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Urbanization generally serves as a key navigator of the economic growth and development of the country. There is a need for fast and accurate urban planning to accommodate more and more people in the city area. Remote sensing technology has been used for planning the expansion and design of city areas. A novel machine learning (ML) classifier formed by combining AdaBoost and extra trees algorithm have been investigated for change detection in the urban area of three cities in the Gujarat region of India. Using Indian Remote Sensing (IRS) Resourcesat-2 LISS IV satellite images, the performance of the object-based AdaBoosted extra trees classifier (ABETC) in terms of overall accuracy (OA) and kappa coefficient (KC) for urban area change detection was compared to benchmarked object-based algorithms. As the first step in object-based classification (OBC), the Shepherd segmentation algorithm was used to segment satellite images. For all three cities, the object-based ABETC demonstrated the highest efficiency when compared to conventional classifiers. The rise in the built-up area of Ahmedabad city has been noted by 87.39 sq km from the year 2011 to 2020 showing the urban development of the city. This increase in the built-up area of Ahmedabad was compensated by the depletion of 30.26 sq. km. vegetation area, and 57.13 sq. km. of open land class. The built-up area of Vadodara and Rajkot city has been enlarged by 17.24 sq km and 6.79 sq km respectively. The highest OA of 96.04% and KC of 0.94 has been noted for a satellite image of Vadodara city with a novel object based ABETC algorithm.

Abstract Background Evaluating geographic access to health services often requires determining the patient travel time to a specified service. For urgent care, many research studies have modeled patient pre-hospital time by ground emergency medical services (EMS) using geographic information systems (GIS). The purpose of this study was to determine if the modeling assumptions proposed through prior United States (US) studies are valid in a non-US context, and to use the resulting information to provide revised recommendations for modeling travel time using GIS in the absence of actual EMS trip data. Methods The study sample contained all emergency adult patient trips within the Calgary area for 2006. Each record included four components of pre-hospital time (activation, response, on-scene and transport interval). The actual activation and on-scene intervals were compared with those used in published models. The transport interval was calculated within GIS using the Network Analyst extension of Esri ArcGIS 10.0 and the response interval was derived using previously established methods. These GIS derived transport and response intervals were compared with the actual times using descriptive methods. We used the information acquired through the analysis of the EMS trip data to create an updated model that could be used to estimate travel time in the absence of actual EMS trip records. Results There were 29,765 complete EMS records for scene locations inside the city and 529 outside. The actual median on-scene intervals were longer than the average previously reported by 7–8 minutes. Actual EMS pre-hospital times across our study area were significantly higher than the estimated times modeled using GIS and the original travel time assumptions. Our updated model, although still underestimating the total pre-hospital time, more accurately represents the true pre-hospital time in our study area. Conclusions The widespread use of generalized EMS pre-hospital time assumptions based on US data may not be appropriate in a non-US context. The preference for researchers should be to use actual EMS trip records from the proposed research study area. In the absence of EMS trip data researchers should determine which modeling assumptions more accurately reflect the EMS protocols across their study area.

Abstract Background The recent increase in childhood obesity is expected to add significantly to the prevalence of chronic diseases. We used multivariate multilevel analysis to examine associations between parks/green space and childhood overweight/obesity across communities in Calgary, Canada, a city characterized by intensified urban sprawl and high car use. Methods Body Mass Index was calculated from measured height and weight data obtained from 6,772 children (mean age = 4.95 years) attending public health clinics for pre-school vaccinations. Each child's home postal code was geocoded using ESRI ArcGIS 9.2. We examined four measures of spatial access to parks/green space (based on Geographic Information Systems): 1) the number of parks/green spaces per 10,000 residents, 2) the area of parks/green space as a proportion of the total area within a community, 3) average distance to a park/green space, and 4) the proportion of parks/green space service area as a proportion of the total area within a community. Analyses were adjusted for dissemination area median family income (as a proxy for an individual child's family income) community-level education, and community-level proportion of visible minorities. Results In general, parks/green space at the community level was not associated with overweight/obesity in Calgary, with the exception of a marginally significant effect whereby a moderate number of parks/green spaces per 10,000 residents was associated with lower odds of overweight/obesity. This effect was non-significant in adjusted analyses. Conclusion Our null findings may reflect the popularity of car travel in Calgary, Canada and suggest that the role built environment characteristics play in explaining health outcomes may differ depending on the type of urban environment being studied.

Abstract Background This study uses geographic information systems (GIS) as a tool to evaluate and visualize the general accessibility of areas within the province of Alberta (Canada) to cardiac catheterization facilities. Current American and European guidelines suggest performing catheterization within 90 minutes of the first medical contact. For this reason, this study evaluates the populated places that are within a 90 minute transfer time to a city with a catheterization facility. The three modes of transport considered in this study are ground ambulance, rotary wing air ambulance and fixed wing air ambulance. Methods Reference data from the Alberta Chart of Call were interpolated into continuous travel time surfaces. These continuous surfaces allowed for the delineation of isochrones: lines that connect areas of equal time. Using Dissemination Area (DA) centroids to represent the adult population, the population numbers were extracted from the isochrones using Statistics Canada census data. Results By extracting the adult population from within isochrones for each emergency transport mode analyzed, it was found that roughly 70% of the adult population of Alberta had access within 90 minutes to catheterization facilities by ground, roughly 66% of the adult population had access by rotary wing air ambulance and that no population had access within 90 minutes using the fixed wing air ambulance. An overall understanding of the nature of air vs. ground emergency travel was also uncovered; zones were revealed where the use of one mode would be faster than the others for reaching a facility. Conclusion Catheter intervention for acute myocardial infarction is a time sensitive procedure. This study revealed that although a relatively small area of the province had access within the 90 minute time constraint, this area represented a large proportion of the population. Within Alberta, fixed wing air ambulance is not an effective means of transporting patients to a catheterization facility within the 90 minute time frame, though it becomes advantageous as a means of transportation for larger distances when there is less urgency.

OBJECTIVE: Infants who sleep prone and face down on soft bedding are particularly vulnerable for sudden infant death syndrome. It has been suggested that 1 mechanism of death in this situation involves rebreathing of expired air. Many infants tolerate rebreathing while lying prone face down for long periods with stable saturations. Others occasionally have rapid desaturations and may require intervention to terminate rebreathing. The present study had 3 objectives: 1) to determine the frequency of rapid desaturations in a large group of healthy infants, 2) to elucidate the mechanism of these desaturations, and 3) to determine the timing of these events during periods of rebreathing. METHODS: We studied respiratory tracings and videotapes of 56 healthy 1- to 6-month-old infants who were sleeping face down and rebreathing on soft bedding in our laboratory. We compared the frequency of desaturations during rebreathing and nonrebreathing periods. We measured respiratory frequency and apnea occurrence before desaturation and nonrebreathing control episodes. We also measured minute ventilation during steady state before desaturation and just before desaturation. RESULTS: There were 25 desaturation episodes in infants while rebreathing, occurring in 11 (19.6%) of the 56 infants. Episodes were significantly more frequent during rebreathing than during nonrebreathing periods. Three desaturation episodes reached <85%; 2 required intervention to terminate rebreathing. The respiratory frequency was not different between nonrebreathing control and desaturation episodes. Brief apneas were significantly more frequent preceding desaturation than control episodes (44% vs 4%). Just before episodes, there was a transient decrease in minute volume despite increasing inspired carbon dioxide in 3 episodes. There was evidence of partial or complete pharyngeal airway obstruction in 3 episodes. Thirty-six percent of all episodes were immediately preceded by behavioral arousal. CONCLUSIONS: Rebreathing in prone sleeping infants is associated with an increased frequency of episodic desaturations. Desaturation may result from respiratory pattern changes such as brief apneas often associated with evidence of behavioral arousal or failure to increase ventilation in the face of rising inspired carbon dioxide, also associated with behavioral arousal. [ABSTRACT FROM AUTHOR]

This was a population-based study to determine the impact of COVID-19 on birth outcomes in the Chicago metropolitan area, comparing pre-pandemic (April-September 2019) versus pandemic (April-September 2020) births. Multivariable regression models that adjusted for demographic and neighborhood characteristics were used to estimate the marginal effects of COVID-19 on intrauterine fetal demise (IUFD)/stillbirth, preterm birth, birth hospital designation, and maternal and infant hospital length of stay (LOS). There were no differences in IUFD/stillbirths or preterm births between eras. Commercially insured preterm and term infants were 4.8 percentage points (2.3, 7.4) and 3.4 percentage points (2.5, 4.2) more likely to be born in an academic medical center during the pandemic, while Medicaid-insured preterm and term infants were 3.6 percentage points less likely (-6.5, -0.7) and 1.8 percentage points less likely (-2.8, -0.9) to be born in an academic medical center compared to the pre-pandemic era. Infant LOS decreased from 2.4 to 2.2 days (-0.35, -0.20), maternal LOS for indicated PTBs decreased from 5.6 to 5.0 days (-0.94, -0.19), and term births decreased from 2.5 to 2.3 days (-0.21, -0.17). The pandemic had a significant effect on the location of births that may have exacerbated health inequities that continue into childhood.

Background: Mothers of very preterm (<32 weeks gestational age [GA]) infants are breast pump dependent and have shorter duration of milk provision than mothers of term infants. The opportunity (i.e., time) cost of pumping and transporting mother's own milk (MOM) from home to the NICU may be a barrier. There is a paucity of data regarding how much time mothers actually spend pumping., Objective: To investigate the variation in pumping behavior by postpartum week, maternal characteristics, and infant GA., Methods: Prospectively collected pump log data from mothers enrolled in ReDiMOM (Reducing Disparity in Mother's Own Milk) randomized, controlled trial included pumping date and start time and end time of each pumping session for the first 10 weeks postpartum or until the infant was discharged from the NICU, whichever occurred first. Outcomes included number of daily pumping sessions, number of minutes spent pumping per day, and pumping behaviors during 24-h periods, aggregated to the postpartum week. Medians (interquartile ranges) were used to describe outcomes overall, and by maternal characteristics and infant GA., Results: Data included 13,994 pump sessions from 75 mothers. Maternal characteristics included 55% Black, 35% Hispanic, and 11% White and 44% <30 years old. The majority (56%) of infants were born at GA 28-31 weeks. Mothers pumped an average of less than 4 times per day, peaking in postpartum week 2. After accounting for mothers who stopped pumping, there was a gradual decrease in daily pumping minutes between postpartum weeks 2 (89 min) and 10 (46 min). Black mothers pumped fewer times daily than non-Black mothers after the first 2 weeks postpartum., Conclusion: On average mothers pumped less intensively than the minimum recommendation of 8 times and 100 min per day. However, these pumping behaviors represent significant maternal opportunity costs that should be valued by the institution and society at large., Competing Interests: PM has received research support and honoraria from Medela. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Patel, Tan, Bucek, Janes, McGee, Mulcahy, Meier and Johnson.)

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

With limited clinical evidence available to guide common nutritional decisions, significant variation exists in approaches to enteral feeding for very preterm infants, specifically when feedings are initiated, what is fed, and the method used for feedings. Preclinical studies have highlighted the benefits associated with avoiding nil per os and providing early-stage mother's own milk or colostrum. However, these recommended approaches are often mutually exclusive due to the delays in lactation associated with very preterm delivery, resulting in uncertainty regarding which approach should be prioritized. Few studies have evaluated feeding frequency in preterm infants, with limited generalizability to extremely preterm infants. Therefore, even evidence-based approaches to very preterm infant feed initiation can differ. Future research is needed to identify optimal strategies for enteral nutrition in very preterm infants, but, until then, evidence-informed approaches may vary depending on each neonatal intensive care unit's assessment of risk and benefit., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18-22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV)., Study Design: Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18-22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis., Results: 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32)., Conclusion: In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18-22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes., (© 2022. The Author(s).)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: This study was aimed to evaluate the impact of donor milk (DM) received in the first 28 days of life (DOL) on neurodevelopmental (ND) outcome at 20-months corrected age (CA) in very low birth weight (VLBW) infants., Study Design: A total of 84 infants born in 2011 to 2012 who received only mother's own milk (MOM) and/or preterm formula (PF) was compared with 69 infants born in 2013 to 2014 who received MOM and/or DM. Daily enteral intake of MOM, DM, and PF was collected through 28 DOL. ND outcomes were assessed with the Bayley-III. Multiple regression analyses adjusted for the effect of social and neonatal risk factors alongside era of birth on ND outcome., Results: Infants exposed to DM were born to older mothers ( p  < 0.01) and had higher incidence of severe brain injury ( p  = 0.013). Although DM group infants received first feed at earlier DOL ( p  < 0.001), there were no differences in MOM intake at DOL 14 or 28 between the two groups. In regression analyses, DM group did not predict 20-month ND outcome., Conclusion: There were no differences in ND outcome between infants born before and after the introduction of DM. This may have been due to the similar percent of MOM at DOL 14 and 28 in the two eras., Key Points: · Donor milk use is increasing in VLBW infant. The impact of donor milk on neurodevelopment is unclear.. · Provision of mother's own milk was high at days of life 14 and 28 for both groups of infants.. · Donor milk was not associated with improved neurodevelopmental outcome.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The study aim was to determine the relationship between hospitalization costs and mother's own milk (MOM) dose for very low birth weight (VLBW; < 1500 g) infants during the initial neonatal intensive care unit (NICU) stay. Additionally, because MOM intake during the NICU hospitalization is associated with a reduction in the risk of late-onset sepsis, necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD), we aimed to quantify the incremental cost of these potentially preventable complications of prematurity., Methods: The study included 430 VLBW infants enrolled in the Longitudinal Outcomes of Very Low Birthweight Infants Exposed to Mothers' Own Milk prospective cohort study between 2008 and 2012 at Rush University Medical Center in Chicago, IL, USA. NICU hospitalization costs included hospital, feeding, and physician costs. The average marginal effect of MOM dose and prematurity-related complications known to be reduced by MOM intake on NICU hospitalization costs were estimated using generalized linear regression., Results: The mean NICU hospitalization cost was $190,586 (standard deviation $119,235). The marginal cost of sepsis was $27,890 (95% confidence interval [CI] $2934-$52,646), of NEC was $46,103 (95% CI $16,829-$75,377), and of BPD was $41,976 (95% CI $24,660-59,292). The cumulative proportion of MOM during the NICU hospitalization was not significantly associated with cost., Conclusions: A reduction in the incidence of complications that are potentially preventable with MOM intake has significant cost implications. Hospitals should prioritize investments in initiatives to support MOM feedings in the NICU., (© 2022. The Author(s).)

Background: In 2017, the neonatal intensive care unit (NICU) at Rush University Medical Center (RUMC) implemented a protocol to provide individualized vitamin D supplementation dosing for very low-birth-weight (VLBW) and very preterm infants. This study evaluated the association of demographic and socioeconomic factors, vitamin D dose, and health indicators, including bone mineral status, measured by alkaline phosphatase and phosphorus levels; linear growth velocity; and occurrence of fractures., Method: This retrospective cross-sectional study included 227 VLBW or very preterm infants (34 VLBW, 12 very preterm, and 181 VLBW and very preterm) born in and discharged from the RUMC NICU between February 1, 2017, and October 31, 2019. Vitamin D dose was classified as adjusted (supplemental dose of 800 IU/day, n = 169) or standard (recommended dose of 400 IU/day, n = 58), per the protocol. Binary logistic and linear regression models were constructed to test the associations between infant and maternal characteristics and vitamin D dose group and between vitamin D dose group and health indicators., Results: The analysis found a statistically significant association between maternal age, gestational age, infant birth weight, and race/ethnicity and receipt of an adjusted vitamin D dose. No significant associations were found between health indicators and vitamin D dose., Conclusion: Sociodemographic factors may influence vitamin D deficiency in VLBW and very preterm infants in the NICU. At this time, there is insufficient evidence to support a tailored approach, but further research in this area is warranted., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Phase separation underlies the organization of the nucleus, including the biogenesis of nucleoli and the packaging of heterochromatin. Here we explore the regulation of transcription factor condensates involved in gene repression by ERK signaling in gastrulating embryos of a simple proto-vertebrate ( Ciona ). ERK signaling induces nuclear export of the transcriptional repressor Ets-2 repressive factor (ERF), which has been linked to various human developmental disorders. Using high-resolution imaging, we show that ERF is localized within discrete nuclear condensates that dissolve upon ERK activation. Interestingly, we observe dynamic pulses of assembly and dissociation during interphase, providing visualization of a nuclear phase separation process regulated by cell signaling. We discuss the implications of these observations for producing sharp on/off switches in gene activity and suppressing noise in cell-cell signaling events., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Background: Little is known about the biology of secretory activation (SA) in overweight and obese (OW/OB) mothers who are breast pump dependent with a premature infant in the neonatal intensive care unit. Objective: To compare time-dependent changes in daily pumped milk volume, maternal milk sodium (Na) concentration, and Na-to-potassium (K) ratios (Na:K) in the first 14 days postpartum in breast pump-dependent mothers with prepregnancy body mass index (BMI) <27 and BMI ≥27 kg/m 2 . Design/Methods: This secondary analysis for 39 subjects, 44% ( n  = 17) with prepregnancy BMI <27 and 56% ( n  = 22) with BMI ≥27, included transformed data of outcome measures, chi-square, t -tests, and growth curve models. Results: For days 1-7, daily pumped milk volume increased significantly more rapidly for mothers with BMI <27 (65.82 mL/d) versus BMI ≥27 (33.08 mL/d), but the daily rate of change in pumped milk volume during days 8-14 was not statistically different. Daily milk Na concentration decreased significantly faster in BMI <27 (-3.93 mM/d) versus BMI ≥27 (-2.00 mM/day) during days 1-7, but was not significantly different for days 8-14. No statistical differences were noted for Na:K ratio for either time period. Conclusion: These data add biologic evidence to previous research, suggesting delayed or impaired SA in OW/OB mothers, and suggest that the window of opportunity for research and clinical interventions is days 1-7 postpartum in this population.

Background: Black very low birth weight (VLBW; < 1500 g birth weight) and very preterm (VP, < 32 weeks gestational age, inclusive of extremely preterm, < 28 weeks gestational age) infants are significantly less likely than other VLBW and VP infants to receive mother's own milk (MOM) through to discharge from the neonatal intensive care unit (NICU). The costs associated with adhering to pumping maternal breast milk are borne by mothers and contribute to this disparity. This randomized controlled trial tests the effectiveness and cost-effectiveness of an intervention to offset maternal costs associated with pumping., Methods: This randomized control trial will enroll 284 mothers and their VP infants to test an intervention (NICU acquires MOM) developed to facilitate maternal adherence to breast pump use by offsetting maternal costs that serve as barriers to sustaining MOM feedings and the receipt of MOM at NICU discharge. Compared to current standard of care (mother provides MOM), the intervention bundle includes three components: a) free hospital-grade electric breast pump, b) pickup of MOM, and c) payment for opportunity costs. The primary outcome is infant receipt of MOM at the time of NICU discharge, and secondary outcomes include infant receipt of any MOM during the NICU hospitalization, duration of MOM feedings (days), and cumulative dose of MOM feedings (total mL/kg of MOM) received by the infant during the NICU hospitalization; maternal duration of MOM pumping (days) and volume of MOM pumped (mLs); and total cost of NICU care. Additionally, we will compare the cost of the NICU acquiring MOM versus NICU acquiring donor human milk if MOM is not available and the cost-effectiveness of the intervention (NICU acquires MOM) versus standard of care (mother provides MOM)., Discussion: This trial will determine the effectiveness of an economic intervention that transfers the costs of feeding VLBWand VP infants from mothers to the NICU to address the disparity in the receipt of MOM feedings at NICU discharge by Black infants. The cost-effectiveness analysis will provide data that inform the adoption and scalability of this intervention., Trial Registration: ClinicalTrials.gov: NCT04540575 , registered September 7, 2020., (© 2022. The Author(s).)

Even though transcriptional repressors are studied with ever-increasing molecular resolution, the temporal aspects of gene repression remain poorly understood. Here, we address the dynamics of transcriptional repression by Capicua (Cic), which is essential for normal development and is commonly mutated in human cancers and neurodegenerative diseases. 1 , 2 We report the speed limit for Cic-dependent gene repression based on live imaging and optogenetic perturbations in the early Drosophila embryo, where Cic was originally discovered. 3 Our measurements of Cic concentration and intranuclear mobility, along with real-time monitoring of the activity of Cic target genes, reveal remarkably fast transcriptional repression within minutes of removing an optogenetic de-repressive signal. In parallel, quantitative analyses of transcriptional bursting of Cic target genes support a repression mechanism providing a fast-acting brake on burst generation. This work sets quantitative constraints on potential mechanisms for gene regulation by Cic., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Modern studies of embryogenesis are increasingly quantitative, powered by rapid advances in imaging, sequencing and genome manipulation technologies. Deriving mechanistic insights from the complex datasets generated by these new tools requires systematic approaches for data-driven analysis of the underlying developmental processes. Here, we use data from our work on signal-dependent gene repression in the Drosophila embryo to illustrate how computational models can compactly summarize quantitative results of live imaging, chromatin immunoprecipitation and optogenetic perturbation experiments. The presented computational approach is ideally suited for integrating rapidly accumulating quantitative data and for guiding future studies of embryogenesis., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation., Study Design: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks., Results: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003)., Conclusions: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life., Trial Registration: Clinicaltrials.gov: NCT03192839., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence-based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting 'breastfeeding denialism' arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Mother's own milk (MOM) feeding is a cost-effective strategy to reduce risks of comorbidities associated with prematurity and improve long-term health of infants hospitalized in the Neonatal Intensive Care Unit (NICU). Significant racial and socioeconomic disparities exist in MOM provision in the NICU, highlighting the importance of developing strategies to reduce these disparities. Mothers of infants in the NICU experience many health concerns which may negatively impact lactation physiology. Objective measures of lactation physiology are limited but may assist in identifying mothers at particular risk. Several strategies to assist mothers of hospitalized infants are essential, including maternal education, qualified lactation professionals, early and frequent milk expression with a hospital-grade double electric breast pump, and providing support for transitioning to direct breastfeeding prior to discharge from the NICU., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess serial secretory activation biomarker concentrations (sodium [Na], potassium [K], Na:K, protein, lactose, and citrate) in mother's own milk (MOM) from breast pump-dependent mothers of preterm infants to determine associations with coming to volume (CTV), defined as producing at least 500 mL/day MOM by day 14 postpartum., Study Design: We collected serial MOM samples and pumped MOM volume data for 14 days postpartum in mothers who delivered at <33 weeks of gestation. Regression models and the Mann-Whitney U test were used to evaluate associations., Results: Among 40 mothers, 39 (mean gestational age, 28.8 weeks; 67% overweight/obese; 59% nonwhite) had paired MOM volume and biomarker data; 33% achieved CTV between postpartum days 6 and 14. In univariate models, MOM Na on postpartum day 5 and Na:K on days 3 and 5 were associated with CTV. Mothers achieving CTV were more likely to have postpartum Na:K ≤1 on day 3 (75% vs 25%; P = .06) and ≤0.8 on day 5 (69% vs 10%; P < .01). In a multivariable regression model, day 5 Na:K (1 unit decrease in Na:K: OR, 18.7; 95% CI, 1.13-311.41; P = .049) and maternal prepregnancy body mass index (BMI) (1 unit increase in BMI: OR, 0.88; 95% CI, 0.78-0.99; P = .04) were associated with CTV between postpartum days 6 and 14., Conclusions: Secretory activation and CTV were compromised in breast pump-dependent mothers with preterm delivery. CTV was predicted by MOM Na level and Na:K. These biomarkers have potential as objective point-of-care measures to detect potentially modifiable lactation problems in a high-risk population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To compare (1) differences in mother's own milk (MOM) provision and enteral feeding outcomes, (2) differences in preterm formula and donor human milk (DHM) uses as bridges to exclusive MOM feedings at discharge, and (3) MOM and enteral feeding outcomes for racial/ethnic subgroups before and after the implementation of a hospital DHM feeding program. Methods: Retrospective data from 313 very low birth weight (VLBW; birth weight <1,500 g) infants born between January 2011 to December 2012 (pre-DHM, n  = 157) and April 2013 to March 2015 (DHM, n  = 156) were analyzed. Results: For this predominantly low-income and minority VLBW infant cohort, the percent of enteral fed hospitalization days was higher in the DHM group (pre-DHM 94% [88, 97] versus DHM 98% [95, 99], p  < 0.001). Although MOM remained the predominant first enteral feeding type, significantly fewer DHM infants received MOM (pre-DHM 89% versus DHM 75%, p  = 0.001). During days of life 1-14, a lower percentage of DHM infants received 100% MOM (pre-DHM 68% versus DHM 55%, p  = 0.02). For the entire cohort, the risk for MOM discontinuation was significantly associated with maternal young age, multiparity, non-Hispanic Black race/ethnicity, and low income. Implementation of a DHM program did not predict duration of MOM feedings. However, non-Hispanic White infants had a longer duration of MOM feedings with DHM availability. Conclusions: Our findings highlight the importance of using precise dose and exposure period methodology to determine the impact of DHM on MOM provision. In addition, DHM availability may be associated with varying effects on MOM provision among racial/ethnic groups.

Very low birth weight (VLBW; <1500 g birth weight) infants are substantially more likely to be born to black than to non-black mothers, predisposing them to potentially preventable morbidities that increase the risk for costly lifelong health problems. Mothers' own milk (MOM) may be considered the ultimate "personalized medicine" since milk composition and bioactive components vary among mothers and multiple milk constituents provide specific protection based on shared exposures between mother and infant. MOM feedings reduce the risks and associated costs of prematurity-associated morbidities, with the greatest reduction afforded by MOM through to NICU discharge. Although black and non-black mothers have similar lactation goals and initiation rates, black VLBW infants are half as likely to receive MOM at NICU discharge in the United States. Black mothers are significantly more likely to be low-income, single heads of household and have more children in the home, increasing the burden of MOM provision. Although rarely considered, the out-of-pocket and opportunity costs associated with providing MOM for VLBW infants are especially onerous for black mothers. When MOM is not available, the NICU assumes the costs of inferior substitutes for MOM, contributing further to disparate outcomes. Novel strategies to mitigate these disparities are urgently needed. IMPACT: Mother's own milk exemplifies personalized medicine through its unique biologic activity. Hospital factors and social determinants of health are associated with mother's own milk feedings for very low-birth-weight infants in the neonatal intensive care unit. Notably, out-of-pocket and opportunity costs associated with providing mother's own milk are borne by mothers. Conceptualizing mother's own milk feedings as an integral part of NICU care requires consideration of who bears the costs of MOM provision-the mother or the NICU?

Objective: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC)., Study Design: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition., Results: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001)., Conclusions: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background/purpose: There is limited research regarding the consequences of treating lactating mothers with intravitreal anti-vascular endothelial growth factor (VEGF) agents. Balancing the need for vision-saving treatment, the benefits of breastfeeding, and the concern for affecting the newborn can present a conflict for both mothers and ophthalmologists. This review summarizes the state of the literature regarding the use of intravitreal anti-VEGF agents during breastfeeding along with details about their pharmacology., Results: Bevacizumab and aflibercept have Fc domains subjecting them to FcRn recycling and extending their half-life compared with ranibizumab which is an antibody fragment and lacks the Fc domain. Case reports and small studies have shown that ranibizumab has the lowest serum concentration after intravitreal injection and the least effect on plasma-free VEGF concentrations and breastmilk VEGF levels., Conclusion: Clinical and pharmacologic data suggest that ranibizumab has less systemic circulation and effect on maternal serum and breastmilk VEGF levels when compared to bevacizumab and aflibercept. However, there is significant need for further research on the degree and duration to which intravitreal agents circulate systemically, what fraction is transferred into breastmilk and is absorbed, and whether this results in any functional adverse effects to the infant. Other factors to consider in the medical decision-making of lactating mothers necessitating intravitreal anti-VEGF treatment include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether.

Objective: To assess the cost-effectiveness of mother's own milk supplemented with donor milk vs mother's own milk supplemented with formula for infants of very low birth weight in the neonatal intensive care unit (NICU)., Study Design: A retrospective analysis of 319 infants with very low birth weight born before (January 2011-December 2012, mother's own milk + formula, n = 150) and after (April 2013-March 2015, mother's own milk + donor milk, n = 169) a donor milk program was implemented in the NICU. Data were retrieved from a prospectively collected research database, the hospital's electronic medical record, and the hospital's cost accounting system. Costs included feedings and other NICU costs incurred by the hospital. A generalized linear regression model was constructed to evaluate the impact of feeding era on NICU total costs, controlling for neonatal and sociodemographic risk factors and morbidities. An incremental cost-effectiveness ratio was calculated for each morbidity that differed significantly between feeding eras., Results: Infants receiving mother's own milk + donor milk had a lower incidence of necrotizing enterocolitis (NEC) than infants receiving mother's own milk + formula (1.8% vs 6.0%, P = .048). Total (hospital + feeding) median costs (2016 USD) were $169 555 for mother's own milk + donor milk and $185 740 for mother's own milk + formula (P = .331), with median feeding costs of $1317 and $936, respectively (P < .001). Mother's own milk + donor milk was associated with $15 555 lower costs per infant (P = .045) and saved $1812 per percentage point decrease in NEC incidence., Conclusions: The additional cost of a donor milk program was small compared with the cost of a NICU hospitalization. After its introduction, the NEC incidence was significantly lower with small cost savings per case. We speculate that NICUs with greater NEC rates may have greater cost savings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

High-dose mother's own milk (MOM) feedings during the first 14 days post birth reduce the risk of necrotizing enterocolitis in very low birthweight (VLBW; <1500 g birthweight). However, high-dose MOM feedings are only possible if mothers provide sufficient quantities of MOM in a timely manner, and data indicate that the lack of MOM during the early post-birth period is a global problem. This paper reviews the modifiable and unmodifiable barriers to accessing adequate quantities of MOM during the early post-birth period and proposes evidence-based strategies to increase and improve the use of MOM during the neonatal intensive care unit (NICU) hospitalization with an emphasis on the critical first 2 weeks post birth.

Objective: To determine if mother's own milk (MOM) dose after gastroschisis repair is associated with time from feeding initiation to discharge. Secondary outcomes included parenteral nutrition (PN) duration and length of stay (LOS)., Study Design: Retrospective study of 44 infants with gastroschisis examined demographics, gastroschisis type, PN days, timing of nutrition milestones, feeding composition, and LOS., Results: MOM dose was significantly associated with shorter time to discharge from feeding initiation (adjusted hazard ratio [HR] for discharge per 10% increase in MOM dose, 1.111; 95% CI, 1.011-1.220, p = 0.029). MOM dose was also significantly associated with shorter LOS (adjusted HR for discharge per 10% increase in MOM dose, 1.130; 95% CI, 1.028-1.242, p = 0.011)., Conclusions: MOM dose was significantly associated with a decrease in time to discharge from feeding initiation and LOS in a dose-dependent manner. Mothers of gastroschisis patients should receive education and proactive lactation support to optimize MOM volume for feedings.

Background: Maternal concern about inadequate milk volume commonly emerges in the first 2 weeks postpartum, a critical lactation period that includes secretory activation. This review summarizes the biology of secretory activation and evaluates the accuracy and feasibility of published measures of secretory activation. Materials and Methods: A systematic search of measures of secretory activation for mothers of healthy term and preterm infants yielded 62 abstracts. Following additional screening, 15 publications qualified for quantitative synthesis review and were evaluated with respect to accuracy (validated with another measure of secretory activation in the same mother) and feasibility (accessibility, cost, and ease of use). Results: Maternal perception of milk coming in (MP) is the most feasible measure, but its accuracy has not been established. Patterns of increase in maternal milk volume have been validated with maternal milk-borne biomarkers in breastfeeding, and breast pump-dependent mothers and normal values have been published. Accuracy of serial maternal urinary lactose concentrations has not been established for secretory activation and lacks feasibility. Maternal milk biomarkers are the accurate standard to which other measures are compared but currently lack feasibility for routine use. Conclusions: Use of secretory activation measures can personalize lactation care by matching maternal risk with appropriate diagnostics. Priorities for research and practice include validation of MP as a population-based screening tool, implementation of techniques that measure patterns of increase in milk volume for moderate risk populations, and the development of milk biomarker science for point-of-care use in the most complicated lactation scenarios.

Optogenetic approaches are transforming quantitative studies of cell-signaling systems. A recently developed photoswitchable mitogen-activated protein kinase kinase 1 (MEK1) enzyme (psMEK) short-circuits the highly conserved Extracellular Signal-Regulated Kinase (ERK)-signaling cascade at the most proximal step of effector kinase activation. However, since this optogenetic tool relies on phosphorylation-mimicking substitutions in the activation loop of MEK, its catalytic activity is predicted to be substantially lower than that of wild-type MEK that has been phosphorylated at these residues. Here, we present evidence that psMEK indeed has suboptimal functionality in vivo and propose a strategy to circumvent this limitation by harnessing gain-of-function, destabilizing mutations in MEK. Specifically, we demonstrate that combining phosphomimetic mutations with additional mutations in MEK, chosen for their activating potential, restores maximal kinase activity in vitro. We establish that this modification can be tuned by the choice of the destabilizing mutation and does not interfere with reversible activation of psMEK in vivo in both Drosophila and zebrafish. To illustrate the types of perturbations enabled by optimized psMEK, we use it to deliver pulses of ERK activation during zebrafish embryogenesis, revealing rheostat-like responses of an ERK-dependent morphogenetic event., Competing Interests: The authors declare no competing interest.

A convenient and effective synthetic approach for benzochalcogendiazole-based small molecules has been achieved using polyaniline (PANI)-anchored palladium as a heterogeneous catalyst. The photophysical properties of the synthesized benzochalcogendiazole-based small molecules, having different terminal substituents, have been compared. Moreover, the structural aspects, including the packing patterns and non-bonding interactions of the conjugated molecules, have been investigated using the single crystal X-ray diffraction (SCXRD) technique.

Objective: To use a social-ecological conceptualization to analyze change of maternal distress, defined as depression, anxiety, and perinatal-specific post-traumatic stress (PPTS), across very low birth weight (VLBW) infants' first year of life and to identify infant, maternal, and neighborhood predictors of these changes over time., Methods: Mothers of VLBW infants (n = 69) completed psychological distress questionnaires 2 to 4 weeks after infant birth, 2 weeks before infant discharge from neonatal intensive care unit, and at infants' 4- and 8-month corrected age (age adjusted for prematurity). Infant and maternal sociodemographic data were collected from medical chart review. Neighborhood data were obtained through US census data. Multilevel linear growth modeling was used to (1) predict unstandardized estimates of mothers' initial levels of depression, anxiety, and PPTS at the time of infant's birth and the rate of change of these markers of distress over time and (2) model unstandardized estimates of infant, maternal, and neighborhood as predictors of distress at infants' birth and change over time., Results: Unstandardized estimates from multilevel linear growth modeling revealed depression (-2.8), anxiety (-1.4), and PPTS (-0.7) declined over infants' first year of life (<0.001). Mothers residing in lower-income homes and neighborhoods, respectively, reported lower anxiety (-11.2, p = 0.03) and PPTS (-31.1, p = 0.01) at infant birth. Greater infant birth weight predicted both lower anxiety (-0.02, p = 0.02) and lower PPTS (-0.02, p = 0.005)., Conclusion: Mothers psychologically recover over VLBW infants' first year of life. Results add to a building literature about socioeconomically disadvantaged mothers of preterm infants, reporting lower distress; this warrants additional research.

Objective: Determine the knowledge and priorities for postpartum contraception and lactation in mothers of premature infants. Design: Twenty-five mothers of premature infants (mean gestational age = 29.9 weeks) hospitalized in a tertiary neonatal intensive care unit (NICU) participated in a multi-methods study using a multiple-choice contraceptive survey and qualitative interview in the first 2 weeks postpartum. Data were analyzed using content analysis and descriptive statistics. Results: Although 60% of mothers planned to use contraception, all questioned the timing of postpartum contraceptive counseling while recovering from a traumatic birth and coping with the critical health status of the infant. All mothers prioritized providing mothers' own milk (MOM) over the use of early hormonal contraception because they did not want to "take any risks" with their milk. They had limited knowledge of risks for repeat preterm birth (e.g., prior preterm birth: n  = 13, 52%; multiple birth: n  = 9, 36%; no knowledge: n  = 3, 12%); only two mothers (0.08%) were counseled about the risks of a short interpregnancy interval. Conclusion: The context of the infants' NICU admission and the mother's desire to "do what is best for the baby" by prioritizing MOM should be integrated into postpartum contraceptive counseling for this population.

Background: Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes., Method: Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates., Results: Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8-33 days), weight gain (5.0-14.6 g/kg/day), ∆z-scores (-0.54 to -1.64), incidence of NEC (1%-13%), and mortality (1%-18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P < .001) than non-GD units, but NEC incidence and mortality were similar., Conclusion: Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Background: Despite high initiation rates for mother's own milk (MOM) provision, MOM feeding at discharge from the neonatal intensive care unit (NICU) drops precipitously and reveals a racial/ethnic disparity. This study sought to identify factors that (1) predict MOM feeding at NICU discharge, and (2) mediate racial/ethnic disparity in MOM feeding at discharge., Methods: Secondary analysis of prospective cohort study of 415 mothers and their very low birth weight infants. Variables were grouped into five categories (demographics, neighborhood structural, social, maternal health, and MOM pumping). Significant predictors from each category were entered into a multivariable logistic regression model., Results: Although 97.6% of infants received MOM feedings, black infants were significantly less likely to receive MOM feeding at discharge. Positive predictors were daily pumping frequency, reaching pumped MOM volume ≥500 mL/day by 14 days, and maternal age. Negative predictors were low socioeconomic status (SES) and perceived breastfeeding support from the infant's maternal grandmother. Low SES, maternal age, and daily pumping frequency mediated the racial/ethnic differences., Conclusions: Multiple potentially modifiable factors predict MOM feeding at NICU discharge. Importantly, low SES, pumping frequency, and maternal age were identified as the mediators of racial and ethnic disparity. Strategies to mitigate the effects of modifiable factors should be developed and evaluated in future research.

Mother's own milk (MOM) reduces the risk of morbidities in very low birth weight (VLBW) infants. When MOM is unavailable, donor breastmilk (DM) is used, with unclear impact on short- and long-term growth. This retrospective analysis compared anthropometric data at six time points from birth to 20⁻24 months corrected age in VLBW infants who received MOM supplements of preterm formula ( n = 160) versus fortified DM ( n = 161) during neonatal intensive care unit (NICU) hospitalization. The cohort was 46% female; mean birth weight and gestational age (GA) were 998 g and 27.3 weeks. Multilevel linear growth models assessed changes in growth z -scores short-term (to NICU discharge) and long-term (post-discharge), controlling for amount of DM or formula received in first 28 days of life, NICU length of stay (LOS), birth GA, and sex. Z -scores for weight and length decreased during hospitalization but increased for all parameters including head circumference post-discharge. Short-term growth was positively associated with LOS and birth GA. A higher preterm formula proportion, but not DM proportion, was associated with slower rates of decline in short-term growth trajectories, but feeding type was unrelated to long-term growth. In conclusion, controlling for total human milk fed, DM did not affect short- or long-term growth.

Background: Premature infants are susceptible to oxidative stress, increasing the risk for serious morbidities. High-dose human milk (HM) feedings decrease morbidity risks and may reduce oxidative stress in this population. The purpose of this study was to compare oxidative stress using serial urinary F 2 -isoprostane concentrations in predominantly HM and preterm formula (PF)-fed premature infants over the first 21 days of life (DOL), while controlling for perinatal oxidative stress exposures including bovine-based human milk fortifier (HMF) or PF introduction to predominantly HM-fed infants., Methods: This was a quasi-experimental design that categorized 22 premature infants into mutually exclusive comparison groups based on exposure to HM and PF. Serial urine samples (before and after first feeding, and DOL 7, 14, and 21) were used to determine urine F 2 -isoprostane concentrations measured by enzyme-linked immunosorbent assays. We analyzed data using Mann-Whitney U test, Wilcoxon rank test, and multilevel models., Results: Comparing the predominantly HM-fed and predominantly PF-fed groups over time, median F 2 -isoprostane concentrations decreased significantly in the predominantly HM group (P = .003) and increased significantly in the predominantly PF group (P = .01). Perinatal oxidant exposures and the introduction of HMF did not affect results., Conclusions: Our results demonstrate that predominantly HM feedings were associated with decreased oxidative stress, whereas PF feedings increased oxidative stress in premature infants, even after controlling for perinatal oxidant exposures of HMF or PF introduction., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objective: To determine the association between human milk (HM) dose and health care utilization at one and 2 years of life in very low birth weight (birth weight < 1500 g; VLBW) infants., Study Design: This study included 345 VLBW infants enrolled in a prospective observational cohort study (2008-2012) who completed a neonatal high-risk follow-up clinic visit. Subsequent health care utilization included hospitalizations, emergency department visits, pediatric subspecialists, and specialized therapies., Results: Each 10 mL/kg/day increase in HM in the first 14 days of life was associated with 0.26 fewer hospitalizations (p = 0.04) at 1 year and 0.21 fewer pediatric subspecialist types (p = 0.04) and 0.20 fewer specialized therapy types (p = 0.04) at 2 years., Conclusion: HM dose in early life for VLBW infants was an independent predictor of the number of hospitalizations at 1 year and types of pediatric subspecialists and specialized therapies at 2 years of life.

Objective: To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants., Study Design: This was a cohort study of VLBW infants who initially received maternal BM and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge., Results: Median gestational age for all infants was 28 weeks (25 th , 75 th percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age., Conclusions: Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The development of an accurate, sensitive, specific, rapid, reproducible, stable-at-room-temperature and cost-effective diagnostic kit, and a low-cost portable fluorescence detector to fulfil the requirements of diagnostic facilities in developing countries., Methods: We developed the 'Chlamy and Ness CT/NG kit' based on molecular beacons for the detection of Chlamydia trachomatis (CT) and Neisseriagonorrhoeae (NG). Multi-centric evaluation of the CT/NG kit was performed using the commercially available nucleic acid amplification test (NAAT)-based FTD Urethritis basic kit for comparison from December 2014 to November 2016. The stability of the kit reagents at 4 and 37 ˚C and the inter-day reproducibility of results were also analysed., Results: The sensitivity and specificity of the kit were found to be 95.83 and 100.00 % for the detection of C. trachomatis and 93.24 and 99.75 % for N. gonorrhoeae, respectively, when tested against the commercial kit. The positive predictive value (PPV) was 100.00 and 98.57 %, whereas the negative predictive value (NPV) was 99.54 and 98.79 % for C. trachomatis and N. gonorrhoeae, respectively. Analysis of the kappa statistics enhanced the 'inter-rater' κ=0.976 for Chlamydia and κ=0.943 for Neisseria., Conclusion: Our kit was found to be as sensitive and specific as commercially available kits. Its low cost and ease of use will make it suitable for the routine diagnosis of C. trachomatis and N. gonorrhoeae in the resource-limited settings of developing countries.

The extracellular signal-regulated kinase (ERK) pathway leads to activation of the effector molecule ERK, which controls downstream responses by phosphorylating a variety of substrates, including transcription factors. Crucial insights into the regulation and function of this pathway came from studying embryos in which specific phenotypes arise from aberrant ERK activation. Despite decades of research, several important questions remain to be addressed for deeper understanding of this highly conserved signaling system and its function. Answering these questions will require quantifying the first steps of pathway activation, elucidating the mechanisms of transcriptional interpretation and measuring the quantitative limits of ERK signaling within which the system must operate to avoid developmental defects., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Objective: Mothers of premature infants confront barriers to coming to volume (CTV; ≥500 mL/day mother's own milk [MOM] by postpartum day 14), a strong predictor of continued MOM provision at neonatal intensive care unit (NICU) discharge. We sought to determine concentrations of secretory activation biomarkers (MOM sodium, total protein, lactose, and citrate) during the first 14 postpartum days and to describe relationships among these biomarkers, pumped MOM volume, CTV, and pumping frequency., Study Design: This descriptive observational study collected serial MOM samples, pumped MOM volume, and pumping frequency during the first 14 postpartum days in 16 breast pump-dependent mothers who delivered <33 weeks gestation. Daily biomarker concentrations were compared to published normal values for mothers of term infants. Relationships among biomarkers, pumped MOM volume, and pumping frequency were determined., Results: On postpartum day 5, only 40% of MOM samples revealed normal concentrations of all four biomarkers, and normalcy was not maintained throughout the first 14 days. All eight mothers (50%) who achieved CTV had normal concentrations for four biomarkers at 5.4 ± 3.5 days postpartum and had more cumulative pumping sessions by day 5 (p = 0.03). A dose-response relationship between number of normal biomarkers and pumped MOM volume was demonstrated for postpartum days 3 (p = 0.01) and 5 (p = 0.04)., Conclusion: Secretory activation is delayed in mothers who deliver prematurely and is closely tied to CTV, MOM volume, and pumping frequency. MOM biomarkers hold promise as objective research outcome measures and for point-of-care testing to identify and proactively manage mothers at risk for compromised lactation.

Objective: Necrotising enterocolitis (NEC) is one of the most common and often fatal intestinal disorders in preterm infants. Markers to identify at-risk infants as well as therapies to prevent and treat NEC are limited and urgently needed. NEC incidence is significantly lower in breast-fed compared with formula-fed infants. Infant formula lacks human milk oligosaccharides (HMO), such as disialyllacto-N-tetraose (DSLNT), which prevents NEC in neonatal rats. However, it is unknown if DSLNT also protects human preterm infants., Design: We conducted a multicentre clinical cohort study and recruited 200 mothers and their very low birthweight infants that were predominantly human milk-fed. We analysed HMO composition in breast milk fed to infants over the first 28 days post partum, matched each NEC case with five controls and used logistic regression and generalised estimating equation to test the hypothesis that infants who develop NEC receive milk with less DSLNT than infants who do not develop NEC., Results: Eight infants in the cohort developed NEC (Bell stage 2 or 3). DSLNT concentrations were significantly lower in almost all milk samples in NEC cases compared with controls, and its abundance could identify NEC cases prior to onset. Aggregate assessment of DSLNT over multiple days enhanced the separation of NEC cases and control subjects., Conclusions: DSLNT content in breast milk is a potential non-invasive marker to identify infants at risk of developing NEC, and screen high-risk donor milk. In addition, DSLNT could serve as a natural template to develop novel therapeutics against this devastating disorder., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: This study sought to determine the maternal prepregnancy, pregnancy, and delivery risk factors that predicted coming to volume (CTV; achieving pumped mother's own milk [MOM] volume ≥500 mLs/day) and the continuation of MOM provision through to discharge from the neonatal intensive care unit (NICU) in mothers and their very low birthweight (VLBW; <1,500 g at birth) infants., Study Design: Secondary analysis of prospectively collected data from 402 mothers of VLBW infants admitted to an urban NICU, including detailed MOM pumping records for a subset (51%) of the cohort. Analyses included inverse probability weighting, multivariate regression, and chi-square statistics., Results: In this high-risk cohort (51.2% black, 27.1% Hispanic, 21.6% white/Asian; 72.6% low income; 61.4% overweight/obese prepregnancy), CTV by day 14 was the strongest predictor of MOM feeding at NICU discharge (odds ratio [OR] 9.70 confidence interval [95% CI] 3.86-24.38, p < 0.01.). Only 39.5% of mothers achieved CTV by postpartum day 14, an outcome that was predicted by gestational age at delivery (OR 1.41, 95% CI 1.15-1.73, p < 0.01), being married (OR 3.66, 95% CI 1.08-12.39, p = 0.04), black race (OR 7.70, 95% CI 2.05-28.97, p < 0.01), cesarean delivery (OR 0.22, 95% CI 0.08-0.63, p = 0.01), and chorioamionitis (OR 0.14, 95% CI 0.02-0.82, p = 0.03)., Conclusion: Continued provision of MOM at NICU discharge can be predicted in the first 14 postpartum days on the basis of achievement of CTV. We posit that CTV can serve as a quality indicator for improving MOM feedings in the NICU and that lactation support resources should target this early critical postbirth period.

NEC is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Human milk feedings, both from the infant's mother and donor human milk, have been associated with reductions in NEC in preterm infants. This article will review the protective factors in human milk, clinical studies of human milk and NEC, and practices to enhance human milk use in neonatal intensive care units., (Copyright © 2018 Elsevier Inc. All rights reserved.)