatal care and collaboration between parents and professionals during infant hospitalization in the neonatal intensive care unit (NICU) is beneficial for infants and their parents. A tool is needed to support parents and to study the effects and implementation of parent-partnered models of neonatal care.MethodsWe developed and psychometrically evaluated a tool measuring active parent participation and collaboration in neonatal care within six domains: Daily Care, Medical Care, Acquiring Information, Parent Advocacy, Time Spent with Infant and Closeness and Comforting the Infant. Items were generated in focus group discussions and in-depth interviews with professionals and parents. The tool was completed at NICU-discharge by 306 parents (174 mothers and 132 fathers) of preterm infants. Subsequently, we studied structural validity with confirmatory factor analysis (CFA), construct validity, using the Average Variance Extracted and Heterotrait-Monotrait ratio of correlations, and hypothesis testing with correlations and univariate linear regression. For internal consistency we calculated composite reliability (CR). We performed multiple imputations by chained equations for missing data.ResultsA 31 item tool for parent participation and collaboration in neonatal care was developed. CFA revealed high factor loadings of items within each domain. Internal consistency was 0.558 to 0.938. Convergent validity and discriminant validity were strong. Higher scores correlated with less parent depressive symptoms (r = -0.141, 95%CI -0.240; -0.029, p = 0.0141), less impaired parent-infant bonding (r = -0.196, 95%CI -0.302; -0.056, p

A six-fold increase in congenital heart defects (CHD) exists among monochorionic (MC) twins compared to singleton or dichorionic twin pregnancies. Though MC twins share an identical genotype, discordant phenotypes related to CHD and other malformations have been described, with reported rates of concordance for various congenital anomalies at less than 20%. Our objective was to characterize the frequency and spectrum of CHD in a contemporary cohort of MC twins, coupled with genetic and clinical variables to provide insight into risk factors and pathophysiology of discordant CHD in MC twins. Retrospective analysis of all twins receiving prenatal fetal echocardiography at a single institution from January 2010 -March 2020 (N = 163) yielded 23 MC twin pairs (46 neonates) with CHD (n = 5 concordant CHD, n = 18 discordant CHD). The most common lesions were septal defects (60% and 45.5% in concordant and discordant cohorts, respectively) and right heart lesions (40% and 18.2% in concordant and discordant cohorts, respectively). Diagnostic genetic testing was abnormal for 20% of the concordant and 5.6% of the discordant pairs, with no difference in rate of abnormal genetic results between the groups (p = 0.395). No significant association was found between clinical risk factors and development of discordant CHD (p>0.05). This data demonstrates the possibility of environmental and epigenetic influences versus genotypic factors in the development of discordant CHD in monochorionic twins.

IntroductionPreventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity.MethodsWe created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015.ResultsWe estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%).ConclusionsOur estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.

BackgroundAtopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults.ObjectiveTo evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort.MethodsThis was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years).ResultsPhysician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups.ConclusionIn a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.

Declines in period life expectancy at birth (PLEB) provide seemingly intuitive indicators of the impact of a cause of death on the individual lifespan. Derived under the assumption that future mortality conditions will remain indefinitely those observed during a reference period, however, their intuitive interpretation becomes problematic when period conditions reflect a temporary mortality "shock", resulting from a natural disaster or the diffusion of a new epidemic in the population for instance. Rather than to make assumptions about future mortality, I propose measuring the difference between a period average age at death and the average expected age at death of the same individuals (death cohort): the Mean Unfulfilled Lifespan (MUL). For fine-grained tracking of the mortality impact of an epidemic, I also provide an empirical shortcut to MUL estimation for small areas or short periods. For illustration, quarterly MUL values in 2020 are derived from estimates of COVID-19 deaths that might substantially underestimate overall mortality change in affected populations. These results nonetheless illustrate how MUL tracks the mortality impact of the pandemic in several national and sub-national populations. Using a seven-day rolling window, the empirical shortcut suggests MUL peaked at 6.43 years in Lombardy, 8.91 years in New Jersey, and 6.24 years in Mexico City for instance. Sensitivity analyses are presented, but in the case of COVID-19, the main uncertainty remains the potential gap between reported COVID-19 deaths and actual increases in the number of deaths induced by the pandemic in some of the most affected countries. Using actual number of deaths rather than reported COVID-19 deaths may increase seven-day MUL from 6.24 to 8.96 years in Mexico City and from 2.67 to 5.49 years in Lima for instance. In Guayas (Ecuador), MUL is estimated to have reached 12.7 years for the entire month of April 2020.

IntroductionPeri-urban settings have high maternal mortality and the quality of care received in different types of health facilities is varied. Yet few studies have explored the construct of person-centered maternity care (PCMC) within peri-urban settings. Understanding women's experience of maternity care in peri-urban settings will allow health facility managers and policy makers to improve services in these settings. This study examines factors associated with PCMC in a peri-urban setting in Kenya.Methods and materialsWe analyzed data from a cross-sectional study with 307 women aged 18-49 years who had delivered a baby within the preceding six weeks. Women were recruited from public (n = 118), private (n = 76), and faith based (n = 113) health facilities. We measured PCMC using the 30-item validated PCMC scale which evaluates women's experiences of dignified and respectful care, supportive care, and communication and autonomy. Factors associated with PCMC were evaluated using multilevel models, with women nested within facilities.ResultsThe average PCMC score was 58.2 (SD = 13.66) out of 90. Controlling for other factors, literate women had, on average, about 6-point higher PCMC scores than women who were not literate (β = 5.758, p = 0.006). Women whose first antenatal care (ANC) visit was in the second (β = -5.030, p = 0.006) and third trimester (β = -7.288, p = 0.003) had lower PCMC scores than those whose first ANC were in the first trimester. Women who were assisted by an unskilled attendant or an auxiliary nurse/midwife at birth had lower PCMC than those assisted by a nurse, midwife or clinical officer (β = -8.962, p = 0.016). Women who were interviewed by phone (β = -7.535, p = 0.006) had lower PCMC scores than those interviewed in person.ConclusionsFactors associated with PCMC include literacy, ANC timing and duration, and delivery provider. There is a need to improve PCMC in these settings as part of broader quality improvement activities to improve maternal and neonatal health.

The MORDOR study, a masked, community-level randomized clinical trial conducted in Niger, Malawi and Tanzania (2015 to 2017), showed that biannual administration of single-dose azithromycin to preschool children reduced all-cause mortality. We sought to evaluate its impact on causes of death in children aged 1-59 months in Tanzania. A random sampling of 614 communities was conducted in Kilosa District, Tanzania, with simple random assignment of communities to receive either azithromycin or placebo. In these communities, a census was carried out every 6 months and children aged 1-59 months received biannual (every 6 months), single-dose azithromycin (~20mg/kg) or placebo depending on community assignment, over a 2-year period. Mortality was determined at the time of the biannual census. For child deaths, a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. A total of 190- (0.58 /100 person-years) and 200 deaths (0.59/100 person-years) were reported in the azithromycin and placebo arms, respectively. Malaria, pneumonia and diarrhea, accounted for 71% and 68% of deaths in the respective arms. Overall, the mortality was not different by treatment arm, nor were the distribution of causes of death after adjusting for community clustering. The cause-specific mortality for diarrhea/pneumonia was no different over time. In children aged 1-5 months, 32 deaths occurred in the placebo arm and 25 deaths occurred in the azithromycin arm; 20 (62.5%) deaths in the placebo- and 10 (40%) in the azithromycin arm were attributed to diarrhea or pneumonia. Neither differences in the number of deaths nor the diarrhea/pneumonia attribution was statistically significant after adjusting for community clustering. In conclusion, azithromycin was not associated with a significant decline in deaths by specific causes compared to placebo. The non-significant lower rates of diarrhea or pneumonia in children

Increasing evidence supports the importance of the breast milk microbiome in seeding the infant gut. However, the origin of bacteria in milk and the process of milk microbe-mediated seeding of infant intestine need further elucidation. Presumed sources of bacteria in milk include locations of mother-infant and mother-environment interactions. We investigate the role of mother-infant interaction on breast milk microbes. Shotgun metagenomics and 16S rRNA gene sequencing identified milk microbes of mother-infant pairs in breastfed infants and in infants that have never latched. Although breast milk has low overall biomass, milk microbes play an important role in seeding the infant gut. Breast milk bacteria were largely comprised of Staphylococcus, Streptococcus, Acinetobacter, and Enterobacter primarily derived from maternal areolar skin and infant oral sites in breastfeeding pairs. This suggests that the process of breastfeeding is a potentially important mechanism for propagation of breast milk microbes through retrograde flux via infant oral and areolar skin contact. In one infant delivered via Caesarian section, a distinct strain of Bifidobacteria breve was identified in maternal rectum, breast milk and the infant's stool potentially suggesting direct transmission. This may support the existence of microbial translocation of this anaerobic bacteria via the enteromammary pathway in humans, where maternal bacteria translocate across the maternal gut and are transferred to the mammary glands. Modulating sources of human milk microbiome seeding potentially imply opportunities to ultimately influence the development of the infant microbiome and health.

Long-term outcomes related to emergency department revisit, hospital readmission, and all-cause mortality, have not been well characterized across the spectrum of pediatric traumatic brain injury (TBI). We evaluated emergency department visit outcomes up to 1 year after pediatric TBI, in comparison to a referent group of trauma patients without TBI. We performed a longitudinal, retrospective study of all pediatric trauma patients who presented to emergency departments and hospitals in California from 2005 to 2014. We compared emergency department visits, dispositions, revisits, readmissions, and mortality in pediatric trauma patients with a TBI diagnosis to those without TBI (Other Trauma patients). We identified 208,222 pediatric patients with an index diagnosis of TBI and 1,314,064 patients with an index diagnosis of Other Trauma. Population growth adjusted TBI visits increased by 5.6% while those for Other Trauma decreased by 40.7%. The majority of patients were discharged from the emergency department on their first visit (93.2% for traumatic brain injury vs. 96.5% for Other Trauma). A greater proportion of TBI patients revisited the emergency department (33.4% vs. 3.0%) or were readmitted to the hospital (0.9% vs. 0.04%) at least once within a year of discharge. The health burden within a year after a pediatric TBI visit is considerable and is greater than that of non-TBI trauma. These data suggest that outpatient strategies to monitor for short-term and longer-term sequelae after pediatric TBI are needed to improve patient outcomes, lessen the burden on families, and more appropriately allocate resources in the healthcare system.

OBJECTIVE:To estimate healthcare expenditures that could be impacted by advanced diagnostic testing for patients hospitalized with meningitis or encephalitis. METHODS:Patients hospitalized with meningitis (N = 23,933) or encephalitis (N = 7,858) in the U.S. were identified in the 2010-2014 Truven Health MarketScan Commercial Claims and Encounters Database using ICD-9-CM diagnostic codes. The database included an average of 40.8 million commercially insured enrollees under age 65 per year. Clinical, demographic and healthcare utilization criteria were used to identify patient subgroups early in their episode who were at risk to have high inpatient expenditures. Healthcare expenditures of patients within each subgroup were bifurcated: those expenditures that remained five days after the patient could be classified into the subgroup versus those that had occurred previously. RESULTS:The hospitalization episode rate per 100,000 enrollee-years for meningitis was 13.0 (95% CI: 12.9-13.2) and for encephalitis was 4.3 (95% CI: 4.2-4.4), with mean inpatient expenditures of $36,891 (SD = $92,636) and $60,181 (SD = $130,276), respectively. If advanced diagnostic testing had been administered on the day that a patient could be classified into a subgroup, then a test with a five-day turnaround time could impact the following mean inpatient expenditures that remained by subgroup for patients with meningitis or encephalitis, respectively: had a neurosurgical procedure ($83,337 and $56,020), had an ICU stay ($34,221 and $46,051), had HIV-1 infection or a previous organ transplant ($37,702 and $62,222), were age 2 days ($18,325 and $30,244). DISCUSSION:Inpatient expenditures for patients hospitalized with meningitis or encephalitis were substantial and varied widely. Patient subgroups who had high healthcare expenditures could be identified early in their stay, raising the potential for advanced diagnostic testing to lower these expenditures.