Search

Progress in health outcomes across Africa has been uneven, marked by significant disparities among countries, which not only challenges the global health security but impede progress towards achieving the United Nations' Sustainable Development Goals 3 and 10 (SDG 3 and SDG 10) and Universal Health Coverage (UHC). This paper examines the progress of African countries in reducing intra-country health outcome disparities between 2000 and 2019. In other words, the paper investigates the convergence hypothesis in health outcome using a panel data from 40 African countries. Data were sourced from the World Development Indicators, the World Governance Indicators, and the World Health Organization database. Employing a non-linear dynamic factor model, the study focused on three health outcomes: infant mortality rate, under-5 mortality rate, and life expectancy at birth. The findings indicate that while the hypothesis of convergence is not supported for the selected countries, evidence of convergence clubs is observed for the three health outcome variables. The paper further examine the factors contributing to club formation by using the marginal effects of the ordered logit regression model. The findings indicate that the overall impact of the control variables aligns with existing research. Moreover, governance quality and domestic government health expenditure emerge as significant determinants influencing the probability of membership in specific clubs for the child mortality rate models. In the life expectancy model, governance quality significantly drives club formation. The results suggest that there is a need for common health policies for the different convergence clubs, while country-specific policies should be implemented for the divergent countries. For instance, policies and strategies promoting health prioritization in national budget allocation and reallocation should be encouraged within each final club. Efforts to promote good governance policies by emphasizing anti-corruption measures and government effectiveness should also be encouraged. Moreover, there is a need to implement regional monitoring mechanisms to ensure progress in meeting health commitments, while prioritizing urbanization plans in countries with poorer health outcomes to enhance sanitation access. [ABSTRACT FROM AUTHOR]

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.

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.

The health costs of economic uncertainty always remain a major concern among policymakers of China. The theoretical and empirical literature on the economic uncertainty-human health nexus is still in its infancy stage. This study is firmly rooted in the economic uncertainty theory advanced by Baker, Bloom, & Davis. In this study, the primary objective of the analysis is to estimate the asymmetric impact of economic uncertainty on human health in China's economy. In order to evaluate the short and long-run estimates of economic uncertainty on human health across various quantiles, we have employed the linear and nonlinear QARDL models. The linear QARDL model shows that the long-run relationship between economic uncertainty and the infant mortality rate is positive and significant at all quantiles, while the long-run relationship between economic uncertainty and the death rate is positive and significant at higher quantiles. The nonlinear QARDL model reveals that, in the long run, the relationship between the positive shock of economic uncertainty and the infant mortality rate is positive and significant at quantiles 0.30 to 0.95, while the long-run relationship between the positive shock of economic uncertainty and the death rate is positive and significant at higher quantiles. The relationship between the negative shock of economic uncertainty and the infant mortality rate is negative and significant at the highest quantiles, while the relationship between the negative shock of economic uncertainty and death rate is negative and significant at higher quantiles in the long run. The findings indicate a positive relationship between economic uncertainty in China and higher rates of infant mortality and death. Thus, adopting suitable policies for controlling economic uncertainty can help in improving human health in China. [ABSTRACT FROM AUTHOR]

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

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.

Background: Infant mortality persists as a global public health concern, particularly in lower-middle-income countries (LIMCs) such as Nigeria. The risk of an infant dying before one year of age is estimated to be six times higher in Africa than in Europe. Nigeria recorded an infant mortality rate of 72.2 deaths per 1,000 live births in 2020, in contrast to the global estimate of 27.4 per 1,000 live births. Several studies have been undertaken to determine the factors influencing infant mortality. Objective: This scoping review sought to identify and summarise the breadth of evidence available on factors associated with infant mortality in Nigeria. Methods: This review followed the five-stage principles of Arksey and O'Malley's framework. Four electronic databases were searched with no limit to publication date or study type: Ovid MEDLINE, PubMed, CINAHL Complete, and Web of Science. Selected studies were imported into Endnote software and then exported to Rayyan software where duplicates were removed. Included articles were thematically analysed and synthesised using the socioecological model. Results: A total of 8,139 references were compiled and screened. Forty-eight articles were included in the final review. At the individual level, maternal- and child-related factors were revealed to influence infant mortality; socioeconomic and sociocultural factors at the interpersonal level; provision and utilisation of health services, health workforce, hospital resources and access to health services at the organisational level; housing/neighbourhood and environmental factors at the community level; and lastly, governmental factors were found to affect infant mortality at the public policy level. Conclusion: Factors related to the individual, interpersonal, organisational, community and public policy levels were associated with infant mortality in Nigeria. [ABSTRACT FROM AUTHOR]

BackgroundResearch on group antenatal care in low- and middle-income contexts suggests high acceptability and preliminary implementation success.MethodsWe studied the effect of group antenatal care on gestational age at birth among women in Rwanda, hypothesizing that participation would increase mean gestational length. For this unblinded cluster randomized trial, 36 health centers were pair-matched and randomized; half continued individual antenatal care (control), half implemented group antenatal care (intervention). Women who initiated antenatal care between May 2017 and December 2018 were invited to participate, and included in analyses if they presented before 24 weeks gestation, attended at least two visits, and their birth outcome was obtained. We used a generalized estimating equations model for analysis.FindingsIn total, 4091 women in 18 control clusters and 4752 women in 18 intervention clusters were included in the analysis. On average, women attended three total antenatal care visits. Gestational length was equivalent in the intervention and control groups (39.3 weeks (SD 1.6) and 39.3 weeks (SD 1.5)). There were no significant differences between groups in secondary outcomes except that more women in control sites attended postnatal care visits (40.1% versus 29.7%, p = 0.003) and more women in intervention sites attended at least three total antenatal care visits (80.7% versus 71.7%, p = 0.003). No harms were observed.InterpretationGroup antenatal care did not result in a difference in gestational length between groups. This may be due to the low intervention dose. We suggest studies of both the effectiveness and costs of higher doses of group antenatal care among women at higher risk of preterm birth. We observed threats to group care due to facility staff shortages; we recommend studies in which antenatal care providers are exclusively allocated to group antenatal care during visits.Trial registrationClinicalTrials.gov NCT03154177.

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.

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

The etiology of necrotizing enterocolitis (NEC) is not known. Alterations in gut microbiome, mucosal barrier function, immune cell activation, and blood flow are characterized events in its development, with stress as a contributing factor. The hormone corticotropin-releasing factor (CRF) is a key mediator of stress responses and influences these aforementioned processes. CRF signaling is modulated by NEC's main risk factors of prematurity and formula feeding. Using an established neonatal rat model of NEC, we tested hypotheses that: (i) increased CRF levels-as seen during stress-promote NEC in formula-fed (FF) newborn rats, and (ii) antagonism of CRF action ameliorates NEC. Newborn pups were formula-fed to initiate gut inflammation and randomized to: no stress, no stress with subcutaneous CRF administration, stress (acute hypoxia followed by cold exposure-NEC model), or stress after pretreatment with the CRF peptide antagonist Astressin. Dam-fed unstressed and stressed littermates served as controls. NEC incidence and severity in the terminal ileum were determined using a histologic scoring system. Changes in CRF, CRF receptor (CRFRs), and toll-like receptor 4 (TLR4) expression levels were determined by immunofluorescence and immunoblotting, respectively. Stress exposure in FF neonates resulted in 40.0% NEC incidence, whereas exogenous CRF administration resulted in 51.7% NEC incidence compared to 8.7% in FF non-stressed neonates (p

Congenital syphilis is the result of placental transmission from mother to fetus of Treponema pallidum. Although congenital syphilis is preventable through timely treatment, the rate of new infections in the United States (US) has increased each year since 2013, and is increasing at a noticeably greater pace in California (CA). Most research into congenital syphilis has focused on individual psychosocial and behavioral factors that contribute to maternal vulnerability for syphilis. The aim of this study was to evaluate structural barriers to prenatal care access and utilization and congenital syphilis prevention in Kern County, CA. Transcripts from 8 in-depth interviews with prenatal care providers and 5 focus group discussions with 42 pregnant and postpartum persons were examined using thematic analysis. Structural barriers experienced by pregnant and postpartum persons to prenatal care access and utilization included (1) burdens of poverty; (2) stigma around substance use in pregnancy; (3) citizenship status; (4) lack of healthcare coverage; (5) low sexual health literacy; and (6) gender inequality Structural barriers experienced by prenatal care providers in congenital syphilis prevention included (1) limited guidance on clinical management of syphilis in pregnancy; (2) decay in public health infrastructure; and (3) inadequate support for managing patients' social comorbidities. The response to congenital syphilis prevention will require an examination of the complex context of social determinants of health in which persons diagnosed with syphilis live in.

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b). [ABSTRACT FROM AUTHOR]

This study investigated the association between parental educational level and infant mortality using data from Vital Statistics and Census in Japan. We used the Census data in 2020 and birth and mortality data from the Vital Statistics from 2018 to 2021 in Japan. Data linkage was conducted between birth data and the Census to link the educational level with parents for birth data and between the birth data and mortality data to identify births that resulted in infant mortality. Four educational levels were compared: "junior high school," "high school," "technical school or junior college," and "university." A multivariate logistic regression model was used to investigate an association between parental educational level and infant mortality using other risk factors as covariates. After the data linkage, data on 890,682 births were analyzed. The proportion of junior high school or high school graduates was higher among fathers and mothers for births with infant mortality compared with that among those for births without infant mortality; in contrast, the proportion of university graduates was lower for births with infant mortality than those without infant mortality. Regression analysis showed that mothers with junior high school or high school graduates were significantly and positively associated with infant mortality compared with those with university graduates. As a conclusion, lower educational level in mothers was positively associated with infant mortality, and it was shown that a difference in infant mortality depending on parental educational level existed in Japan. [ABSTRACT FROM AUTHOR]

Microbes alter their transcriptomic profiles in response to the environment. The physiological conditions experienced by a microbial community can thus be inferred using meta-transcriptomic sequencing by comparing transcription levels of specifically chosen genes. However, this analysis requires accurate reference genomes to identify the specific genes from which RNA reads originate. In addition, such an analysis should avoid biases in transcript counts related to differences in organism abundance. In this study we describe an approach to address these difficulties. Sample-specific meta-genomic assembled genomes (MAGs) were used as reference genomes to accurately identify the origin of RNA reads, and transcript ratios of genes with opposite transcription responses were compared to eliminate biases related to differences in organismal abundance, an approach hereafter named the "diametric ratio" method. We used this approach to probe the environmental conditions experienced by Escherichia spp. in the gut of 4 premature infants, 2 of whom developed necrotizing enterocolitis (NEC), a severe inflammatory intestinal disease. We analyzed twenty fecal samples taken from four premature infants (4-6 time points from each infant), and found significantly higher diametric ratios of genes associated with low oxygen levels in samples of infants later diagnosed with NEC than in samples without NEC. We also show this method can be used for examining other physiological conditions, such as exposure to nitric oxide and osmotic pressure. These study results should be treated with caution, due to the presence of confounding factors that might also distinguish between NEC and control infants. Nevertheless, together with benchmarking analyses, we show here that the diametric ratio approach can be applied for evaluating the physiological conditions experienced by microbes in situ. Results from similar studies can be further applied for designing diagnostic methods to detect NEC in its early developmental stages.

The purpose of this systematic review and meta-analysis of the literature was to analyze and evaluate the impact of prematurity and accelerated weight gain on the risk of childhood and adolescent obesity. CINAHL, Embase, PubMed, and Web of Science databases were searched until December 2019 which yielded 19 studies with a total of 169,439 children enrolled were systematically reviewed. The results revealed that preterm infants had a greater likelihood of childhood obesity (defined as BMI ≥95th percentile for age-sex), than term infants (OR = 1.19, 95% CI [1.13, 1.26]). However, no difference of childhood obesity was found between "small for gestational age"(SGA) and "appropriate for gestational age"(AGA) among preterms. Accelerated weight gain (defined as weight gain velocity during first two years after birth) significantly increased the likelihood of subsequent childhood obesity among preterms (aOR = 1.87, 95% CI [1.57, 2.231]). In conclusion, accelerated weight gain at infancy among preterm children may be a critical contributor to obesity in later life. Establishing optimal growth trajectories and timely referral to health care providers may be of clinical importance.

Obtaining a nutrient-rich diet during pregnancy is a challenge for pregnant women living in low-income countries. This randomized, controlled trial was designed to determine if a freshly prepared food supplement from local animal-source foods and dark-green leafy vegetables given prior to and/or during pregnancy improved birth outcomes in rural Vietnamese women. Primiparous women, 18 to 30 years of age, who participated in the study were assigned to one of three groups: PC-T women received the supplement from pre-conception to term, MG-T women received the supplement from mid-gestation to term, and the RPC women received routine prenatal care. Supplement intake was observed and quantified. Infant anthropometry was measured at birth and/or within seven days of delivery. The effect of the intervention on maternal and birth outcomes was determined using linear regression modeling. Of the 460 women enrolled in the study, 317 women completed the study. Those not completing the study had either moved from the area, did not conceive within 12 months of study enrollment, or miscarried. The food-based supplement increased protein, iron, zinc, folate, vitamin A and B12 intakes in the PC-T and the MG-T groups. However, it failed to alter infant anthropometric measurements at birth. In the entire cohort, maternal gestational weight gain was greater in women with a low pre-pregnancy BMI (

Growth faltering among children during the first five years of life is a common problem among low and middle-income countries. The purpose of this study was to determine the effect of a nutrient-rich, food-based supplement given to Vietnamese rural women prior to and/or during pregnancy on the growth of their infants during first 24 months of life and to identify maternal and newborn factors associated with the infant's growth. This prospective cohort study included 236 infants born to mothers who had received nutritional advice or a food supplement from pre-conception to term or from mid-gestation to term as part of a prior randomized controlled trial. Infant anthropometry and feeding information were monitored monthly and the infant weight for age Z-score (WAZ), length for age Z-score (LAZ), and weight for length Z-score (WLZ) were assessed at 6, 12, 18, and 24 months of age using mixed-effects regression modeling. Compared to the non-supplemented mothers, infants born to mothers receiving food supplementation from mid-gestation to term had significantly higher WLZ only at 18 months (p = 0.03) and did not differ in other outcomes. Supplementation from pre-conception to term did not affect infant growth at any time point during the first 24 months. In the entire study cohort, maternal height and gestational weight gain were positively associated with the infant's WAZ and LAZ from 6 to 24 months of age. Programs designed to improve gestational weight gain among women performing demanding physical work throughout a reproductive cycle may improve postnatal infant growth. Trial registration: Registered Clinical Trials.Gov: NCT01235767.

ObjectivePreterm birth is the primary driver of neonatal mortality worldwide, but it is defined by gestational age (GA) which is challenging to accurately assess in low-resource settings. In a commitment to reducing preterm birth while reinforcing and strengthening facility data sources, the East Africa Preterm Birth Initiative (PTBi-EA) chose eligibility criteria that combined GA and birth weight. This analysis evaluated the quality of the GA data as recorded in maternity registers in PTBi-EA study facilities and the strength of the PTBi-EA eligibility criteria.MethodsWe conducted a retrospective analysis of maternity register data from March-September 2016. GA data from 23 study facilities in Migori, Kenya and the Busoga Region of Uganda were evaluated for completeness (variable present), consistency (recorded versus calculated GA), and plausibility (falling within the 3rd and 97th birth weight percentiles for GA of the INTERGROWTH-21st Newborn Birth Weight Standards). Preterm birth rates were calculated using: 1) recorded GA

INTRODUCTION:As facility-based deliveries increase globally, maternity registers offer a promising way of documenting pregnancy outcomes and understanding opportunities for perinatal mortality prevention. This study aims to contribute to global quality improvement efforts by characterizing facility-based pregnancy outcomes in Kenya and Uganda including maternal, neonatal, and fetal outcomes at the time of delivery and neonatal discharge outcomes using strengthened maternity registers. METHODS:Cross sectional data were collected from strengthened maternity registers at 23 facilities over 18 months. Data strengthening efforts included provision of supplies, training on standard indicator definitions, and monthly feedback on completeness. Pregnancy outcomes were classified as live births, early stillbirths, late stillbirths, or spontaneous abortions according to birth weight or gestational age. Discharge outcomes were assessed for all live births. Outcomes were assessed by country and by infant, maternal, and facility characteristics. Maternal mortality was also examined. RESULTS:Among 50,981 deliveries, 91.3% were live born and, of those, 1.6% died before discharge. An additional 0.5% of deliveries were early stillbirths, 3.6% late stillbirths, and 4.7% spontaneous abortions. There were 64 documented maternal deaths (0.1%). Preterm and low birthweight infants represented a disproportionate number of stillbirths and pre-discharge deaths, yet very few were born at ≤1500g or

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.

ObjectiveTo identify current maternal and infant predictors of infant mortality, including maternal sociodemographic and economic status, maternal perinatal smoking and obesity, mode of delivery, and infant birthweight and gestational age.MethodsThis retrospective study analyzed data from the linked birth and infant death files (birth cohort) and live births from the Birth Statistical Master files (BSMF) in California compiled by the California Department of Public Health for 2007-2015. The birth cohort study comprised 4,503,197 singleton births including 19,301 infant deaths during the nine-year study period. A subpopulation to study fetal growth consisted of 4,448,300 birth cohort records including 13,891 infant deaths.ResultsThe infant mortality rate (IMR) for singleton births decreased linearly (p

BackgroundGoal 3.2 from the Sustainable Development Goals (SDG) calls for reductions in national averages of Under-5 Mortality. However, it is well known that within countries these reductions can coexist with left behind populations that have mortality rates higher than national averages. To measure inequality in under-5 mortality and to identify left behind populations, mortality rates are often disaggregated by socioeconomic status within countries. While socioeconomic disparities are important, this approach does not quantify within group variability since births from the same socioeconomic group may have different mortality risks. This is the case because mortality risk depends on several risk factors and their interactions and births from the same socioeconomic group may have different risk factor combinations. Therefore mortality risk can be highly variable within socioeconomic groups. We develop a comprehensive approach using information from multiple risk factors simultaneously to measure inequality in mortality and to identify left behind populations.MethodsWe use Demographic and Health Surveys (DHS) data on 1,691,039 births from 182 different surveys from 67 low and middle income countries, 51 of which had at least two surveys. We estimate mortality risk for each child in the data using a Bayesian hierarchical logistic regression model. We include commonly used risk factors for monitoring inequality in early life mortality for the SDG as well as their interactions. We quantify variability in mortality risk within and between socioeconomic groups and describe the highest risk sub-populations.FindingsFor all countries there is more variability in mortality within socioeconomic groups than between them. Within countries, socioeconomic membership usually explains less than 20% of the total variation in mortality risk. In contrast, country of birth explains 19% of the total variance in mortality risk. Targeting the 20% highest risk children based on our model better identifies under-5 deaths than targeting the 20% poorest. For all surveys, we report efficiency gains from 26% in Mali to 578% in Guyana. High risk births tend to be births from mothers who are in the lowest socioeconomic group, live in rural areas and/or have already experienced a prior death of a child.InterpretationWhile important, differences in under-5 mortality across socioeconomic groups do not explain most of overall inequality in mortality risk because births from the same socioeconomic groups have different mortality risks. Similarly, policy makers can reach the highest risk children by targeting births based on several risk factors (socioeconomic status, residing in rural areas, having a previous death of a child and more) instead of using a single risk factor such as socioeconomic status. We suggest that researchers and policy makers monitor inequality in under-5 mortality using multiple risk factors simultaneously, quantifying inequality as a function of several risk factors to identify left behind populations in need of policy interventions and to help monitor progress toward the SDG.

Spontaneous preterm birth (sPTB) is a major cause of infant morbidity and mortality. While metabolic changes leading to preterm birth are unknown, several factors including dyslipidemia and inflammation have been implicated and paradoxically both low (30 kg/m2) body mass indices (BMIs) are risk factors for this condition. The objective of the study was to identify BMI-associated metabolic perturbations and potential mid-gestation serum biomarkers of preterm birth in a cohort of underweight, normal weight and obese women experiencing either sPTB or full-term deliveries (n = 102; n = 17/group). For this purpose, we combined untargeted metabolomics and lipidomics with targeted metabolic profiling of major regulators of inflammation and metabolism, including oxylipins, endocannabinoids, bile acids and ceramides. Women who were obese and had sPTB showed elevated oxidative stress and dyslipidemia characterized by elevated serum free fatty acids. Women who were underweight-associated sPTB also showed evidence of dyslipidemia characterized by elevated phospholipids, unsaturated triglycerides, sphingomyelins, cholesteryl esters and long-chain acylcarnitines. In normal weight women experiencing sPTB, the relative abundance of 14(15)-epoxyeicosatrienoic acid and 14,15-dihydroxyeicosatrienoic acids to other regioisomers were altered at mid-pregnancy. This phenomenon is not yet associated with any biological process, but may be linked to estrogen metabolism. These changes were differentially modulated across BMI groups. In conclusion, using metabolomics we observed distinct BMI-dependent metabolic manifestations among women who had sPTB. These observations suggest the potential to predict sPTB mid-gestation using a new set of metabolomic markers and BMI stratification. This study opens the door to further investigate the role of cytochrome P450/epoxide hydrolase metabolism in sPTB.

ObjectivePlacental malaria is a known risk factor for small for gestational age (SGA) neonates. However, currently utilized international and African birthweight standards have not controlled for placental malaria and/or lack obstetrical ultrasound dating. We developed a neonatal birthweight standard based on obstetrically dated pregnancies that excluded individuals with clinical malaria, asymptomatic parasitemia, and placental malaria infection. We hypothesized that current curves underestimate true ideal birthweight and the prevalence of SGA.Study designParticipants were pooled from two double-blind randomized control trials of intermittent preventive therapy during pregnancy in Uganda. HIV-negative women without comorbidities were enrolled from 12-20 weeks gestation. Gestational age was confirmed by ultrasound dating. Women were followed through pregnancy and delivery for clinical malaria, asymptomatic parasitemia, and placental malaria. Women without malaria, asymptomatic parasitemia, or placental malaria formed the malaria negative cohort and generated the Ugandan birthweight standard. The Ugandan standard was then used to estimate the prevalence of SGA neonates in the malaria positive cohort. These findings were compared to international (Williams, World Health Organization (WHO), and INTERGROWTH-21st) and regional standards (Tanzanian and Malawi).Results926 women had complete delivery data; 393 (42.4%) met criteria for the malaria negative cohort and 533 (57.6%) were malaria positive. The Ugandan standard diagnosed SGA in 17.1% of malaria positive neonates; similar to the INTERGROWTH-21st and Schmiegelow curves. The WHO curve diagnosed SGA in significantly more neonates (32.1%, p =

BackgroundDespite being one of the wealthiest nations, disparities in adverse birth outcomes persist across racial and ethnic lines in the United States. We studied the association between historical redlining and preterm birth, low birth weight (LBW), small-for-gestational age (SGA), and perinatal mortality over a ten-year period (2006-2015) in Los Angeles, Oakland, and San Francisco, California.MethodsWe used birth outcomes data from the California Office of Statewide Health Planning and Development between January 1, 2006 and December 31, 2015. Home Owners' Loan Corporation (HOLC) Security Maps developed in the 1930s assigned neighborhoods one of four grades that pertained to perceived investment risk of borrowers from that neighborhood: green (grade A) were considered "Best", blue (grade B) "Still Desirable", yellow (grade C) "Definitely Declining", and red (grade D, hence the term "redlining") "Hazardous". Geocoded residential addresses at the time of birth were superimposed on HOLC Security Maps to assign each birth a HOLC grade. We adjusted for potential confounders present at the time of Security Map creation by assigning HOLC polygons areal-weighted 1940s Census measures. We then employed propensity score matching methods to estimate the association of historical HOLC grades on current birth outcomes. Because tracts graded A had almost no propensity of receiving grade C or D and because grade B tracts had low propensity of receiving grade D, we examined birth outcomes in the three following comparisons: B vs. A, C vs. B, and D vs. C.ResultsThe prevalence of preterm birth, SGA and mortality tended to be higher in worse HOLC grades, while the prevalence of LBW varied across grades. Overall odds of mortality and preterm birth increased as HOLC grade worsened. Propensity score matching balanced 1940s census measures across contrasting groups. Logistic regression models revealed significantly elevated odds of preterm birth (odds ratio (OR): 1.02, 95% confidence interval (CI): 1.00-1.05), and SGA (OR: 1.03, 95% CI: 1.00-1.05) in the C vs. B comparison and significantly reduced odds of preterm birth (OR: 0.93, 95% CI: 0.91-0.95), LBW (OR: 0.94-95% CI: 0.92-0.97), and SGA (OR: 0.94, 95% CI: 0.92-0.96) in the D vs. C comparison. Results differed by metropolitan area and maternal race.ConclusionSimilar to prior studies on redlining, we found that worsening HOLC grade was associated with adverse birth outcomes, although this relationship was less clear after propensity score matching and stratifying by metropolitan area. Higher odds of preterm birth and SGA in grade C versus grade B neighborhoods may be caused by higher-stress environments, racial segregation, and lack of access to resources, while lower odds of preterm birth, SGA, and LBW in grade D versus grade C neighborhoods may due to population shifts in those neighborhoods related to gentrification.

The global fallout from atmospheric nuclear weapons testing in the 1950s and 1960s caused by far the greatest exposure of mankind to ionizing radiation. Surprisingly few epidemiological studies of the possible health effects of atmospheric testing have been conducted. Here, long-term trends in infant mortality rates in the United States (U.S.) and five major European countries (EU5) were examined: The United Kingdom, Germany, France, Italy, and Spain. Bell-shaped deviations from a uniformly decreasing secular trend were found beginning in 1950, with maxima around 1965 in the U.S. and 1970 in EU5. From the difference between observed and predicted infant mortality rates, in the period 1950–2000, the overall increase in infant mortality rates was estimated to be 20.6 (90% CI: 18.6 to 22.9) percent in the U.S. and 14.2 (90% CI: 11.7 to 18.3) percent in EU5 which translates to 568,624 (90% CI: 522,359 to 619,705) excess infant deaths in the U.S. and 559,370 (90% CI: 469,308 to 694,589) in the combined five European countries. The results should be interpreted with caution because they rely on the assumption of a uniformly decreasing secular trend if there had been no nuclear tests, but this cannot be verified. It is concluded that atmospheric nuclear weapons testing may be responsible for the deaths of several million babies in the Northern Hemisphere. [ABSTRACT FROM AUTHOR]

The emergence of environmental nongovernmental organizations (ENGOs) has proved beneficial in improving environmental quality and related health issues. Therefore, this study attempts to investigate the impact of ENGO on human health in China from 1995 to 2020. To investigate the relationship between the variables, we have employed the ARDL model. The ARDL model results demonstrate that the long-run impact of ENGO is negative on infant mortality and death rate, meaning that an increase in the proportion of ENGOs in China considerably decreases infant mortality and death rate. On the other hand, ENGOs have a favorable influence on life expectancy in China, demonstrating ENGOs' supporting role in raising birth life expectancy. In the short run, estimates of ENGOs have no substantial influence on newborn mortality and death rates in China, whereas ENGOs have a positive and significant impact on life expectancy. These results imply that ENGOs help improves people's health status in China, which is also supported by the rise in GDP, technology, and health expenditures. The causal analysis confirms the bi-directional causal link between ENGO and IMR and ENGO and LE, while the unidirectional causal link runs from ENGO to DR. The results of the study provide insights into the impact of environmental NGOs on human health in China and may help guide policies aimed at improving public health outcomes through environmental protection efforts. [ABSTRACT FROM AUTHOR]

Introduction: Infant mortality declined globally in the last three decades. However, it is still a major public health concern in Ethiopia. The burden of infant mortality varies geographically with the highest rate in Sub-Saharan Africa. Although different kinds of literature are available regarding infant mortality in Ethiopia, an up to date information is needed to design strategies against the problem. Thus, this study aimed to determine the prevalence, show the spatial variations and identify determinants of infant mortality in Ethiopia. Methods: The prevalence, spatial distribution, and predictors of infant mortality among 5,687 weighted live births were investigated using secondary data from the Ethiopian Demographic and Health Survey 2019. Spatial autocorrelation analysis was used to determine the spatial dependency of infant mortality. The spatial clustering of infant mortality was studied using hotspot analyses. In an unsampled area, ordinary interpolation was employed to forecast infant mortality. A mixed multilevel logistic regression model was used to find determinants of infant mortality. Variables with a p-value less than 0.05 were judged statistically significant and adjusted odds ratios with 95 percent confidence intervals were calculated. Result: The prevalence of infant mortality in Ethiopia was 44.5 infant deaths per 1000 live births with significant spatial variations across the country. The highest rate of infant mortality was observed in Eastern, Northwestern, and Southwestern parts of Ethiopia. Maternal age between 15&19 (adjusted odds ratio (AOR) = 2.51, 95% Confidence Interval (CI): 1.37, 4.61) and 45&49(AOR = 5.72, 95% CI: 2.81, 11.67), having no antenatal care follow-up (AOR = 1.71, 95% CI: 1.05, 2.79) and Somali region (AOR = 2.78, 95% CI: 1.05, 7.36) were significantly associated with infant mortality in Ethiopia. Conclusion: In Ethiopia, infant mortality was higher than the worldwide objective with significant spatial variations. As a result, policy measures and strategies aimed at lowering infant mortality should be devised and strengthened in clustered areas of the country. Special attention should be also given to infants born to mothers in the age groups of 15–19 and 45–49, infants of mothers with no antenatal care checkups, and infants born to mothers living in the Somali region. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Short Birth Interval (SBI) is higher in Low- and Middle-Income countries (LMICs), including Bangladesh. Previous studies in LMICs have estimated the effects of SBI on child mortality by comparing two unequal groups of mothers based on their socio-economic status. This approach may lead to overestimation or underestimation of the true effect of birth interval on child mortality, particularly when sample sizes are relatively small. Objective: We determined the effects of SBI on several forms of child mortality in Bangladesh by comparing two equal groups created by applying the propensity score matching technique. Methods: This study analyzed data from 5,941 mothers and 1,594 health facilities extracted from the 2017/18 Bangladesh Demographic and Health Survey and the 2017 Bangladesh Health Facility Survey. The exposure variable was SBI (defined as the interval between two subsequent births <33 months: yes, no), while the outcome variables were neonatal mortality (defined as mortality within 28 days of birth: yes, no), infant mortality (defined as mortality within 1 year of birth: yes, no), and under-five mortality (defined as mortality within 5 years of birth: yes, no). Multilevel Poisson regression based on inverse probability treatment weights was used to determine the association between exposure and outcome variables. Results: The prevalence rates of neonatal, infant, and under-five mortality were 48.8, 30.8, and 23.1 per 1000 live births, respectively. Newborns of SBI mothers were found to have a 63% higher likelihood of neonatal mortality (aPR, 1.63; 95% CI, 1.08–2.46) compared to newborns of non-SBI mothers. Furthermore, the prevalence of infant mortality and under-five mortality was 1.45 times higher (aPR, 1.45; 95% CI, 1.01–2.08) and 2.82 times higher (aPR, 2.82; 95% CI, 2.16–3.70), respectively, among babies born in a short interval of their immediately preceding sibling as compared to babies born in a normal interval of their immediately preceding sibling. Conclusions: Findings of this study indicate that SBI is an important predictor of child mortality. Consequently, around 1 million children born in a short interval every year in Bangladesh are at risk of dying before reaching their fifth birthday. This indicates a challenge for Bangladesh to achieve the SDG 3 target to reduce neonatal and under-five mortality to 12 and 25 deaths per 1000 live births, respectively. Hence, awareness-building programs about the adverse effects of SBI and strengthening existing healthcare facilities are important. [ABSTRACT FROM AUTHOR]

IntroductionBrain tumors are the most common solid malignancy and leading cause of cancer-related deaths in infants. Current epidemiological data is limited by low numbers of reported cases. This study used a population-based approach with analysis of contemporary and historical survival curves to provide up-to-date prognostication.MethodsObservational cohort analysis was performed using the Surveillance, Epidemiology and End Results (SEER) database. Infants with brain tumors diagnosed from 1973 to 2013 were categorized by the most common tumor types (diffuse astrocytic and oligodendroglioma, choroid plexus, embryonal, ependymal, medulloblastoma and pilocytic astrocytoma). The 1, 5 and 10 year survival was stratified by decade, with trends in management and outcomes analyzed.ResultsWe identified 2996 affected infants satisfying inclusion criteria. All tumor types, except embryonal and choroid plexus, demonstrated improving survival with time. Infants with embryonal tumors showed a decline in survival from the 1970s to 1990s (p = 0.009), whereas infants with choroid plexus tumors had no change in survival. Infants with ependymal tumors experienced the greatest improvement in survival from 1980s to 1990s and 1990s to 2000s (p = 0.0001, p = 0.01), with 5-year survival probability improving from 28% (95% CI 15-42%) in the 1980s to 77% (95% CI 69-83%) the 2000s. The use of radiation declined from 1970 to 2000 for all tumors; however, radiation treatment for embryonal and ependymal subtypes increased after 2000.ConclusionsWhile overall survival for infants with brain tumors has improved from the 1970s onwards, not every tumor type has seen a statistically significant change. Given changes in management and survival, prognostication of infants with brain tumor should be updated.

BACKGROUND:Information is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases. METHODS AND FINDINGS:Between 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn's Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumab-exposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort (adjusted odds ratio 1.10, 95% confidence interval [CI] 0.45 to 2.73). Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the diseased unexposed cohort (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were noted with adalimumab exposure for any other study outcomes. CONCLUSIONS:Adalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn's Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.

ObjectiveTo determine recent trends in maternal prepregnancy body mass index (BMI) and to quantify its association with birth and maternal outcomes.MethodsA population-based retrospective cohort study included resident women with singleton births in the California Birth Statistical Master Files (BSMF) database from 2007 to 2016. There were 4,621,082 women included out of 5,054,968 women registered in the database. 433,886 (8.6%) women were excluded due to invalid or missing information for BMI. Exposures were underweight (BMI < 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥ 30 kg/m2) at the onset of pregnancy. Obesity was subcategorized into class I (30.0-34.9 kg/m2), class II (35.0-39.9 kg/m2), and class III (≥ 40 kg/m2), while adverse outcomes examined were low birth weight (LBW), very low birth weight (VLBW), macrosomic births, preterm birth (PTB), very preterm birth (VPTB), small-for-gestational-age birth (SGA), large-for-gestational-age birth (LGA), and cesarean delivery (CD). Descriptive analysis, simple linear regression, and multivariate logistic regression were performed, and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations were estimated.ResultsOver the ten-year study period, the prevalence of underweight and normal weight women at time of birth declined by 10.6% and 9.7%, respectively, while the prevalence of overweight and obese increased by 4.3% and 22.9%, respectively. VLBW increased significantly with increasing BMI, by 24% in overweight women and by 76% in women with class III obesity from 2007 to 2016. Women with class III obesity also had a significant increase in macrosomic birth (170%) and were more likely to deliver PTB (33%), VPTB (66%), LGA (231%), and CD (208%) than women with a normal BMI. However, obese women were less likely to have SGA infants; underweight women were 51% more likely to have SGA infants than women with a normal BMI.ConclusionsIn California from 2007 to 2016, there was a declining trend in women with prepregnancy normal weight, and a rising trend in overweight and obese women, particularly obesity class III. Both extremes of prepregnancy BMI were associated with an increased incidence of adverse neonatal outcomes; however, the worse outcomes were prominent in those women classified as obese.

Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Histopathological studies of preterm birth suggest advanced villous maturity may have a role in idiopathic spontaneous preterm birth (isPTB). To better understand pathological and molecular basis of isPTB, we compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB between 28-36 weeks gestation and healthy term placentas. Transcriptomic analyses revealed a unique expression signature for isPTB distinct from the age-matched controls that were delivered prematurely due to infection. This signature included the upregulation of three IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for aberrant IGF signaling in isPTB. However, within the isPTB expression signature, we detected secondary signature of inflammatory markers including TNC, C3, CFH, and C1R, which have been associated with placental maturity. In contrast, the expression signature of the gestational age-matched infected samples included upregulation of proliferative genes along with cell cycling and mitosis pathways. Together, these data suggest an isPTB molecular signature of placental hypermaturity, likely contributing to the premature activation of inflammatory pathways associated with birth and providing a molecular basis for idiopathic spontaneous birth.

Background and objectiveAs of 2016, 43 US states have policies regarding alcohol use during pregnancy. A recent study found that out of eight state-level alcohol/pregnancy policies, six are significantly associated with poorer birth outcomes, and two are not associated with any outcomes. Here we estimate the excess numbers of low birthweight (LBW) and preterm births (PTB) related to these policies and their associated additional costs in the first year of life.MethodsCost study using birth certificate data for 155,446,714 singleton live births in the United States between 1972-2015. Exposures were state- and month/year-specific indicators of having each of eight alcohol/pregnancy policies in place. Outcomes were excess numbers of LBW and PTB and associated costs in the first year of life. Fixed effects regressions with state-specific time trends were used for statistical analyses in 2018.ResultsIn 2015, policies mandating warning signs were associated with an excess of 7,375 LBW; policies defining alcohol use during pregnancy as child abuse/neglect were associated with an excess of 12,372 PTB; these excess adverse outcomes are associated with additional costs of $151,928,002 and $582,698,853 in the first year of life, respectively.ConclusionsMultiple state-level alcohol pregnancy policies lead to increased prevalence of LBW and PTB, which cost hundreds of millions of dollars annually. Policymakers should consider adverse public health impacts of alcohol/pregnancy policies before expanding extant policies to new substances or adopting existing policies in new states.

Physical activity (PA) is important from birth to promote health and motor development. Parents of young children are gatekeepers of opportunities for PA, yet little is known about their perceptions of PA. We describe the development of the Parent Perceptions of Physical Activity Scale (PPPAS) across two studies (N = 241 parents). In Study 1, 143 parents of infants and toddlers recruited from neonatal intensive care units (NICUs) and childcare centers completed a 48-item PPPAS. In Study 2, 98 parents of premature infants completed the revised 34-item PPPAS. Study 1 principal components analysis (PCA) identified three components (benefits of, barriers to, and perceived influence on PA), and the scale was reduced. Scores for Perceived Barriers to PA were significantly different between groups, U = 1,108, z = -4.777, p < .0001, with NICU parents reporting more barriers to PA than childcare parents. In Study 2, PCA revealed the same components, and the scale was further reduced to 25 items. Three subscales measuring perceived benefits of, barriers to, and influence over an infant's PA produced Cronbach's alphas of .93, .85, .81, respectively. Results demonstrated sufficient construct validity and internal consistency of PPPAS scores, supporting its use in future PA research.

Although average contraceptive use has increased globally in recent decades, an estimated 222 million (26%) of women of child-bearing age worldwide face an unmet need for family planning—defined as a discrepancy between fertility preferences and contraception practice, or failing to translate desires to avoid pregnancy into preventative behaviours and practices. While many studies have reported relationships between availability/quality of contraception and family planning, infant mortality, and fertility, these relationships have not been evaluated quantitatively across a broad range of low- and middle-income countries. Using publicly available data from 64 low- and middle-income countries, we collated test and control variables in six themes: (i) availability of family planning, (ii) quality of family planning, (iii) female education, (iv) religion, (v) mortality, and (vi) socio-economic conditions. We predicted that higher nation-level availability/quality of family-planning services and female education reduce average fertility, whereas higher infant mortality, greater household size (a proxy for population density), and religious adherence increase it. Given the sample size, we first constructed general linear models to test for relationships between fertility and the variables from each theme, from which we retained those with the highest explanatory power within a final general linear model set to determine the partial correlation of dominant test variables. We also applied boosted regression trees, generalised least-squares models, and generalised linear mixed-effects models to account for non-linearity and spatial autocorrelation. On average among all countries, we found the strongest associations between fertility and infant mortality, household size, and access to any form of contraception. Higher infant mortality and household size increased fertility, whereas greater access to any form of contraception decreased fertility. Female education, home visitations by health workers, quality of family planning, and religious adherence all had weak, if any, explanatory power. Our models suggest that decreasing infant mortality, ensuring sufficient housing to reduce household size, and increasing access to contraception will have the greatest effect on decreasing global fertility. We thus provide new evidence that progressing the United Nation's Sustainable Development Goals for reducing infant mortality can be accelerated by increasing access to family planning. [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between postpartum depression and infant feeding practice may help to reduce the indirect impact of postpartum depression on infant feeding practice. This will further have a positive impact on reducing infant morbidity and mortality attributed to improper feeding practices. Although studies in the country have assessed the prevalence of infant feeding practices, those assessing the association between postpartum depression and infant feeding practices are lacking. Therefore, this study aimed to compare appropriate infant feeding practices and their associated factors among postpartum depressed and non-depressed mothers in Eastern Tigray. Methods: A comparative cross-sectional study was conducted from March 2019 to April 2019. A multistage random sampling technique was used to select 171 mothers with postpartum depression and 342 mothers without postpartum depression. Data were collected using a structured questionnaire from the Monitoring and Evaluating for Breastfeeding Practices toolkit, then entered into Epi- info and exported into SPSS for further analysis. A binary logistic regression was applied to determine the association between postpartum depression and appropriate infant feeding practice. Results: The overall prevalence of appropriate infant feeding practice was 37.6% (95% CI: 33.5%-41.9%). The prevalence was higher among mothers without postpartum depression 42.7% (95% CI: 42.9%-53.2%) than among postpartum depressed mothers 27.5% (95% CI: 24.7%-32.5%). The odds of appropriate infant feeding practice among mothers with infant birth orders of three or above was 58% (AOR = 0.42; 95% CI: 0.26–0.97) less than those mothers with infant birth orders of three and below. Households with monthly income 1000–1999 ETB (AOR = 2.26; 95% CI: 1.01–5.08), 2000–2999 ETB (AOR = 1.96; 95% CI: 1.21–4.73) and 3000–3999 ETB (AOR = 5.13; 95% CI: 1.97–13.4) were more likely to practice appropriate infant feeding. Conclusion: The overall prevalence of appropriate infant feeding practices in the study area was low. A significantly higher proportion of mothers without postpartum depression practice appropriate infant feeding compared to mothers with postpartum depression. In addition, households with higher monthly incomes and mothers with infant birth orders three or above were significant determinants of appropriate infant feeding practice. Therefore, strengthening the provisions of nutritional education, integrating maternal mental health with routine maternal health care services, providing economic support to mothers with low income, and health education for multiparous women is a critical interventions to improve appropriate infant feeding practice. [ABSTRACT FROM AUTHOR]

BackgroundGlobally, there were 2.7 million neonatal deaths in 2015. Significant mortality reduction could be achieved by improving care in low- and middle-income countries (LMIC), where the majority of deaths occur. Determining the physical readiness of facilities to identify and manage complications is an essential component of strategies to reduce neonatal mortality.MethodsWe developed clinical cascades for 6 common neonatal conditions then utilized these to assess 23 health facilities in Kenya and Uganda at 2 time-points in 2016 and 2017. We calculated changes in resource availability over time by facility using McNemar's test. We estimated mean readiness and loss of readiness for the 6 conditions and 3 stages of care (identification, treatment, monitoring-modifying treatment). We estimated overall mean readiness and readiness loss across all conditions and stages. Finally, we compared readiness of facilities with a newborn special care unit (NSCU) to those without using the two-sample test of proportions.ResultsThe cascade model estimated mean readiness of 26.3-26.6% across the 3 stages for all conditions. Mean readiness ranged from 11.6% (respiratory distress-apnea) to 47.8% (essential newborn care) across both time-points. The model estimated overall mean readiness loss of 30.4-31.9%. There was mild to moderate variability in the timing of readiness loss, with the majority occurring in the identification stage. Overall mean readiness was higher among facilities with a NSCU (36.8%) compared to those without (20.0%).ConclusionThe cascade model provides a novel approach to quantitatively assess physical readiness for neonatal care. Among 23 facilities in Kenya and Uganda, we identified a consistent pattern of 30-32% readiness loss across cascades and stages. This aggregate measure could be used to monitor and compare readiness at the facility-, health system-, or national-level. Estimates of readiness and loss of readiness may help guide strategies to improve care, prioritize resources, and promote neonatal survival in LMICs.

BackgroundWhereas poor maternal nutritional status before and during pregnancy is widely associated with adverse birth outcomes, studies quantifying this association in low income countries are scarce. We examined whether maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy are associated with birth outcomes in rural Malawi.MethodsWe analyzed the associations between pre-pregnancy BMI and average weekly gestational weight gain (WWG) and birth outcomes [duration of gestation, birth weight, length-for-age z-score (LAZ), and head circumference-for-age z-score (HCZ)]. We also determined whether women with low or high pre-pregnancy BMI or women with inadequate or excessive WWG were at increased risk of adverse birth outcomes.ResultsThe analyses included 1287 women with a mean BMI of 21.8 kg/m2, of whom 5.9% were underweight (< 18.5 kg/m2), 10.9% were overweight (≥ 25 kg/m2), 71.8% had low WWG [below the lower limit of the Institute of Medicine (IOM) recommendation], and 5.2% had high WWG (above IOM recommendation). In adjusted models, pre-pregnancy BMI was not associated with duration of pregnancy (p = 0.926), but was positively associated with birth weight and HCZ (

BackgroundMen who have sex with men (MSM) and transgender women in Peru are at high risk for acquiring syphilis and HIV infection. The World Health Organization highly recommends screening for HIV and syphilis to reduce morbidity and mortality associated with untreated infections. We aimed to identify factors associated with dual testing preferences for HIV and syphilis infection among MSM and transgender women in Lima, Peru.MethodsWe used conjoint analysis, an innovative method for systematically estimating consumer preferences. We created eight hypothetical test profiles varying across six dichotomous attributes: cost (free vs. $4), potential for false positive syphilis result (no false positive vs. some risk of false positive), time-to-result (20 minutes vs. 1 week), blood draw method (finger prick vs. venipuncture), test type (rapid vs. laboratory), and number of draws (1 vs. 2). We fit a conjoint analysis model for each participant using a simple main effects ANOVA. Attribute importance values were calculated using percentages from relative ranges in the attribute's utility values. Results were summarized across participants and averages were reported.ResultsWe recruited 415 MSM/transgender women over 18 years of age from two STD clinics in Lima, Peru. No potential for syphilis false positive result (no false positive vs. some potential for false positive) had the largest average impact on willingness to use the test and on average accounted for 23.8% of test type preference, followed by cost (free vs. ~USD$4; 21.6%), time to results (20 minutes vs. 1 week; 17.4%), number of blood draws (1 draw vs. 2 draws; 13.8%), method of blood draw (fingerprick vs. venipuncture; 13.7%), and test type (rapid POC vs. laboratory; 9.7%).ConclusionMSM/transgender women in Peru prioritized accuracy, cost, timeliness and number of blood draws for HIV and syphilis testing. Implementing a low cost, accurate, rapid and dual testing strategy for HIV and syphilis could improve screening uptake and accessibility of testing to accelerate time to treatment.

BackgroundGlobally, the rate of reduction in delivery-associated maternal and perinatal mortality has been slow compared to improvements in post-delivery mortality in children under five. Improving clinical readiness for basic obstetric emergencies is crucial for reducing facility-based maternal deaths. Emergency readiness is commonly assessed using tracers derived from the maternal signal functions model.Objective-methodWe compare emergency readiness using the signal functions model and a novel clinical cascade. The cascades model readiness as the proportion of facilities with resources to identify the emergency (stage 1), treat it (stage 2) and monitor-modify therapy (stage 3). Data were collected from 44 Kenyan clinics as part of an implementation trial.FindingsAlthough most facilities (77.0%) stock maternal signal function tracer drugs, far fewer have resources to practically identify and treat emergencies. In hypertensive emergencies for example, 38.6% of facilities have resources to identify the emergency (Stage 1 readiness, including sphygmomanometer, stethoscope, urine collection device, protein test). 6.8% have the resources to treat the emergency (Stage 2, consumables (IV Kit, fluids), durable goods (IV pole) and drugs (magnesium sulfate and hydralazine). No facilities could monitor or modify therapy (Stage 3). Across five maternal emergencies, the signal functions overestimate readiness by 54.5%. A consistent, step-wise pattern of readiness loss across signal functions and care stage emerged and was profoundly consistent at 33.0%.SignificanceComparing estimates from the maternal signal functions and cascades illustrates four themes. First, signal functions overestimate practical readiness by 55%. Second, the cascade's intuitive indicators can support cross-sector health system or program planners to more precisely measure and improve emergency care. Third, adding few variables to existing readiness inventories permits step-wise modeling of readiness loss and can inform more precise interventions. Fourth, the novel aggregate readiness loss indicator provides an innovative and intuitive approach for modeling health system emergency readiness. Additional testing in diverse contexts is warranted.

BackgroundIntrauterine growth restriction (IUGR) results from a lack of nutrients transferred to the developing fetus, particularly oxygen and glucose. Increased expression of the cytoprotective mitochondrial peptide, humanin (HN), and the glucose transporter 8, GLUT8, has been reported under conditions of hypoxic stress. However, the presence and cellular localization of HN and GLUT8 in IUGR-related placental pathology remain unexplored. Thus, we undertook this study to investigate placental expression of HN and GLUT8 in IUGR-affected versus normal pregnancies.ResultsWe found 1) increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for gestational age) pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells.ConclusionsThere was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine.

As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (

Maternal lipid profiles during pregnancy are associated with risk for preterm birth. This study investigates the association between maternal dyslipidemia and subsequent preterm birth among pregnant women in the state of California. Births were identified from California birth certificate and hospital discharge records from 2007-2012 (N = 2,865,987). Preterm birth was defined as

ObjectiveReducing environmental noise benefits premature infants in neonatal intensive care units (NICU), but excessive reduction may lead to sensory deprivation, compromising development. Instead of minimal noise levels, environments that mimic intrauterine soundscapes may facilitate infant development by providing a sound environment reflecting fetal life. This soundscape may support autonomic and emotional development in preterm infants. We aimed to assess the efficacy and feasibility of external non-invasive recordings in pregnant women, endeavoring to capture intra-abdominal or womb sounds during pregnancy with electronic stethoscopes and build a womb sound library to assess sound trends with gestational development. We also compared these sounds to popular commercial womb sounds marketed to new parents.Study designIntra-abdominal sounds from 50 mothers in their second and third trimester (13 to 40 weeks) of pregnancy were recorded for 6 minutes in a quiet clinic room with 4 electronic stethoscopes, placed in the right upper and lower quadrants, and left upper and lower quadrants of the abdomen. These recording were partitioned into 2-minute intervals in three different positions: standing, sitting and lying supine. Maternal and gestational age, Body Mass Index (BMI) and time since last meal were collected during recordings. Recordings were analyzed using long-term average spectral and waveform analysis, and compared to sounds from non-pregnant abdomens and commercially-marketed womb sounds selected for their availability, popularity, and claims they mimic the intrauterine environment.ResultsMaternal sounds shared certain common characteristics, but varied with gestational age. With fetal development, the maternal abdomen filtered high (500-5,000 Hz) and mid-frequency (100-500 Hz) energy bands, but no change appeared in contributions from low-frequency signals (10-100 Hz) with gestational age. Variation appeared between mothers, suggesting a resonant chamber role for intra-abdominal space. Compared to commercially-marketed sounds, womb signals were dominated by bowel sounds, were of lower frequency, and showed more variation in intensity.ConclusionsHigh-fidelity intra-abdominal or womb sounds during pregnancy can be recorded non-invasively. Recordings vary with gestational age, and show a predominance of low frequency noise and bowel sounds which are distinct from popular commercial products. Such recordings may be utilized to determine whether sounds influence preterm infant development in the NICU.